Phage , the virus that cures

[William Gaatjes]

A gut bacteria that affect multiple sclerosis in mice.


http://www.sciencedaily.com/releases/2010/07/100719162643.htm

he work -- led by Sarkis K. Mazmanian, an assistant professor of biology at Caltech, and postdoctoral scholar Yun Kyung Lee -- appears online the week of July 19-23 in the Proceedings of the National Academy of Sciences.

Multiple sclerosis results from the progressive deterioration of the protective fatty myelin sheath surrounding nerve cells. The loss of myelin hinders nerve cells from communicating with one another, leading to a host of neurological symptoms including loss of sensation, muscle spasms and weakness, fatigue, and pain. Multiple sclerosis is estimated to affect about half a million people in the United States alone, with rates of diagnosis rapidly increasing. There is currently no cure for MS.

Although the cause of MS is unknown, microorganisms seem to play some sort of role. "In the literature from clinical studies, there are papers showing that microbes affect MS," Mazmanian says. "For example, the disease gets worse after viral infections, and bacterial infections cause an increase in MS symptoms."

On the other hand, he concedes, "it seems counterintuitive that a microbe would be involved in a disease of the central nervous system, because these are sterile tissues."

And yet, as Mazmanian found when he began examining the multiple sclerosis literature, the suggestion of a link between bacteria and the disease is more than anecdotal. Notably, back in 1993, Caltech biochemist Leroy Hood -- who was then at the University of Washington -- published a paper describing a genetically engineered strain of mouse that developed a lab-induced form of multiple sclerosis known as experimental autoimmune encephalomyelitis, or EAE.

When Hood's animals were housed at Caltech, they developed the disease. But, oddly, when the mice were shipped to a cleaner biotech facility -- where their resident gut bacterial populations were reduced -- they didn't get sick. The question was, why? At the time, Mazmanian says, "the authors speculated that some environmental component was modulating MS in these animals." Just what that environmental component was, however, remained a mystery for almost two decades.

But Mazmanian -- whose laboratory examines the relationships between gut microbes, both harmful and helpful, and the immune systems of their mammalian hosts -- had a hunch that intestinal bacteria were the key. "As we gained an appreciation for how profoundly the gut microbiota can affect the immune system, we decided to ask if symbiotic bacteria are the missing variable in these mice with MS," he says.

To find out, Mazmanian and his colleagues tried to induce MS in animals that were completely devoid of the microbes that normally inhabit the digestive system. "Lo and behold, these sterile animals did not get sick," he says.

Then the researchers decided to see what would happen if bacteria were reintroduced to the germ-free mice. But not just any bacteria. They inoculated mice with one specific organism, an unculturable bug from a group known as segmented filamentous bacteria. In prior studies, these bacteria had been shown to lead to intestinal inflammation and, more intriguingly, to induce in the gut the appearance of a particular immune-system cell known as Th17. Th17 cells are a type of T helper cell -- cells that help activate and direct other immune system cells. Furthermore, Th17 cells induce the inflammatory cascade that leads to multiple sclerosis in animals.

"The question was, if this organism is inducing Th17 cells in the gut, will it be able to do so in the brain and central nervous system?" Mazmanian says. "Furthermore, with that one organism, can we restore to sterile animals the entire inflammatory response normally seen in animals with hundreds of species of gut bacteria?"

The answer? Yes on all counts. Giving the formerly germ-free mice a dose of one species of segmented filamentous bacteria induced Th17 not only in the gut but in the central nervous system and brain -- and caused the formerly healthy mice to become ill with MS-like symptoms.

"It definitely shows that gut microbes have a strong role in MS, because the genetics of the animals were the same. In fact, everything was the same except for the presence of those otherwise benign bacteria, which are clearly playing a role in shaping the immune system," Mazmanian says. "This study shows for the first time that specific intestinal bacteria have a significant role in affecting the nervous system during MS -- and they do so from the gut, an anatomical location very, very far from the brain."

Mazmanian and his colleagues don't, however, suggest that gut bacteria are the direct cause of multiple sclerosis, which is known to be genetically linked. Rather, the bacteria may be helping to shape the immune system's inflammatory response, thus creating conditions that could allow the disease to develop. Indeed, multiple sclerosis also has a strong environmental component; identical twins, who possess the same genome and share all of their genes, only have a 25 percent chance of sharing the disease. "We would like to suggest that gut bacteria may be the missing environmental component," he says.

For their part, Th17 cells are needed for the immune system to properly combat infection. Problems only arise when the cells are activated in the absence of infection -- just as disease can arise, Mazmanian and others suspect, when the species composition of gut bacteria become imbalanced, say, by changes in diet, because of improved hygiene (which kills off the beneficial bacteria as well as the dangerous ones), or because of stress or antibiotic use. One impact of the dysregulation of normal gut bacterial populations -- a phenomenon dubbed "dysbiosis" -- may be the rising rate of multiple sclerosis seen in recent years in more hygienic societies.

"As we live cleaner, we're not just changing our exposure to infectious agents, but we're changing our relationship with the entire microbial world, both around and inside us, and we may be altering the balance between pro- and anti-inflammatory bacteria," leading to diseases like MS, Mazmanian says. "Perhaps treatments for diseases such as multiple sclerosis may someday include probiotic bacteria that can restore normal immune function in the gut… and the brain."

 

[tcsenter]

Since there is no definitive diagnosis for MS and its etiology is almost completely unknown, it creates the potential for 'many like things' to get diagnosed as MS (or something else) which do not have the same underlying etiology. e.g.

http://en.wikipedia.org/wiki/Chronic_cerebrospinal_venous_insufficiency

http://www.hbotreatment.com/The&#37...New and Extended Vascular- Ischemic Model.pdf

 

[William Gaatjes]

Since there is no definitive diagnosis for MS and its etiology is almost completely unknown, it creates the potential for 'many like things' to get diagnosed as MS (or something else) which do not have the same underlying etiology. e.g.

http://en.wikipedia.org/wiki/Chronic_cerebrospinal_venous_insufficiency

http://www.hbotreatment.com/The&#37...New and Extended Vascular- Ischemic Model.pdf

Oh, i agree. There are many different perspectives to research from. The interesting part is that the immune system can be "controlled" or at least informed by bacteria. I am still wondering if the human immune system can listen in on the quorum sensing language of bacteria. Some researchers suggest that the language of bacteria is a bit more complex then just voting and keeping track of votes. Bacteria may have more to say then we think. From a certain perspective, one can say that the human body after birth is conditioned by bacteria to stay alive in nature. More and more research in this direction seems to reveal so... In this thread is a lot of information to be found about examples. And that is just what i collected when i have nothing to do. There must be so much more information out there waiting to be collected.... ^_^

Forgot, thank you for the pdf. I stored it.

 

[William Gaatjes]

Virus time ! 4 articles .^_^

http://www.sciencedaily.com/releases/2010/01/100107103621.htm

About eight percent of human genetic material comes from a virus and not from our ancestors, according to researchers in Japan and the U.S.
The study, and an accompanying News & Views article by University of Texas at Arlington biology professor Cédric Feschotte, is published in the journal Nature.The research showed that the genomes of humans and other mammals contain DNA derived from the insertion of bornaviruses, RNA viruses whose replication and transcription takes place in the nucleus.

Feschotte wrote on recent research led by Professor Keizo Tomonaga at Osaka University in Japan. Feschotte said this virally transmitted DNA may be a cause of mutation and psychiatric disorders such as schizophrenia and mood disorders.In his article, Feschotte speculates about the role of such viral insertions in causing mutations with evolutionary and medical consequences.
The assimilation of viral sequences into the host genome is a process referred to as endogenization. This occurs when viral DNA integrates into a chromosome of reproductive cells and is subsequently passed from parent to offspring. Until now, retroviruses were the only viruses known to generate such endogenous copies in vertebrates. But Feschotte said that scientists have found that non-retroviral viruses called bornaviruses have been endogenized repeatedly in mammals throughout evolution.Bornavirus (BDV) owes its name to the town of Borna, Germany, where a virus epidemic in 1885 wiped out a regiment of cavalry horses. BDV infects a range of birds and mammals, including humans. It is unique because it infects only neurons, establishing a persistent infection in its host's brain, and its entire life cycle takes place in the nucleus of the infected cells. Feschotte said this intimate association of BDV with the cell nucleus prompted researchers to investigate whether bornaviruses may have left behind a record of past infection in the form of endogenous elements. They searched the 234 known eukaryotic genomes (those genomes that have been fully sequenced) for sequences that are similar to that of BDV. "The researchers unearthed a plethora of endogenous Borna-like N (EBLN) elements in many diverse mammals, " Feschotte said.The scientists also were able to recover spontaneous BDV insertions in the chromosomes of human cultured cells persistently infected by BVD.Based on these data, Feschotte proposes that BDV insertions could be a source of mutations in the brain cells of infected individuals."These data yield a testable hypothesis for the alleged, but still controversial, causative association of BDV infection with schizophrenia and mood disorders," Feschotte said. The research in Feschotte 's laboratory, which largely focuses on transposable elements, the genetic elements that are able to move and replicate within the genomes of virtually all living organisms, is representative of the research under way at UT Arlington, an institution of 28,000 students on its way to becoming a nationally recognized, top-tier research university.

http://www.sciencedaily.com/releases/2008/06/080624111015.htm

Viruses can travel around cells they infect by hitching a ride on a microscopic transport system, according to new research.
Cells are exposed to foreign DNA and RNA and it is understood that some of this genetic material can be integrated into the host genome. Using modern microscopic techniques, scientists have been able to see how virus DNA is transported in the cell.Professor Dr Urs Greber from the University of Zurich will describe interactions between viruses and the cell cytoskeleton on June 24 2008 at the new SGM-RMS satellite meeting, part of the MICROSCIENCE 2008 conference being held at the ExCeL conference centre in London.
"We have been using human adenoviruses (Ads) to investigate transport processes of foreign DNA in the cytoplasm of human cells," said Professor Dr Greber. "Adenoviruses are a diverse family of agents that replicate their DNA genome in the cell nucleus. We wanted to find out how the virus gets to the nucleus to replicate. To do this we have been using live cell fluorescence microscopy, which means we can literally watch the virus travelling inside the cell."Human adenoviruses can cause respiratory, urinary and digestive infections. They occasionally cause epidemic conjunctivitis, and can be fatal in immunocompromised patients. Adenoviruses can aggravate asthmatic conditions, and are associated with deadly gastroenteritis in babies. This research improves our knowledge of how the virus replicates in host cells.
"Virus DNA is transported from the edge of the cell to the nucleus in the middle by attaching to microtubules. These are microscopic tubes that form part of the cytoskeleton, keeping the cell in shape and carrying molecules around in the cytoplasm," said Professor Dr Greber. "We found an unexpected new link between microtubule-based transport in the cytoplasm of the cell and the import of virus DNA to the nucleus."Other talks at the one-day SGM meeting will concentrate on the 'tussle' that takes place when a host cell tries to fight back against an invading pathogen. Sir David King will start the day by talking about the 'Twenty first century challenges of sustainability and wellbeing'. Professor Timo Hyypia (University of Turku) will speak on 'Cellular interactions of enteroviruses' and Dr Mark Jepson (University of Bristol) will look at the way in which bacteria invade cells. The manipulation of cellular compartments by the SARS coronavirus for replication purposes will also be discussed by Dr Marjolein Kikkert (Leiden University Medical Centre).

http://www.sciencedaily.com/releases/2010/07/100729172330.htm

Over millions of years, retroviruses, which insert their genetic material into the host genome as part of their replication, have left behind bits of their genetic material in vertebrate genomes.
In a recent study, published July 29 in the open-access journal PLoS Pathogens, a team of researchers have now found that human and other vertebrate genomes also contain many ancient sequences from Ebola/Marburgviruses and Bornaviruses -- two deadly virus families.Because neither virus family inserts their genetic material into the host genome during replication, as retroviruses do, the discovery was all the more unexpected."This was a surprise for us," says author Anna Marie Skalka, Ph.D., Director Emerita of the Institute for Cancer Research at Fox Chase Cancer. "It says that the source of our genetic material is considerably wider than we thought. It includes our own genes and unexpected viral genes as well."The team, which included lead author Vladimir A. Belyi, Ph.D., and co-author Arnold J. Levine, Ph.D., both at the Institute for Advanced Study in Princeton, compared 5,666 viral genes from all known non-retroviral families with single-stranded RNA genomes to the genomes of 48 vertebrate species, including humans. In doing so, they uncovered 80 separate viral sequence integrations into 19 different vertebrate species. Interestingly, nearly all of the viral sequences come from ancient relatives of just two viral families, the Ebola/Marburgviruses and Bornaviruses, both of which cause hemorrhagic fevers and neurological disease."These viruses are RNA viruses," Skalka says. "They replicate their RNA and are not known to make any DNA. And they have no known mechanism for getting their genetic material integrated into the DNA of the host genome. Indeed, some of them don't even enter the nucleus when they replicate."That the sequences, some of which may have been integrated into the genomes more than 40 million years ago, have been largely conserved over evolutionary time suggests that they give the host a selective advantage, perhaps protecting them from future infections by viruses from those families. The study shows that integration of the ancient viral sequences was probably mediated by movable elements, LINEs, which are abundant in mammalian genomes."In a way, one might even think of these integrations as genomic vaccinations," says Skalka.Demonstrating conclusively that the viral sequences have some biological function will take additional work. However, the team has noted that expression of some of these viral open reading frames has been detected in human tissues, which supports the possibility that they are biologically active in host species.

http://www.sciencedaily.com/releases/2008/05/080531090353.htm

A Weizmann Institute study provides important new insights into the process of viral infection. The study, reported in the online journal PLoS Biology, reveals certain mechanisms by which mimivirus – a virus so called because it was originally thought to mimic bacteria in various aspects of their behavior – invades amoeba cells.

Living cells become infected by viruses in two steps. First, the virus penetrates the cell. Next, in the second and crucial step, the cell starts producing new viruses, which spread and infect additional cells. At the beginning of this production process, the cell makes the outer wall of the virus, which is a container of sorts composed of proteins and known as the capsid. The cell then makes copies of viral DNA and inserts it into the capsid. The result is a new, functioning virus that is ready to leave the host cell and infect more cells.Understanding how viruses infect cells and how new viruses are produced in the course of the infection allows scientists to interrupt the infection cycle, blocking viral diseases. One of the difficulties, however, is that the invasion strategies of different viruses greatly vary from one another.
The mimivirus, known, among other things, for its exceptional size – it is five to ten times larger than any other known virus – poses an interesting challenge in this respect. This virus was discovered only in the late twentieth century, as its extraordinary size made it impossible to identify it by regular means. In addition, it contains much more genetic material than other viruses, a feature that forces the mimivirus to develop particularly efficient methods for introducing its viral DNA into the host cell and for inserting the genetic “parcel” into the protein container during the production of new viruses in the host cell.The Weizmann Institute’s Prof. Abraham Minsky and graduate students Nathan Zauberman and Yael Mutsafi of the Organic Chemistry Department, together with Drs. Eugenia Klein and Eyal Shimoni of Chemical Research Support, have now revealed the details of some of the methods used by this virus. In their new study, the scientists have obtained, for the first time, three-dimensional pictures of the openings through which the viral genetic material is injected into an infected cell, and of the process by which this genetic material is inserted into the protein capsid.In all previously studied viruses, viral genetic material was shown to be injected into the cell (during the cell’s infection) and to enter the newly formed protein container (during the production of new viruses inside the cell) through the same channel, which was created in the viral container. In contrast, the Institute scientists discovered that the giant mimivirus uses a different channel – located in a different part of its capsid – for each of these two goals. The scientists also discovered that the DNA helix in both these processes does not form a long thread, as in other viruses, but rather is organized into a densely packed block. The researchers believe that these unique traits serve to specifically facilitate both the injection into the host cell and the insertion of the large quantity of genetic material in the mimivirus.
In the Weizmann study, electron microscope images of the mimivirus invading an amoeba cell showed that just after invasion, the walls of the protein capsid – a polygon composed of 20 triangles – separate from one another and open up like flower petals to create a large, star-shaped entry nicknamed the “stargate.” The viral membrane underneath the stargate fuses with the amoeba cell membrane, creating a broad channel that leads into the amoeba. The pressure released with the sudden opening of the walls – which is 20 times greater than the pressure pushing the cork out of a Champagne bottle – pushes the viral DNA into the channel, whose large dimensions allow the genetic material to pass quickly into the amoeba cell.Additional images show how the viral genetic material is inserted into the newly formed protein container when new viruses are produced in the host cell. In this process, the viral genetic material is delivered to its destination through an opening in the new container’s wall opposite the stargate. The insertion must overcome the pressure inside the container and is probably driven by an “engine” located within the wall that harbors the opening.
The scientists believe that the study of the mimivirus’s life cycle, from cellular infection to the production of new viruses, may yield valuable insights into the mechanisms of action of numerous other viruses, including those that cause human diseases.

http://www.sciencedaily.com/releases/2010/05/100528210736.htm

Nihal Altan-Bonnet, assistant professor of cell biology, Rutgers University in Newark, and her research team have made a significant new discovery about RNA (ribonucleic acid) viruses and how they replicate themselves.

Certain RNA viruses -- poliovirus, hepatitis C virus and coxsackievirus -- and possibly many other families of viruses copy themselves by seizing an enzyme from their host cell to create replication factories enriched in a specific lipid, explains Altan-Bonnet. Minus that lipid -- phosphatidylinositol-4-phosphate (Pl4P) -- these RNA viruses are not able to synthesize their viral RNA and replicate. The key structural components on cell membranes, lipids often serve as signaling molecules and docking sites for proteins.Viral replication is the process by which virus particles make new copies of themselves within a host cell. Those copies then can go on to infect other cells. An RNA virus is a virus that has RNA, rather than DNA, as its genetic material. Many human pathogens are RNA viruses, including SARS virus, West Nile virus, HIV, and the ones Altan-Bonnet has been studying.As reported in the May 28, 2010 issue of Cell, Altan-Bonnet and her co-researchers for the first time have uncovered that certain RNA viruses take control of a cellular enzyme to design a replication compartment on the cell's membrane filled with PI4P lipids. Those lipids, in turn, allow the RNA viruses to attract and stimulate the enzymes they need for replication. In uninfected cells, the levels of PI4P lipids are kept low, but in virally infected cells those levels increase dramatically. The findings by Altan-Bonnet and her colleagues not only open several possibilities for preventing the spread of various viral infections, but also may help to shed new light on the regulation of RNA synthesis at the cellular level and potentially on how some cancers develop."The goal of the virus is to replicate itself," notes Altan-Bonnet. "For its replication machines to work, the virus needs to create an ideal lipid environment which it does by hijacking a key enzyme from its host cell."Altan-Bonnet and her team also were able to identify the viral protein (the so-called 3A protein in poliovirus and coxsackievirus infections) that captures and recruits the cellular enzyme (phosphatidylinositol-4-kinase III beta). Additionally, her lab was able to impede the replication process by administering a drug that blocked the activity of the cellular enzyme once it had been hijacked. Drug therapies to prevent viral replication potentially also could be targeted to prevent the hijacking of the enzyme.
Once that enzyme is hijacked, cells are prevented from normally operating their secretory pathway, the process by which they move proteins to the outside of the cell. In many cases, the impeding of that process can result in the slow death of the cell, leading to such problems as cardiac and vascular complications in those infected with the coxsackievirus and neurological damage in those with poliovirus.
Utilizing their recent findings, Altan-Bonnet and her team now plan to investigate PI4P dependence in other viruses as well as the role other lipids may play in different virus families. For example, the SARS virus also requires a lipid-rich environment for its replication, so her lab now is working with SARS researchers on determining what lipid is necessary for that virus's replication. In addition, they will be examining the role of lipids in regulating RNA synthesis in cells, potentially providing new insight into some of the cellular mutations that occur in cancer.
"Given that a lot of what we know about cellular processes historically comes from the study of viruses, our studies may provide insight into the novel roles lipids play in regulating the expression of genetic material in cells," notes Altan-Bonnet.Altan-Bonnet's research into RNA replication is supported with grants from the National Science Foundation and the Busch Foundation.

 

[William Gaatjes]

Just a strange question. But is Herpes simplex virus not infecting Schwann cells ?

I was wondering about the coincidence between the Devil facial tumour disease
in tasmanian devils. This disease is an parasitic cancer. And the hypothesis is that it originated inside schwann cells.

Parasitic cancers or transmissible cancers are very rare but i find it very interesting that the immunesystem from tasmanian devils does not seem to mind that an foreign cell can just start to grow like a tumor. Perhaps this has something to do with the fact that tasmanian devils are isolated as an species. Interbreeding might occur and may cause unwanted side effects as for example that the immune system becomes dumbed down. I do not know.

 

[William Gaatjes]

To return to the interesting subject of autoimmune diseases...

I posted here about diabetes mellitus type 1 and the islets of Langerhans.
And that a suspected virus infection causes this. Probably through antigen mimicry as Gibsons mentioned.

My colleague is back. And i had the story about the experimental treatment a bit wrong. As it turns out, the experimental treatment in Canada was about :
Transplantation of tissue containing the islets of Langerhans. The patient was given immune suppression medicines to prevent tissue rejection. After a while they noticed the immune system did not attack the islets of Langerhans and the person no longer suffered from diabetes type 1.
The interesting part is that this was not a result of the immune suppression medicines, but as is suspected a result of a transplantation where the donor tissue was not virus infected. The original Langerhans tissue produced viruses or partial virus particles and where as such destroyed by the immune system. And the result was diabetes type 1. It was the virus infection that caused the auto immune disease. I did some research and it seems that the lymphocytic choriomeningitis virus which can be present inside the house mouse might be the cause. At least in some situations it has been found to be the case. There is lot of this information on the internet.
I find it interesting that it seems that a lot of rodents or similar mammals are carriers of viruses causing dangerous diseases.



I myself have been researched in the recent past for Bechterew disease also known as ankylosing spondylitis. And i luckily do not have this disease.
But it is an auto immune disease with an interesting hypothesis :
Almost all Bechterew patients have the HLA-B27 protein. And this protein is very similar to proteins found on the outside of the bacteria klebsiella pneumoniae. If this bacteria comes in contact with the immune system, the immune system will attack the body protein HLA-B27 inside bones and eyes because of antigenic mimicry if all conditions are met.

 

[ModestGamer]

To return to the interesting subject of autoimmune diseases...

I posted here about diabetes mellitus type 1 and the islets of Langerhans.
And that a suspected virus infection causes this. Probably through antigen mimicry as Gibsons mentioned.

My colleague is back. And i had the story about the experimental treatment a bit wrong. As it turns out, the experimental treatment in Canada was about :
Transplantation of tissue containing the islets of Langerhans. The patient was given immune suppression medicines to prevent tissue rejection. After a while they noticed the immune system did not attack the islets of Langerhans and the person no longer suffered from diabetes type 1.
The interesting part is that this was not a result of the immune suppression medicines, but as is suspected a result of a transplantation where the donor tissue was not virus infected. The original Langerhans tissue produced viruses or partial virus particles and where as such destroyed by the immune system. And the result was diabetes type 1. It was the virus infection that caused the auto immune disease. I did some research and it seems that the lymphocytic choriomeningitis virus which can be present inside the house mouse might be the cause. At least in some situations it has been found to be the case. There is lot of this information on the internet.
I find it interesting that it seems that a lot of rodents or similar mammals are carriers of viruses causing dangerous diseases.



I myself have been researched in the recent past for Bechterew disease also known as ankylosing spondylitis. And i luckily do not have this disease.
But it is an auto immune disease with an interesting hypothesis :
Almost all Bechterew patients have the HLA-B27 protein. And this protein is very similar to proteins found on the outside of the bacteria klebsiella pneumoniae. If this bacteria comes in contact with the immune system, the immune system will attack the body protein HLA-B27 inside bones and eyes because of antigenic mimicry if all conditions are met.

Now here is a great question. How would artificial immune system stimulation via vaccination affect this immune response in predisposed but non symptopmatic patients ?

IE look at the pandemic of type 1 diabetes.

 

[Mr. Pedantic]

There's a pandemic of Type 1 diabetes?

 

[ModestGamer]

There's a pandemic of Type 1 diabetes?

here in the USA. absofuckinglutely effects as many as 1 in 20 children. Up from 1-1000

number of vaccinations by age 3 is as high as 45. That rediculous.

 

[William Gaatjes]

here in the USA. absofuckinglutely effects as many as 1 in 20 children. Up from 1-1000

number of vaccinations by age 3 is as high as 45. That rediculous.

Well, I think it is a good idea to start to do some biological tests on the rodents living near by those cases of diabetes -1. What are the relations between the children. What do they have in common ? Age, quality of living, quality of houses, geographic locations, rodent infestation, do they have cats that bring mouses in the house as prey ? Perhaps the cats have carried the viruses for a short while.
Maybe a cat that starts to spin and rubs it's scent while producing slime can transmit the virus while being infected for a short time. Maybe there is an indirect link to be found with Toxoplasma gondii and lymphocytic choriomeningitis virus.

http://en.wikipedia.org/wiki/Toxoplasma_gondii



Maybe you are partially right when you mentioned that viruses come from cells.
Maybe viruses do not only spread in the wild but also become inserted completely in the genome of the host. Now when a certain trigger( other virus or bacteria or just a chemical molecule) starts that part of dna to become expressed, a virus would be produced. The host would then need to be in a situation where the infected tissue or it's blood (where the viruses can roam around freely because maybe the immune system of the host see the viruses no longer as foreign because the viruses have been incorporated many generations before) would be shared with other possible hosts(can be from different species). I am just mentioning a few possibilities.

 

[William Gaatjes]

I will just add these post here as well for the usual reason of collecting information :

Deinococcus radiodurans

http://www.usuhs.mil/pat/deinococcus/index_20.htm

Bacteria belonging to the family Deinococcaceae are some of the most radiation-resistant organisms yet discovered. Deinococcus (Micrococcus) radiodurans strain R1 (ATCC BAA-816) was first reported in 1956 by A. W. Anderson and coworkers of the Oregon Agricultural Experimental Station, Corvalis, Oregon. This obligate aerobic bacterium typically grows in rich medium as clusters of two cells (diplococci) in the early stages of growth, and as clusters of four cells (tetracocci) in the late stages of growth, is non-pathogenic, and best known for its ability to survive extremely high doses of acute ionizing radiation (10,000 Gy) without cell-killing. For comparison, 5 Gy is lethal to the average human, and 2,000 Gy can sterilize a culture of Escherichia coli. D. radiodurans is capable of growth under chronic radiation (60 Gy/hour) and resistant to other DNA damaging conditions including exposure to desiccation, ultraviolet (UV) light, and hydrogen peroxide. The genes and cellular pathways underlying the survival strategies of D. radiodurans are under investigation, and its resistance characteristics are being exploited in the development of bioremediation processes for cleanup of highly radioactive US Department of Energy waste sites, and in the development of radioprotectors.

Death By Protein Damage

The modern founding concept of radiation biology that deals with X-rays and g-rays is that ionizing radiation is dangerous because of its damaging effects on DNA. Mounting experimental evidence does not fit into this theoretical framework, instead supporting that radiation resistance is governed by protein damage. Recent studies from several independent labs implicate protein damage as the major probable cause of death in irradiated cells. Whereas DNA lesion-yields in cells exposed to a given dose of radiation appear to be fixed, protein-lesion yields are variable and closely related to survival. There are profound practical implications to this new view of radiation toxicity � Basically, if you want to survive radiation, protect your proteins! D. radiodurans has shown us how to protect proteins from radiation and other sources of reactive oxygen species (ROS), which is the subject of several experimental manuscripts working their way to press. For a history which led to this emerging paradigm shift in radiation biology, see Nat Rev Microbiol, 2009; 7(3):237-45, as well as others.

One original goal of radiobiology was to explain why cells are so sensitive to ionizing radiation (IR). Early studies in bacteria incriminated DNA as the principal radiosensitive target, an assertion that remains central to modern radiation toxicity models. More recently, the emphasis has shifted to understanding why bacteria such as Deinococcus radiodurans are extremely resistant to IR (1), by focusing on DNA repair systems expressed during recovery from high doses of IR (2). Unfortunately, as key features of DNA-centric hypotheses of extreme resistance have grown weaker (3), the study of alternative cellular targets has lagged far behind, mostly because of their relative biological complexity. Recent studies have shown that extreme levels of bacterial IR resistance correlate with high intracellular Mn(II) concentrations (4), and resistant and sensitive bacteria are equally susceptible to IR-induced DNA damage (~0.005 DSB/Gy/haploid genome). Our recent work has established a mechanistic link between the orthophosphate complex of Mn2+ and protection of proteins from radiation damage (5a, 5b). In contrast to resistant bacteria, naturally sensitive bacteria are highly susceptible to IR-induced protein oxidation. We have proposed that sensitive bacteria sustain lethal levels of protein damage at radiation doses that elicit relatively little DNA damage, and that extreme resistance in bacteria is dependent on protein protection (6).

In the months ahead, published papers that deal with "Death by Protein Damage" in irradiated cells will be listed on this site. Most important, we will show the critical role of combining orthophosphate (Pi) complexes of Mn2+ with common metabolites (e.g., uridine and peptides) in the protection of enzymes from extreme oxidative damage caused during irradiation. These complexes are immensely radioprotective of proteins but not DNA. For more information contact Michael Daly (mdaly@usuhs.mil).


Image overlay of transmission electron microscopy, light microscopy, and x-ray fluorescence microprobe analyses of Deinococcus radiodurans. Depth-average abundance of Mn (blue, green, pink) and Fe (red) are shown within a single D. radiodurans diplococcus.

http://www.sciencedaily.com/releases/2010/08/100816095719.htm

A team of marine microbiologists at Newcastle University have discovered for the first time that bacteria have a molecular "nose" that is able to detect airborne, smell-producing chemicals such as ammonia.

Published in Biotechnology Journal, their study shows how bacteria are capable of 'olfaction' -- sensing volatile chemicals in the air such as ammonia produced by rival bacteria present in the environment.

Led by Dr Reindert Nijland, the research also shows that bacteria respond to this smell by producing a biofilm -- or 'slime' -- the individual bacteria joining together to colonise an area in a bid to push out any potential competitor.

Biofilm is a major cause of infection on medical implants such as heart valves, artificial hips and even breast implants. Also known as 'biofouling' it costs the marine industry millions every year, slowing ships down and wasting precious fuel. But it also has its advantages. Certain biofilms thrive on petroleum oil and can be used to clean up an oil spill.

Dr Nijland, who carried out the work at Newcastle University's Dove Marine Laboratory, said the findings would help to further our understanding of how biofilms are formed and how we might be able to manipulate them to our advantage.

"This is the first evidence of a bacterial 'nose' capable of detecting potential competitors," he said.

"Slime is important in medical and industrial settings and the fact that the cells formed slime on exposure to ammonia has important implications for understanding how biofilms are formed and how we might be able to use this to our advantage.

"The next step will be to identify the nose or sensor that actually does the smelling."

This latest discovery shows that bacteria are capable of at least four of the five senses; a responsiveness to light -- sight -- contact-dependent gene expression -- touch -- and a response to chemicals and toxins in their environment either through direct contact -- taste -- or through the air -- smell.

Ammonia is one of the simplest sources of nitrogen -- a key nutrient for bacterial growth. Using rival bacteria Bacillus subtilis and B.licheniformus, both commonly found in the soil, the team found that each produced a biofilm in response to airborne ammonia and that the response decreased as the distance between the two bacterial colonies increased.

Project supervisor Professor Grant Burgess, director of the Dove Marine Laboratory, said that understanding the triggers that prompt this sort of response had huge potential.

"The sense of smell has been observed in many creatures, even yeasts and slime moulds, but our work shows for the first time that a sense of smell even exists in lowly bacteria.

"From an evolutionary perspective, we believe this may be the first example of how living creatures first learned to smell other living creatures.

"It is an early observation and much work is still to be done but, nevertheless, this is an important breakthrough which also shows how complex bacteria are and how they use a growing number of ways to communicate with each other.

"Bacterial infections kill millions of people every year and discovering how your bacterial enemies communicate with each other is an important step in winning this war. This research provides clues to so far unknown ways of bacterial communication."

 

[William Gaatjes]

p53 has been studied pretty intensely for a very long time. Lots of people have sequenced lots of p53 genes from many many different cancers and normal tissues. When you compile this data, you see some bases mutated very often in cancer samples (usually leading to specific amino acid changes), some not so much.

The general theory is that all the bases are, roughly, equally prone to mutation (this is never exactly true). So, when you sequence p53 from cancer cells, your data is selected - you're looking at mutations that lead to cancer (with some noise too, of course). If you see a few bases mutated over and over again, and a lot of other bases only rarely mutated, the conclusion is usually that those bases lead to cancer.

Another explanation though, is simply that cancer cells have a high mutation rate and there's some bias in these mutations. i.e. the mutations are an effect of cancer, not a cause.

Other data suggests that the former is correct - the mutations in p53 lead to cancer. When you look at the mutated proteins for instance, the common mutations lead to loss or change of function of the protein. Also, some unfortunate people are born with a mutated p53 and they get cancer early and often.
http://en.wikipedia.org/wiki/Li-Fraumeni_syndrome

What the article I linked is talking about is that they can detect a known mutagen/carcinogen binding to some of the specific sequences. I didn't read the whole paper, but they might be suggesting that benzopyrene has a higher than-you-might-expect propensity to cause the cancer associated mutations. i.e. it's not randomly mutating all bases, it's more prone to mutate the important ones than unimportant ones.

I just read this post again and for some reason i had to think about the prion first. The benzopyrene may not be a prion. But maybe the mechanisms are similar. When it is subjected to the dna, it forces another electron distribution in the sequence. Causing the sequence to behave different. That is also why i had to think about quantum mirages principles and super atoms principles as the basic mechanisms of life in the first place :


http://www.almaden.ibm.com/almaden/media/mirage.html

To create the quantum mirage, the scientists first moved several dozen cobalt atoms on a copper surface into an ellipse-shaped ring. As Michael Crommie (who is now a professor at the University of California-Berkeley), Lutz and Eigler had shown in 1993, the ring atoms acted as a "quantum corral" -- reflecting the copper's surface electrons within the ring into a wave pattern predicted by quantum mechanics.

The size and shape of the elliptical corral determine its "quantum states" -- the energy and spatial distribution of the confined electrons. The IBM scientists used a quantum state that concentrated large electron densities at each focus point of the elliptical corral. When the scientists placed an atom of magnetic cobalt at one focus, a mirage appeared at the other focus: the same electronic states in the surface electrons surrounding the cobalt atom were detected even though no magnetic atom was actually there. The intensity of the mirage is about one-third of the intensity around the cobalt atom.

"We have become quantum mechanics -- engineering and exploring the properties of quantum states," Eigler said. "We're paving the way for the future nanotechnicians."

The operation of the quantum mirage is similar to how light or sound waves is focused to a single spot by optical lenses, mirrors, parabolic reflectors or "whisper spots" in buildings. For example, faint sounds generated at either of the two "whisper spots" in the Old House of Representatives Chamber (now called Statuary Hall) in the U.S. Capitol Building in Washington, D.C., can be heard clearly far across the chamber at the other whisper spot.

"The quantum mirage technique permits us to do some very interesting scientific experiments such as remotely probing atoms and molecules, studying the origins of magnetism at the atomic level, and ultimately manipulating individual electron or nuclear spins," said Dr. Manoharan. "But we must make significant improvements before this method becomes useful in actual circuits. Making each ellipse with the STM is currently impractically slow. They would have to be easily and rapidly produced, connections to other components would also have to be devised and a rapid and power-efficient way to modulate the available quantum states would need to be developed."

 

[tcsenter]

I posted here about diabetes mellitus type 1 and the islets of Langerhans. And that a suspected virus infection causes this. Probably through antigen mimicry as Gibsons mentioned.

See HLA DQB1*0602 allele, which is strongly protective against Type 1 IDDM, even among Islet cell antibody-positive first-degree relatives of patients with IDDM. So much, that investigational studies on IDDM typically exclude any subjects with DQB1*0602.

Only reason I know about it is because DQB1*0602 was previously implicated in narcolepsy and cataplexy, which mounting evidence strongly suggests is an auto-immune disease (or results from one).

 

[William Gaatjes]

%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%

See HLA DQB1*0602 allele, which is strongly protective against Type 1 IDDM, even among Islet cell antibody-positive first-degree relatives of patients with IDDM. So much, that investigational studies on IDDM typically exclude any subjects with DQB1*0602.

Only reason I know about it is because DQB1*0602 was previously implicated in narcolepsy and cataplexy, which mounting evidence strongly suggests is an auto-immune disease (or results from one).

I found some information about a small number study :

http://diabetes.diabetesjournals.org/content/44/6/608.abstract

HLA-DQB1 alleles confer susceptibility and resistance to insulin-dependent diabetes mellitus (IDDM). We investigated whether the susceptibility alleles DQB1*0302 and DQB1*0201 affect progression to diabetes among islet cell antibody-positive (ICA+) first-degree relatives of IDDM patients and whether the protective allele DQB1*0602 can be found and is still protective among such relatives. We human leukocyte antigen-typed and periodically tested beta-cell function (first-phase insulin release [FPIR] during the intravenous glucose tolerance test) in 72 ICA+ relatives, of whom 30 became diabetic on follow-up (longest follow-up 12 years); 54 (75%) relatives carried DQB1*0302 and/or DQB1*0201. The frequency of DQB1*0302 and DQB1*0201 and of the high-risk genotype DQB1*0302/DQB1*0201 did not differ significantly between diabetic relatives and those remaining nondiabetic. On follow-up, progression to IDDM was not statistically different for relatives with or without the DQB1*0302/DQB1*0201 genotype. However, those relatives with the DQB1*0302/DQB1*0201 genotype had a tendency to develop diabetes at an earlier age (log-rank P = 0.02). We found DQB1*0602 in 8 of 72 (11.1%) ICA+ relatives. Relatives with DQB1*0602 did not develop diabetes or show any decline of FPIR versus 28 of 64 DQB1*0602- relatives who developed IDDM (log-rank P = 0.006; Wilcoxon's P = 0.02). The protective allele DQB1*0602 is found in ICA+ relatives who have minimal risk of progression to IDDM. Therefore, DQB1*0602 is associated with protection from IDDM both in population studies and among relatives with evidence of autoimmunity who should not enter prevention trials.

If i understand correctly, when you carry the DQB1*0602 allele you do not get IDDM. But why ? Is the immune system when having DQB1*0602 blind for the lymphocytic choriomeningitis virus ? For particular viral parts ? Or is the immune system more effective in killing the virus before the virus can infect the cells of the pancreas ?


The reason why i mention this is because the IDDM does not happen after birth. Acquiring IDDM always seem to happen at a later age when the child can run around, move freely and interact with others. Thus becoming prone to infection.

EDIT :

I found some information about narcolepsy.

http://med.stanford.edu/school/Psychiatry/narcolepsy/faq1.html

What is the cause of narcolepsy?
Recent studies have shown that narcolepsy with cataplexy is usually caused (>90%) by the lack of two related brain chemicals called "hypocretin-1" and "hypocretin-2". The cause of narcolepsy without cataplexy is still under investigation.

What are these so-called hypocretin (orexin) molecules?
Hypocretins (orexins) were discovered by two groups of researchers almost simultaneously, hence the two names "hypocretins" and "orexins". The first group called them "hypocretin-1" and "hypocretin-2" after discovering that the molecules were found only in the hypothalamus and had some weak resemblance with the gut hormone secretin. Only 10,000-20,000 cells in the entire human brain (out of many billions) secrete these specific hypocretin molecules. The hypothalamus, a region localized deep in the base of the brain, regulates many basic functions such as the release of hormones, blood pressure, sex, food intake regulation and sleep. The subregion of the hypothalamus containing the hypocretin cells was known to be especially important for the regulation of feeding. These molecules were thus first hypothesized to be important in feeding regulation. In fact, the second group that discovered the hypocretin molecules called them "orexin A and orexin B" (from orexis=appetite in grec) and suggested that they stimulated appetite. Orexins and hypocretins are thus interchangeable terms and the scientific community is divided on what is the best name to use.

How can I have my hypocretin levels measured?
Hypocretin-1 (but not 2) can be measured in the cerebrospinal fluid (CSF) but not in the blood or in any other peripheral tissue. A lumbar puncture is required to collect CSF. Most patients with narcolepsy-cataplexy have no hypocretin-1 molecules in their CSF. If you are interested in having your CSF hypocretin levels measured, please contact Mali Einen at the Center for Narcolepsy.

How do you collect cerebrospinal fluid (CSF)?
To draw CSF requires a lumbar puncture (spinal tap). This is a safe but not completely insignificant procedure (the main problem is that temporary headaches can occur in about 5% of the cases following the procedure). The procedure is a little similar to an epidural anesthesia (actually safer and easier), is used a lot by neurologists to exclude many neurological problems such as brain hemorrhage, brain infections, multiple sclerosis, etc... We have tried to measure hypocretins in other tissues such as blood but this molecule probably exists in sufficient amount only in the brain and the CSF. Clearly, some effort should be devoted in measuring hypocretin levels more easily.

What is HLA?
HLA stands for " Human Leukocyte Antigens". HLA antigens are molecules produced by the HLA genes. HLA molecules are expressed on the surface of white blood cells to coordinate the immune response. DR and DQ are two different types of HLA molecules. HLA genes are very important systems to keep the immune system in check. The HLA molecules are very particular in that different individuals generally carry different HLA "subtypes" (for example DR1, DR2, subtypes of HLA-DR; DQ1, DQB1*0602, subtypes of HLA-DQ). The fact HLA molecules are slightly different from one individual to another makes our immune system slightly different from each other.

What is the best HLA marker in narcolepsy?
The best HLA marker for narcolepsy is HLA-DQB1*0602. Over 90% of patients with narcolepsy-cataplexy carry HLA-DQB1*0602. This marker is more specific and sensitive than the old marker HLA-DR2, especially in African Americans.

Can HLA testing be used to diagnosed narcolepsy?
Absolutely not. About 20% of the general population carry the exact same HLA subtypes (HLA-DR2, DQB1*0602, etc). Furthermore, many patients without cataplexy do not have HLA-DQB1*0602. The HLA subtypes are only predisposing factors but are not sufficient by themselves to cause narcolepsy.

How is HLA involved in narcolepsy?
No one knows for sure. A large number of other diseases (>80) like Multiple sclerosis or Juvenile Onset (type I) Insulin Dependent Diabetes Mellitus are also associated with specific HLA subtypes. Most of these diseases are autoimmune disorders.

I did not quote all text.
But i wonder if there is a pathogen to be found in those hypocretin producing cells.

what is narcolepsy ?

http://en.wikipedia.org/wiki/Narcolepsy

Narcolepsy is a chronic sleep disorder, or dyssomnia, characterized by excessive daytime sleepiness (EDS) in which a person experiences extreme fatigue and possibly falls asleep at inappropriate times, such as while at work or at school. Narcoleptics usually experience disturbed nocturnal sleep and an abnormal daytime sleep pattern, which is often confused with insomnia. When a narcoleptic falls asleep they generally experience the REM stage of sleep within 10 minutes; whereas most people do not experience REM sleep until after 90 minutes. There is no evidence to suggest that narcoleptics tend to have a shorter life span.

Another problem that some narcoleptics experience is cataplexy, a sudden muscular weakness brought on by strong emotions (though many people experience cataplexy without having an emotional trigger).[1] It often manifests as muscular weaknesses ranging from a barely perceptible slackening of the facial muscles to the dropping of the jaw or head, weakness at the knees, or a total collapse. Usually only speech is slurred, vision is impaired (double vision, inability to focus), but hearing and awareness remain normal. In some rare cases, an individual's body becomes paralyzed and muscles become stiff.

 

[William Gaatjes]

%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%

A post about parts of the ebola virus (a filovirus) being embedded in bats and wallabies.

http://www.sciencecodex.com/wallabi..._from_the_most_deadly_family_of_human_viruses

BUFFALO, N.Y. -- Modern marsupials may be popular animals at the zoo and in children's books, but new findings by University at Buffalo biologists reveal that they harbor a "fossil" copy of a gene that codes for filoviruses, which cause Ebola and Marburg hemorrhagic fevers and are the most lethal viruses known to humans.

Published this week in the online journal BMC Evolutionary Biology, the paper ("Filoviruses are ancient and integrated into mammalian genomes") demonstrates for the first time that mammals have harbored filoviruses for at least tens of millions of years, in contrast to the existing estimate of a few thousand.

It suggests that these species, which maintain a filovirus infection without negative health consequences, could have selectively maintained these so-called "fossil" genes as a genetic defense.

The work has important implications for the development of potential human vaccines, as well as for the modeling of disease outbreaks and the discovery of emerging diseases, including new filoviruses.

"This paper identifies the first captured 'fossil' copies of filovirus-like genes in mammalian genomes," says Derek J. Taylor, PhD, associate professor of biological sciences in the UB College of Arts and Sciences and co-author. "Our results confirm for the first time that several groups of mammals, including groups such as marsupials that never colonized Africa, have had an association with filoviruses."

The UB co-authors say that if the rarely captured genes represent antiviral defenses or genomic scars from persistent infections, then the work opens up new possibilities for identifying reservoir species for filoviruses, which harbor the virus but remain asymptomatic.

"The reservoir for filovirus has remained a huge mystery," says Jeremy A. Bruenn, PhD, UB professor of biological sciences and co-author. "We need to identify it because once a filovirus hits humans, it can be deadly."

When the UB researchers studied samples from the fur of a wallaby at the Buffalo Zoo and a brown bat caught on the UB campus, they found that the genomes of both animals as well as some other small mammals contain "fossil" copies of the gene for these deadly viruses, and thus could be candidate reservoir species for them.

"Who knew that the bats in the attic as well as modern marsupials harbored fossil gene copies of the group of viruses that is most lethal to humans," asks Taylor.

The research also demonstrates a new mechanism by which different species of mammals can acquire genes, through non-retroviral integrated RNA viruses, which the UB scientists had previously identified in eukaryotes but was unknown in mammals.

The UB scientists note that it is well-known that RNA retroviruses, like HIV-AIDS, can be integrated into mammal genomes.

"But because filoviruses infect only the cytoplasm of cells and not the nucleus and because they have no means of making DNA copies that might be integrated into the genome -- as retroviruses do -- it was never thought gene transfer could occur between non-retroviral RNA viruses and hosts," says Bruenn. "This paper shows that it does and it may prove to be a far more general phenomenon than is currently known."

The research also reveals that existing estimates that filoviruses originated in mammals a few thousand years ago were way off the mark.

"Our findings demonstrate that filoviruses are, at a minimum, between 10 million and 24 million years old, and probably much older," says Taylor. "Instead of having evolved during the rise of agriculture, they more likely evolved during the rise of mammals."

I think integration can happen when the host is infected by multiple different types of viruses.
But i must stress that the mutation must happen in dna that ends up in reproductive cells as sperm or eggs.

But does this mean that the the specific animals can produce life complete filo viruses ?
Or is again another pathogen needed to complement the missing genes ?


Another link :
http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1001030

 

[tcsenter]

Mouse virus link to chronic fatigue is studied

 

[William Gaatjes]

Mouse virus link to chronic fatigue is studied

Interesting.

It seems i cannot find my other post anymore where i posted my worries about that rodents might be the carrier of a lot of viruses. It was also about marsupials.

But what i find strange is that the CDC did not do a larger screening for different viruses.

 

[William Gaatjes]

To remove forum parser issue : %%%%%%%%%%%%%%%%%%%%


I read your post and did some research about the virus :

The XMRV virus mentioned in the text is associated with prostate cancer.
Interesting, another cancer candidate caused by i expect multiple virus infections or a virus together with a bacteria infection.
It is only known since 2006 it seems. It is suggested to be responsible for the chronic fatigue syndrome.

We have the Murine leukemia virus.
And we have the Xenotropic murine leukemia virus-related virus. Both found in humans.

http://news.sciencemag.org/sciencenow/2010/08/second-paper-supports-viral-link.html

There's a new twist in the ongoing battle over whether a virus is linked to chronic fatigue syndrome (CFS). After the journal held it for 2 months, a study supporting a link between a mouse retrovirus and CFS was published today in the Proceedings of the National Academy of Science (PNAS). Many are still doubtful of the link, but they're impressed by the authors' efforts to ensure accuracy.

In the new study, conducted by scientists at the National Institutes of Health (NIH), the U.S. Food and Drug Administration (FDA), and Harvard University, researchers scanned for traces of a virus known as XMRV in samples taken from 37 CFS patients, collected by Harvard Medical School CFS specialist Anthony Komaroff in the mid-1990s. They found evidence for the virus in 32 (87%) of the patients, but in only three out of 44 healthy controls (6.8%). It remains to be seen whether the infection causes the disease or vice versa, says NIH virologist and co-author Harvey Alter—but he's "confident" that the findings are correct.

XMRV—less succinctly known as xenotropic murine leukemia virus-related virus—was first implicated for its potential involvement in prostate cancer, a link that's still under intense debate. Then, in a Science paper published last year, a team led by retrovirologist Judy Mikovits of the Whittemore Peterson Institute for Neuro-Immune Disease (WPI) in Reno, Nevada, found evidence of infection in 67% of CFS patients, compared with just 3.4% of healthy controls. But since then, four other papers failed to find the link, or any evidence of XMRV infection in humans at all. The last of the four, by researchers at the U.S. Centers for Disease Control and Prevention (CDC), was also held for a while, at the researchers' request, while they tried to figure out how government labs could come to such opposite conclusions. The CDC paper was eventually published on 1 July in Retrovirology.

Skeptics were concerned that the XMRV Mikovits had found might be the result of contamination by mouse DNA in the lab. To address this, the new study's first author—FDA virologist Shyh-Ching Lo—and his colleagues tested every positive sample for murine mitochondrial DNA. They found none.

While the paper was on hold—also because of conflicts with other studies—the team ran additional checks that bolstered the data further, says Alter. "I felt we needed to do more to prove our case," Alter says, in part because an additional, third reviewer, had looked at the paper at PNAS's request. For instance, the researchers took fresh samples from eight of the patients and found that, 15 years on, they were still infected and that the virus had evolved, "just as we would expect from a retrovirus," says Alter. The wait was "time well spent," he adds.

The data do seem solid, admits Steve Monroe, who co-authored the conflicting CDC paper. "It's simply a good paper," adds Reinhard Kurth, the former director of the Robert Koch Institute in Germany, who helped test some of CDC's samples and did not find the virus either. Alter—a widely respected virologist and winner of the Albert Lasker Award for Clinical Medical Research—"clearly knows what he is doing. They did everything correctly," says Kurth, who nonetheless says he remains skeptical.

So too does virologist Robin Weiss of Imperial College London (ICL), who says he's seen too many instances of proposed new human retroviruses that fell apart on closer inspection, including one he reported in arthritis and lupus patients in 1999 that turned out to be an innocuous rabbit virus. (In a 40-page review that he co-authored in 2008, Weiss called such mishaps "human rumor viruses.") "You can have a very good reputation and be very careful and still get it wrong," Weiss says.

Part of the problem, skeptics say, is that the researchers didn't exactly replicate the Science paper. XMRV is a so-called xenotropic murine virus, which means it can no longer enter mouse cells but can infect cells of other species. (Murine means "from mice.") The researchers in the PNAS paper say the viral sequences they find are more diverse than that and resemble more closely the so-called polytropic viruses, which is why they adopted the term MLV-related virus, for murine leukemia virus. "Let's be clear: This is another virus. They did not confirm [Mikovits's] results," says retrovirologist Myra McClure of ICL, a co-author of one of the four negative studies.

Still, "in the grand scheme of things," the viral sequence found in the PNAS paper closely resembles those of XMRV, says Celia Witten, the director of FDA's Office of Cellular, Tissue and Gene Therapies, who was not an author of the paper herself but spoke on Lo's behalf. Witten adds that the data "support" the Science paper. Mikovits—who is "delighted" by the new paper—says the difference is not important. In as-yet-unpublished results, her group finds more genetic diversity in the virus as well, she says.

Meanwhile, a working group coordinated by the National Heart, Lung, and Blood Institute (NHLBI) is coordinating an effort to answer the most baffling question: Why some labs find the virus in both patients and healthy people, and others find it in neither. Initially, some believed there might be geographical reasons, because the first three negative studies were all from Europe—but that theory seems unlikely after the CDC paper, whose patients were from Kansas and Georgia. Patient selection could play a role: Different studies have used different diagnostic and recruitment criteria. But even given this messiness, it's hard to explain why four studies wouldn't have included a single infected patient.

The discordant results may also stem from subtle differences in handling the samples or performing the tests that would have led the four labs to miss the virus. But CDC's Monroe says he's confident that the lab can identify the virus. As part of the NHLBI program, researchers at FDA, CDC, WPI, and other labs have all blindly tested a panel of samples, some of them "spiked" with different amounts of the virus; all of them performed well. Further exchange of samples and reagents is now under way to understand where the differences came from. "They should be able to clear this up by Christmas," says Kurth.

Many of the main players in the controversy plan to attend a workshop organized by NIH on 7 and 8 September. Mikovits, who is on the scientific committee, says she has seen the abstracts of two presentations confirming her findings. "I think it will be fun," she says.

http://en.wikipedia.org/wiki/Xenotropic_murine_leukemia_virus-related_virus

http://en.wikipedia.org/wiki/Murine_leukemia_virus

 

[William Gaatjes]

Plasmids must be added as well :

Can plasmids and viruses exchange dna ?
I would say yes. I just read that the Epstein barr virus turns itself into a plasmid after entering the cell.
Epstein barr virus is a herpes virus that can cause cancer.
I would think viruses started out as plasmids when looking at the way bacteria exchange plasmids...

http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/R/RecombinantDNA.html

Plasmids are molecules of DNA that are found in bacteria separate from the bacterial chromosome.
They:
are small (a few thousand base pairs)
usually carry only one or a few genes
are circular
have a single origin of replication

Plasmids are replicated by the same machinery that replicates the bacterial chromosome. Some plasmids are copied at about the same rate as the chromosome, so a single cell is apt to have only a single copy of the plasmid. Other plasmids are copied at a high rate and a single cell may have 50 or more of them.

Genes on plasmids with high numbers of copies are usually expressed at high levels. In nature, these genes often encode proteins (e.g., enzymes) that protect the bacterium from one or more antibiotics.

Plasmids enter the bacterial cell with relative ease. This occurs in nature and may account for the rapid spread of antibiotic resistance in hospitals and elsewhere. Plasmids can be deliberately introduced into bacteria in the laboratory transforming the cell with the incoming genes.

http://en.wikipedia.org/wiki/Plasmid

 

[Mr. Pedantic]

I would think it unlikely that viruses originated as plasmids given out by bacteria; generally, evolution tends towards complexity; simplicity is very hard to do. Also, I find it unlikely that any bacterial genome would have the functions that a virus would need to function.

 

[William Gaatjes]

I would think it unlikely that viruses originated as plasmids given out by bacteria; generally, evolution tends towards complexity; simplicity is very hard to do. Also, I find it unlikely that any bacterial genome would have the functions that a virus would need to function.

Well, maybe it is not , maybe it is :
Maybe it is the other way around.
Here i have some more information from a discussion.

http://www.bio.net/bionet/mm/virology/1996-January/005314.html

The distinction between viruses and plasmids is further blurred
by the habit of some viruses of converting into plasmid form
upon entry to the cell. For example, Eptein-Barr virus will
circularise in the cell to form a stable plasmid that replicates
in phase with the cell. Expression of latency-associated proteins
allows the virus to persist without lysing the cell.

Circularisation of DNA is also not sufficient to distinguish a
plasmid from a virus, since some viruses, for example baculoviruses
(Nucleopolyhedrovirus, Granulovirus), circoviruses (Circovirus) and
corticoviruses (Corticovirus) have circular genomes.

The ability of a virus to package its DNA (or RNA) into a protein
capsid would be a feature that no plasmid shares; in other words,
plasmid DNA outside the cell would be "naked". However, given the
complex means that bacteria have developed for transferring plasmids
between themselves, I would not be surprised if some bacteria have
developed packaging systems for plasmids. However, this packaging
would not have been coded by the plasmid. Also, it is possible for
some viruses to integrate into the genome of the host cells and be
transmitted vertically from a parent to its progeny without the
need for expression of viral structural proteins. The retrovirus
mouse mammary tumour virus is such an example.

 

[William Gaatjes]

The mimivirus.
A virus that can be infected by another virus "sputnik", a so called virophage.

http://www.microbiologybytes.com/virology/Mimivirus.html

Mimivirus is one of the largest and most complex viruses known. The virus was first isolated in 1992 from amoebae growing in a water tower in Bradford. La Scola, B. et al. (2003) A giant virus in amoebae. Science 299: 2033.

Both the particle size and the genome size of mimivirus is larger than that of some small bacteria. The 1.2 Mbp genome, which contains 911 protein coding genes, provides sufficient information to allow the virus to perform most (but not quite all) of the functions of living cells. The complexity and magnitude of the Mimivirus genome, combined with the large size of the virus, calls into question some of the established divisions between viruses and single-celled organisms, as well as raising questions about their evolution. Suzan-Monti M. (2005) Genomic and evolutionary aspects of Mimivirus. Virus Res.

Examination using cryo-electron microscopy has shown that the particle has a capsid with a diameter of 750 nm, including an array of 125 nm long closely packed fibres projecting out from the capsid surface. Based on a large number of open reading frames with collagen triple helix repeats in the viral genome, these fibers might consist of collagen. The dense, 200 thick base of these fibers might be formed by cross-linking. The capsid itself appeared to contain three layers of dense matter, probably representing two successive 4 nm thick lipid membranes inside a protein shell approximately 7 nm thick (Mimivirus and the emerging concept of giant virus. Claverie JM. et al. 2006 Virus Res. 117: 133-144). Similar double lipid membrane layers have been found in some poxviruses and in African swine fever virus (ASFV), another very large virus. Mimivirus particles also have a unique protruding vertex similar to that seen in tailed bacteriophages.

Mimivirus has many characteristics which put it at the boundary between living organisms and non-living entities. It is as large as several bacteria, such as Rickettsia conorii and Tropheryma whipplei, has a genome larger than a number of bacteria, and encodes some genetic products previously not known to be possessed by any virus. In particular, mimivirus contains genes coding for nucleotide and amino acid synthesis which even some small obligate intracellular bacteria lack. This means that unlike these bacteria, mimivirus is not dependent on the host cell genome for coding the metabolic pathways for these products. It does however, lack genes for ribosomal proteins, making mimivirus dependent on a host cell for protein synthesis and energy metabolism.

So, is mimivirus alive? Like all viruses, mimivirus particles do not reproduce by division, but are replicated by the self-assembly of preformed components. This differentiates it from cellular living organisms such as bacteria.

Patients with pneumonia have shown positive serological tests for mimivirus, and a laboratory technician working with the virus developed pneumonia and seroconverted. However, neither of these observations was definitive proof that mimivirus can cause disease, so experimental infections have been carried out in mice, which also developed pneumonia (Khan M. et al.

http://www.nature.com/news/2008/080806/full/454677a.html

An excerpt :

Closer inspection showed the microbe to be a huge virus with, as later work revealed, a genome harbouring more than 900 protein-coding genes3 — at least three times more than that of the biggest previously known viruses and bigger than that of some bacteria. It was named Acanthamoeba polyphaga mimivirus (for mimicking microbe), and is thought to be part of a much larger family. “It was the cause of great excitement in virology,” says Eugene Koonin at the National Center for Biotechnology Information in Bethesda, Maryland. “It crossed the imaginary boundary between viruses and cellular organisms.”

Now Raoult, Koonin and their colleagues report the isolation of a new strain of giant virus from a cooling tower in Paris, which they have named mamavirus because it seemed slightly larger than mimivirus. Their electron microscopy studies also revealed a second, small virus closely associated with mamavirus that has earned the name Sputnik, after the first man-made satellite.

With just 21 genes, Sputnik is tiny compared with its mama — but insidious. When the giant mamavirus infects an amoeba, it uses its large array of genes to build a ‘viral factory’, a hub where new viral particles are made. Sputnik infects this viral factory and seems to hijack its machinery in order to replicate. The team found that cells co-infected with Sputnik produce fewer and often deformed mamavirus particles, making the virus less infective. This suggests that Sputnik is effectively a viral parasite that sickens its host — seemingly the first such example.

The team suggests that Sputnik is a ‘virophage’, much like the bacteriophage viruses that infect and sicken bacteria. “It infects this factory like a phage infects a bacterium,” Koonin says. “It’s doing what every parasite can — exploiting its host for its own replication.”

Sputnik’s genome reveals further insight into its biology. Although 13 of its genes show little similarity to any other known genes, three are closely related to mimivirus and mamavirus genes, perhaps cannibalized by the tiny virus as it packaged up particles sometime in its history. This suggests that the satellite virus could perform horizontal gene transfer between viruses — paralleling the way that bacteriophages ferry genes between bacteria.

And 3 old news items how the immune system of bacteria can work.

http://www.sciencedaily.com/releases/2009/12/091231153907.htm
For the entire post click the link.

I find this most interesting :

In response to the unlimited number of foreign antigens (bits of microbes, chemicals and other substances) that can invade our bodies, the immune system must be able to tailor-make an unlimited number of antibodies. However, the amount of DNA in a cell is limited, so antibody-producing B cells must mutate and re-arrange their antibody genes to step up to the challenge (using processes called somatic hypermutation and class switch recombination, respectively).

In collaboration with the Papavasiliou lab, Dunnick discovered that mice carrying the artificial chromosomes with the antibody genes behave in ways that are indistinguishable from unmanipulated mice: they recombine and mutate their antibody genes to generate highly specific attacks on foreign invader. But for that, they absolutely need their enhancers: without them, the cell's machinery can transcribe and translate the antibody genes, but can't rearrange or mutate them, suggesting that the enhancers function as a loading dock for a common initiator molecule, which is then hauled to the antibody genes.

The experiments show that the enhancers of antibody genes are vital in springing the immune system to action, and suggest that mutations in the enhancers may make an individual more susceptible to infections, even infections for which he should have been vaccinated. "The main goal of vaccination is to produce, in a short amount of time, antibodies that are diversified to be most effective against a particular virus or bacterium," says Dunnick. "We were fortunate to identify the control elements that are critical for this antibody diversification."

http://www.sciencedaily.com/releases/2009/11/091125134703.htm

Still, bacteria and another class of microorganisms called archaea (first discovered in extreme environments such as deep-sea volcanic vents) manage just fine, thank you, in part because they have a built-in defense system that helps protect them from many viruses and other invaders.

A team of scientists led by researchers at the University of Georgia has now discovered how this bacterial defense system works, and it could lead to new classes of targeted antibiotics, new tools to study gene function in microorganisms and more stable bacterial cultures used by food and biotechnology industries to make products such as yogurt and cheese.

The research was published November 26 in the journal Cell.

"Understanding how bacteria defend themselves gives us important information that can be used to weaken bacteria that are harmful and strengthen bacteria that are helpful," said Michael Terns, a professor of biochemistry and molecular biology in UGA's Franklin College of Arts and Sciences. "We also hope to exploit this knowledge to develop new tools to speed research on microorganisms."

Other authors on the Cell paper include Rebecca Terns, a senior research scientist in biochemistry and molecular biology at UGA; Caryn Hale, a graduate student in the Terns lab at UGA; Lance Wells, an assistant professor of biochemistry and molecular biology and Georgia Cancer Coalition Scholar at UGA and his graduate student Peng Zhao; and research associate Sara Olson, assistant professor Michael Duff and associate professor Brenton Graveley of the University of Connecticut Health Center.

The system, whose mechanism of action was uncovered in the Terns lab (Michael and Rebecca Terns are a husband-wife team), involves a "dynamic duo" made up of a bacterial RNA that recognizes and physically attaches itself to a viral target molecule, and partner proteins that cut up the target, thereby "silencing" the would-be cell killer.

The invader surveillance component of the dynamic duo (an RNA with a viral recognition sequence) comes from sites in the genomes of bacteria and archaea, known technically as "clustered regularly interspaced short palindromic repeats" or more familiarly called CRISPRs. (A palindrome is a word or sentence that reads the same forward and backward.) CRISPR RNAs don't work alone in fighting invaders, though.

Their partners in invader defense are Cas proteins that arise from a suite of genes called "CRISPR-associated" or Cas genes. Together, they form the "CRISPR-Cas system," and the new paper describes this dynamic duo and how they protect bacteria from viruses.

"You can look at one as a police dog that tracks down and latches onto an invader, and the other as a police officer that follows along and `silences' the offender," said Rebecca Terns. "It functions like our own immune system, constantly watching for and neutralizing intruders. But the surveillance is done by tiny CRISPR RNAs rather than antibodies."

What the team discovered was that a particular complex of CRISPR RNAs and a subset of the Cas proteins termed the RAMP module recognizes and destroys invader RNAs that it encounters.

"This work has uncovered intriguing parallels between the bacterial CRISPR-Cas system and the human immune system, suggesting a novel way to target disease-causing bacteria," said Laurie Tompkins, Ph.D., who oversees genetic mechanisms grants at the National Institutes of Health's National Institute of General Medical Sciences. "It may be possible to turn CRISPR-Cas into a suicide machine, killing pathogenic bacteria by an attack on their own molecules, similar to the self-destruction seen in human autoimmune diseases."

Understanding how the system silences invaders opens up opportunities to exploit it. So far, CRISPRs have been found in about half of the bacterial genomes that have been mapped or sequenced and in nearly all sequenced archaeal genomes. Such pervasiveness indicates that an ability to manipulate the CRISPR-Cas system could yield a broad range of applications. For example, using the knowledge that they have obtained in this work, the Terns now envision being able to design new CRISPR RNAs that will take advantage of the system to selectively cleave target RNAs in bacterial cells.

"These could target viruses that wipe out cultures of bacteria used by industry to produce enzymes," said Michael Terns, "or could target the gene products of the bacteria themselves. With this set of Cas proteins, we now know how to cut a target RNA at the site we choose."

"Believe it or not, we have only recently recognized that these microorganisms have a heritable immune system [because it is so different from our own]," added Rebecca Terns.

Remarkably, scientists are already in a position to begin to capitalize on their rapidly growing knowledge of this bacterial immune system.

http://www.sciencedaily.com/releases/2010/09/100915171531.htm

The team led by Professor Sylvain Moineau of Université Laval's Department of Biochemistry, Microbiology, and Bioinformatics showed that this mechanism, called CRISPR/Cas, works by selecting foreign DNA segments and inserting them into very specific locations in a bacterium's genome. These segments then serve as a kind of immune factor in fighting off future invasions by cleaving incoming DNA.

The researchers demonstrated this mechanism using plasmids, DNA molecules that are regularly exchanged by bacteria. The plasmid used in the experiment, which contained a gene for antibiotic resistance, was inserted into bacteria used in making yogurt, Streptococcus thermophilus. Some of the bacteria integrated the segments of DNA from the resistance gene into their genome, and subsequent attempts to reinsert the plasmid into these bacteria failed. "These bacteria had simply been immunized against acquiring the resistance gene, commented Professor Moineau. This phenomenon could explain, among other things, why some bacteria develop antibiotic resistance while others don't."

The CRISPR/Cas immune system also protects bacteria from bacteriophages, a group of viruses that specifically target bacteria. This makes Professor Moineau's discovery particularly interesting for food and biotechnology sectors that use bacterial cultures, such as the yogurt, cheese, and probiotics industries. Bacterial culture contamination by bacteriophages is a serious concern with considerable financial implications for those industries.

 

[wirednuts]

i have had acute chrons disease for 10 years. it took at least 5 years before i was able to find a way to regulate it a bit. and now it doesnt effect me often, and even when it does im not completely disabled like i used to be.

bacteria in the gut is the absolute key. the relationship between beneficial bacterial and your body's immune system is CRUCIAL. i am living proof of this. all the meds the doctors gave me only cured symptoms like pain and fatigue. my body was still wasting away, until i started taking probiotics. and every time i go south and i dont start taking the beneficial bacteria it simply never gets better. the longer you let the disease have free reign, the longer it takes to come back from it. i still have spurts of 3-5 months where i am not as healthy as i should be, but thats better then the 6 months of diarrhea and days of hospital stays that i used to have.

i have read countless articles on anything that might relate to chrons, so this one in OP is interesting to me too. there was one article i read that told of brainwave experiments focused on the intestines. same tests they do on the brain, only pointed on the gut. they were absolutely shocked when they found the same exact types of brainwaves that we have in our head. they now believe the stomach is actually a sub-brain, that controls the physical parts of our bodies like muscle control and immune system. it makes sense too, like a car's main ecm computer and its sub-computer on the transmission, or the body's ecm that controls the lights and buttons. the main computer (our brains) dictate actual descision making, while the sub-computer (our gut) controls the actual parts of our bodies into doing what our brain wants.

this is why it seems VITAL to have the proper organisms in your stomach. right now, sterile is not so great because we cant evolve away quick enough from our thousands of years of being connected to the outside environment. this is why probiotics help, because they reintroduce those organisms that our body manipulates into fighting the bad bacteria that is always trying to grow inside of us.

and if our stomach is healthy, our immune system is healthy. which means our bodies are healthy... which helps the brain function properly. its all tightly interconnected and were only starting to figure out the details, but its fascinating none the less.

 

[William Gaatjes]

Good for you that you discovered the link between your disease and the bacteria inside your gut.

I do not know if i would call the bowls a brain. But i do think that the brain and the digestive system keep good contact with each other as does the immunesystem. A triangle of power generation, protection and command structure.


I do not have chrone disease but i did discover that any processed food product or advised normal amounts of sugar gives me pain , bowl movement problems or constipation changing rapidly into diarrhea for days in a row. And as a side effect acne like skin problems.
Since i make my own food recipes with reduced sugar and eat healthy this has improved for me :
My physical strength and stamina has increased.
Fighting of common diseases like flu or common cold in a matter of 4 hours while only feeling tired and a hunger for protein rich diet, after consuming i can sleep immediately. When awake i am no longer feeling feverish and the next day cured. I account this to that my body can stop the infection from spreading because i already have a lot of antibodies (public transport advantage) and because of my protein/vitamin/essential elements rich(low carbon hydrate) diet my immune system works better.
while i eat apparently the same, my bloated belly has gone.
My vertebrate problem hurts a lot less.

I do not take supplements. I just eat healthy and normal and moderate.

I too believe that the modern medical world underestimates the importance of a healthy diverse bacteria culture in the gut. But we need the right bacteria and wrong food can cause the wrong balance of bacteria.
The old true asian ways ( not that fake rhino horn or tiger penis bullshit) but using the right plants and roots (with accompanying bacteria) can help solve or relieve many problems by restoring the balance in the gut.

EDIT:
The old middle east and the old celtics and germanic tribes had similar knowledge about the healing powers of plants and roots( without knowing that bacteria existed on these plants and roots). Unfortunately the roman catholic church destroyed the knowledge because this knowledge was seen as heresy.
The old islam renaissance ( or islamic golden age) saved the asian version of this knowledge but got lost as well when the religion got divided by power hungry people. Until unfortunately the islam became similar as the roman catholic church dogma. Knowledge lost, lies gained.

Fun to know is that during the islamic golden age people theorized that there existed living creatures that can make you sick but where to small to see with the eye ? That is around the same time when quarantine was discovered/invented.

 

[William Gaatjes]

I had not added this yet. Different types of bacteria movement :

http://forums.anandtech.com/showthread.php?t=2091742

Picture of a phage, and a photo about a model how an bacteria flagellum works.

A video about how it works :

http://www.youtube.com/watch?v=Ey7Emmddf7Y

And research that seem to suggest that bacteriophages can be responsible for the fine tuning of interaction between bacteria and their host :

Our data suggest that horizontal transfer of type III dependent effector proteins by lysogenic infection with bacteriophages (lysogenic conversion) may provide an efficient mechanism for fine-tuning the interaction of Salmonella spp. with their hosts.