Jemal
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That certainly helped to clarify things Alex, thanks.
Human APOBEC3 proteins can inhibit XMRV
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Thanks Garcia and Sunshine for that link. That's as I remembered and suspected it: seems to me that APOBEC3 and XMRV are right on the front line in a genetic war, given that either can inhibit the other's function.
I don't think it's been mentioned on this thread, that what APOBEC3 does is actively go around editing bits of dud genetic code so as to render them inactive. That's my understanding of it anyway: once XMRV has written its DNA into a cell, APOBEC3 is attaching to the parts of that cell that have now got the XMRV genetic code in them, and "swapping" key bits of that sequence so as to render the sequence inactive. If XMRV can stop APOBEC3 from doing that, it can survive inside the infected cell.
Hope I've got that right...as usual I can't remember where I read that.
I don't think it's been mentioned on this thread, that what APOBEC3 does is actively go around editing bits of dud genetic code so as to render them inactive. That's my understanding of it anyway: once XMRV has written its DNA into a cell, APOBEC3 is attaching to the parts of that cell that have now got the XMRV genetic code in them, and "swapping" key bits of that sequence so as to render the sequence inactive. If XMRV can stop APOBEC3 from doing that, it can survive inside the infected cell.
Hope I've got that right...as usual I can't remember where I read that.
usedtobeperkytina
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Well, I have always subscribed to the theory that the immune system response was not abnormal, but actually a normal response to something else in the body that is abnormal.
I always thought that the inflammation was the body trying to fight something. Way I see it, we know we have infections at higher levels, and it is natural the body would go into attack mode to fight them.. That is normal. So since the infections are chronic, so is the inflammation.
The question then becomes what causes the infections to flourish. Well, considering studies, seems logically another part of immune system is defective. And so it is, Natural Killer cells. So what would cause that? genetics, some other problem in the CNS or endocrine system or retrovirus.
It seems to me, there is a first cause. And all the rest of it is a loop of normal body reactions that eventually goes back and exacerbates the first cause. So much of what we experience is normal body immune system reacting to something abnormal. Then, that something is triggered again, causing the loop to go, which then triggers that something.
So, I would not be surprised that our bodies fight XMRV, but something prevents it from killing it or completely subduing it effectively. Or something causes it to come back and replicate again, starting the loop, and the virus goes down, but then something makes it go back up again, etc.
When you look at the nature of our illness, good days / bad days, chronic, doesn't kill us within two years, you see that there is a Vietnam War going on inside. One side makes some advances, which creates a push back and so it goes, back and forth.
Just my theory.
But all this fits.
Tina
I always thought that the inflammation was the body trying to fight something. Way I see it, we know we have infections at higher levels, and it is natural the body would go into attack mode to fight them.. That is normal. So since the infections are chronic, so is the inflammation.
The question then becomes what causes the infections to flourish. Well, considering studies, seems logically another part of immune system is defective. And so it is, Natural Killer cells. So what would cause that? genetics, some other problem in the CNS or endocrine system or retrovirus.
It seems to me, there is a first cause. And all the rest of it is a loop of normal body reactions that eventually goes back and exacerbates the first cause. So much of what we experience is normal body immune system reacting to something abnormal. Then, that something is triggered again, causing the loop to go, which then triggers that something.
So, I would not be surprised that our bodies fight XMRV, but something prevents it from killing it or completely subduing it effectively. Or something causes it to come back and replicate again, starting the loop, and the virus goes down, but then something makes it go back up again, etc.
When you look at the nature of our illness, good days / bad days, chronic, doesn't kill us within two years, you see that there is a Vietnam War going on inside. One side makes some advances, which creates a push back and so it goes, back and forth.
Just my theory.
But all this fits.
Tina
Agree Tina, and I think the key to that is going to be the way that XMRV is kind of 'parasitic' on our immune response, and subverts it. Which is why the inhibition of APOBEC3 by XMRV is a key part, because it shows XMRV acting directly against our body's own defences to it. Much of that is intuitive to me as a computer scientist, by analogy to the more powerful types of computer virus. But what you've described is totally intuitive to most of us as patients I expect, because we all, surely, understand the wall that surrounds us and means that as soon as we start to improve and make progress, the whole thing crashes and we go back round the cycle all over again. I've conceived of that phenomenon as a 'parasite' living off whatever energy I can generate for quite a few years now.
urbantravels
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All viruses are parasites, by definition.
Jemal
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I subscribe to this theory
Retroviruses by default are very hard to clear by the immune system. They have mechanisms to combat the immune system and/or they are using the immune system to replicate, so a stronger immune response, will only make the virus stronger. It's a vicious cycle and I think we need drugs to turn the tide in our favour.
It could even be that in the end, our immune system is causing the biggest problems. XMRV might be a pretty innocent virus, that the immune system wants to eridicate at all costs. The immune system can tire itself over time and even deplete certain resources. This could set the door open for cancer or other infections. So the virus might not even be directly responsible for that... it would be more like an autoimmune disorder, where the body is attacking its own cells. It's now suspected by some that quite a few autoimmune disorders are caused by debris of ancient (retro)viruses, still in our DNA.
Daffodil
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one of the discoverers of XMRV once told me that he does not think the virus itself is a "serious, life-threatening" infection.
Cort
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Its not in the prostate or testes I think and I was just told that it is either missing or weakly present in nerve cells. In monkeys which presumably have similar proteins (?) XMRV was found in alot of organs - kidney's, liver, lungs...
Its an enzyme which means its a protein as well.
Cort
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XMRV can fend off A3B,C and F - and is tweaked by 3G -so 3G is of special interest to us.
This paper suggests that levels of 3G can differ between donors - so there is variance in the human population. It is induced by alpha interferon - which suggests that low alpha interferon levels could leave a cell susceptible to 3 AG.....
August59
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Is this information that will soon be published or is it already available? Thanks!
Cort
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Its out. I think I just looked up apobec 3 and XMRV on the internet.
guest
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http://www.sciencedaily.com/releases/2010/12/101222173041.htm
Discovery Suggests a New Way to Prevent HIV from Infecting Human Cells
ScienceDaily (Dec. 23, 2010) — Researchers at the University of Minnesota have discovered how HIV binds to and destroys a specific human antiviral protein called APOBEC3F. The results suggest that a simple chemical change can convert APOBEC3F to a more effective antiviral agent and that shielding of a common feature shared by related proteins may yield a similar outcome.
This discovery highlights the potential for a novel approach to combating HIV/AIDS that would seek to stabilize and harness the innate antiviral activity of certain human proteins, according to lead author John Albin, a researcher in the laboratory of Reuben Harris, associate professor of biochemistry, molecular biology and biophysics in the College of Biological Sciences.
The finding was published in the Journal of Biological Chemistry.
Human cells produce a family of antiviral proteins (called APOBECs) that have the unique and natural ability to destroy HIV. But HIV has evolved a way to overcome restriction using an accessory protein called Vif (virion infectivity factor) to degrade the APOBEC proteins and allow the virus to spread. Albin and colleagues learned where Vif interacts with one antiviral protein, APOBEC3F, and showed how the connection can be interrupted by a simple chemical change on the surface of APOBEC3F. They also noted that similar interaction sites are found on the same surface in other members of this antiviral protein family.
"This suggests that the interaction between Vif and these antiviral APOBEC proteins could be blocked with a drug that would shield the Vif interaction region," Albin says. "Such an intervention has the potential to allow as many as seven natural antiviral drugs to spring into action and prevent HIV from spreading."
The Harris lab is focuses on understanding every level of the vital interaction between these human cellular proteins and HIV Vif. They envision that future studies will involve a more refined mapping of the physical interactions between Vif and APOBEC3 proteins, investigation of the potential for HIV to resist stabilizing changes in APOBEC3 proteins, and screens for drug-like compounds that help the cellular APOBECs destroy HIV.
John Albin, a student in the Combined MD-PhD Training Program at the University of Minnesota Medical School, and is completing a thesis under the guidance of his advisor, Reuben Harris, through the Microbiology, Immunology & Cancer Biology PhD program. His studies in the Harris lab focus on the potential of APOBEC proteins to impact HIV evolution and pathogenesis.
This latest finding builds on a body of research from Harris's lab about the relationship between HIV and APOBEC proteins. In 2003 and 2004, Harris helped discover that the APOBEC proteins have the ability to counteract HIV infection.
Harris, who won a 2009 challenge grant from the Bill & Melinda Gates Foundation to explore ways to block HIV and APOBEC3 interaction, has been studying mechanisms of mutation for nearly 20 years, first as a doctoral student at the University of Alberta, then as a post-doctoral fellow at the Laboratory of Molecular Biology in Cambridge, England, and for the past seven years as an NIH supported principal investigator at the University of Minnesota. His laboratory focuses on how mutations can be harnessed to destroy pathogens.
Discovery Suggests a New Way to Prevent HIV from Infecting Human Cells
ScienceDaily (Dec. 23, 2010) — Researchers at the University of Minnesota have discovered how HIV binds to and destroys a specific human antiviral protein called APOBEC3F. The results suggest that a simple chemical change can convert APOBEC3F to a more effective antiviral agent and that shielding of a common feature shared by related proteins may yield a similar outcome.
This discovery highlights the potential for a novel approach to combating HIV/AIDS that would seek to stabilize and harness the innate antiviral activity of certain human proteins, according to lead author John Albin, a researcher in the laboratory of Reuben Harris, associate professor of biochemistry, molecular biology and biophysics in the College of Biological Sciences.
The finding was published in the Journal of Biological Chemistry.
Human cells produce a family of antiviral proteins (called APOBECs) that have the unique and natural ability to destroy HIV. But HIV has evolved a way to overcome restriction using an accessory protein called Vif (virion infectivity factor) to degrade the APOBEC proteins and allow the virus to spread. Albin and colleagues learned where Vif interacts with one antiviral protein, APOBEC3F, and showed how the connection can be interrupted by a simple chemical change on the surface of APOBEC3F. They also noted that similar interaction sites are found on the same surface in other members of this antiviral protein family.
"This suggests that the interaction between Vif and these antiviral APOBEC proteins could be blocked with a drug that would shield the Vif interaction region," Albin says. "Such an intervention has the potential to allow as many as seven natural antiviral drugs to spring into action and prevent HIV from spreading."
The Harris lab is focuses on understanding every level of the vital interaction between these human cellular proteins and HIV Vif. They envision that future studies will involve a more refined mapping of the physical interactions between Vif and APOBEC3 proteins, investigation of the potential for HIV to resist stabilizing changes in APOBEC3 proteins, and screens for drug-like compounds that help the cellular APOBECs destroy HIV.
John Albin, a student in the Combined MD-PhD Training Program at the University of Minnesota Medical School, and is completing a thesis under the guidance of his advisor, Reuben Harris, through the Microbiology, Immunology & Cancer Biology PhD program. His studies in the Harris lab focus on the potential of APOBEC proteins to impact HIV evolution and pathogenesis.
This latest finding builds on a body of research from Harris's lab about the relationship between HIV and APOBEC proteins. In 2003 and 2004, Harris helped discover that the APOBEC proteins have the ability to counteract HIV infection.
Harris, who won a 2009 challenge grant from the Bill & Melinda Gates Foundation to explore ways to block HIV and APOBEC3 interaction, has been studying mechanisms of mutation for nearly 20 years, first as a doctoral student at the University of Alberta, then as a post-doctoral fellow at the Laboratory of Molecular Biology in Cambridge, England, and for the past seven years as an NIH supported principal investigator at the University of Minnesota. His laboratory focuses on how mutations can be harnessed to destroy pathogens.