New paper: Apobec 3G reduces infectivity of the XMRV

RustyJ

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XMRV replication in vivo most likely takes place in cells which not, or only weakly, express hA3G.
I am not sure how this extends the previous 2 studies. Regarding above point, I think someone commented that XMRV may still be bypassing A3G in cells that do contain that protein. One other point, are there any other parts of the body that do not contain A3G where XMRV is more likely to find refuge. I guess this information is important for treatment, for targetting persistent reservoirs of XMRV after ARVs have beaten it back to these reservoirs. Can anyone add to this?

I note that someone has started another thread on this subject, some time after this one. I don't know the protocol in this situation - should they be merged?
 

RustyJ

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I had another rare thought. What if this is why many people don't contact XMRV: because A3G kills it off in most tissue before it can get a hold. In other words, some people are lucky and some just ain't. Also could mean that genetics, environmental factors etc play little part in whether the virus takes hold.
 

Otis

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I wondered about that as well? Maybe in the sickest patients APOBEC is not working as well?
An interesting topic for speculation, to be sure.

Seems like there are some interesting study possibilities here.

Type of onset may be a consideration with APOBEC effectiveness.
 

RustyJ

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Yep I thought this and does it explain why we may have good weeks and bad weeks maybe the APOBEC works better at times.
I think it reads that APOBEC is a gatekeeper. Once the virus is in the cell without getting pinned by APOBEC it's there for keeps. So it is unlikely APOBEC would have the sort of impact you are talking about. APOBEC would either stop the virus at its initial contact, or once the virus had a foothold APOBEC would slow down its spread, but not stop it entirely.

Maybe temporary symptom relief is more due to the relative effectiveness of the immune system and/or stage of concurrent infections.
 

judderwocky

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I think it reads that APOBEC is a gatekeeper. Once the virus is in the cell without getting pinned by APOBEC it's there for keeps. So it is unlikely APOBEC would have the sort of impact you are talking about. APOBEC would either stop the virus at its initial contact, or once the virus had a foothold APOBEC would slow down its spread, but not stop it entirely.

Maybe temporary symptom relief is more due to the relative effectiveness of the immune system and/or stage of concurrent infections.
a good point... and a lot of these defense factors work "in conjunction" with one another....

it could also be that like they are now discovering with HIV.. you need other viruses to weaken the body before it can take hold....like herpes helps hiv infect the mucosa.... maybe an entero virus or something could be what is weakening our system to let it in... then once it is established... it takes hold and becomes a permanent root cause... the defreitas retrovirus?
 

RustyJ

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Judder, Cort, you may be right. APOBEC may be affected in ME patients. Could it be that everyone has underestimated the role APOBEC has played? Mikovits has only recently suggested there might be 2 types of XMRV - one type in the prostate and one in ME patients. In fact, Cort, you highlighted this in "A different kind of XMRV?" http://www.forums.aboutmecfs.org/con...niello-on-XMRV

I thought it was important, so I started a new thread on it. http://www.forums.aboutmecfs.org/showthread.php?6526-Two-different-types-of-XMRV-revisited&


Researchers are looking for XMRV in CFS in the immune cells (T and B and others) in the blood. The papers indicated that the genetic sequences of the virus in T and B cells can get altered (or edited) over time by what are called APOBEC3 editing enzymes. Cells use these enzymes to attack retroviruses that have become integrated into our genome. Simply by exchanging the guanine bases in the retroviral sequences to adenine APOBEC3 stops the virus from replicating. Basically, except for the few virions that manage to escape this defense mechanism, T and B cells in the blood are a dead end for XMRV.

The XMRV in prostate cancer cells may be different, however, because the APOBEC3 enzyme is not found in those cells, thus allowing them to escape this editing process. Since XMRV was first discovered in prostate cancer cells it's not surprising that prostate cancer XMRV forms the basis for many of the PCR probes but it does mean studies using this form of the XMRV could miss the different looking virus in the T and B cells
 

JillBohr

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In this study I read that anti-viral protein APOBEC3G is induced by interferon-alpha stimulation in human hepatocytes http://www.ncbi.nlm.nih.gov/pubmed/16426578
When we then consider the following medicine, interferon-a http://www.oncolink.org/treatment/article.cfm?c=2&id=320&s=10 may we then be looking at a potential xmrv treatment candidate? Or should we aim to increase our own interferon-a production?
Very interesting leaves since Judy stated that the only immune marker associated with XMRV is decreased interferon alpha.

http://www.forums.aboutmecfs.org/sh...Mikovits-IACFS-ME-Newsletter-Apr-2010-Q-amp-A

The ONLY immune marker which correlated with XMRV infection 100% was decreased Interferon alpha.