In vivo hypermutation of XMRV in rhesus macaque by APOBEC3 proteins

RustyJ

RustyJ

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In vivo hypermutation of xenotropic murine leukemia virus-related virus DNA in peripheral blood mononuclear cells of rhesus macaque by APOBEC3 proteins

Ao Zhanga, b, 1, Hal Bogerdc, 1, Francois Villingerd, Jaydip Das Guptab, Beihua Dongb, Eric A. Kleine, John Hackett Jr.f, Gerald Schochetmanf, Bryan R. Cullenc, Robert H. Silvermana, b, Corresponding Author Contact Information, E-mail The Corresponding Author
Purchase

Received 13 July 2011; revised 26 July 2011; Accepted 17 August 2011. Available online 6 October 2011.
Abstract

The gammaretrovirus, xenotropic murine leukemia virus-related virus (XMRV), replicates to high titers in some human cell lines and is able to infect non-human primates. To determine whether APOBEC3 (A3) proteins restrict XMRV infections in a non-human primate model, we sequenced proviral DNA from peripheral blood mononuclear cells of XMRV-infected rhesus macaques. Hypermutation characteristic of A3DE, A3F and A3G activities was observed in the XMRV proviral sequences in vivo. Furthermore, expression of rhesus A3DE, A3F, or A3G in human cells inhibited XMRV infection and caused hypermutation of XMRV DNA. These studies show that some rhesus A3 isoforms are highly effective against XMRV in the blood of a non-human primate model of infection and in cultured human cells.
Click to expand...

http://www.sciencedirect.com/science/article/pii/S0042682211004375

Not sure if this has been picked up previously. Note Silverman is involved, so not sure about whether he is talking about generic XMRV or the VP62/XMRV which is his pet contaminant/lab artifact ;).

Note, there has been some fuss made about Apobec3 stopping XMRV/HGRVs dead in the water. This is not true. It appears to be another attempt to water down any causal link to disease. Here is a quick summary of why Apobec3 does not stop all HGRV, although it may be why HGRVs appear to retreat to tissue reservoirs.


  • HGRVs don't need reverse transcriptase, they can increase their titre by using T and B cells via clonal expansion. That evades APOBEC, which has no effect on none dividing cells.
  • The gag region of HGRVs also protects against APOBEC, reducing hypermutation.
  • So variation is limited, except from what the APOBEC or oxidative stress causes.
  • MuLV glycogag also protects against APOBEC and APOBEC is inactivated in mitotic cells and MuLVs integrate into B cells to evade APOBEC.

http://www.mecfsforums.com/index.php/topic,9926.msg117934.html#msg117934
 
Enid

Enid

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Thanks Rusty - I don't understand the science but guess this has to be important - none of the suspects "dead in the water" yet.
 
B

barbc56

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Lol, Rusty. Great minds must think alike. I was about to start a thread on this and happened to see you beat me to it
.
Abstract
The gammaretrovirus, xenotropic murine leukemia virus-related virus (XMRV), replicates to high titers in some human cell lines and is able to infect non-human primates. To determine whether APOBEC3 (A3) proteins restrict XMRV infections in a non-human primate model, we sequenced proviral DNA from peripheral blood mononuclear cells of XMRV-infected rhesus macaques. Hypermutation characteristic of A3DE, A3F and A3G activities was observed in the XMRV proviral sequences in vivo. Furthermore, expression of rhesus A3DE, A3F, or A3G in human cells inhibited XMRV infection and caused hypermutation of XMRV DNA. These studies show that some rhesus A3 isoforms are highly effective against XMRV in the blood of a non-human primate model of infection and in cultured human cells.
Click to expand...

http://www.sciencedirect.com/science/article/pii/S0042682211004375

It does appear that Apobec3 stops XMRV/HGRVs. I am double checking this information with several friends who are scientist. Neither have a vested interest in this subject other than me.

In the meantime if you could find another source that backs up what you read on the mecfs forums. TBH, I don't find I am that comfortable with the science that comes from that place compared. I will report back when I find more information on this and maybe we as well as others can reconoiter about this subject. I have always found this study fascinating and I am just now beginning to really understand it. I just want to double check some of the facts.

Thanks.
 
alex3619

alex3619

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Hi RustyJ, its nice to see this paper, it supports what I was already thinking - an MLV infection in humans will be slow and mostly in tissue, it isn't impossible. Which of course fits with ME. Even if the MLLV-ME link doesn't work out, the world still has to research this to get on top of it before it becomes a problem, especially since XMRV is in so many cultures.Bye, Alex
 
SilverbladeTE

SilverbladeTE

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as I keep saying...takes at least 5 years for such work to come to fruition, so folk cawing happily for the death of XMRV/MLV are being very foolish.
Same with any new avenue in science.

Article seems more evidence of a highly evolved "stealth" routine, doesn't it? Which is indicative of a very susccessful and thus very old (time ot evolve such effective routines), or combinate of successful virii?
 
C

currer

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I have never been very convinced that we have an infection in the usual meaning that the virus is actively replicating to high titres.
People with ME can be ill for decades but the disease does not usually progress. Indeed many sufferers reach a plateau, or may improve.

I am more interested in the possibility that a retrovirus which by its nature cannot be completely eliminated from the body, could spark off an auto-immune state.

Most people just do not seem ill enough or sustain enough organic damage, for an active viral infection.
 
B

barbc56

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Well this might be true, but it doesn't look like it's from xmrv or hgrvs.

What we think or are convinced of may or may not match the science.

In this case it doesn't.
 
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