Mouse retroviruses and chronic fatigue syndrome: Does X (or P) mark the spot?

mojoey

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So what I get is that the X-type can only infect human cells, but the P-type both mouse and human cells. I heard one leading CFS doctor say that the P-type is likely much more virulent that the X-type, but I'm not aware of the basis for this.

Both use the XPR1 receptor to mediate cell entry, so will future therapy comprise of XPR1 receptor-lacking stem cells (analogue to the CCR-5 receptor-lacking stem cells that cured AIDS patient?)

I also love that the commentary ends with this bit:
As we currently lack postulates to prove a causal association with a prevalent agent and a chronic disease with genetic predisposition, it would also be appropriate to conduct interventional studies. Indeed, the Helicobacter pylori hypothesis of peptic ulcer disease was only accepted after Barry Marshall showed that bacterial eradication with antibiotics cured peptic ulcer disease (21). Studies to gain proof of principle have been performed with antivirals in other chronic, idiopathic diseases linked to retroviral infection, such as primary biliary cirrhosis associated with mouse mammary tumor virus, another possible murine zoonosis (22). Trials using a combination of reverse transcriptase inhibitors led to significant improvements in clinical, histological, and biochemical outcomes in these patients, albeit with some evidence of viral resistance to therapy (23). Such studies are now feasible for CFS, because reverse-transcriptase inhibitors, such as tenofovir and emtracitabine, and the integrase inhibitor raltegravir can inhibit XMRV (24).
 

alex3619

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HI

The reference for the other retrovirus in post 2 is:

22. Xu L, et al. (2003) Does a betaretrovirus infection trigger
primary biliary cirrhosis? Proc Natl Acad Sci USA
100:8454–8459.

I have not read this, but it might mean that XMRV is the fourth human retrovirus, and that the only path to proof of causation is a successful clinical trial with antiretrovirals.

Bye
Alex
 

Rrrr

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YES, clinical trials now!!!!!!!!!!!!!!!

i think this has to be our chant.

also, i had never heard of the ARV "emtracitabine" -- as mentioned in the quote from joey's post. has anyone else heard of it?

i thought that the 3 meds found to work in vitro (check on the doses, i'm not sure about them!!!!!!!!!) were:
AZT: 300 mg, 2x/day
Raltegravir (Isentress): 400 mg, 2x/day
Tenofovir (Viread): 300 mg, 1x/day

This below study by Dr. Singh states that raltegravir is the most effective against xmrv in vitro, and dr coffin and others have told me it is the one with the least side effects in vivo.
"Anti-HIV drugs inhibit emerging virus linked to prostate cancer and chronic fatigue syndrome"
http://www.aidsmap.com/en/news/7783CFCE-5022-40C8-AE08-0A99D440CAC2.asp
 

anciendaze

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Indeed the multiple origins of these xenotropic sequences, the hybrid nature of the XMRV genome, and the occlusion of the otherwise necessary glycogag ORF underscore the potential complementation and recombinational events that may lead to their transmission into humans. ... These observations suggest a scenario in which retroviruses, MLV-related agents, and potentially, other viral agents may cross-complement to promote coinfection and enable pathogenicity.
If the Lo/Alter paper was the elephant in the room, that hypothesis has been the dinosaur nobody admitted seeing. Complementation and recombination of multiple infections is finally out there as a possible cause of human disease, including the baffling affliction called CFS/ME.

Added: In reading through the earlier post, this time I caught an indirect implication.
...such as primary biliary cirrhosis associated with mouse mammary tumor virus, another possible murine zoonosis...
By mentioning MMTV they indirectly bring in a possible HMTV, without explicitly mentioning relevance to breast cancer research. The implications keep growing.
 

mojoey

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Reading over the commentary, I can't for the life of me figure out if the polytropic MLV is endogenous or exogenous. I've heard CFS researchers imply that it is "definitely" exogenous, but the commentary muddles that a bit
 

anciendaze

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It is definitely exogenous. It should not be able to reinfect the species from which it originated otherwise. That is the distinction between xenotropic and polytropic.

Remember, these names are all only strong hypotheses at this point. Everything will need to be nailed down. Even so, implications run off in many directions. I don't expect anyone to declare the excitment over anytime soon.