Today I read a post by "ukxmrv", and that's what he said there: So then I searched for papers about HTLV-1's replication, to see if it can give us hints about why XMRV has a low mutation rate, if it has a low mutation rate (which I'm not sure of - because I don't know if the Lo/Alter sequences shouldn't be called "XMRV" - in fact, I don't understand why they don't call them by that name - and they represent a significant mutation rate from VP62). Anyway, I think that I found some interesting stuff (Warning: I'm not a scientist, and it's very possible that I'm wrong in some of the things that I say. If you know that I'm wrong, or think that I'm wrong - please say so and say why): 1) It seems that HTLV-1's main route of replication is not by reverse transcriptase of the virion (virion is the infectious virus particle when it's OUTSIDE of the host's cell) - like most of the retroviruses (inlcudin HIV-1) - but through another mechanism: It replicates with with the cell - when the cell replicates, the virus replicates. Here are some parts of studies where they talk about that: http://jnci.oxfordjournals.org/content/93/5/367.full http://www.ncbi.nlm.nih.gov/pmc/articles/PMC112382/ So, perhaps XMRV is replicating like HTLV-1 - mostly through cell division and less by reverse transcriptase of the virion. And that would cause it to have less mutations: http://jnci.oxfordjournals.org/content/93/5/336.full.pdf 2) HTLV-1 has an oncogene - it's called "tax". XMRV doesn't have an oncogene (its only genes are gag, envelope and polymerase). Now look what they say about the "tax" gene in HTLV-1: http://jnci.oxfordjournals.org/content/93/5/367.full http://jnci.oxfordjournals.org/content/93/5/336.full.pdf So, when HTLV-1 is causing cancer - you should expect - if I understand it correctly - to find a greater variability than when it doesn't, and that's because when you have cancer, you cells are dividing more often - which would give HTLV-1 more opportunity to change his genome. Also, theye say that the "tax" gene interferes with cellular DNA repair pathways, so perhaps that's also helping it mutate, I think. Now, a cancer caused by XMRV might be a different thing, but when you are talking about XMRV in patients without cancer - and if XMRV replicates in a similar way to HTLV-1, meaning, mostly by cell-division - I think that you should expect that XMRV would even have less mutations, because if there is no cancer, than the cells are dividing much slower, giving XMRV much less opportunities to change its genome. And even if you do have cancer - if I understand correclty, retroviruses without oncogenes (as XMRV is) can cause cancer, but in a different way (I think it depends on where they integrate - whether they integrate into an oncogene or something like that), and XMRV won't have the "tax" gene that would interfere with cellular DNA repair pathways - so even if you have cancer, you might expect lower variation of XMRV, in comparison to HTLV-1. 3) Even when HTLV-1 virions are replicating, using reverse transcriptase, it seems that their mutation rate is significantly lower than the mutation rate of HIV-1: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC112382/ 4) You must remember that while HTLV-1 is a complex retrovirus, XMRV is a simple retrovirus. As far as I understand it, simple retroviruses, because of the small number of genes, are mutating less than complex retroviruses, which have more genes (while XMRV has 3 genes - gag, polymerase and envelope - HTLV-1 has 5 genes: gag, polymerase, envelope, tax and rex). Now, it seems that XMRV is a retrovirus that is replicating slowly and that usually has little variation. One way of explaining this would be to say: "It's just contamination". But another way would be: "Hey, we already know of a human retrovirus that replicates slowly and that has little variation. And we can also see that if XMRV replicates mostly by cell-division, than it would be expected that it would replicate even less than HTLV-1 and would have even less variation than HTLV-1". Now, there is another thing, and that's regarding the PMRVs found by Lo and Alter (and their colleagues - I must mention them as I think it's unfair to them that we never mention their names... so: Natalia Pripuzova, Guo-Chiuan Hung, Bingjie Li, Richard Wang and Anthony Komaroff): These sequences are "just" 84%-96% (mostly about 95%) identical to the VP62-strains. Since HIV-1 and HCV (and probably many other viruses that I did not check) has strains that are only 85% and 79% identical to one another - and still all of these are named "HIV-1" and "HCV", I currently don't understand why some of the scientists say that the PMRVs and XMRV are different viruses. So, let's assume that they are the same virus - which in my unscientifically-educate opinion is the more reasonable thing to think - how would we explain why those strains have more variability? I mean, we just explained why you might not expect XMRV to have a large variability. I think I might have an explanation for that: http://jnci.oxfordjournals.org/content/93/5/336.full.pdf http://jvi.asm.org/cgi/reprint/67/2/1015.pdf So there, they found a strain of HTLV-1 that was "only" 91.5% identical to the reference strain (and actually, I think, that was about the percentage of difference from other strains too). All of the other strains (and I did not find many complete genome strains, unfortunately) are highly identical to one another, as was said in one of the quotes above. It should be said, however, that this strain was found in Oceania while the reference strain was from Japan - and in our case the PMRVs were found in the USA, although in another state (but anyway Dr. Mikovits is finding the P strain also in her samples, which I guess are mostly from Nevada, although I can't be sure of that - but it's probable that she finds the P variant at least in some samples from Nevada). So I don't know how to explain that, but even if nobody knows how to explain that, there could be an explanation - and actually I guess that scientists can give numerous explanations for that, at least if they would think about it deeply. Anyway, I think that what we can see is the following: 1) There is already an example of a human retrovirus that replicates slowly and have little variability in the vast majoirty of its strains. 2) It's reasonable to expect that XMRV would have even less variability, and I explained why. 3) Despite usually having a low degree if variability, HTLV-1 does have a strain that is subtantially mutated - although that's from another part of the world, and the PMRVs are from a place pretty close to where the XMRVs where found (and anyway the WPI found PMRVs in their samples - probably from Nevada also - and XMRVs in the Lo/Alter samples). 4) I didn't talk about it in the above text, but I think that one bad, very bad thing that we might have to deal with if the thoery that XMRV replicates much like HTLV-1 is correct (and it's important to say that right now it's just a theory, and we, or at least I, cannot know if that theory is correct or not) is that it would probably be hard to fight it with antiretrovirals - because, at least as far as I understand it, when the virus is replicating by the cell-division route, it doesn't do all the reverse transcription and things that it does when it replicates outside of the cells, and therefore - and correct me if I'm wrong - the antiretrovirals that works against HIV won't be of a major help, because I think that they are acting only against a virus that replicates in a way different from replication by cell-division. I would like to say, however, that my hunch is that in the very-sick patients there is probably more viral replication by the reverse transcriptase route, and therefore perhaps anti-retrovirals can help them more, although just to some degree (because than you arrive at the cell-division replication, and as I said, I think that antiretrovirals does not act against that). By the way, I think that somewhere here or in the other forum it was posted before about scientists who are trying to eliminate retroviruses with a method that is based on chemotherapy - and it seems to me that this is the kind of things that can help those who are sick due to integrated retroviruses (in order to eliminate the cells that have retroviruses integrated into them). If they would be able to attack only, or at least mostly, the cells that have a provirus of XMRV integrated into them, I think that might be fantastic. I would very much like to hear your thoughts about that - and if I was mistaken somewhere, please correct me (but also explain why you think I was wrong).