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Well they looked at their tissues....prostate and LN (lymph nodes?)
Tabloid virology, firestormm.
Facepalm. Of course.
I just found it in the full length paper. Poor things.
During reverse transcription, APOBEC introduces lots of unwelcome mutations. Which means even if that new cell is 'infected', the virus that inserts into its genome is crap. It cant make any more babby viruses.
This editing process may inhibit virus replication through lethal mutagenesis (hypermutation), but could also contribute to viral diversification leading to the emergence of escape forms.
...Most striking in this study was the organ-specific kinetics of viral replication. The initial targeting of prostatic epithelium and the reproductive tract suggests that the enhancement of XMRV replication in response to androgen stimulation in vitro may represent a physiological mechanism (5) and may reflect lack of APOBEC3G expression in this tissue (2) in vivo. The finding that XMRV replication is controlled in prostate but not in testes suggests immune control of the virus as well, which is muted in the immuno-privileged environment of testes but not in the immune-competent prostate. Furthermore, continued replication in lymphoid organs may be secondary to localized immune activation, as suggested by other investigators (17), a finding that needs to be explored in more detail. ... http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3126245/
Natasha, why do you think these statements are not credible. Thanks.
http://www.ncbi.nlm.nih.gov/pubmed/21325415
"We and others have shown that host restriction factors APOBEC3G (A3G) and APOBEC3F (A3F), which are expressed in human PBMCs, inhibit XMRV in transient-transfection assays involving a single cycle of viral replication. However, the recovery of infectious XMRV from human PBMCs suggested that XMRV can replicate in these cells despite the expression of APOBEC3 proteins.........
.....However, infectious XMRV could be recovered from the infected PBMCs by cocultivation with a canine indicator cell line, and we observed hypermutation of XMRV genomes in PBMCs. Thus, PBMCs can potentially act as a source of infectious XMRV for spread to cells that express low levels of host restriction factors"
Yes currer, restriction factors slow and reduce infection, they don't stop it. So it will result in decreased infection rates, and a slower spread of infection in a host, and perhaps mostly restrict the infection to more optimum tissue types. It does not stop infection. Only lack of receptors that allow entry can do that. This is in accordance with other viral findings. A claim of non-infectivity due to restriction factors is not plausible. One thing it might do though is reduce infection via blood plasma (cell free blood products) to almost zero. Bye, Alex
I am wondering if in fact this paper says the same as what Abbie was herself concluding - that the virus which 'survives' is so mutated as to render it neutered:
From the paper abstract: 'Overall, these results suggest that hypermutation of XMRV in human PBMCs constitutes one of the blocks to replication and spread of XMRV.'
We can look at the papers as they come out and discuss those papers and try to interpret them in lay-language or we can 'cherry-pick' to suit our own beliefs.
You are highlighting the bits that suit the agenda of 'no need to worry folks lets look the other way' brigade (which imo is highly driven by wanting to avoid the issue of contaminated biologicals, avoiding the V word).
Again they don't account for very real and documented possibility of this suposed hypermutation by human APOBEC being very much dependent on you APOBEC polymorphism. In other words not everyone's APOBEC acts in the same way or has the same effect etc. Do I need to repost those papers once again? Have you even read them?
What if there is a tiny minority of humans (say 1%) whose APOBEC is no match for your average gammaretrovirus. It is a no-brainer that medical science should err on the side of caution, and these attempts to write of MulVs as harmless to humans are scientists simply trying to cover their behinds. Or not doing their job properly. Ignorance or willful spin?
Methinks that is exactly what the authors above are doing in the bits that you highlighted. They are leaving out some very pertinent facts and possibilities. ERV, who you love to quote, also does just that. Through ignorance or spin, take your pick.
Hypermutation does not necessarily mean the virus is no longer replication-competent. Both Mikovits and Ruscetti have reported isolating proviral sequences from patients that showed extensive G to A hypermutation, yet these viruses appeared to still be replication-competent (they could be cultured).
An assumption by those who make the restriction argument is that the virus would infect via blood rather than via other tissue routes, yet we don't know what the means of transmission would be for a hypothetical HGRV. This is very significant because cells in some tissues, like lymphoid tissue, don't necessarily have the same level of APOBEC activity that peripheral blood cells do.. from Cadima-Couto and Goncalves, 2010:
A3G exists either as enzymatically active low-molecular-mass (LMM) forms consistent with enzyme monomers or dimers, or as an enzymatically inactive high-molecular-mass (HMM) ribonucleoprotein complex larger than 2?MDa [8]. LMM A3G is found in resting CD4+ T cells of peripheral blood and macrophages where it may act as a powerful antiviral restriction factor for HIV-1 [8]. Conversely, resting CD4+ T cells in lymphoid tissues are permissive to HIV-1 infection as A3G is expressed predominantly in HMM complexes due to the lymphoid microenvironment [9]. It was reported that in lymphoid tissues, cytokines such as IL-2 and IL-5 are responsible for the stimulation of HMM complexes, which in turn may confer the permissive phenotype for HIV-1 infection [9]. Nonetheless, only one research group have provided data to support a role for APOBEC3G in restriction of HIV-1 in quiescent CD4+ T cells.
The above authors cite Kreisberg et al 2006, who stated:
In terms of the molecular basis underlying permissivity of tissue-resident naive CD4 T cells to HIV infection, these cells display enzymatically inactive HMM A3G complexes, whereas nonpermissive naive CD4 T cells from peripheral blood contain LMM A3G, which functions as a potent postentry restriction factor (15).
[....]
Because the vast majority of CD4 T cells reside in tissues (7), our findings help explain how massive numbers of resting CD4 T cells can be infected and depleted during acute lentiviral infections (4, 8) while circulating resting CD4 T cells remain entirely refractory to HIV infection (1, 2).
I would appreciate if you would repost these papers or point in their direction.
I don't understand how you can guess what the authors are doing or thinking ... What pertinent facts are left out?
You can't judge scientiest just because the theories happen to be something you disagree with unless you can back them with facts.