For quite a while, now, there has been a connection between Endogenous Retroviruses and HIV. For some unknown reason, some of the young ERVs in humans, the ones that can still code for a protein here and there, are reactivated in HIV+ patients. Scientists have found ERV RNA in HIV+ patient plasma, and they have even found cytotoxic T-cells that target ERV proteins.
This lead some scientists to believe that maybe, maybe, ERVs could be a good target for an anti-HIV therapy.
HIV changes a lot. It is really hard to train your immune system to fight it.
ERVs are 'human', now. Which means they are 'self', and attacking them could be bad (it would be a kind of purposeful autoimmunity), but because the ERVs are 'human', they wont mutate much. HIV is a moving target. Targeting the ERV activated by HIV infection could be a non-moving alternative anti-HIV target.
Bad news. Targeting ERVs as a 'sneak attack' on HIV is probably a bad idea.
The problem is, we dont know exactly how or why ERV RNA/DNA/proteins are being expressed in HIV+ individuals.
If it is something very very specific, something that only happens in a CD4+ T-cell in direct response to that being infected by HIV, that would mean targeting the ERV is a great idea. You could train the HIV+ individuals immune system to 'see' the ERV components in an HIV infected CD4+ T-cell, and BAM! Kill the HIV infected cell!
BUT, if it is something very very broad-- like, over activation of the immune system leads to wide-spread disregulation and expression of ERV RNA/DNA/proteins, that would be targeting ERVs is a terrible idea. If you trained the HIV+ individuals immune system to 'see' ERV components... the immune system could not only target the HIV infected cells, but also other immune cells-- The B-cells the patient needs to fight HIV, the CTL cells the patient needs to fight HIV, the CD4+ T-cells the patient is trying to preserve... and who knows what else.
In this paper, they still havent nailed down *WHY* ERV components are expressed in HIV+ individuals, but they did determine that ERV activation is broad.
... total PBMCs from HIV-infected and uninfected patients were sorted into CD4+ and CD8+ T cell subsets, in addition to B cells and monocytes. These cell types represent the major constituents of PBMCs, although smaller populations, including dendritic cells and NK cells, could potentially represent sources of HML-2 expression. When HML-2 RNA upregulation was assessed in sorted cells, we saw no significant difference in expression in any subset from HIV patients compared to controls, although each subset individually showed a small increase in patients compared to controls, with the greatest difference in monocytes, a cell type that is not a target for HIV infection in vivo (59). The lack of enrichment in the CD4+ T cell population is consistent with HML-2 RNA expression having no clear relationship to HIV replication (Fig. 4), while the lack of enrichment in other cell populations could exemplify the indirect mechanism regulating HML-2 expression in HIV-1-infected patients. The differences in the magnitude of HML-2 transcription in cell subsets could be due to cell-specific transcription factors, methylation patterns, or other epigenetic changes, which are believed to control endogenous retrovirus expression in differentiated tissues (60, 61). Based on these results, it appears that differential expression from multiple cell sources may lead to the 2-fold difference in HML-2 expression in HIV-infected versus control individuals.
There was a slight increase in ERV RNA in each cell type in HIV+ vs controls. The difference between HIV+ and control is all of these little differences adding together, NOT because ERV RNA is expressed in HIV infected CD4+ T-cells.
Based on these observations, it appears that the use of HML-2 expression as a way to target HIV infection carries a significant risk of off-target effects. Our data suggest that HML-2 protein may be expressed in CD8+ T cells and B cells. Thus, targeting HML-2 epitopes may affect these cells and weaken the cytotoxic and humoral arms of an individual's immune response to HIV-1 infection (69).
How very interesting
awesome blog. i believe it's only when HIV decides to take the plunge and become an ERV, i.e., integrate into our germline, that HIV will spell the beginning of it's end, as we currently know it. i once heard Will Taylor refer to HIV as a "fallen angel". that comment fits well with your blog tagline. i wonder what HIV will create in us if and when it does become an ERV????????