ERVs vs HIV-- Maybe a bad idea

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.

HIVs controlled by HERVs

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.

HERVs and HIV-1

Bad news. Targeting ERVs as a 'sneak attack' on HIV is probably a bad idea.

HIV-1 Infection Leads to Increased Transcription of Human Endogenous Retrovirus HERV-K (HML-2) Proviruses In Vivo but Not to Increased Virion Production

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).

Damn.

More like this

Technically, its the immune response to the HERVs that can control the HIVs, not the HERVs directly. :-D Ive written about the proposed connection between ERVs and HIV a couple times before-- Briefly, viruses do lots of things by accident.  Things just happen.  Sometimes viruses make us blind for…
CTL-based vaccines and HIV-1. Ive written about them quite a few times here on ERV. Quick recap-- All of your cells fly 'flags' that show circulating cytotoxic T-cells what proteins they are making. Normally, a virus-infected cell will put up virus/pirate 'flags', the T-cell will 'see' something…
You all might have heard about 'delta32' or 'delta-CCR5' people in association with HIV infection. People who naturally, by chance, have deletions and mutations in the CCR5 gene of their DNA dont make functional CCR5 proteins. It doesnt appear to be 'a big deal', and people who have this particular…
HIV-- Its a terrible game of chance. Odds of HIV transmission are, superficially, rather low (its no measles). And, we can make the risk of transmission even lower various pro-active ways-- antiretroviral use to keep viral loads down in HIV+ people (especially in pregnant women about to give birth…

How very interesting

By Sarah Young (not verified) on 16 Oct 2014 #permalink

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????????

By Nathan J Bowen, PhD (not verified) on 23 Oct 2014 #permalink