HIVs controlled by HERVs

Technically, its the immune response to the HERVs that can control the HIVs, not the HERVs directly.


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 no good reason, or give us cancer for no good reason, 'bad' things happen to us because of viruses we are infected with that are actually 'bad' for the virus too.  But when you are dealing with the population/infection numbers we deal with in virology, and all the blind randomness going on, 'bad' things happen.

Well, it might be that HIV-1 is making a mistake in its life-cycle that we can exploit for 'good'.

For instance, it has been suggested that HIV-1 might, on accident, induce expression of some relatively young HERV proteins.  Because HERVs are 'self' you would not normally make an immune response to them, but some people infected with HIV 'break tolerance' and generate cytotoxic T-cells that recognize HERV epitopes in MHC class I molecules.

Since the HERV proteins are JUNK and only expressed in HIV+ cells, HERV epitopes are only present on the surface of HIV+ cells, which means these anti-HERV CTLs target HIV+ cells for death.

While there have been papers that identify anti-HERV CTLs in HIV+ people, and they have suggested that these anti-HERV CTLs help keep viral loads down/control HIV replication in some of these patients, they havent 'proven' it yet.  The conclusion has just been deduced from a collection of observations.

Sooooooooo they tested it!

HERV-K–specific T cells eliminate diverse HIV-1/2 and SIV primary isolates

Im going to quickly summarize a LOT of work--

They found a CTL reaction to a HERV envelope protein in an HIV patient that was controlling HIV infection very well (elite controller).  When they mixed those CD8+ T-cells with CD4+ T-cells infected with different kinds of HIV, the CD8s got all pissed off and wanted to kill everyone in the tissue culture dish.

This lead to the control pool of cells being infected at ~45% HIV+, while the anti-HERV pool of cells was only infected at 5.85%

They got similar results when they looked at a different anti-HERV CTL, one that targeted a HERV gag epitope (that pool of cells was down to 3.99% infected!).

So one of the Main Problems in HIV World is that HIV changes a lot.  But HERVs are in the human DNA genome, so they do not change.  These anti-HERV CTLs could work on lots of different kinds of HIV.  Not just HIV-1, but HIV-2, and even SIV!

And, I think the immunologists say 'You only need one CTL-MHC interaction to initiate cell death!', and this paper reenforced that.  When they grew the infected cells in the presence of anti-retrovirals, there was still, of course, a tiny bit of HIV replication.  The anti-HERV CTLs were still able to recognize that tiny bit of infection via the expression of the HERVs, and kill those cells, relatively quickly (<16 hours).

All this on TOP of finding ANOTHER anti-HERV CTL that works in a totally different way.  The first two work via  the HIV accessory protein, Vif, going rogue.  They did not investigate how, but it is probably Vif making a mistake, allowing the HERV Env to be made and get presented in MHC.

The other anti-HERV CTLs work because of similarity between a HERV pol protein, and HIV pol protein.  It is anti-HERV, but it can see HIV too.  Because of this, this CTL was not as cross-reactive, that is, it did not work on some SIV infected cells, because the SIV pol sequence was too different from the human HERV pol sequence.

What does this mean?

Because HERVs are junk, and not expressed outside of a disease state, this might mean that an 'HIV vaccine' wouldnt target the rapidly mutating HIV at all.

It would target a HERV. A nice, stationary target.

More like this

But if HERVs are only expressed in disease states and if their expression is 'a sign something is very wrong' (your words), then how come they are expressed in autism?…

Oh wait, could it mean that autism is a disease state, where something is very wrong?? Oh No No, it just cannot be. We know there is nothing wrong in autism, and we cannot let it be talked about as a disease state.

Some better debunk this study, quick !!

I would change "Because HERVs are junk, and not expressed outside of a disease state, this might mean that an ‘HIV vaccine’ wouldnt target the rapidly mutating HIV at all."


"Because MOST HERVs are junk, and not expressed outside of a disease state, this might mean that an ‘HIV vaccine’ wouldnt target the rapidly mutating HIV at all."

given the use for HERVs in placental formation =)

By Poodle Stomper (not verified) on 19 Nov 2012 #permalink