'HIV infection en route to endogenization: two cases' *facepalm*

For some reason, pop news became enamored with this paper last month (unfortunately while I was away at a conference):

HIV infection en route to endogenization: two cases

Inexplicable media frenzy--

Scientists find mechanism for spontaneous HIV cure

French scientists find genetic mechanism by which two men were spontaneously cured of HIV.

HIV discovery offers new lead in finding cure

I have a lot of problems with this paper. Starting with the first sentence.

The long-term spontaneous evolution between humans and the human immunodeficiency virus (HIV) is not well characterized.

"Spontaneous evolution"? Wat? Do they mean basic co-evolution of HIV and humans? While the field hasnt 'done everything', co-evolution has been explored, to the point where I have written about it on my blog (which covers only the smallest percentage of HIV papers).

And this paper doesnt improve at all from there. I mean basic stuff like descriptions of reagents used (peptide library. neat. WHICH ONE?) This paper is functionally useless to me.

But because they issued some press release, every pop news outlet from MSN to Al Jazeera was talking about their paper, and now I have to to dispel some flat-out bad science.

 

1-- Are these two people 'cured' of HIV/AIDS?

No. Nothing in this paper suggests they are. The two patients are long-term non-progressors.

 

2-- Is HIV becoming an endogenous retrovirus?

No.

Firstly, there are very, very, very few endogenous lentiviruses. There is something about them that is not conducive to endogenization. There are no endogenous SIVs in primate populations that have been co-evolving with their SIVs for much longer than humans ~100 years with HIV (the 'best' we have in that lemur ERV, linked above). In fact pin-pointing exactly how old HIV/SIV viruses are has been extremely difficult because of this, so scientists have had to study the evolution of SIV in geographically/temporally isolated colonies of animals, and study the evolution of primate genomes to extrapolate the age of SIV-like retroviruses:

Paleovirology– HIV-1s ancestors just got older

HIV-1s ancestors just got older-er

Indeed the 'example' they gave in this paper is the retrovirus in the process of endogenization in Koalas, is a gammaretrovirus. Another common example-- MMTV in mice-- is a betatretrovirus. Gammas and betas are the retroviruses that tolerate being endogenized 'the best', and even *then* it is an accident. To people not familiar with retroviurses, theyre all just 'retroviruses', when in reality, they are two entirely different creatures.

There is also nothing, nothing, in this paper that suggests HIV is becoming an ERV. Nothing. Step 1 would be sequencing the genomes of sperm. Is HIV getting into sperm genomes, thus potentially creating an ERV? No idea. They didnt look.

Is there a child born to an HIV+ mother who is 'HIV+', and has 'HIV+' skin cells, liver cells, smooth muscle cells, etc and no immune response to HIV? Cause that would be evidence for endogenization!

But they dont have anything like that.

 

However, because I want you readers to learn SOMETHING for clicking on this post, Im going to thought-experiment-answer a third question:

3-- Is an HIV ERV a cure for HIV?

Again, this is thought-experiment country, here.

With MMTV, having endogenous MMTVs can protect against infection from exogenous MMTVs. The key here is how. Well, your immune system automatically kills developing immune cells that recognize 'self'. If you have an ERV active at the right place/right time, your immune system will kill any immune cell that recognize the retroviral proteins.

With MMTV, the protein of interest is 'SAg'. Exogenous MMTV needs the immune system to react to SAg to establish infection. But if there is an endogenous MMTV, any immune cell that sees MMTV SAg will be killed. No immune reaction=Protection from exogenous infection.

Maybe.

Because sometimes an endogenous MMTV leaves a mouse *more* susceptible to infection.

Getting back to HIV-- HIV does not have a protein homologous to MMTV SAg, because HIV and MMTV are not the same creature.

I think a likely outcome from an endogenous HIV would be... nothing.

The world-wide HIV quasispecies is so diverse, its likely that one would be exposed to an exogenous HIV that looked nothing like the endogenous HIV (ie, the reason why we have a hard time making an HIV vaccine). An endogenous HIV would look so different from the HIV a person was actually exposed to, that any negative selection of B- and T-cells would likely be pointless.

IF the exogenous and endogenous were similar enough, you would still be infected with HIV, but have fewer CD4+ and CD8+ and B-cells that could be activated to fight that infection. Now, a lot of the 'problems' with HIV/AIDS come from an over-activated immune system, so maybe no reaction would be a good thing? But you are not going to clear an infection by not fighting it, either.

None of this equals endogenous HIV as a cure for HIV.

Even for fun, I cannot think of a pathway from endogenous HIV-->CURE, and there is nothing in this paper to help us make that connection.

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To add to your thought experiment: I would assume, in order for any virus that becomes endogenized/part of the germ line genome (retroviruses being, of course, the ones that do so the most) to be of direct benefit in protecting us from like viruses, they would have to already have a mechanism of superinfection exclusion - like you describe for MMTV. Does HIV have any way of preventing an already-HIV-infected cell from getting re-infected with HIV? Because then you could imagine a beneficial outcome to endogenization (if it's at all possible) in terms of protection from HIV and similar viruses in the future... But if not, then there isn't really a direct benefit.
On a related note, we already know of individuals that can be infected with more than one HIV strain, right? Because unless these two men were born with HIV already in their genomes (ie. everyhwere), their ability to not progress has nothing to do with their existing HIV preventing other HIV infections...