HIV-1s ancestors just got older-er

More HIV news!

HIVs ancestor, SIV (simian immunodeficiency virus), has been around a LOT longer than we previously thought.

As I have mentioned before, we always assumed retroviruses like HIV, lentiviruses, are evolutionarily ‘young’. They are relatively complex, so probably ‘newish’ in retrovirus-world, but they do not fossilize well (we have found very few lentiviral ERVs), so it has been hard to elucidate HIVs ancient genealogy.

Several years ago, researchers used an isolated colony of primates to estimate SIVs age at 32,821-132,780 years old.

Well, HIVs ancestors just got older… er!

Five to six million years old.

Maybe even 12 million years old!!

This is a ridiculously fun paper:

Convergence and Divergence in the Evolution of the APOBEC3G-Vif Interaction Reveal Ancient Origins of Simian Immunodeficiency Viruses

Okay, so, we dont have many lentiviral, and even fewer SIV-like ERVs.

We also cant rely on finding more geographically isolated colonies of SIV-infected monkeys.

How the heck did they push SIVs age from tens of thousands of years old to MILLIONS of years old?

By looking at the genomes of animals that SIV infects!

Not only do SIV populations change based on selective pressure from their hosts, the host populations also change in response to the virus! That is, animals that are better able to control the infection live longer/reproduce more than those that die early in infection.

Some of these random mutations that turned out being positive were mutations within the host APOBEC genes.

Everyone knows HIV mutates a LOT… but its not just a LOT. It is an evolutionarily defined rate of mutation. See, if HIV does not mutate enough, the immune system will eventually ‘catch up’, and clear the infection. If HIV evolves too much, then it will introduce too many negative mutations, and the population will go extinct.

APOBEC proteins are endogenous (everyone has them!) anti-retrovirals that push retroviruses to mutate ‘too much’. APOBEC proteins get into budding babby viruses, and when that babby tries to infect a new cell and reverse transcribe, it makes too many mistakes, and dies.

BUT!

APOBEC proteins are, obviously then, also a selective pressure on retroviruses. Complex retroviruses have evolved ways to ameliorate APOBEC– Vif!

SO!

These scientists looked at APOBEC genes in various SIV hosts, and how those APOBEC proteins interacted with Vif, to extrapolate how long SIV Vif has been a selective pressure on host APOBEC sequences–

Five to six million years!

And maybe as old as 12 million years–

Moreover, we reveal an even older ancestral insertion event in the N-terminus of A3G of theColobinae subfamily that conceals the Vif-binding site and precludes interaction with Vif proteins, suggesting that lentiviruses may have infected primates as much as 12 MYA. Coincident with this unique host adaptation, a Vif protein from a lentivirus currently infecting one of the Colobinae species has evolved to recognize a novel surface of A3G.

My take away messages from this paper–

  • YAY EVILUTION! Using Evilutionary theory, we now know more about the world we live in than we did before.
  • HIVs ancestors have been around for a long time. A looooooooong time.
  • It is remarkable that HIV did not become a ‘normal’ part of human-hood until the 19th century.

 

 

 

Comments

  1. #1 Lyle
    March 12, 2014

    Is it possible HIV has been around in humans longer but was not known because TB is common with it, and those with HIV were thought to have died of TB, or other old wasting diseases? Even today TB is the most opportunistic of infections of HIV patients. Before we had adequate treatment of TB could the TB infection just have been ascribed as the cause of death. So that it is only now with the ability to treat TB meaning it has become more rare, along with improved medical technology HIV was detected.
    I am not sure of the above but it seems at least a possibility.

  2. #2 ERV
    March 12, 2014

    Good question, Lyle!

    In fact, HIV was around a long time before we noticed, ‘hiding’ in people dying from other causes.

    It was homosexual men in the west getting sick from ‘absurd’ pathogens (previously healthy young men should not die of pneumonia/have KS lesions/etc) that sent up the red flag for us to start looking for something else (turned out to be HIV).

    So, we ‘found’ HIV in the 1980s, but genetic analysis shows it had been infecting humans since 1902-1921.

    http://scienceblogs.com/erv/2008/10/02/paleovirology/

  3. #3 Bryan
    March 12, 2014

    Lyle: I’m sure Abbie will give a more complete answer, but the answer to your question is ‘no’. Based on a mixture of genetic mapping & old laboratory samples the timing of the SIV “jump” to humans (thus creating HIV) is pretty firmly established. TB is quite lethal without HIV-co-infection. Chronic TB alone = you’re probably going to die. Chronic TB + HIV = you are almost certainty going to die. In other words, HIV makes a terrible situation a little more terrible.

    Abbie: I’m confused about exactly what their results mean – its of no surprise that SIV-like viruses have been along for a long time. I wouldn’t be surprized if SIV (or another retrovirus) were found to be continually co-evolving with primates all the way back from when primates separated off of the other mammals (as opposed to species-jumping in). But would it be fair to call that retrovirus “SIV”. I guess what I’m asking is if the 100K-ish “old” SIV is actually SIV, or a separate ancestral species – e.g. the SIV equivalent of birds & dinosaurs?

  4. #4 ERV
    March 12, 2014

    Bryan–

    Viral nomenclature is a trainwreck. They went with SIV, but yes, SIV-like is probably a much more accurate descriptor :)

    It is surprising, though. I was surprised because 1) It really never got a foot-hold in humans in all that time? Really? Maybe it did and individual communities died out, but man. Surprised me! 2) Lentiviruses are supposed to be ‘young’. One of the few lentiviral ERVs we have, RELIK, is 7 million years old. So, if lentis were in rabbits and primates 7 million years ago, lentis are a heckovalot older than we assumed!

    http://www.pnas.org/content/104/15/6261.full

  5. #5 Bryan
    March 13, 2014

    Cool & thanx!