Monkey poop! ... and the evolutionary power of HIV

The story of 'How we know where HIV-1 came from' is really cool-- A group of researchers went into the jungles of Africa, collected lots of monkey poop, and figured out pretty much the exact colony of chimpanzees that transmitted their SIV into humans, which lead to the HIV epidemic we know today.

Those researchers have struck brown gold again!

Eastern Chimpanzees, but not Bonobos, Represent a  Simian Immunodeficiency Virus Reservoir

There are lots of different kinds of 'HIV'. Apparently, all of the  HIV-1 (Group M is causing the HIV epidemic in humans, and then Group N and O) we know today came from chimpanzees that live in the same West-Central region of Africa (these same chimpanzees also infected gorillas).

But this isnt the only place chimpanzees live.

Why did HIV-1 originate from these chimpanzees in this part of Africa?  It could be that chimpanzees in other parts of Africa are not infected with their version of SIV, or at least, at the same rates as the chimpanzees in West-Central Africa.

To help answer this question, these researchers went to Eastern Africa and collected even MORE monkey poop-- from chimpanzees and bonobos.  3108 samples of monkey poop.

YAY!!

After doing genetic analysis on the poop to make sure they werent sampling from the same monkey pooping 3000 times, but lots of different monkeys, they then tested the samples for evidence of SIV infection (presence of SIV proteins, genome, or antibodies to SIV).

The infection rates were as high as 30% in some locations, but on average, were at about 13%.  This is pretty much exactly what they found when looking at chimpanzees in West-Central Africa.

So why the heck did humans get HIV from the West-Central chimpanzees, on several occasions, and not the Eastern chimpanzees, ever??

It might have something to do with differences in the viruses infected the Western vs Eastern chimpanzees.

The scientists did a genetic analysis of the SIV they found in the Eastern chimpanzees and determined that the virus would need to make more changes in gag and vpu to replicate well in humans than the West-Central virus had to make.

The hurdle to go from chimpanzee-->human is not only about the differences between chimpanzees and humans, but also about the genetics of the viruses in the chimpanzees.  Here is a fantastic bit from the paper-- those of you who have followed the Vpu saga from the beginning will love this:

It has been shown that upon cross-species transmission, the ape precursors of HIV-1 had to switch from Nef- to Vpu-mediated tetherin antagonism (36, 61). However, only the pandemic M group viruses acquired efficient antitetherin activity, while the much-less-prevalent group N, O, and P viruses either failed to gain this activity or lost other Vpu functions (36, 61, 62, 81, 85, 86). These findings have been taken to indicate that successful SIV zoonoses require effective tetherin antagonism (23). When we compared ape virus Vpu sequences to that of the HIV-1 group M consensus, we found that some SIVcpzPtt Vpu proteins required only very few changes to gain key functional motifs (Fig. 8). In contrast, most SIVcpzPts Vpu proteins required a substantially larger number of substitutions to acquire these same human-specific signatures (Fig. 8).

All of this really cool new information that helps us learn why HIV happened-- all of this info we got from monkey poop.

YAY!!

More like this

That's SIV. The first HIV sample is from 1959 with nothing earlier. There is no real explanation for how they managed to jump specifies at that time when they had not done so previously.

The earliest samples are from ~1960. However, genetic analysis of those samples tells us that by 1960, HIV had been in humans long enough to diverge into at least two different subtypes, which places the cross-over from chimpanzees to humans at ~1900.

And, SIV *has* crossed over into humans on more than one occasion. The current epidemic was caused by that ~1900 cross-over and led to HIV-1 Group M. Other cross-over events lead to Groups N and O (and HIV-2 came from another non-human primate).

The odds are it happened many more times in human history, but remained a local infection because of various properties of the infecting virus (like the Gag and Vpu hurdles highlighted in this paper) and properties of human interactions (as population numbers go up, diseases go up, increase in local and global travel, etc).

The earliest HIV sample is from 1959. All other calculations are an estimate, or "educated guess". There is still no virus that predates this. The early 1900 viruses are thought to be ancestral, but are not HIV.

"Using a comprehensive full-length envelope sequence alignment, we estimated the date of the last common ancestor of the main group of HIV-1 to be 1931 (1915–41)."

"Our first control case was the viral sequence ZR.59, obtained from a blood sample collected in 1959 in the Democratic Republic of the Congo (formerly Zaire) (11). ...The alignment used for this analysis was restricted to short fragments of the envelope sequence available from the 1959 sample (23)."

"The accuracy of these estimates suggests both that the central location of the root position was reasonable and that our assumption of a molecular clock is consistent with the data, at least back to 1959."

http://www.sciencemag.org/content/288/5472/1789.short

When you incorporate the 1960 sequence (http://www.nature.com/nature/journal/v455/n7213/full/nature07390.html), the date gets pushed back a few decades. Nucleotide models are notorious for underestimating times to most recent common ancestor, so it isn't surprising that the date gets pushed back when more data is added.

This revised date, as well as other evidence for the ease of host switching, suggests that these host switch events could have been happening throughout history. Only once the major cities (like Kinshasa) were founded could the population size sustain and spread the epidemic. So we don't really need an "explanation for how they managed to jump specifies at that time when they had not done so previously".

Chimp,

If you are looking for the actual ancestral viruses that actually crossed over to prove that SIV to HIV jump took place, then you'll forever remain skeptical about the true origin of HIV. What's your favorite theory? Contaminated vaccines?

Lineage construction based on accumulated mutations is a pretty sophisticated method in determining evolutionary change. Based on accumulated knowledge about the diversity of existing SIVs in nature, and how close the existing HIVs are genetically to different subtypes of SIV, it's getting more difficult to think of introduction of SIV into humans as intentional.

The data is assumption, but not strong empirical evidence that estimates are correct. Samples exist before 1959, but none are infected. There is no need to overstate that.

Yeah, this does not seem like solid evidence to support the origin of HIV. Either way, I am glad to hear that we are on a road to discovering the cure for this awful disease.

Let me know what you think about my evolution post if you get a chance.
http://noobpost.com/detail/29/

By chris hawkes (not verified) on 22 Sep 2012 #permalink

I'm a bit puzzled about what exactly the objection is. There are two very early sequences: one from 1959 and one from 1960. They happen to be very different. Far too different to have had a very recent common ancestor. So, either you have to postulate two chimp->human transmission events (and the phylogenetic evidence argues against this: the two are part of a single human-infecting clade), or you have to think that there was some mutational miracle, where the evolutionary rate was *much* larger then ever observed elsewhere, or you could just sensibly conclude that the chimp->human transmission event happened earlier, around 1910. The date of the earliest obtained infected sample is an upperbound - not a lowerbound - on the transmission date.

Scientists collect poo. Anti-scientists fling it.