I have previously posted a number of articles on “molecular archaeology” of viruses, and how one can use extant sequences, archived tissue samples, or even blood of pandemic survivors to speculate on the origins of specific viruses, of viruses generally, or on the nature of old pandemic strains.Now HIV falls under the spotlight – again – as the 2nd October issue of Nature publishes three articles (one letter, a commentary on it and an independent commentary) on the origins of HIV-1 pandemic strains.I picked up on the first news – evidence for an older-than-previously-thought origin for HIV-1 – via our local paper this morning. Now this is VERY impressive; they usually keep science news for a slow day, and here they were telling us about a Nature paper on the day it was published! Accessing Nature brought up the Nature News commentary by Heidi Ledford, titled “Tissue sample suggests HIV has been infecting humans for a century”. Essentially, the commentary summarises the findings of Michael Worobey of the University of Arizona and his colleagues, who managed to amplify and sequence HIV-specific cDNA and DNA from a paraffin-embedded lymph node biopsy dating from 1960 from a woman in Léopoldville (now Kinshasa) in what is now the DR Congo. To quote Ledford:
“Their results showed that the most likely date for HIV’s emergence was about 1908, when Léopoldville was emerging as a centre for trade.”
Their findings added credibility to an earlier demonstration of HIV-1 in a 1959 sample, also from Kinshasa. What was interesting was that the sequences of the two viruses differed by 12%: this indicates that there was already significant divergence in the HIV-1 strains infecting people as early as 1960, pointing to a longer history of human infection than the previous estimate of the 1930s.Which led on to the Comments section, where one finds gems like this:
“This is one of the most stupid discovery I have ever heard. You will blame every single human plague on Africa, This is against all the Theories of evolutionary biology where The descents of the people that lived in the area might have developed a kind of resistance instead of being vulnerable to a new strain of the Virus.”
“HIV is older than your great-grandparents, uh-huh! And I’ll bet that the US bio weapons effort is just ecstatic about this deflection. So now these members of science play to the bio-jackboot population controllers with this ‘revelation’ that those sex-crazed Africans of course just couldn’t stop themselves from pulling chimpanzees (I thought the original scientific theory was “green monkeys”) out of the trees for a quickie.”
I couldn’t take this, so I replied:
“It continues to amaze me, as a teacher of virology who tells big classes every year where HIV comes from, how every year some clique of students takes the African origin of HIV personally, as a direct affront. I echo the correspondent above: it is a virus, people. Viruses infect animals, they infect people, and sometimes spread from one to the other – and back, if you are a zoo animal and catch something from your handler. The AIDS pandemic is an accident of sociology, demography, access to high-speed, long-distance travel – and truck routes, and truck drivers. It happens that it originated in Africa. So did the human race – only a lot longer ago. Inevitably, as humans encroached on apes, things get passed across. And don’t spread, much, until…someone puts a road through the village.Why don’t people get more exercised about the origins of HTLV, another retrovirus that almost certainly jumped from monkeys to humans? Except that happened many thousands of years ago, and in south-east Asia, not Africa. And for the same reasons: people eat monkeys and great apes. For that matter, it is speculated that chimpanzees got SIV-CPZ from vervet (I HATE the term “green”) monkeys – and that it may have caused a population bottleneck, some 100 000 years ago. I note that chimpanzees are known to eat vervets, incidentally – so they caught the virus the same way we did.
Ah, well…. In any case, Paul Sharp of the University of Edinburgh – and phylogenetics guru – and the godmother of HIV/SIV diversity, Beatrice Hahn of the University of Alabama (from whom I got the chimp-vervet virus link), have an independent commentary in the same issue, wherein they speculate on “The prehistory of HIV-1”. They make this very interesting comment:
“If the epidemic grew roughly exponentially from only one or a few infected individuals around 1910 to the more than 55 million estimated to have been infected by 2007, there were probably only a few thousand HIV-infected individuals by 1960, all in central Africa. Given the diverse array of symptoms characteristic of AIDS, and the often-long asymptomatic period following infection, it is easy to imagine how the nascent epidemic went unrecognized.”
They also make the important point that the findings of the Worobey group were replicated – with similar but non-identical virus sequences being found – by another group working independently with the same tissue sample. This is important because it nails down the findings more firmly, as HIV sequences within an individual do differ, and:
“…the distance along the evolutionary tree from the group M ancestor to the ZR59 or DRC60 sequences is much shorter than those between the ancestor and modern strains, consistent with the earlier dates of isolation of ZR59 and DRC60, and confirming that these viruses are indeed old”.
a, The HIV-1 genome fragments that were successfully amplified from DRC60 (red) and are available for ZR59 (black). The numbering for the HIV-1 sequences corresponds to the HXB2 reference sequence (Supplementary Table 1). b, The A/A1 subtree from the unconstrained (in which a molecular clock is not enforced) BMCMC phylogenetic analysis. 1960.DRC60A is the University of Arizona consensus sequence, and 1960.DRC60N is the Northwestern University consensus sequence (that is, the sequences independently recovered in each of the two laboratories). The DRC60 sequences form a strongly supported clade with three modern sequences also sampled in the DRC.
Reproduced with permission from Nature Publishing Group (RightsLink License No 2041420001096) from:
Direct evidence of extensive diversity of HIV-1 in Kinshasa by 1960
Michael Worobey, Marlea Gemmel, Dirk E. Teuwen, Tamara Haselkorn, Kevin Kunstman, Michael Bunce, Jean-Jacques Muyembe, Jean-Marie M. Kabongo, Raphaël M. Kalengayi, Eric Van Marck, M. Thomas P. Gilbert & Steven M. Wolinsky
Nature 455, 661-664(2 October 2008) doi:10.1038/nature07390
So where did the virus infecting humans come from? The best guess, from the paper and the commentaries, is that it originated – as do the extant chimpanzee virus supposed to have descended from the common origin – in chimpanzees somewhere in southeast Cameroon.How did it get into people? Sharp and Hahn again:
“The simplest explanation for how SIV jumped to humans would be through exposure of humans to the blood of chimpanzees butchered locally for bushmeat.”
No sex, no weird practices…just eating our cousins. And how and why did it get to Léopoldville? Trade…and in those days before widespread truck routes, that would have been via rivers – which, Sharp & Hahn point out, drain from southeast Cameroon into the Congo River, which flows past what is now Kinshasa. The Worobey paper has some interesting history in it, documenting times of founding and rates of growth of cities in equatorial west Africa: Léopoldville/Kinshasa was and probably still is by far the fastest-growing of these, and was the earliest founded (in 1885). All that was needed to seed a pandemic, then, was that people infected by a virus as a result of butchering chimpanzees, moved some 700 km down natural trade routes to an emergent trade centre – and settled, and passed it on.Then, of course, it is the same old story, told so well by Jared Diamond in “Guns, Germs and Steel“: increased human population density and breakdown in social structure leads to increase in rate of transmission and incidence / prevalence of a disease agent, until it reaches the threshold necessary to break out. It is interesting that it took so long to become noticed – but then, HIV is passed on considerably less efficiently than Hepatitis B virus, so the pace of the epidemic was necessarily slow.But very sure….