Tracking the Origins of HIV

For the better part of a decade, Beatrice Hahn, a professor of medicine and microbiology at the University of Alabama at Birmingham, has researched the evolution of AIDS by tracking HIV-like viruses that afflict chimpanzees. Recently, in the journal Science, her team announced a stunning discovery: Through viral DNA testing, they discovered that the virus that causes AIDS in humans originated in a small community of chimps in southern Cameroon. While Hahn doesn't believe this finding will stop the epidemic in its tracks, it gives researchers a better understanding of how the disease first found its way into humans—and, hopefully, another tool to help combat AIDS.

Courtesy UAB Beatrice Hahn

Four years ago, I spent a few months working as Hahn's field assistant in Kibale National Park, Uganda. In order to find out whether the chimps being studied there had SIV—simian immunodeficiency virus, the chimp version of HIV—I collected fecal and urine samples to bring back to the lab in Birmingham. I was basically a glorified pooper-scooper, following around habituated animals while armed with gloves, pipettes, test tubes, and, yes, a bag and miniature shovel. None of the chimps in my study group had SIV, but several of the ones at Jane Goodall's site in Gombe Streams National Park, Tanzania did.

The Gombe chimps, like other chimps in East Africa, are members of the subspecies Pan troglodytes schweinfurthii (Pts). Though some do have SIV, their particular strain of the virus is not closely related to HIV. Besides helping to characterize the evolutionary tree of the SIV viruses, though, the research on those habituated chimps also allowed Hahn's team to tweak their method of getting viral DNA from chimp droppings, and later allowed her to study the viruses' path through other chimp communities.

Using the methods perfected in East Africa, Hahn turned her attention to Pan troglodytes troglodytes (Ptt), a subspecies of chimps that lives in Cameroon, the Republic of Congo, Gabon, and Equatorial Guinea. Because these chimps she was studying were not habituated, she had hunters and field assistants collect fecal samples from the forest floor. After spending years analyzing the viral DNA in the lab, her team was able to pinpoint the group of chimps that harbors the virus that led to the AIDS epidemic.

Gelf talked with Hahn about the science behind her research, the implications of her findings, and why she doesn't believe another SIV-based epidemic is on its way. Below is a transcript of the interview, edited for clarity.

Gelf Magazine: I didn't know if you were ever going to be able to find this.

Beatrice Hahn: Neither did we. When you helped us in the very beginning, that was important to test the methods and try new things and eventually we got lucky.

GM: I remember when I was working with you, you were very interested in getting urine samples. Has the methodology changed?

BH: Absolutely. And that was the breakthrough, really. The credit goes to Brandon Keele, who was the first author on the paper and a post-doc of mine. He figured out what RNA-later [the solution used to preserve the fecal samples] was all about. As he developed the antibody assay, we had a very sensitive screening method. We actually tested it in Gombe by collecting fecal samples from the floor, but we already knew who was infected and who wasn’t, and the sensitivity was 92%. So that was a great screening assay, and once we had samples that were antibody-positive, we didn’t stop until we had the sequence. It did take three years, though.

GM: Now that you have the methodology down, does that mean you can move a lot faster as you collect samples?

BH: Yes and no. What we can move a lot faster on is screening. And we've done so. We now have a fantastic guy in the Democratic Republic of Congo who's collecting samples. That's Pts. But at this point we want to know the whole gamut. We want to screen all the chimp populations in sub-Saharan Africa to get a sense of what the geographic distribution is and what the genetic diversity of the virus is in general. So far it's been holding up 100 percent. Ptt viruses all cluster in one group, and Pts viruses all cluster in another group.

GM: Are you worried that another version will cross over into people?

BH: I would suspect it already has. But it doesn’t go epidemic.

GM: Why not?

BH: Whatever circumstances you need for that aren't provided. That, of course, is the $10 million question. What does it take? And what epidemiologists will tell you is that it's a combination of virus, hosts, and the environment.

GM: Do you think there will ever be another epidemic version?

BH: No. I don’t necessarily think there will be another epidemic version. I think there are what we call dead-end transmissions. We already found sooty mangabey virus transmissions into people, so why would chimp viruses do this less frequently? We just can't find them because the only way you'd find them is if you characterized molecularly every single "HIV-1" infection that walks through the door. With 50 million infections out there, that's impossible.

GM: In Asia right now, they're killing all of these chickens to prevent a possible transmission of avian flu. Would it make sense from a health point of view to go about killing off all the chimps?

BH: I don’t think so. If you leave them alone, nothing happens. It's not like avian flu that gets transmitted so easily. You don’t touch the chimps, you don’t get infected. So why would you kill them?

GM: Is the prevailing notion still that people got HIV initially in that hunters contracted it from their chimp prey?

BH: Yes, but there isn't any more or any less data today than there was 10 years ago. It's just based on the biology of these viruses the most likely scenario, but no one has ever identified a transmission there to identify that.

GM: Why was it important to find the natural reservoir of HIV-1?

BH: To tie up some loose ends here.

GM: Does it mean anything in terms of combating the disease?

BH: Nothing directly practical tomorrow. In the long run, science tends to cross-fertilize different fields and if we study enough chimp viruses in the chimp host versus enough human viruses in the human host, we may come up with an explanation as to what makes a chimp virus tick in a chimp and what makes a human virus tick in a human and all the species-specific adaptations that are necessary as well as where the pathogenic phenotype is coming from in terms of HIV-1. The more access you have to things that you didn’t have access to before, the more you're going to learn.

David Goldenberg Berg, an SIV-negative chimp from Uganda

GM: Do you have any ideas as to why certain communities of chimps have much higher rates of SIV than others?

BH: We saw that in the study we did with you, if you remember. Gombe had prevalence rates up to 35% and we found nothing in Kibale and other places and now in the DRC we see the same thing. It's a feature of this virus. There are endemic foci in some communities and there is nothing in others. That's the way it works.

GM: Does it have any relevance to the spread of HIV in humans?

BH: Not really.

GM: What does that tell us about how fast the virus evolves?

BH: If neighboring communities were separated by a geographic barrier, like a river, then they had different viruses. If the communities did not have the barrier between them, then they had the same virus. As you know, chimps don’t like to swim so they tend to not cross the river. That means the chimps stay put and so does the virus.

GM: The Ptt virus is closer to HIV than it is to the Pts virus, right?

BH: Much much closer. The Pts virus and the Ptt viruses are on average 50% different from each other across the genome. The HIVs are falling within the Ptt radiation because they're Ptt viruses.

GM: In the New York Times article about your research, you state that it's not known whether the chimps with SIV become ill.

BH: That's correct. Because only two captive chimps that were naturally infected have ever been observed for any period of time.

GM: But what about the ones in communities that have been followed for a long time, like the ones in Gombe?

BH: We've been doing this for six years, and in the meantime, yeah, there have been some chimps that have disappeared or died that were SIV-infected and then there have been other chimps that were not infected that also have disappeared and died. So what are you going to conclude from that?

GM: Would it mean anything if they don’t get sick from this?

BH: Yes, in the sense that it would be easier to compare why humans do get sick, because humans and chimps are genetically so similar and the viruses are genetically so similar, so you don’t start with a huge difference. You could perhaps hone in more readily on what the pathogenic determinants are in humans.

GM: But several chimps in captivity have been infected with HIV, right?

BH: No, not many, because HIV doesn’t take in chimps. You have to go through all sorts of adaptations processes and not every strain works. And then when you do infect them, usually nothing happens. In a single case, this chimp over 15 years developed something that looked like AIDS. That's why people have abandoned this altogether. It's not practical.

GM: So do you think chimps get sick?

BH: I just don't know. I know that it will most likely not look like a general HIV-1 infection, but HIV-2 symptoms start after 20 years. If that's true [in chimps], we'd never know. I would suspect that they don’t have anything comparable to HIV-1, but that doesn’t mean it's completely nonpathogenic.

GM: Are you happy with how the media has been covering your most recent paper?

BH: I have no expectations.

GM: Why not?

BH: Why should I? By and large, it's such a short blurb that people write that almost without exception, simply by omission, is not as accurate as I would like it to be. And people don’t have the background to understand all the ins and outs and rather simplistic statements are made that I would not exactly write if I was writing the story. But that’s true and it has been true in the past but it's just unavoidable. It's usually something in each article that's not completely correct.

GM: What's the next step for you?

BH: We're continuing the molecular epidemiological survey of chimp viruses in chimps and there are a lot more countries to screen. We want to know what the prevalence is, the geographic distribution, the subspecies association, the extent of genetic diversity out there to get a complete picture.

GM: How long will that take?

BH: Hopefully until I retire. I'm pretty sure I'll finish by then.

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