A couple of weeks ago, I ran across an article in the New York Times on some recent discoveries that totally rewrote the known history of HIV. Needless to say, I was intrigued. The article was actually about simian immunodeficiency virus (or SIV), the precursor for HIV that affects other primates. It is thought that SIV crossed into humans (thus becoming HIV) sometime in the early part of the 20th century, though the exact time frame isn’t known.
According to the NYT article, the scientific community thought that SIV was a relatively new virus, emerging in primates sometime in the last few hundred years, and that this new research basically trumps that idea. However, that’s only half the story, as you’ll discover if you actually read the paper presenting the research, which was published in Science on September 17 of this year.
In the paper, Worobey, et al., (the authors) set out to clear up the history of SIV. It turns out there were two competing theories for the evolution of SIV, one being the few centuries version mentioned in the NYT article. The other theory, which the new research supports, basically just said that SIV was old–probably very old, as some research suggests that similar viruses arose as much as 14 million years ago (see http://www.pnas.org/content/105/51/20362).
To solve this mystery, Worobey, et al., looked into six monkey species from Bioko Island, an island that separated from mainland Africa 10-12 thousand years ago. Interestly enough, they found 4 species-specific strains of SIV. Each of those monkey species (the red-eared guenon, the black colobus, the drill, and Preuss’s guenon) has a relative on the mainland that also possesses a strain of SIV, which makes it relatively easy to build a phylogenetic tree to help figure out just how long ago the strains split off from each other.
From what Worobey, et al., discovered, some strains of SIV have been around approximately 33,000 years ago, and quite possibly as much as 133,000. Here’s how.
- Ignoring the possibility of human contamination, we know that the island strains diverged from their mainland counterparts at least 10,000 years ago, since that’s when the island became an island.
- They then used amino acid sequence differences to estimate the most recent common ancestor (TMRCA) of the SIV variants. (Presumably using standard methods to make the estimates, but it’s not spelled out how they get their figures.) That gives us our estimate for sequence divergence roughly 77,000 years ago, with a 95% confidence interval ranging from ~33,000 to ~133,000 years ago.
- They repeated their analysis using nucleotide differences and third codon differences. Each of those estimates came in much lower than the amino acid estimate (though still considerably more than the supposed SIV age of a few hundred years–so much for that theory).
So, why is this important? The authors give two main reasons.
- If we’ve just pushed back the origin of SIV 33 thousand years or more, what does that mean for HIV, which we think only arose about 100 years ago? Could that also have an even longer history than we can even imagine right now? We should investigate.
- We now know (or are extremely confident) that SIV is ancient, giving its hosts thousands of years to adapt to its effects. This probably explains why monkeys infected with SIV seem to exhibit such relatively minor problems from the virus, at least for some strains. All other things being equal (which is a huge assumption), that means that humans are not likely to develop a major resistance to HIV any time soon. That’s frustrating, but not totally surprising.
Needless to say, this research gives us a lot of insight into the origins of SIV and HIV, even if it doesn’t really help us from a practical perspective. It does bring up a couple new points for research, as mentioned by the authors, plus at least one more I thought of while researching some background information for this article. It seems the strain of SIV that actually causes major problems for its host resides primarily in chimpanzees. Since chimpanzees are the closest relatives of humans, genetically speaking, I wonder if the solution to stopping SIV or HIV might lie in the regions of the genome where we overlap, yet are different from the other primate species that serve as hosts for SIV. It’s a stretch, I’ll admit, but it could narrow the search space for a cure substantially, and I, at least, think that’s a good option to have.