HIV's time of origin confirmed

Analysis of a newly-identified 48-year-old tissue sample from a woman infected with linkurl:HIV;http://www.the-scientist.com/article/display/53516/ has confirmed that the virus emerged in the early 20th century, researchers report today in Nature. By comparing the differences between the sequence of this sample from 1960, the second-oldest ever found, and that of a 1959 sample identified a decade ago, linkurl:Michael Worobey;http://eebweb.arizona.edu/Faculty/Bios/worobey.html of the University of Arizona and colleagues were able to calibrate the molecular clock of HIV. "I think that improved the dating of the epidemic, and moved it back by a couple of decades," he said. Also, he noted, having two samples from so far back has opened the door to detailed studies of the virus's molecular evolution. "We could make inferences before this point," he said, "but until you really see it you're going on assumption rather than direct evidence." Based on analysis of the 1959 sample, first analyzed by David Ho's group [link paper], and later samples from the 1970s, researchers had ballparked the early 20th century as the time when HIV became transmissible in humans, said linkurl:Beatrice Hahn,;http://www.microbio.uab.edu/faculty/hahn/ a virologist at the University of Alabama who wrote the accompanying review article to the study. But the current study "really nails it," she said. Worobey and his colleagues decided to look for more old samples of the virus, and screened 27 paraffin-embedded tissue blocks from what is now Kinshasa, in the Democratic Republic of Congo. Using linkurl:extremely sensitive PCR;http://www.the-scientist.com/2008/4/1/81/1/ techniques, they identified the HIV virus in a tissue taken in 1960 from a lymph node biopsy in an adult woman. The sequences they compared from the 1960 sample and the 1959 sample differed by about 12%. "In HIV, genetic difference equals time," said Hahn. Based on the rate of viral mutation, that means the two viruses in those samples had a common ancestor at least 50 years earlier, she explained. "In Kinshasa in 1960, you already had two very different branches of [HIV's] viral evolutionary tree, which means it was probably circulating amongst quite a few people at that point, totally under everyone's radar," Worobey said. Worobey's 1960 sample is a member of the M (main) group of HIV-1 viruses, which comprises more than 90% of all infections. But there are also two other known groups: the O (outlier) group, which seems to be restricted to Central Africa, and the N (new) group, which is extremely rare. "One is rare, one is sort of local, and one has taken off," said Hahn. "Of the three times we know [HIV] was transmitting, only once did it start an epidemic." The question, then, is what conditions allowed the M group to accomplish this feat, while the other two did not? Worobey and his colleagues speculate that the answer lies in linkurl:history;http://www.the-scientist.com/article/display/17643/ as much as in biology. Their estimate placed the date of the viral ancestor sometime between 1884 and 1924. "That's almost simultaneous with the appearance of cities in the area where we think the linkurl:virus crossed;http://www.the-scientist.com/article/display/13821/ from chimps," he said -- a factor that could easily have created the right condition for a virus to spread. This is just a hypothesis, Hahn noted, but she agreed that it made sense. "A big city gives the virus a chance for secondary transmission," she said. Worobey said that the group is now trying to extract longer sequences from the 1960 sample that contains entire genes, rather than short snippets of genetic material. With more information, he said, they could "explore not just molecular evolution, but maybe some of the actual phenotypes circulating at this point." They are also searching for other old samples. "There is lots more archival data to search," he said. "I'm pretty certain we'll have other examples."

HIV's time of origin confirmed

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