VIENNA—Thousands of years ago, a piece of West Africa separated from the mainland and formed the island of Bioko. The monkeys that inhabit the island may be crucial to unraveling the puzzling origins of the AIDS epidemic in humans, according to a study presented here last week at the 18th International AIDS Conference.
Scientists have argued about the origin of the AIDS epidemic since it surfaced in 1981, but this much is widely accepted today: Sometime around 1931, HIV-1, the main virus driving the epidemic, likely entered humans from chimpanzees, which are infected with a related virus called SIVcpz. The chimp virus, in turn, is a blend of SIVs from two different monkey species.
Less clear is when the monkey viruses moved into chimpanzees. Last year, one prominent investigator in the origin field, evolutionary biologist Michael Worobey of the University of Arizona in Tucson, found evidence that the monkey-to-chimp jump occurred sometime between 1266 and 1685. Worobey and his team used changes in the RNA of these SIVs to calculate their age. These so-called molecular clocks depend on how they're calibrated, however, and not everyone was convinced.
Skeptics, including virologist Preston Marx of the Tulane National Primate Research Center in Covington, Louisiana, suspected the leap from monkeys to chimps occurred tens of thousands of years earlier. SIVs and SIVcpz are found everywhere from East to West Africa, and Marx reasoned that it "was just not possible" for the viruses to have spread so widely in 500 years. So he came up with a new way to calibrate the molecular clock that relied on Bioko's known separation date from the mainland, and he recruited Worobey to help him analyze the data.
Marx and his team collected samples of SIV in dead monkeys on Bioko, which were killed for bushmeat. The researchers isolated SIVs from four different species on the island. One species, the Bioko drill (Mandrillus leucophaeus poensis), has a mainland counterpart that also harbors SIV. The fact that the virus was in both drills and that the island separated from the mainland 12,000 years ago provided a precise way to calibrate the molecular clock, and comparisons of the SIVs confirmed Marx's suspicion that the jump into chimpanzees must have occurred much earlier than Worobey's previous estimates.
As it turned out, the SIV from the drills closely matches SIV from red-capped mangabeys, one of the two contributors to SIVcpz. So an ancestor of this drill could have infected chimpanzees. According to Marx's analysis, a virus related to the Bioko drill's SIV infected chimpanzees at least 22,000 years ago.
Worobey's earlier studies did not date the origin of SIV itself but suggested that it was "relatively young." Others have argued that the SIVs emerged millions of years ago. The new analysis of all four monkey species suggests that, at a minimum, the SIVs are 76,000 years old—although Marx suspects that they evolved far earlier. This longer history of primates harboring the viruses may explain why SIVs cause no harm in the African monkeys they infect, Marx noted: The hosts have had more time to evolve appropriate immune responses or cellular changes that make them less vulnerable to the viruses. (Recent reports strongly indicate that SIVcpz can cause AIDS in chimpanzees.)
"The data are excellent," says Simon Wain-Hobson, a virologist at the Pasteur Institute in Paris who has been involved in origin studies since the start of the AIDS epidemic. But he cautions that the SIV on the island may have been introduced recently, upending Marx and Worobey's clock calibration. "The jury is out," says Wain-Hobson, noting that he is not ready to discard the substantial evidence from other molecular-clock analyses that SIVcpz is younger.
Paul Sharp, an evolutionary biologist at the University of Edinburgh in the United Kingdom who first described the SIVs that led to SIVcpz, has more confidence that the new findings will hold up to scrutiny. "Molecular-clock analyses have suggested that the SIVs arose within the last few thousand years," he says. "These Bioko viruses are clear evidence that the SIVs must be much older than that."