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Outflanked. Arrows show how five unusually powerful antibodies attach to various parts of HIV’s surface protein.

William Schief/The Scripps Research Institute and International AIDS Vaccine Initiative

Some chimpanzees infected with AIDS virus may harbor protective, humanlike gene

When Peter Parham’s postdoc first showed him data suggesting a gene in some wild chimpanzees infected with the AIDS virus closely resembled one that protects humans from HIV, he was skeptical.

The postdoc, Emily Wroblewski, had joined Parham’s microbiology and immunology group at Stanford University in Palo Alto, California, after doing behavioral studies of wild chimpanzees at Gombe Stream National Park in Tanzania. Her new genetic analysis studied a few hundred fecal samples collected from Gombe chimps, many of which were infected with SIVcpz, a retrovirus that is HIV’s predecessor. She found a gene for what’s known as the major histocompatibility complex (MHC)—cell surface molecules that help the immune system recognize foreigners—that was remarkably similar to one in humans that allows infected people to keep the virus in check for decades. And it seemed to be doing the same thing in SIVcpz-infected Gombe chimps. “I thought she might not know what she’s doing here,” says Parham, noting the MHC genetics are notoriously difficult to study and that her fieldwork had focused on mating patterns. “But I was wrong.”

As Wroblewski, Parham, and co-authors explain in a PLOS Biology study published online today, they analyzed stool samples dating back 15 years and sequenced immune system genes from 125 chimpanzees. The animals live in three separate but overlapping communities: Two have a SIVcpz prevalence of about 12%, whereas the third, in the southern portion of the park, has a prevalence of 46.1%. SIVcpz-infected chimps have a significantly higher frequency of the relatively rare genetic variant that is linked to protection from disease in humans. “It possibly puts a finger on natural selection in the act,” says Pascal Gagneux, an evolutionary biologist at the University of California, San Diego, who has done both genetic analyses of chimpanzees and behavioral studies of wild communities. “When humans and chimps were part of the same population, there may have been a retrovirus that used a couple of tricks still effective against HIV and SIVcpz today. This super-old genetic variant may be shared between humans and chimps because the pathogens can’t adapt to it.” Chimpanzees and humans had a common ancestor some 6 million years ago.

In humans, the protective MHC gene, known as HLA-B*57:01, has acquired a level of fame in HIV research. The gene is found at a higher frequency in humans known as “elite controllers,” who for many years keep the virus at very low levels without taking antiretroviral drugs. Studies have shown that the gene works by revving up production of killer cells that directly target and eliminate cells infected with HIV. In essence, HLA-B*57:01 codes for a protein on cell surfaces that hoists up little pieces of the virus, which, in turn, tell immune killer cells that this is an enemy that should be destroyed.

The chimpanzee gene, dubbed Patr-B_06:03, is not identical to HLA-B*57:01, but is closely aligned on a genetic tree.  Wroblewski and co-workers analyzed the levels of SIVcpz in infected chimps that had this genetic variant and those that did not. They found it significantly more difficult to detect SIVcpz in the stools of chimps that have Patr-B_06:03.

Beatrice Hahn, a virologist at the University of Pennsylvania and co-author on the study who has pioneered the study of SIVcpz in chimp fecal samples, describes this as a “poor man’s way” to assess viral levels, because it does not quantify the amount of virus in an animal. But Hahn stresses that ethics prohibit taking blood samples from wild chimpanzees, and her own lab has only recently developed a way to quantify SIVcpz in fecal samples—which she sees as an important future experiment with the Gombe chimps. “I’m excited about their finding an allele closely related to B57, albeit in preliminary experiments,” Hahn says. “It could be protective, and it could be quickly checked by looking at all the other chimp populations that harbor SIVcpz.”

These findings may help explain the impact of SIVcpz on the Gombe population, Hahn says. SIVcpz may have killed off many of the chimpanzees that do not have Patr-B_06:03, clarifying why the researchers found that the gene became far more common in the Gombe chimp population between 2000 and 2010. The relative increase in the gene’s prevalence in infected animals may have led to lower viral levels in the communities, Hahn suggests, which may help account for why no transmission has been detected at Gombe in more than 2 years.

Ultimately, knowledge about the differences and similarities of Patr-B_06:03 and HLA-B*57:01 may inform AIDS vaccine design, which could benefit both species.