Monkey Gene May Give Viral Protection

Researchers at Harvard Medical School have identified a gene in Asian macaques that helps prevent infection by HIV-like lentiviruses.

The gene, TRIM5-CypA, produces a protein that is a fusion between two existing proteins—TRIM5 and CypA. TRIM5 binds to viruses related to HIV and destroys them while viruses use the CypA protein to shield themselves from the host cell, said Medical School professor Shawn P. O’Neil, one of the authors of the study.

Because the CypA protein attracts HIV-like viruses and the TRIM5 protein destroys them, the fused protein “might be able to target lentiviruses.”

The researcher’s estimate of when this hybrid gene appeared in the monkey’s genome suggests that lentiviruses have been around for longer than previously believed.

In 2004, the gene that expresses the fused protein was found in owl monkeys, which are classified as “New World” for their South American origin.

“The protein very effectively prevents owl monkeys from being affected by HIV and other related lentiviruses,” O’Neil said.

While looking at the natural variation in the TRIM5 gene in Asian macaques, which are considered Old World monkeys, Harvard microbiologist Ruchi M. Newman accidentally discovered a second example of the TRIM5-CypA fusion, according to Medical School professor Welkin P. Johnson, the study’s senior author.

“The surprise we found with our study was that macaque monkeys from Asia have a different strategy that involved the same two proteins,” O’Neil said. “They make a similar fusion protein that also can prevent certain lentiviruses from affecting their species.”

Newman and Johnson said that Old World and New World monkeys split from each other a long time ago, and that this was a rare instance of evolution producing virtually exactly the same protein twice. The gene must have been under strong selective pressure, according to the authors.

“It’s an eloquent example of convergent evolution, of two different lines arriving at the same solution to a problem,” O’Neil said.

The gene is not found in any New World monkeys besides the owl monkey. It is found in three species of macaques—the Asian Old World monkeys—but not in sooty mangabeys, which are African Old World monkeys that are the closest relative to the macaques. Based on these facts, researchers estimated that the gene appeared between five and ten million years ago, Johnson said.

“It suggests that lentiviruses were probably around quite a long time ago,” Johnson said. “They were probably causing epidemics in the ancestors of modern primates.”

Simian immunodeficiency virus (SIV), a lentivirus, is commonly found in primates, according to O’Neil.

“HIV is really a form of SIV that made the species jump from chimpanzees to humans sometime in the last century,” he said.

Still, the study adds little to understanding about the evolution of HIV, according to Joseph G. Sodroski, a professor of pathology at the Medical School.

“I don’t think it says anything about HIV evolution, that I can see,” he said.

—Staff writer Alissa M. D’Gama can be reached at adgama@fas.harvard.edu.

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