January 3, 2018

What doesn’t kill you might just save your life.

At least, that’s the new thinking on how to combat SIV, a variant of HIV. This comes after researchers at the Yerkes National Primate Research Center sequenced the genome of the sooty mangabey – a nonhuman primate that can coexist with SIV – and discovered how an immune system deficiency actually stops SIV from turning into AIDS.

“We found two big differences in proteins of the immune system in the sooty mangabey genome, which we hope will help us better understand why sooty mangabeys avoid AIDS despite SIV infection,” said David Palesch, a Yerkes postdoctoral fellow and co-author of the study documenting the discovery.

These differences aren’t some biological defense system or super-simian invulnerability. Technically, they’re handicaps. Instead of a more robust immune system, the sooty mangabey is playing a man down in the fight against SIV and winning.

So what are these immune deficiencies? A missing piece in the the ICAM2 gene stops the corresponding protein from functioning – a genetic anomaly unique to the mangabey species.

Similarly, the TLR4 protein – a molecule that senses bacteria and triggers an immune defense against it – has limited functioning because of a genetic alteration.

“This finding is intriguing because damage to intestinal barriers and bacterial release contributes to chronic immune activation, which is associated with AIDS progression in HIV-infected humans and SIV-infected non-natural hosts,” said Guido Silvestri, chief of Microbiology and Immunology at the Yerkes Research Center.

Inspired by these findings, the Yerkes team is already planning its next study where the ICAM2 and TLR4 proteins will be manipulated in a living nonhuman primate host to determine how those genetic anomalies halt SIV’s progression.

“It’s a really exciting time in AIDS research,” said Dr. Steve Bosinger, assistant professor of Pathology and Laboratory Medicine and director of Yerkes’ Genomics Core. “We’ve seen that an HIV cure is possible.” Now, that’s something to be excited about.

Photo credit: Yerkes National Primate Research Center

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