XSEDE Helps Scientists Understand Monkey Protein that Confers Immunity to HIV

Why It’s Important:

Globally, nearly a million people died of AIDS in 2017, according to the World Health Organization. That number is down from its peak in 2004-2005. Still, it’s fair to say that we have HIV, the AIDS virus, on the ropes but have not yet knocked it out. We can control the virus in infected people and extend their lives. But we can’t cure them. We can give drugs that reduce the risk of infection to people at high risk. But we can’t prevent infection. The drugs we have already are lifesavers. Still, new avenues for attacking the virus might be needed before cures, and true preventives, are possible.

“There’s this protein called TRIM5α. It’s an HIV restriction factor, which means that it inhibits infection. The protein is naturally occurring in old-world monkeys and rhesus monkeys. The big question is that we [humans] also have this protein; it’s just that it doesn’t make us immune to HIV.” —Juan Perilla, University of Delaware

Possible new targets for therapy are the reason why Juan Perilla of the University of Delaware and colleagues there and at the University of Pittsburgh are interested in a protein called TRIM5α (“trim five alpha”). In old-world and rhesus monkeys, TRIM5α provides a hard stop to the HIV’s ability to infect cells. Its ability to destabilize HIV’s capsid, the protective shell around the virus’s genetic material, is what makes HIV unable to infect monkeys. On the other hand, humans do have a version of TRIM5α—but for reasons we don’t yet understand it can’t stop the virus like the monkey version does. Perilla and his collaborators would like to find out how monkey TRIM5α works, and possibly how the human version can be helped to do the same trick. This knowledge could provide a new way of attacking the virus that might stop HIV much more fully than the current generation of drugs.

How XSEDE and PSC Helped:

The scientists studied the problem in two ways. Angela Gronenborn of Pitt and Tatyana Polenova of Delaware used a lab technique called nuclear magnetic resonance (NMR) to study which parts of the virus’s capsid protein, called CA, are affected when TRIM5α is present. NMR can tell what parts of the protein are affected, but not how they’re affected. So, alongside the lab work, Perilla and his graduate students studied the system using simulations on PSC’s Bridges supercomputer.

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