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Two New Anti-HIV Molecules Identified

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Justine Alford

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2673 Two New Anti-HIV Molecules Identified
HIV infecting a white blood cell. Chris Bjornberg/Shutterstock

Back in the ‘80s, before rigorous screening was implemented, a number of individuals in Australia became infected with HIV following transfusions with contaminated blood. Known as the Sydney Blood Bank cohort, they all received blood from a single HIV-infected donor.

A fatal error, one would assume, but 30 years on, around half of them still have no detectable viral replication in their blood, and the others only showed low levels of replication – not enough to drive progression to AIDS. So what was behind this unusual resistance? Two new studies, published in Nature, are offering us some crucial pieces of the puzzle.

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The donor, and hence the recipients, was infected with a strain of virus that didn’t produce one of its proteins, called Nef. Originally believed to hinder viral replication, hence its name “Negative factor,” we now know it’s important for both efficient viral replication and infectivity of HIV particles. Viruses generated in the absence of Nef appear normal and can escape the cells that made them successfully, but they can’t go on to attack new cells. Interestingly, though, this doesn’t seem to be universal to all infected cells.

“We noticed that this effect was very much dependent on what cell type was used to generate HIV,” lead researcher of one of the studies Massimo Pizzato told IFLScience. “Some cells don’t care about the presence or absence of Nef and would generate infectious viruses anyway.”

So what Pizzato’s team did was compare the host genes that were switched on, or expressed, in cells that churned out crippled viruses without Nef with those that still managed to create infectious particles. This led them to two membrane-spanning proteins, called SERINC3 and SERINC5, which seem to be able to dampen HIV infectivity, but only when Nef is absent, although the former is significantly less potent in its ability than the latter.

What seems to be happening, Pizzato told IFLScience, is that as newly created HIV particles push their way through the host cell’s membrane to escape, they take part of it with them, which means they inadvertently also end up carrying these inhibitory proteins. Too bad for the virus, but of course, it’s armed with its own counter-defense: Nef. This manages to act like a road sign, diverting the traffic of these inhibitory proteins from the membrane to a compartment that’s out of the way. With the membranes now cleared, the viruses are free to “bud” from the cell without the unwanted baggage.

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Interestingly, a second study also honed in on the same two cellular factors, which were identified after researchers compared the protein composition of normal HIV particles and those that didn’t produce Nef. And when the team used Nef-deficient viruses to infect cells that were engineered to not produce these proteins, their infectivity was increased by more than 100-fold.

So what exactly are these proteins doing? “Good question,” Heinrich Göttlinger, lead researcher of the second study, told IFLScience. One idea, he says, is that they could be preventing the spiky proteins present on HIV’s surface from clustering together at the virus-cell contact zones, making entry difficult. But Pizzato has another suggestion: He thinks they could somehow be preventing the virus from injecting its contents into a cell, perhaps by messing up the equipment that it uses to poke a hole into the cell’s membrane.

Whether or not this finding could benefit HIV patients remains to be seen. We don’t know at this stage whether these inhibitors actually directly interact with Nef, but if they do, that gives scientists an opportunity to design some kind of blocking molecule that could be turned into a treatment.


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healthHealth and Medicine
  • tag
  • virus,

  • hiv,

  • aids,

  • blood transfusion,

  • cell,

  • membrane,

  • Nef

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