HIV's Sugar Stash

HIV isn't sweet on the idea of sugar. It manages to evade its enemies by mutating so that antibodies, which need sugar to penetrate the HIV viral cell, can’t find a way inside.

In the past, when HIV antibodies have attempted to zero in on sugars that coat HIV viral proteins known as glycans, the virus has shifted the glycans to someplace else. By hiding the sugar, the antibody can’t find the virus.

But now scientists have learned of a way to get some antibodies inside HIV cells even when the virus has mutated in an effort to vanish.These antibodies can stop at a nearby “candy store,” so to speak, known as a high-mannose patch. Some antibodies can zero in on specific cell targets and are able to pierce them even when HIV suddenly shifts the sugar elsewhere.

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Scientists at The Scripps Research Institute in La Jolla, Calif. are targeting a site on the high-mannose patch known as N332. They presented their findings this week in the journal Science Translational Medicine.

Researcher Devin Sok told Healthline that scientists already knew that antibodies could bind to the high-mannose patch. “But now we are getting a better understanding of how the antibodies are recognizing the glycans in the patch, and a better understanding of why some antibodies appear to be super-broad and super-potent based... how they recognize the sugars.”

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“What we show here is that because the antibodies can recognize a single site in slightly different ways, we can achieve the same sort of coverage that we thought only would be possible by targeting multiple sites,” Sok added.

Sok said that by using a cocktail of antibodies to trigger multiple responses against sites on an HIV cell’s protein envelope, “This is definitely still a viable approach.” Researchers so far have identified about five so-called “broadly-neutralizing sites” like N332.

The scientists hope that by targeting N332 and other sites like it, they can defeat multiple strains of HIV. This would be useful for creating a vaccine and other antibody-based treatments.

Much of the excitement in research circles these days centers on PGT121. This antibody, or immunogen, has proven effective at curbing the spread of SIV, the monkey version of HIV, in chronically infected macaques.

The researchers believe that targeting these sites, instead of CD4 “helper” cells, might create a more effective immune response in vaccines against HIV.

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