Glycan Interaction Could Help HIV-Infected Cells Avoid NK Cells

A new study by researchers at The Wistar Institute shows how key features on the surface of HIV-infected cells help the disease evade detection by the immune system. The findings were published in PLOS Pathogens.

“We identified a glyco-immune checkpoint interaction as a novel mechanism that allows HIV-infected cells to evade immune surveillance,” said Mohamed Abdel-Mohsen, a coauthor on the paper. “And we developed a novel approach that selectively targets these interactions on the surface of these infected cells.”

For the new study, researchers looked at sialic acid found on the surface of HIV-infected cells. These sugars bind with special receptors called siglec9 on the surface of disease-fighting natural killer immune cells. “We thought, ‘is it possible that these HIV-infected cells are using this interaction — covering themselves with these sugars to evade the natural killer immune surveillance?’” said Abdel-Mohsen.

The scientists found that to be the case and that these infected cells took advantage of this inhibitory connection to evade immune surveillance. Researchers then developed a sialidase conjugate linked to HIV antibodies. This antibody-sialidase conjugate only targeted sialic acid on HIV cells. With the sialic acid removed from these cells, the killer immune cells killed the HIV-infected cells.

“The killer cells become a super killer for the HIV-infected cells and they now attack them in a selective manner,” said Abdel-Mohsen. “The discovery could be a missing link in the “shock and kill” approach to HIV treatment that has been a focus of research for the past several years,” he added. This two-step process involves first “shocking” the HIV out of latency so it can be detected, and then stimulating the immune system to “kill” the virus once and for all. However, while effective methods have been discovered to reverse latency, scientists haven’t yet found a way to make HIV-infected cells more killable once reactivated.  “We may have the shock, but we don’t have yet the kill,” Abdel-Mohsen concluded.