HIV Discovery Could Lead to New Infection-Blocking Drugs

Researchers at the National Institutes of Health have successfully prevented HIV from infecting cells by chemically blocking a previously unidentified step in the viral invasion process.

While benefits to patients may not be realized immediately, the new findings could allow scientists to begin developing treatments that halt the infection process entirely, according to Leonid V Chernomordik (pictured), PhD, senior investigator at the Eunice Kennedy Shriver National Institute of Child Health and Human Development.

“It will now be possible to begin [a] series of studies to determine how this inhibition can be accomplished in vivo, in hopes of finding new therapies to reduce the chance for infection,” Chernomordik told MD Magazine.

To infect a cell, a protein on the surface of HIV binds to molecules on the cell’s surface. This binding process initiates a sequence of events that ends with HIV’s outer membrane fusing with the cell’s membrane, which allows it to pass its genetic material into the cell.

Researchers discovered that the binding process activates a protein, called TMEM 16F, that transfers another molecule inside the cell membrane — phosphatidylserine – to the membrane’s outer surface.

“It was known that binding of the HIV envelope glycoprotein ENV with CD4 and one of the two coreceptors (CCR5 and CXCR4) triggers calcium signaling. It was also known from other studies that a rise in intracellular calcium may trigger a redistribution of phosphatidylserine from the inner leaflet of the plasma membrane to the cell surface,” Chernomordik said. “We hypothesized that HIV-cell binding delivers phosphatidylserine to the cell surface and that this may be important for the HIV entry.”

The study confirmed Chernomordik’s hypothesis.

“We found that cell surface phosphatidylserine facilitates fusion between the HIV envelope and the cell membrane before injecting viral nucleic acid into the cell,” he said.

Blocking the transfer of phosphatidylserine to the cell surface — or attaching another molecule to phosphatidylserine so it can’t bind with HIV – prevents the virus from infecting the cell. Theoretically, developing drugs that could block each of these steps could provide the basis for treatments to prevent HIV from infecting cells, according to an NIH statement, but much more research is needed.

“It is premature to talk about immediate benefits for patients,” Chernomordik said. “Ultimately, however, the goal is to develop new treatments to halt the infection process.”

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