HIV has a voracious sweet tooth, which may be its Achilles’ heel, reports a new study from Northwestern Medicine and collaborators.
After the virus invades an activated immune cell, it craves sugar and nutrients from the cell to replicate and fuel its wild growth throughout the body.
Scientists discovered the switch that turns on the immune cell’s abundant sugar and nutrient pipeline. Then they blocked the switch with an experimental compound, shutting down the pipeline, and, thereby, starving HIV to death. The virus was unable to replicate in human cells in vitro.
The discovery may have applications in treating cancer, which also has an immense appetite for sugar and other nutrients in the cell, which it needs to grow and spread.
The study was published May 28 in PLOS Pathogens.
“Our findings represent a novel way of stopping HIV from replicating by targeting cellular pathways that it depends on to make more copies of itself," says Harry Taylor, medicine: infectious diseases and corresponding study author. “This compound can be the precursor for something that can be used in the future as part of a cocktail to treat HIV that improves on the effective medicines we have today.”
HIV needs to grow in a type of immune cell (CD4+ T cell) that is active, meaning it is already responding to pathogens in the blood. Activation increases the T cell's supplies of sugar and other critical nutrients needed for both cell and virus growth.
Until now, no one knew the first step that signaled a newly activated T cell to stock up on sugar and other nutrients. Those nutrients become the building blocks of genetic material the cell and the virus need to grow.
Northwestern and Vanderbilt scientists figured out that first step in stocking the T cell’s pantry involved turning on a cell component called phospholipase D1 (PLD1). Then they used an experimental compound to block PLD1 and shut down the pipeline.
“This is just the beginning of an exciting line of investigation for our group,” Taylor says. “We are actively searching for other compounds that inhibit HIV in a similar fashion.”
This research was supported in part by Northwestern Medicine’s HIV Translational Research Center, the National Institute of Mental Health grant U54-MH084659, National Institute of Diabetes and Digestive and Kidney Diseases grant 5R21DK094735, the National Center for Research Resources grant 5KL2RR024977 and the National Cancer Institute grant CA060553, of the National Institutes of Health.