How Do You Thwart HIV? By Cutting Off its Food Supply

Scientists may have found a way to sabotage that ultimate saboteur, HIV. The crafty virus, which invades a healthy immune cell, replicates itself, then moves on to infect others, has been a challenge to combat, mainly because it has evolved into such an efficient virus. So researchers are taking a more direct approach - they're stopping the virus through simple starvation.

The HIV virus has a voracious appetite. In order to fuel its rapid growth, it gobbles up the sugar and nutrients of the invaded cell.

So researchers from Northwestern Medicine and Vanderbilt University have developed a way to starve the virus by shutting down the nutrient pipeline. They do this by blocking the switch that feeds the cell, thereby starving the virus within. And their experiments have shown that once the nutrients and sugar have been cut off, the virus can no longer replicate.

HIV targets a specific type of active immune cell, the CD4+ T cell. Since this type of immune cell is already activated, usually responding to pathogens in the blood, HIV takes advantage of the increase in critical nutrients that fuel the activated cell, and commandeers them for its own purpose.

Scientists at Northwestern and Vanderbilt figured out a way to keep the T cell from stocking its pantry by blocking the activation of phospholipase D1 (PLD1), a cell component that triggers the boost in nutrients. Without the stocked pantry, HIV starves and can no longer replicate and spread.

"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," says Harry Taylor, coauthor of the study and researcher at Northwestern University's Feinberg School of Medicine.

Another benefit to starving the virus is a reduction in organ damage associated with current drug therapies for HIV. Although today's drugs can halt growth of the virus, they do nothing for the proliferation of abnormally activated immune cells triggered by HIV. This proliferation of immune cell growth causes excess inflammation in the body, leading to premature organ damage in patients.

"Perhaps this new approach, which slows the growth of the immune cells, could reduce the dangerous inflammation and thwart the life-long persistence of HIV," Taylor says.

This same approach has been used to block the growth of breast cancer cells. Blocking the PLD1 kept breast cancer cells from spreading, so Taylor had a hunch this the same technique might work on CD4+ T cells in HIV. And that's exactly what their studies have shown.

 "This discovery opens new avenues for further research to solve today's persisting problems in treating HIV infection: avoiding virus resistance to medicines, decreasing the inflammation that leads to premature aging, and maybe even one day being able to cure HIV infection," says Dr. Richard D'Aquila, director of Northwestern's HIV Translational Research Center.

Their study was published May 28th in the journal PLOS Pathogens.