Scientists have discovered a new way to starve the dangerous human immunodeficiency virus (HIV) to death – by cutting its sugar supply. The HIV has a voracious sweet tooth which can turn out to be its undoing, according to new results by Northwestern Medicine and Vanderbilt University researchers. 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 pipeline. 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.
“This compound can be the precursor for something that can be used in the future to treat HIV that improves on the effective medicines we have today,” said study author Harry Taylor from Northwestern University. “It is essential to find new ways to block HIV growth, because the virus is constantly mutating,” said Taylor. “A drug targeting HIV that works today may be less effective a few years down the road, because HIV can mutate itself to evade the drug.”
HIV needs to grow in a type of immune cell (CD4+ T cell) which is already responsive 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 signalled 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.
Scientists figured out that the 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. When HIV enters the bloodstream, it searches out active CD4+ T cells, the commanders-in-chief of the immune system. When HIV finds an active CD4+ T cell, it hijacks the cell’s glucose supply to build millions of copies of itself and invade other cells.