New strategy to starve HIV to death

Scientists have found a new strategy to starve the human immunodeficiency virus (HIV) to death - by blocking its sugar and nutrient pipeline.
HIV has a voracious sweet tooth, which turns out to be its Achilles' heel, according to researchers from Northwestern Medicine and Vanderbilt University.
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.

"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," said Harry Taylor, assistant professor in Medicine-Infectious Diseases.
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 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.
Northwestern and Vanderbilt 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.
This is believed to be the first time scientists have targeted the virus's ability to pilfer the cell's pantry to stop its growth.

The compound also slowed the proliferation of the abnormally activated immune cells, the study found.
Current HIV medications stop HIV growth but do not affect the abnormal excess activation and growth of immune cells triggered by HIV.
The excess immune cell growth is believed to contribute to the life-long persistence of HIV and leads to excess inflammation that causes premature organ damage in HIV patients - even when the virus is suppressed by current medicines.
"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 added.

The study was published in the journal PLOS Pathogens.