Unexpected find may lead to novel ways to stop HIV

WASHINGTON - New techniques to fight HIV could be on their way, as scientists have found that the virus adapts in a surprising way to survive and thrive in its hiding spot within the human immune system.

For more than 15 years, Baek Kim has been fascinated by HIV’s ability to take cover in a cell whose very job is to kill foreign cells.

In the last couple of years, Kim, of the University of Rochester Medical Center, has teamed with Emory scientist Raymond F. Schinazi to test whether the virus is somehow able to sidestep its usual way of replicating when it’s in the macrophage.

The pair found that when HIV faces a shortage of the molecular machinery needed to copy itself within the macrophage, the virus adapts by bypassing one of the molecules it usually uses and instead tapping another molecule that is available.

Normally, the virus uses dNTP (deoxynucleoside triphosphate, the building blocks for making the viral genetic machinery) to get the job done, but dNTP is hardly present in macrophages - macrophages don’t need it, since they don’t replicate.

But macrophages do have high levels of a closely related molecule called rNTP (ribonucleoside triphosphate), which is more versatile and is used in cells in a variety of ways. The team found that HIV uses primarily rNTP instead of dNTP to replicate inside macrophages.

“The virus would normally just use dNTP, but it’s simply not available in great quantities in the macrophage. So HIV begins to use rNTP, which is quite similar from a chemical perspective. This is a surprise. The virus just wants to finish replicating, and it will utilize any resource it can to do so,” said Kim.

When the team blocked the ability of the virus to interact with rNTP, HIV’s ability to replicate in macrophages was slashed by more than 90 percent.

The work opens up a new front in the battle against HIV. Current drugs generally target dNTP, not rNTP, and take aim at the infection in immune cells known at CD4+ T cells. The new research opens up the possibility of targeting the virus in macrophages - where the virus is out of reach of most of today’s drugs.

“The first cells that HIV infects in the genital tract are non-dividing target cell types such as macrophages and resting T cells” said Kim. “Current drugs were developed to be effective only when the infection has already moved beyond these cells. Perhaps we can use this information to help create a microbicide to stop the virus or limit its activity much earlier.”

Kim noted that a compound that targets rNTP already exists.

Cordycepin in an experimental compound, derived from wild mushrooms, that is currently being tested as an anti-cancer drug. The team now plans to test similar compounds for anti-HIV activity.

The findings were published in the Journal of Biological Chemistry. (ANI)