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Unexpected find opens up new front in effort to stop HIV
Date:1/22/2011

cleoside 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," said Kim. "The virus just wants to finish replicating, and it will utilize any resource it can to do so."

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 notes 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 plans to test similar compounds for anti-HIV activity.

"This significant breakthrough was unappreciated prior to our paper. We are now exploiting new anti-HIV drugs jointly based on this novel approach that are essentially not toxic and that can be used to treat and prevent HIV infections," said Schinazi, who has developed several of the drugs currently used to treat HIV patients.


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Contact: Tom Rickey
tom_rickey@urmc.rochester.edu
585-275-7954
University of Rochester Medical Center
Source:Eurekalert

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