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Scientists discover enzyme crucial to HIV replication

n," explains Dr. Jeang. "We found that the virus also uses a human enzyme known as DDX3 to straighten its RNA before threading it through a small pore in the nucleus." The team's experiments offer the first evidence that HIV uses DDX3 in the complex process that moves its RNA out of the nucleus. They also demonstrated that DDX3, a human RNA helicase enzyme, is essential to this process. RNA helicases are enzymes that untwist RNA molecules.

The researchers now plan to look for inhibitors, small molecules that could either lock or gum up DDX3's ability to straighten a twisted strand of RNA. Although it would take many years to develop, in the best scenario, an inhibitor for DDX3 could effectively block HIV replication. Researchers would need to find a balance between a potential inhibitor's action in shutting down viral replication and any detriment it might cause to human cells.

In the past decade, two classes of HIV inhibitor drugs, protease inhibitors and reverse transcriptase inhibitors, have greatly extended the lives of HIV-positive individuals. While these drugs target HIV enzymes, a DDX3 inhibitor would target a cellular enzyme. The researchers see a great therapeutic advantage to blocking a cellular enzyme rather than a viral enzyme.

"Unlike viral enzymes, cellular enzymes can not mutate to escape from drugs," says Dr. Jeang. The problem of drug resistance that occurs with protease and reverse transcriptase inhibitors might thus be eliminated with a successful DDX3 inhibitor.


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Contact: Linda Joy
ljoy@niaid.nih.gov
301-402-1663
NIH/National Institute of Allergy and Infectious Diseases
29-Oct-2004


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