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Cold Spring Harbor scientists reveal a protein's role in enabling AIDS virus to reproduce
Date:5/23/2008

life cycle that helped the virus invade macrophage target cells. Recent studies had further shown that Vpx proteins in both monkey and human viruses promoted the process of reverse transcription that underlies the conversion of viral RNA to DNA.

In their study, which consisted of several steps, the CSHL team showed that when the vpx gene (the gene that encodes the Vpx protein) was deliberately deleted, the virus went about reverse transcription very inefficiently.

This suggests that the Vpx protein is key to the process by which the virus infects macrophages, Dr. Skowronski comments, and further, that it seems to be acting either before and/or during the reverse transcription process. This new view of Vpxs role contrasts with a prior hypothesis that it was involved in the transporting of genetic material that had already undergone reverse transcription.

The teams experiments revealed that the Vpx protein in the SIVmac virus binds to a complex of three cellular proteins that in turn engage a molecular machinery involved in the degradation of proteins. Thus, the team revealed for the first time not only that Vpx interacted with this system -- called the ubiquitin-dependent proteosomal protein degradation mechanism -- but also identified precisely the way it does so, via a series of intermediate steps.

The net result, says Dr. Skowronski, is that we show how Vpx enables efficient reverse transcription in the simian virus, and in so doing, overcomes an innate block that otherwise prevents viral replication.

By implication, this suggests a strategy by which a future drug might interfere with the reproductive machinery of the virus to prevent or limit is ability to spread. There are no guarantees, of course, that such an approach will work, Dr. Skowronski says, but unless we understand molecular mechanisms such as this one that empower this remarkable virus, we are not likely to devise a means of stopping it.


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Contact: Jim Bono
bono@cshl.edu
516-367-8455
Cold Spring Harbor Laboratory
Source:Eurekalert

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