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Researchers open door to new HIV therapy
Date:1/28/2014

he body," he said.

HIV hijacks cellular machinery

HIV contains a small number of genes that produce only 15 different proteins, all of which hijack some aspect of immune cells' internal machinery to produce more copies of the virus.

Current anti-AIDS drugs block three HIV enzymes proteins that transcribe and insert the virus' genetic material, and snip some of the encoded proteins but researchers are now looking for drugs that target the other proteins as backups to current therapies. In particular, they are searching for ways to block sites on host proteins to which the virus proteins bind in order to stop HIV. This has to be done without interfering with normal cell function, however.

Nearly 20 years ago, scientists showed that without the protein Nef short for negative factor HIV is far less infective. Some patients can live for decades without problems if infected with a Nef-defective virus.

Since then, more details have emerged about Nef's role. HIV enters immune system cells via a receptor called CD4, but once "HIV gets into cells through the CD4 door, it slams the door shut behind itself to prevent unproductive re-infection," Hurley said.

Scientists aren't sure why HIV slams the door on other viruses, he said, though it may be a way to prevent too many viruses entering the same cell, making the cellular environment less favorable for productive viral replication.

Whatever the reason, the virus prevents further HIV infection by ridding the cell surface of all other CD4 receptors. Nef achieves this by tagging the CD4 receptor so that the cell thinks it is trash and carries it to the cell's incinerator, the lysosome, where it is destroyed. Six years ago, Bonifacino and colleagues found that Nef does this by directly binding to a host protein, AP2, that latches onto a protein called clathrin. This causes the cell membrane to bulge inward and pinch off to form a small membrane bubble that ca
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Contact: Robert Sanders
rlsanders@berkeley.edu
510-643-6998
University of California - Berkeley
Source:Eurekalert  

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