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273 New Possible Targets for HIV Drugs

Hundreds of Human Proteins Essential to HIV Survival Discovered
By
WebMD Health News
Reviewed by Louise Chang, MD

Jan. 10, 2008 -- Scientists have discovered 273 new human proteins that, if blocked, keep the AIDS virus from doing its dirty work.

Only 36 of these proteins were previously known to interact with HIV, the virus that causes AIDS. The finding is thus a mind-boggling expansion of what science knows about the virus. It also offers more than 200 new targets for future anti-HIV drugs.

HIV itself makes only 15 proteins. In order to replicate -- to make new copies of itself -- the virus has to take over the complex machinery of human immune cells. The new findings give scientists a vastly closer look at how HIV pulls off this coup.

"We found dozens and dozens of new things not implicated before in HIV replication," Harvard and Massachusetts General Hospital researcher Stephen J. Elledge, PhD, tells WebMD.

What made the study possible is the discovery of "gene silencing" using interfering RNA molecules, a technique that garnered the 2006 Nobel Prize in Physiology or Medicine for U.S. scientists Andrew Fire, PhD, and Craig Mello, PhD. The technique allowed Elledge and colleagues to eliminate, one by one, 21,000 proteins in a human cell line. By infecting each of these cell lines with HIV, the researchers were able to see whether a protein was an "HIV dependency factor" -- something HIV absolutely must have in order to survive in the human body.

"This is one of the first explosions of information people will get from this technique," Elledge says.

Experts Say Finding Is Major Advance

Janet Young, PhD, a program officer in the AIDS division of the National Institute for Allergy and Infectious Diseases, says the findings are a big step forward.

"On first glance at this, my first thought was, 'What will we do with all these proteins they identified?" Young tells WebMD. "But the key thing is we now have a clearer understanding of how HIV infects cells and causes disease. We can now home in on many of the proteins involved. The potential for developing therapeutics is exciting."

AIDS research pioneer Barton Haynes, MD, director of the Duke Human Vaccine Institute, calls the findings "very important."

"This study uses new technology to come up with questions we really didn't know how to ask. And it points to areas and systems in the host cells we weren't aware were important," Haynes tells WebMD.

With the exception of a single new agent, all existing HIV drugs target proteins made by HIV itself. Because HIV mutates rapidly, it eventually develops resistance to these drugs by slightly changing its proteins.

The AIDS virus would have a much harder time getting around drugs that target the human proteins it needs. On the other hand, drugs that attack human proteins could do harm if the proteins turn out to be crucial to humans, too.

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