273 New Possible Targets for HIV Drugs

Hundreds of Human Proteins Essential to HIV Survival Discovered

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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."

Continued

"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.

One hopeful finding is that some people carry a mutant version of one of the proteins identified by the Elledge team, apparently with no harmful consequences. This mutant version of the protein, Haynes and colleagues recently learned, is found in some of the rare individuals who do not progress to AIDS when they become infected with HIV.

"One of the critical challenges of HIV research is to learn as much about the virus as we can, as fast as possible," Haynes tells WebMD. "Studies like this have the potential to move our knowledge forward quickly, which is important given the growing worldwide epidemic of HIV and AIDS."

The findings have broad significant beyond AIDS research. They show that the same techniques can be used to dissect the workings of other viruses -- and of cancers. Elledge says his team is now looking for the Achilles' heels of cancer cells.

Elledge and colleagues report their findings in the Jan. 10 issue of the online journal Science Express.

WebMD Health News Reviewed by Louise Chang, MD on January 10, 2008

Sources

SOURCES: Brass, A.L. Science Express, published online Jan. 10, 2008.Stephen J. Elledge, professor of genetics, Harvard Medical School and Brigham & Women's Hospital, Boston, and Howard Hughes Medical Institute. Janet Young, PhD, program officer, Division of AIDS, National Institute for Allergy and Infectious Diseases, Bethesda, Md. Barton Haynes, MD, director, Human Vaccine Institute and the Center for HIV/AIDS Vaccine Immunology, Duke University, Durham, N.C.

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