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Reseachers Identify New Targets to Disrupt HIV Lifecycle


In what is being hailed as a major step in the fight against HIV/AIDS, U.S. researchers have identified 273 proteins that are key to reproduction of the virus that causes AIDS. As we hear from VOA science correspondent Art Chimes, that gives scientists many potential new targets for drugs to disrupt the sophisticated lifecycle of the virus.

Publication of this new study promises to give researchers more avenues to follow as they look for better ways to stop the AIDS epidemic.

"The set of proteins will provide a lot of insight into how the virus actually functions. And people may be able to use that information to somehow circumvent the virus. But the other way you can look at it is that now there are more targets. They're potential targets," says

Stephen Elledge of Harvard Medical School, he lead author of the paper describing the discovery. It was published Thursday online in SciencExpress.

HIV has little genetic material of its own, so when it infects a cell, it hijacks the cell's genetic code to reproduce. This new study identifies some of the cell proteins the virus uses in that process.

Speaking in a Science magazine podcast, Elledge said current anti-AIDS drugs generally focus on the virus itself.

"But the problem is that HIV is a highly mutable virus, so it can change the target of the drug so that it no longer binds the drug that well."

Which is why Elledge focused on human proteins. Of the 273 he identified as being essential to HIV reproduction, only 36 were previously known.

Leading AIDS researchers hailed Elledge's work. HIV co-discoverer Robert Gallo called it "terrific." Dr. Anthony Fauci, head of the U.S. National Institute of Allergy and Infectious Diseases described it as "elegant science," but he told The New York Times that it's too soon to tell if this laboratory discovery will actually prove useful in treating patients.

Elledge also admits there could be side effects to any treatments developed using his discovery.

"And the downside, the potential downside, is that if the organism — us — needs that particular protein, [then] if you inhibit it, you might get sick. And of course, that's true for any drug. If anyone finds a drug target and they decide they're going to make a drug that inhibits it, it has to be tested in people to see how people tolerate having that pathway reduced."

To find the 273 proteins that are part of the HIV life cycle, Elledge and his colleagues screened thousands of possibilities using a technique honored with a Nobel Prize a year ago, RNA interference, which can be used to effectively shut down one gene at a time within a cell. Then the researchers infected the cell with HIV to see if the virus could reproduce.

"And we did this for over 20,000 human proteins, all the known, currently known proteins to figure out which ones might be important," Elledge explained. "We wanted to cover everything, we wanted to leave no stone unturned to see what the list looked like. And that's how we did it."

Stephen Elledge, of Harvard Medical School and the Howard Hughes Medical Institute, says the same approach could be used to help find targets in the fight against other virus infections as well.

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