01/11/08

UNITED STATES:  HIV Research Opens Up Potential Targets for Drugs

A study published Thursday identified at least 273 proteins the human cell produces that HIV requires in order to enter the host and replicate.

In the study, geneticist Dr. Stephen J. Elledge and colleagues at Harvard Medical School used tens of thousands of short interfering RNAs (siRNAs), each a bit of genetic code that blocks the creation of a protein made by a human cell. The team then introduced HIV to about 21,000 samples of cells - each sample blocked from producing a protein.

If HIV could reproduce normally in a sample, the missing protein was not considered one the virus needed. Through this process, the researchers found there were 273 human proteins without which HIV would not reproduce normally; only 36 of the proteins had been previously identified as necessary to HIV. Many proteins identified by the study are known to be important to the immune system.

An advantage to a potential treatment targeting human proteins is that HIV presumably would be unable to develop immunity to them, said Elledge. But blocking human proteins could be fatal. Among AIDS drugs, only the CCR5 entry inhibitor targets a human protein to block HIV from replicating.

"It remains to be seen if any of these proteins they identified are useful clinically," said Dr. Anthony S. Fauci, director of the National Institute of Allergy and Infectious Diseases. "This is hypothesis-generating, not hypothesis-solving. It creates a lot of work - someone has to go down each of these pathways."

There are undoubtedly other proteins HIV needs in order to reproduce, "but the majority of the ones we found are highly likely to play a role in HIV propagation," said study co-author Dr. Abraham L. Brass.

The full report, "Identification of Host Proteins Required for HIV Infection Through a Functional Genomic Screen," was published online in Science Express (2008;doi:10.1126/science.1152725).

Source: New York Times:: Donald G. McNeil Jr.; Courtesy of the CDC National Center for HIV, STD, and TB Prevention