More potent ways to design HIV drugs found

Many virus-human protein connections identified

In perhaps the most comprehensive survey of the inner workings of HIV, an international team of scientists led by researchers at the University of California, San Francisco has mapped every apparent physical interaction the virus makes with components of the human cells it infects.

This work may reveal new ways to design future HIV/AIDS drugs.

In back-to-back papers published today (December 22) in the journal

Nature , the survey reveals a pathogenic landscape in which HIV's handful of proteins makes hundreds of physical connections with human proteins and other components inside the cell.

In one paper, the team details 497 such connections, only a handful of which had been previously recognized by scientists. Disrupting these connections may interfere with HIV's lifecycle, and the existence of so many new connections suggests there may be several novel ways to target the virus.

“Have we identified new drug targets?” said Nevan Krogan, who led the research. “I believe we have.” Krogan is an associate professor of Cellular and Molecular Pharmacology at UCSF.

In a companion paper, Krogan and collaborating labs investigated one such connection in detail. They discovered that an HIV protein called Vif makes a physical connection with a human protein called CBF-â, hijacking its function.

This virus requires this action to function, said Krogan, which suggests that disrupting the connection may be a viable way to design new HIV/AIDS therapies.

Unlocking the doors

The UCSF-led study has provided the most comprehensive and detailed picture to date of all the interactions HIV has with the human cells it infects, and identifying these interactions may lead to the development of new drugs to treat the disease.

Of the 497 specific interactions between HIV and human proteins discovered in the new work, only 19 of those were previously reported.

What accounts for the discrepancy, Krogan said, is that this was the first study to look for such interactions globally and in an unbiased fashion – unlike previous studies, which had been more focused.

Interfering with this association may be a way to block the virus. Ultimately, if scientists can design compounds to do this safely and effectively, those compounds could form the basis for a new type of HIV/AIDS treatment.