University researchers 'shut down' HIV

University molecular biology professor Thomas Shenk and postdoctorate researcher Leor Weinberger have discovered a way to force human immunodeficiency virus (HIV), the virus that causes AIDS, into a latent state.

The immediate significance of the research is that scientists may be able to "shut down" HIV viruses, rendering them dormant if not eliminating them.

The HIV virus usually infects cells and forces them to create more copies of the virus, killing the cells in the process.

Under other conditions, however, it may become latent. Researchers had previously demonstrated that a protein called Tat was instrumental in deciding whether the virus would become active or latent. If Tat concentration is low, the virus becomes latent, and if Tat concentration is high, the virus becomes active and infectious.

Shenk and Weinberger discovered that two other proteins, p300 and SirT1, regulate the expression of Tat. The former accelerates the production of Tat, while the latter inactivates it. This means that if the infected cell has a high concentration of SirT1 protein, the virus is forced into its dormant phase, significantly reducing the threat to the host.

Nathaniel Moorman, a postdoctorate researcher in Shenk's lab, emphasized the unique significance of Weinberger and Shenk's discovery.

"This is a fundamental shift in the way we view this viral circuit," Moorman said. "A lot of other viruses appear to behave in a similar way, but they haven't been looked at in this manner."

Shenk and Weinberger's results suggest that raising the concentration of SirT1 in the cells targeted by HIV may be an effective treatment to delay or prevent the full onset of AIDS.

Similar treatments have been developed for other diseases.

"Unfortunately," Weinberger said in an e-mail, the ways in which a latent virus may become infectious "are not as well understood as we would like," and additional work would be needed to develop a truly effective treatment.

Shenk and Weinberger's findings were published last December in the journal Public Library of Science Biology.