Disrupting HIV Dance

HIV vaccine developed by MIT has a new target

(RxWiki News) Researchers at the Massachusetts Institute of Technology (MIT) and Harvard University have made more progress in figuring out how HIV survives in the body. The protein called Gag has been targeted for future vaccine development.

Harvard Medical School Professor Bruce Walker, M.D., Director of the Ragon Institute and a senior author of this new paper reports that there are treatments for HIV, but the number of people in need of treatment around the world exceeds the ability of the medical establishment and drug companies to provide those drugs. The only solution, he says, is developing an effective vaccine.

"New HIV vaccine development is underway."

Recent research involving developing vaccines tried to target single amino acids (building blocks of proteins) that the HIV virus is unable to change without losing function. The idea was that if the virus tried to evolve around these viral targest, the mutations would incapacitate a virus. Success is there, but it is limited as mutations other places in the viral protein can assist in restoring the amino acid to its preferred state by the virus.

The Ragon Institute researchers took a bigger picture approach by not just looking at single mutations, but by looking at the amino groups in concert to identify which group is most effective at proliferating the virus. After identifying these groups, the researchers then determined whether multiple mutations in the groups helped or hurt the virus.

The team zeroed in on an HIV polyprotein called Gag, which gives the virus much of its structure along with five co-evolving groups of amino acids within Gag.

Then, researchers looked at each pair of sites within the groupings and calculated whether a double mutation was beneficial or detrimental to the HIV’s survival. One of these groups, which the team calls sector 3, had the most detrimental multiple mutations.

Arup Chakraborty, Ph.D., the Robert T. Haslam (1911) Professor at MIT and senior author of a paper on the work explains that structural analysis of Gag revealed that amino acids in sector 3 are involved with making the protective shell of the virus. If multiple mutations are made to these amino acids it would be difficult for the virus to assemble its protein shell.

The Ragon researchers suggest designs for test vaccines based on the vulnerabilities they found in the Gag protein, and are now looking for vulnerable targets in other HIV proteins.

Rafi Ahmed, professor of immunology at the Emory University Vaccine Center, says the paper offers an exciting new approach to designing HIV vaccines as it breaks new ground in terms of vaccine design, and also presents additional protein regions to study for vaccine development.

This paper will be published in Proceedings of the National Academy of Sciences.

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Review Date: 
June 24, 2011