Key HIV protein structure revealed

Env structure engineered by the Scripps/Cornell team (click to enlarge)--Courtesy of Wilson Lab, The Scripps Research Institute

Scientists have unraveled one of the mysteries of HIV--they've mapped out the structure of an envelope protein that allows the virus to get into human cells to cause infection.

A team of researchers at the California campus of The Scripps Research Institute along with collaborators at the Weill Medical College of Cornell University say the breakthrough--which could provide the groundwork for developing an effective vaccine against HIV/AIDS--has been a dozen years in the making.

Their new findings, detailed in two studies published Oct. 31 in the journal Science Express, provide the most detailed picture yet of the virus' complex protein envelope--known to virologists as 'Env'--including sites that could be imitated by future vaccines to induce a protective immune response in the body. Previous studies have focused on individual subunits of this envelope complex, but the scientists say this is the first time the whole structure has been engineered.

"What we think we have now is a stable scaffold for doing rational based vaccine design," Andrew Ward, one of the investigators and an assistant professor in Scripps' Department of Integrative Structural and Computational Biology, said in an interview with FierceBiotechResearch.

HIV is currently managed by antiretroviral therapeutics, but scientists agree that a vaccine to prevent the disease would be ideal. But an effective vaccine has so far evaded discovery despite many ongoing efforts. One of the biggest challenges to developing a vaccine, Scripps scientists say, was that the structure of HIV's envelope protein up until now has not been understood.

Env's structure is complex and delicate, and scientists have so far been unsuccessful at obtaining the protein in a form suitable for atomic-resolution imaging. Ward said the protein is not very stable, and it took the team 12 years to engineer a copycat Env trimer--a three-component structure--that can be studied.

Using electron microscopy and X-ray crystallography imaging methods, the Scripps/Cornell team was able to observe the new Env trimer at a greater level of detail than has been previously reported.

Ward said that while an HIV/AIDS vaccine is still a long way off, his team is next aiming to apply what they now know about the HIV envelope protein to test the target in animals.

"We have a structure now but don't have any idea of what a response in animals or humans will be," Ward said.

- read the press release
- and see the study abstracts here and here

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