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Scientists capture most detailed picture yet of key AIDS protein
Date:10/31/2013

of two imaging methods, X-ray crystallography and electron microscopy. The X-ray crystallography study was the first ever of an Env trimer, and both methods resolved the trimer structure to a finer level of detail than has been reported before.

"The new data are consistent with the findings on Env subunits over the last 15 years, but also have enabled us to explain many prior observations about HIV in structural terms for the first time," said Dr. Jean-Philippe Julien, a senior research associate in the Wilson laboratory at TSRI, who was first author of the X-ray crystallography study.

The data illuminated the complex process by which the Env trimer assembles and later undergoes radical shape changes during infection and clarified how it compares to envelope proteins on other dangerous viruses, such as flu and Ebola.

Arguably the most important implications of the new findings are for HIV vaccine design. In both of the new studies, Env trimers were imaged while bound to broadly neutralizing antibodies against HIV. Such antibodies, isolated from naturally infected patients, are the very rare ones that somehow bind to Env in a way that blocks the infectivity of a high proportion of HIV strains.

Ideally an HIV vaccine would elicit large numbers of such antibodies from patients, and to achieve that, vaccine designers would like to know the precise structural details of the sites where these antibodies bind to the virus--so that they can mimic those viral "epitopes" with the vaccine.

"It's been a privilege for us to work with the Scripps' team on this project," said Dr. Moore, a professor of microbiology and immunology at Weill Cornell. "Now we all need to harness this new knowledge to design and test next-generation trimers and see if we can induce the broadly active neutralizing antibodies that an effective vaccine is going to need."

"One surprise from this study was the revelation of the complexity and the relati
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Contact: Sarah Smith
sas2072@med.cornell.edu
646-317-7401
Weill Cornell Medical College
Source:Eurekalert

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