Run time: 17m

To view this video content in its entirety, click on the "Access Content" button and login to your account.

If you do not have an account, register for free.

Please note that the account you create here is different than your Keystone Symposia account at www.keystonesymposia.org used to register for our multi-day conferences and is uniquely for viewing our virtual content.


On Demand

Deciphering the molecular basis of unusually high neutralization resistance in a tier 3 HIV-1 strain

Free

Description

Deciphering the molecular basis of unusually high neutralization resistance in a tier 3 HIV-1 strain

Understanding the mechanisms used by HIV-1 to evade antibody neutralization may contribute to the design of a high-coverage vaccine. The tier 3 (highly neutralization-resistant) virus, 253-11, is poorly recognized by subtype-matched and subtype C sera, even when compared to other tier 3 viruses, and is also recognized poorly by V3/glycan targeting monoclonal antibodies. We found that sequence polymorphism in the V3 loop and N-linked glycosylation sites only marginally contribute to the high neutralization resistance of 253-11. Interestingly, the 253-11 membrane proximal external region (MPER) is rarely recognized by sera in the context of the wild-type virus, but is commonly recognized in the context of an HIV-2 chimeric virus. Mutations in the 253-11 MPER – which were previously reported to increase the lifetime of the pre-fusion Envelope (Env) conformation –affected the resistance of 253-11 to antibodies targeting various epitopes on HIV-1 Env and destabilized its otherwise stable, closed trimer structure. To gain insight into the structure of 253-11, we constructed and crystallized a recombinant 253-11 SOSIP trimer, the first crystal structure of a tier 3 SOSIP trimer from chronic infection. The resulting structure revealed that the heptad repeat helices in gp41 are drawn closer to the trimer axis and that gp120 protomers also showed a relatively compact disposition around the trimer axis. These observations give substantial insight into the structure of an envelope spike from a tier 3 virus and into possible mechanisms that may contribute to its unusually high neutralization resistance.



This Keystone Symposia SciTalk was made possible by a collaboration with

custom image


Speaker(s):

Tags: HIV SciTalk

You must be logged in and own this session in order to post comments.