Distinct allosteric remodeling of HIV-1 Env dynamics on virions by gp41-directed antibodies reveals two modes of neutralization.

Gp41-directed antibodies neutralize HIV-1 by allosterically stabilizing or opening Env conformations, revealing two distinct modes of neutralization with long-range effects.

• Why it matters: Understanding how different antibodies influence Env dynamics is crucial for designing effective HIV vaccines and therapies, as Env's conformational flexibility aids immune evasion.
• What they did: Using bioorthogonal tagging and single-molecule FRET, the study monitored real-time conformational changes of Env on intact virions, focusing on gp41-targeting broadly neutralizing antibodies.
• The result: Findings show that gp41 antibodies either stabilize the prefusion-closed state or favor open conformations, both modulating Env dynamics allosterically and enabling neutralization through distinct mechanisms.