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

Most gp41-directed broadly neutralizing antibodies allosterically stabilize the prefusion-closed Env state, while the bivalent 10E8.4/iMab antibody favors both closed and open states.

• Why it matters: Understanding how gp41-targeting antibodies influence Env dynamics is crucial for developing effective HIV-1 neutralization strategies, as their impact on conformational states affects immune evasion and neutralization mechanisms.
• What they did: Using bioorthogonal tagging and single-molecule FRET, the study monitored real-time conformational changes of Env on intact virions, revealing how different gp41-directed antibodies alter Env populations and kinetics.
• The result: Findings demonstrate two modes of neutralization: fixing Env in the closed state or opening it, both through long-range allosteric control, which advances knowledge of antibody-mediated Env regulation and HIV-1 neutralization.