Year: 2023
Type: article
Abstract: Human immunodeficiency virus 1 (HIV-1) infection is initiated by binding of the viral envelope glycoprotein (Env) to the cell-surface receptor CD4. Although high resolution structures of Env complexed with soluble domains of CD4 have been determined, the binding process is less understood on native membranes. Here, we apply cryo-electron tomography (cryo-ET) to monitor Env-CD4 interactions at membrane-membrane interfaces formed between HIV-1 and CD4-presenting virus-like particles. Env-CD4 complexes organized into clusters and rings, bringing opposing membranes closer together. Additionally, Env-CD4 clustering was dependent on capsid maturation. Subtomogram averaging and classification revealed that Env bound one, two, and finally three CD4 molecules, upon which Env adopted a partially open state. Our data indicate that asymmetric HIV-1 Env trimers bound to one and two CD4 molecules are detectable intermediates during virus binding to host cell membranes, which likely has consequences for antibody-mediated immune responses and vaccine immunogen design.
Source: Nature
Language: English
Topic: HIV Research and Treatment
Subfield: Virology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $11,690
Awards: G1059067488, G1234541941, G2289013418, G2412820185, G4509529604, G4689185066, G5202512869, G6012682559, G8422249695, HIV-1 vaccine design emphasizing bnAb targets on membrane Env liposomes, G8882569155, G9000022018, G9000069516, G9000166470, G9000205106, HIV-1 Env protein structure and function assessed by parallel smFRET and cryoET, Yale Clinical and Translational Science Award, CHEETAH Center for the Structural Biology of HIV Infection, Restriction, and Viral Dynamics
OpenAlex ID: W4388897375