Enhancement of CD4 Binding, Host Cell Entry, and Sensitivity to CD4bs Antibody Inhibition Conferred by a Natural but Rare Polymorphism in the HIV-1 Envelope.

ABSTRACT: A rare but natural polymorphism in the HIV-1 envelope (Env) glycoprotein, lysine at position 425 was selected as a mutation conferring resistance to maraviroc (MVC) in vitro. N425K has not been identified in HIV-infected individuals failing an MVC-based treatment. This study reports that the rare K425 polymorphism in an HIV-1 subtype A Env has increased affinity for CD4, resulting in faster host cell entry kinetics and the ability to scavenge for low cell surface expression of CD4 to mediate entry. Whereas the subtype A wild-type isolate-74 Env (N425) is inhibited by soluble (s) CD4, HIV-1 with K425 A74 Env shows enhanced infection and the ability to infect CCR5+ cells when pretreated with sCD4. Upon adding K425 or N425 HIV-1 to CD4⁺/CCR5+ cells along with RANTES/CCL3, on

SUBMITTER: Ratcliff AN 

PROVIDER: S-EPMC9327689 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature