Nef homodimers down-regulate SERINC5 by AP-2-mediated endocytosis to promote HIV-1 infectivity.

ABSTRACT: SERINC5 is a multipass intrinsic membrane protein that suppresses HIV-1 infectivity when incorporated into budding virions. The HIV-1 Nef virulence factor prevents viral incorporation of SERINC5 by triggering its down-regulation from the producer cell membrane through an AP-2-dependent endolysosomal pathway. However, the mechanistic basis for SERINC5 down-regulation by Nef remains elusive. Here we demonstrate that Nef homodimers are important for SERINC5 down-regulation, trafficking to late endosomes, and exclusion from newly synthesized viral particles. Based on previous X-ray crystal structures, we mutated three conserved residues in the Nef dimer interface (Leu¹¹², Tyr¹¹⁵, and Phe¹²¹) and demonstrated attenuated homodimer formation in a cell-based fluore

SUBMITTER: Staudt RP 

PROVIDER: S-EPMC7667984 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature