HIV-1 Balances the Fitness Costs and Benefits of Disrupting the Host Cell Actin Cytoskeleton Early after Mucosal Transmission.

ABSTRACT: HIV-1 primarily infects T lymphocytes and uses these motile cells as migratory vehicles for effective dissemination in the host. Paradoxically, the virus at the same time disrupts multiple cellular processes underlying lymphocyte motility, seemingly counterproductive to rapid systemic infection. Here we show by intravital microscopy in humanized mice that perturbation of the actin cytoskeleton via the lentiviral protein Nef, and not changes to chemokine receptor expression or function, is the dominant cause of dysregulated infected T cell motility in lymphoid tissue by preventing stable cellular polarization required for fast migration. Accordingly, disrupting the Nef hydrophobic patch that facilitates actin cytoskeletal perturbation initially accelerates systemic viral dissemination after

SUBMITTER: Usmani SM 

PROVIDER: S-EPMC6456338 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature