Paper Chase

Paper Chase is a research database designed to offer abstracts of research articles published in journals that have a highly rated impact factor as determined by ISI Impact Factor and PageRank. Abstracts are organized by date, with the most recently published papers listed first.

Cell host & microbe
01 09, 2019 25 (1) 73-86.e5
Vol. 25, Issue 1, Medline Page 73-86.e5

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

Authors: Usmani SM, Murooka TT, Deruaz M, Koh WH, Sharaf RR, Di Pilato M, Power KA, Lopez P, Hnatiuk R, Vrbanac VD, Tager AM, Allen TM, Luster AD, Mempel TR
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 female genital transmission. However, the same feature of Nef was subsequently critical for viral persistence in immune-competent hosts. Therefore, a highly conserved activity of lentiviral Nef proteins has dual effects and imposes both fitness costs and benefits on the virus at different stages of infection.