title: Macropinocytosis and cytoskeleton contribute to dendritic cell-mediated HIV-1 transmission to CD4+ T cells.
abstract: Dendritic cells (DCs) are among the first immune cells to encounter HIV-1 at the initial infection. DCs efficiently transfer HIV-1 to CD4+ T cells via infectious or virological synapses formed between DCs and T cells. Retroviruses exploit the cytoskeletal network to facilitate viral infection and dissemination; however, the role of the cytoskeleton in DC-mediated HIV-1 transmission is unknown. Here, we report that intact cytoskeleton is essential for DC-mediated HIV-1 transmission to CD4+ T cells. We found that macropinocytosis of HIV-1 contributes to DC-mediated HIV-1 endocytosis and transmission. Blocking HIV-1 macropinocytosis and disrupting actin or microtubules in DCs with specific inhibitors significantly prevented DC-mediated HIV-1 trans-infection of CD4+ T cells. Altered HIV-1 trafficking and impaired formation of virological synapses primarily accounted for the inhibition of viral transmission by cytoskeletal inhibitors. Our results provide new insights into the mechanisms underlying DC-mediated HIV-1 transmission to CD4+ T cells via the cytoskeletal network.
authors.affiliation: Department of Microbiology and Molecular Genetics, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA.
authors.forename: Jian-Hua
authors.initials: JH
authors.lastname: Wang
authors.forename: Clive
authors.initials: C
authors.lastname: Wells
authors.forename: Li
authors.initials: L
authors.lastname: Wu
mesh_terms: D000199:Actins / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism / Q000821:virology*; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000378:metabolism*; D003713:Dendritic Cells / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure / Q000821:virology*; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology; D015658:HIV Infections / Q000635:transmission* / Q000821:virology; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D015739:Nocodazole / Q000494:pharmacology; D010873:Pinocytosis / Q000502:physiology*; D050257:Tubulin Modulators / Q000494:pharmacology
chemical_list: D000199:Actins; D016166:Free Radical Scavengers; D050257:Tubulin Modulators; D015739:Nocodazole; D004121:Dimethyl Sulfoxide