title: Actin Dynamics Regulates Dendritic Cell-Mediated Transfer of HIV-1 to T Cells.
abstract: Whereas human dendritic cells (DCs) are largely resistant to productive infection with HIV-1, they have a unique ability to take up the virus and transmit it efficiently to T lymphocytes through a process of trans-infection or trans-enhancement. To elucidate the molecular and cell biological mechanism for trans-enhancement, we performed an shRNA screen of several hundred genes involved in organelle and membrane trafficking in immature human monocyte-derived dendritic cells (MDDCs). We identified TSPAN7 and DNM2, which control actin nucleation and stabilization, as having important and distinct roles in limiting HIV-1 endocytosis and in maintaining virus particles on dendrites, which is required for efficient transfer to T lymphocytes. Further characterization of this process may provide insights not only into the role of DCs in transmission and dissemination of HIV-1 but also more broadly into mechanisms controlling capture and internalization of pathogens.
authors.affiliation: Molecular Pathogenesis Program, The Kimmel Center for Biology and Medicine of the Skirball Institute, New York University School of Medicine, New York, NY 10016, USA. Electronic address: mickael.menager@med.nyu.edu.
authors.forename: Mickaël M
authors.initials: MM
authors.lastname: Ménager
authors.affiliation: Molecular Pathogenesis Program, The Kimmel Center for Biology and Medicine of the Skirball Institute, New York University School of Medicine, New York, NY 10016, USA; Howard Hughes Medical Institute. Electronic address: dan.littman@med.nyu.edu.
authors.forename: Dan R
authors.initials: DR
authors.lastname: Littman
mesh_terms: D051376:Actin-Related Protein 2-3 Complex / Q000378:metabolism; D000199:Actins / Q000378:metabolism*; D000205:Actomyosin / Q000378:metabolism; D003599:Cytoskeleton / Q000187:drug effects; D003713:Dendritic Cells / Q000276:immunology* / Q000821:virology; D034285:Dynamin II; D034281:Dynamins / Q000378:metabolism; D004705:Endocytosis; D055785:Gene Knockdown Techniques; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D054992:Immunological Synapses; D009000:Monocytes / Q000276:immunology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000821:virology; D059470:Tetraspanins / Q000378:metabolism
chemical_list: D051376:Actin-Related Protein 2-3 Complex; D000199:Actins; D009419:Nerve Tissue Proteins; C404405:TSPAN7 protein, human; D059470:Tetraspanins; D000205:Actomyosin; C000593490:DNM2 protein, human; D034285:Dynamin II; D034281:Dynamins
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