Dendritic cells (DCs) have essential roles in early detection of pathogens and activation of both innate and adaptive immune responses. Whereas human DCs are resistant to productive HIV-1 replication, they have a unique ability to take up virus and transmit it efficiently to T lymphocytes. By doing that, HIV-1 may evade, at least in part, the first line of defense of the immune system, exploiting DCs instead to facilitate rapid infection of a large pool of immune cells. While performing an shRNA screen in human primary monocyte-derived DCs, to gain insights into this cell biological process, we discovered the role played by tetraspanin-7 (TSPAN7). This member of the tetraspanin family appears to be a positive regulator of actin nucleation and stabilization, through the ARP2/3 complex. By doing so, TSPAN7 limits HIV-1 endocytosis and maintains viral particles on actin-rich dendrites for an efficient transfer toward T lymphocytes. While studying the function of TSPAN7 in the control of actin nucleation, we also discovered the existence in DCs of two opposing forces at the plasma membrane: actin nucleation, a protrusive force which seems to counterbalance actomyosin contraction.
Review Article| June 15 2017
TSPAN7, effector of actin nucleation required for dendritic cell-mediated transfer of HIV-1 to T cells
Mickaël M. Ménager
Mickaël M. Ménager *
1Molecular Pathogenesis Program, The Kimmel Center for Biology and Medicine of the Skirball Institute, New York University School of Medicine, New York, NY, U.S.A.
Correspondence: Mickaël M. Ménager (email@example.com)
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Mickaël M. Ménager; TSPAN7, effector of actin nucleation required for dendritic cell-mediated transfer of HIV-1 to T cells. Biochem Soc Trans 15 June 2017; 45 (3): 703–708. doi: https://doi.org/10.1042/BST20160439
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