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Cell. 2016 Feb 11;164(4):695-709. doi: 10.1016/j.cell.2015.12.036. Epub 2016 Jan 28.

Actin Dynamics Regulates Dendritic Cell-Mediated Transfer of HIV-1 to T Cells.

Author information

1
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.
2
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.

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.

Comment in

PMID:
26830877
PMCID:
PMC4752894
DOI:
10.1016/j.cell.2015.12.036
[Indexed for MEDLINE]
Free PMC Article

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