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Snapin promotes HIV ‐1 transmission from dendritic cells by dampening TLR 8 signaling
Author(s) -
Khatamzas Elham,
Hipp Madeleine Maria,
Gaughan Daniel,
Pichulik Tica,
Leslie Alasdair,
Fernandes Ricardo A,
Muraro Daniele,
Booth Sarah,
Zausmer Kieran,
Sun MeiYi,
Kessler Benedikt,
RowlandJones Sarah,
Cerundolo Vincenzo,
Simmons Alison
Publication year - 2017
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201695364
Subject(s) - endosome , microbiology and biotechnology , innate immune system , biology , immune system , signal transduction , immunology , receptor , dendritic cell , genetics , intracellular
HIV ‐1 traffics through dendritic cells ( DC s) en route to establishing a productive infection in T lymphocytes but fails to induce an innate immune response. Within DC endosomes, HIV ‐1 somehow evades detection by the pattern‐recognition receptor ( PRR ) Toll‐like receptor 8 ( TLR 8). Using a phosphoproteomic approach, we identified a robust and diverse signaling cascade triggered by HIV ‐1 upon entry into human DC s. A secondary si RNA screen of the identified signaling factors revealed several new mediators of HIV ‐1 trans ‐infection of CD 4 + T cells in DC s, including the dynein motor protein Snapin. Inhibition of Snapin enhanced localization of HIV ‐1 with TLR 8 + early endosomes, triggered a pro‐inflammatory response, and inhibited trans ‐infection of CD 4 + T cells. Snapin inhibited TLR 8 signaling in the absence of HIV ‐1 and is a general regulator of endosomal maturation. Thus, we identify a new mechanism of innate immune sensing by TLR 8 in DC s, which is exploited by HIV ‐1 to promote transmission.