Khatamzas, E;
Hipp, MM;
Gaughan, D;
Pichulik, T;
Leslie, A;
Fernandes, RA;
Muraro, D;
... Simmons, A; + view all
(2017)
Snapin promotes HIV-1 transmission from dendritic cells by dampening TLR8 signaling.
The EMBO Journal
, 36
(20)
pp. 2998-3011.
10.15252/embj.201695364.
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Abstract
HIV-1 traffics through dendritic cells (DCs) 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 (TLR8). Using a phosphoproteomic approach, we identified a robust and diverse signaling cascade triggered by HIV-1 upon entry into human DCs. A secondary siRNA screen of the identified signaling factors revealed several new mediators of HIV-1 trans-infection of CD4+ T cells in DCs, including the dynein motor protein Snapin. Inhibition of Snapin enhanced localization of HIV-1 with TLR8+ early endosomes, triggered a pro-inflammatory response, and inhibited trans-infection of CD4+ T cells. Snapin inhibited TLR8 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 TLR8 in DCs, which is exploited by HIV-1 to promote transmission.
| Type: | Article |
|---|---|
| Title: | Snapin promotes HIV-1 transmission from dendritic cells by dampening TLR8 signaling |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.15252/embj.201695364 |
| Publisher version: | https://doi.org/10.15252/embj.201695364 |
| Language: | English |
| Additional information: | This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
| Keywords: | HIV‐1 and dendritic cells, HIV‐1 transmission, Snapin and vesicular trafficking, TLR8 sensing, CD4-Positive T-Lymphocytes, Cell Line, Dendritic Cells, HIV-1, Host-Pathogen Interactions, Humans, Signal Transduction, Toll-Like Receptor 8, Vesicular Transport Proteins |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10065975 |
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