Cargando…

Snapin promotes HIV‐1 transmission from dendritic cells by dampening TLR8 signaling

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 phosphoprote...

Descripción completa

Detalles Bibliográficos
Autores principales: Khatamzas, Elham, Hipp, Madeleine Maria, Gaughan, Daniel, Pichulik, Tica, Leslie, Alasdair, Fernandes, Ricardo A, Muraro, Daniele, Booth, Sarah, Zausmer, Kieran, Sun, Mei‐Yi, Kessler, Benedikt, Rowland‐Jones, Sarah, Cerundolo, Vincenzo, Simmons, Alison
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5641917/
https://www.ncbi.nlm.nih.gov/pubmed/28923824
http://dx.doi.org/10.15252/embj.201695364
_version_ 1783271285577482240
author Khatamzas, Elham
Hipp, Madeleine Maria
Gaughan, Daniel
Pichulik, Tica
Leslie, Alasdair
Fernandes, Ricardo A
Muraro, Daniele
Booth, Sarah
Zausmer, Kieran
Sun, Mei‐Yi
Kessler, Benedikt
Rowland‐Jones, Sarah
Cerundolo, Vincenzo
Simmons, Alison
author_facet Khatamzas, Elham
Hipp, Madeleine Maria
Gaughan, Daniel
Pichulik, Tica
Leslie, Alasdair
Fernandes, Ricardo A
Muraro, Daniele
Booth, Sarah
Zausmer, Kieran
Sun, Mei‐Yi
Kessler, Benedikt
Rowland‐Jones, Sarah
Cerundolo, Vincenzo
Simmons, Alison
author_sort Khatamzas, Elham
collection PubMed
description 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.
format Online
Article
Text
id pubmed-5641917
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher John Wiley and Sons Inc.
record_format MEDLINE/PubMed
spelling pubmed-56419172017-10-19 Snapin promotes HIV‐1 transmission from dendritic cells by dampening TLR8 signaling Khatamzas, Elham Hipp, Madeleine Maria Gaughan, Daniel Pichulik, Tica Leslie, Alasdair Fernandes, Ricardo A Muraro, Daniele Booth, Sarah Zausmer, Kieran Sun, Mei‐Yi Kessler, Benedikt Rowland‐Jones, Sarah Cerundolo, Vincenzo Simmons, Alison EMBO J Articles 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. John Wiley and Sons Inc. 2017-10-16 2017-10-16 /pmc/articles/PMC5641917/ /pubmed/28923824 http://dx.doi.org/10.15252/embj.201695364 Text en © 2017 The Authors. Published under the terms of the CC BY 4.0 license This is an open access article under the terms of the Creative Commons Attribution 4.0 (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Articles
Khatamzas, Elham
Hipp, Madeleine Maria
Gaughan, Daniel
Pichulik, Tica
Leslie, Alasdair
Fernandes, Ricardo A
Muraro, Daniele
Booth, Sarah
Zausmer, Kieran
Sun, Mei‐Yi
Kessler, Benedikt
Rowland‐Jones, Sarah
Cerundolo, Vincenzo
Simmons, Alison
Snapin promotes HIV‐1 transmission from dendritic cells by dampening TLR8 signaling
title Snapin promotes HIV‐1 transmission from dendritic cells by dampening TLR8 signaling
title_full Snapin promotes HIV‐1 transmission from dendritic cells by dampening TLR8 signaling
title_fullStr Snapin promotes HIV‐1 transmission from dendritic cells by dampening TLR8 signaling
title_full_unstemmed Snapin promotes HIV‐1 transmission from dendritic cells by dampening TLR8 signaling
title_short Snapin promotes HIV‐1 transmission from dendritic cells by dampening TLR8 signaling
title_sort snapin promotes hiv‐1 transmission from dendritic cells by dampening tlr8 signaling
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5641917/
https://www.ncbi.nlm.nih.gov/pubmed/28923824
http://dx.doi.org/10.15252/embj.201695364
work_keys_str_mv AT khatamzaselham snapinpromoteshiv1transmissionfromdendriticcellsbydampeningtlr8signaling
AT hippmadeleinemaria snapinpromoteshiv1transmissionfromdendriticcellsbydampeningtlr8signaling
AT gaughandaniel snapinpromoteshiv1transmissionfromdendriticcellsbydampeningtlr8signaling
AT pichuliktica snapinpromoteshiv1transmissionfromdendriticcellsbydampeningtlr8signaling
AT lesliealasdair snapinpromoteshiv1transmissionfromdendriticcellsbydampeningtlr8signaling
AT fernandesricardoa snapinpromoteshiv1transmissionfromdendriticcellsbydampeningtlr8signaling
AT murarodaniele snapinpromoteshiv1transmissionfromdendriticcellsbydampeningtlr8signaling
AT boothsarah snapinpromoteshiv1transmissionfromdendriticcellsbydampeningtlr8signaling
AT zausmerkieran snapinpromoteshiv1transmissionfromdendriticcellsbydampeningtlr8signaling
AT sunmeiyi snapinpromoteshiv1transmissionfromdendriticcellsbydampeningtlr8signaling
AT kesslerbenedikt snapinpromoteshiv1transmissionfromdendriticcellsbydampeningtlr8signaling
AT rowlandjonessarah snapinpromoteshiv1transmissionfromdendriticcellsbydampeningtlr8signaling
AT cerundolovincenzo snapinpromoteshiv1transmissionfromdendriticcellsbydampeningtlr8signaling
AT simmonsalison snapinpromoteshiv1transmissionfromdendriticcellsbydampeningtlr8signaling