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Caveolin-1 mediated uptake via langerin restricts HIV-1 infection in human Langerhans cells

BACKGROUND: Human Langerhans cells (LCs) reside in foreskin and vaginal mucosa and are the first immune cells to interact with HIV-1 during sexual transmission. LCs capture HIV-1 through the C-type lectin receptor langerin, which routes the virus into Birbeck granules (BGs), thereby preventing HIV-1...

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Autores principales: van den Berg, Linda M, Ribeiro, Carla M S, Zijlstra-Willems, Esther M, de Witte, Lot, Fluitsma, Donna, Tigchelaar, Wikky, Everts, Vincent, Geijtenbeek, Teunis B H
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4301922/
https://www.ncbi.nlm.nih.gov/pubmed/25551286
http://dx.doi.org/10.1186/s12977-014-0123-7
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author van den Berg, Linda M
Ribeiro, Carla M S
Zijlstra-Willems, Esther M
de Witte, Lot
Fluitsma, Donna
Tigchelaar, Wikky
Everts, Vincent
Geijtenbeek, Teunis B H
author_facet van den Berg, Linda M
Ribeiro, Carla M S
Zijlstra-Willems, Esther M
de Witte, Lot
Fluitsma, Donna
Tigchelaar, Wikky
Everts, Vincent
Geijtenbeek, Teunis B H
author_sort van den Berg, Linda M
collection PubMed
description BACKGROUND: Human Langerhans cells (LCs) reside in foreskin and vaginal mucosa and are the first immune cells to interact with HIV-1 during sexual transmission. LCs capture HIV-1 through the C-type lectin receptor langerin, which routes the virus into Birbeck granules (BGs), thereby preventing HIV-1 infection. BGs are langerin-positive organelles exclusively present in LCs, however, their origin and function are unknown. RESULTS: Here, we not only show that langerin and caveolin-1 co-localize at the cell membrane and in vesicles but also that BGs are langerin/caveolin-1-positive vesicles are linked to the lysosomal degradation pathway in LCs. Moreover, inhibition of caveolar endocytosis in primary LCs abrogated HIV-1 sequestering into langerin(+) caveolar structures. Notably, both inhibition of caveolar uptake and silencing of caveolar structure protein caveolin-1 resulted in increased HIV-1 integration and subsequent infection. In contrast, inhibition of clathrin-mediated endocytosis did not affect HIV-1 integration, even though HIV-1 uptake was decreased, suggesting that clathrin-mediated endocytosis is not involved in HIV-1 restriction in LCs. CONCLUSIONS: Thus, our data strongly indicate that BGs belong to the caveolar endocytosis pathway and that caveolin-1 mediated HIV-1 uptake is an intrinsic restriction mechanism present in human LCs that prevents HIV-1 infection. Harnessing this particular internalization pathway has the potential to facilitate strategies to combat HIV-1 transmission. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12977-014-0123-7) contains supplementary material, which is available to authorized users.
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spelling pubmed-43019222015-01-22 Caveolin-1 mediated uptake via langerin restricts HIV-1 infection in human Langerhans cells van den Berg, Linda M Ribeiro, Carla M S Zijlstra-Willems, Esther M de Witte, Lot Fluitsma, Donna Tigchelaar, Wikky Everts, Vincent Geijtenbeek, Teunis B H Retrovirology Research BACKGROUND: Human Langerhans cells (LCs) reside in foreskin and vaginal mucosa and are the first immune cells to interact with HIV-1 during sexual transmission. LCs capture HIV-1 through the C-type lectin receptor langerin, which routes the virus into Birbeck granules (BGs), thereby preventing HIV-1 infection. BGs are langerin-positive organelles exclusively present in LCs, however, their origin and function are unknown. RESULTS: Here, we not only show that langerin and caveolin-1 co-localize at the cell membrane and in vesicles but also that BGs are langerin/caveolin-1-positive vesicles are linked to the lysosomal degradation pathway in LCs. Moreover, inhibition of caveolar endocytosis in primary LCs abrogated HIV-1 sequestering into langerin(+) caveolar structures. Notably, both inhibition of caveolar uptake and silencing of caveolar structure protein caveolin-1 resulted in increased HIV-1 integration and subsequent infection. In contrast, inhibition of clathrin-mediated endocytosis did not affect HIV-1 integration, even though HIV-1 uptake was decreased, suggesting that clathrin-mediated endocytosis is not involved in HIV-1 restriction in LCs. CONCLUSIONS: Thus, our data strongly indicate that BGs belong to the caveolar endocytosis pathway and that caveolin-1 mediated HIV-1 uptake is an intrinsic restriction mechanism present in human LCs that prevents HIV-1 infection. Harnessing this particular internalization pathway has the potential to facilitate strategies to combat HIV-1 transmission. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12977-014-0123-7) contains supplementary material, which is available to authorized users. BioMed Central 2014-12-31 /pmc/articles/PMC4301922/ /pubmed/25551286 http://dx.doi.org/10.1186/s12977-014-0123-7 Text en © van den Berg et al.; licensee BioMed Central. 2014 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
van den Berg, Linda M
Ribeiro, Carla M S
Zijlstra-Willems, Esther M
de Witte, Lot
Fluitsma, Donna
Tigchelaar, Wikky
Everts, Vincent
Geijtenbeek, Teunis B H
Caveolin-1 mediated uptake via langerin restricts HIV-1 infection in human Langerhans cells
title Caveolin-1 mediated uptake via langerin restricts HIV-1 infection in human Langerhans cells
title_full Caveolin-1 mediated uptake via langerin restricts HIV-1 infection in human Langerhans cells
title_fullStr Caveolin-1 mediated uptake via langerin restricts HIV-1 infection in human Langerhans cells
title_full_unstemmed Caveolin-1 mediated uptake via langerin restricts HIV-1 infection in human Langerhans cells
title_short Caveolin-1 mediated uptake via langerin restricts HIV-1 infection in human Langerhans cells
title_sort caveolin-1 mediated uptake via langerin restricts hiv-1 infection in human langerhans cells
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4301922/
https://www.ncbi.nlm.nih.gov/pubmed/25551286
http://dx.doi.org/10.1186/s12977-014-0123-7
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