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Chlamydia trachomatis Infection of Endocervical Epithelial Cells Enhances Early HIV Transmission Events

Chlamydia trachomatis causes a predominantly asymptomatic, but generally inflammatory, genital infection that is associated with an increased risk for HIV acquisition. Endocervical epithelial cells provide the major niche for this obligate intracellular bacterium in women, and the endocervix is also...

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Autores principales: Buckner, Lyndsey R., Amedee, Angela M., Albritton, Hannah L., Kozlowski, Pamela A., Lacour, Nedra, McGowin, Chris L., Schust, Danny J., Quayle, Alison J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4701475/
https://www.ncbi.nlm.nih.gov/pubmed/26730599
http://dx.doi.org/10.1371/journal.pone.0146663
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author Buckner, Lyndsey R.
Amedee, Angela M.
Albritton, Hannah L.
Kozlowski, Pamela A.
Lacour, Nedra
McGowin, Chris L.
Schust, Danny J.
Quayle, Alison J.
author_facet Buckner, Lyndsey R.
Amedee, Angela M.
Albritton, Hannah L.
Kozlowski, Pamela A.
Lacour, Nedra
McGowin, Chris L.
Schust, Danny J.
Quayle, Alison J.
author_sort Buckner, Lyndsey R.
collection PubMed
description Chlamydia trachomatis causes a predominantly asymptomatic, but generally inflammatory, genital infection that is associated with an increased risk for HIV acquisition. Endocervical epithelial cells provide the major niche for this obligate intracellular bacterium in women, and the endocervix is also a tissue in which HIV transmission can occur. The mechanism by which CT infection enhances HIV susceptibility at this site, however, is not well understood. Utilizing the A2EN immortalized endocervical epithelial cell line grown on cell culture inserts, we evaluated the direct role that CT-infected epithelial cells play in facilitating HIV transmission events. We determined that CT infection significantly enhanced the apical-to-basolateral migration of cell-associated, but not cell-free, HIV(BaL), a CCR5-tropic strain of virus, across the endocervical epithelial barrier. We also established that basolateral supernatants from CT-infected A2EN cells significantly enhanced HIV replication in peripheral mononuclear cells and a CCR5+ T cell line. These results suggest that CT infection of endocervical epithelial cells could facilitate both HIV crossing the mucosal barrier and subsequent infection or replication in underlying target cells. Our studies provide a mechanism by which this common STI could potentially promote the establishment of founder virus populations and the maintenance of local HIV reservoirs in the endocervix. Development of an HIV/STI co-infection model also provides a tool to further explore the role of other sexually transmitted infections in enhancing HIV acquisition.
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spelling pubmed-47014752016-01-15 Chlamydia trachomatis Infection of Endocervical Epithelial Cells Enhances Early HIV Transmission Events Buckner, Lyndsey R. Amedee, Angela M. Albritton, Hannah L. Kozlowski, Pamela A. Lacour, Nedra McGowin, Chris L. Schust, Danny J. Quayle, Alison J. PLoS One Research Article Chlamydia trachomatis causes a predominantly asymptomatic, but generally inflammatory, genital infection that is associated with an increased risk for HIV acquisition. Endocervical epithelial cells provide the major niche for this obligate intracellular bacterium in women, and the endocervix is also a tissue in which HIV transmission can occur. The mechanism by which CT infection enhances HIV susceptibility at this site, however, is not well understood. Utilizing the A2EN immortalized endocervical epithelial cell line grown on cell culture inserts, we evaluated the direct role that CT-infected epithelial cells play in facilitating HIV transmission events. We determined that CT infection significantly enhanced the apical-to-basolateral migration of cell-associated, but not cell-free, HIV(BaL), a CCR5-tropic strain of virus, across the endocervical epithelial barrier. We also established that basolateral supernatants from CT-infected A2EN cells significantly enhanced HIV replication in peripheral mononuclear cells and a CCR5+ T cell line. These results suggest that CT infection of endocervical epithelial cells could facilitate both HIV crossing the mucosal barrier and subsequent infection or replication in underlying target cells. Our studies provide a mechanism by which this common STI could potentially promote the establishment of founder virus populations and the maintenance of local HIV reservoirs in the endocervix. Development of an HIV/STI co-infection model also provides a tool to further explore the role of other sexually transmitted infections in enhancing HIV acquisition. Public Library of Science 2016-01-05 /pmc/articles/PMC4701475/ /pubmed/26730599 http://dx.doi.org/10.1371/journal.pone.0146663 Text en © 2016 Buckner et al http://creativecommons.org/licenses/by/4.0/ 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 author and source are credited.
spellingShingle Research Article
Buckner, Lyndsey R.
Amedee, Angela M.
Albritton, Hannah L.
Kozlowski, Pamela A.
Lacour, Nedra
McGowin, Chris L.
Schust, Danny J.
Quayle, Alison J.
Chlamydia trachomatis Infection of Endocervical Epithelial Cells Enhances Early HIV Transmission Events
title Chlamydia trachomatis Infection of Endocervical Epithelial Cells Enhances Early HIV Transmission Events
title_full Chlamydia trachomatis Infection of Endocervical Epithelial Cells Enhances Early HIV Transmission Events
title_fullStr Chlamydia trachomatis Infection of Endocervical Epithelial Cells Enhances Early HIV Transmission Events
title_full_unstemmed Chlamydia trachomatis Infection of Endocervical Epithelial Cells Enhances Early HIV Transmission Events
title_short Chlamydia trachomatis Infection of Endocervical Epithelial Cells Enhances Early HIV Transmission Events
title_sort chlamydia trachomatis infection of endocervical epithelial cells enhances early hiv transmission events
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4701475/
https://www.ncbi.nlm.nih.gov/pubmed/26730599
http://dx.doi.org/10.1371/journal.pone.0146663
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