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Follicular Dendritic Cells Retain Infectious HIV in Cycling Endosomes

Despite the success of antiretroviral therapy (ART), it does not cure Human Immunodeficiency Virus (HIV) and discontinuation results in viral rebound. Follicular dendritic cells (FDC) are in direct contact with CD4+ T cells and they retain intact antigen for prolonged periods. We found that human FD...

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Autores principales: Heesters, Balthasar A., Lindqvist, Madelene, Vagefi, Parsia A., Scully, Eileen P., Schildberg, Frank A., Altfeld, Marcus, Walker, Bruce D., Kaufmann, Daniel E., Carroll, Michael C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4666623/
https://www.ncbi.nlm.nih.gov/pubmed/26623655
http://dx.doi.org/10.1371/journal.ppat.1005285
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author Heesters, Balthasar A.
Lindqvist, Madelene
Vagefi, Parsia A.
Scully, Eileen P.
Schildberg, Frank A.
Altfeld, Marcus
Walker, Bruce D.
Kaufmann, Daniel E.
Carroll, Michael C.
author_facet Heesters, Balthasar A.
Lindqvist, Madelene
Vagefi, Parsia A.
Scully, Eileen P.
Schildberg, Frank A.
Altfeld, Marcus
Walker, Bruce D.
Kaufmann, Daniel E.
Carroll, Michael C.
author_sort Heesters, Balthasar A.
collection PubMed
description Despite the success of antiretroviral therapy (ART), it does not cure Human Immunodeficiency Virus (HIV) and discontinuation results in viral rebound. Follicular dendritic cells (FDC) are in direct contact with CD4+ T cells and they retain intact antigen for prolonged periods. We found that human FDC isolated from patients on ART retain infectious HIV within a non-degradative cycling compartment and transmit infectious virus to uninfected CD4 T cells in vitro. Importantly, treatment of the HIV+ FDC with a soluble complement receptor 2 purges the FDC of HIV virions and prevents viral transmission in vitro. Our results provide an explanation for how FDC can retain infectious HIV for extended periods and suggest a therapeutic strategy to achieve cure in HIV-infected humans.
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spelling pubmed-46666232015-12-10 Follicular Dendritic Cells Retain Infectious HIV in Cycling Endosomes Heesters, Balthasar A. Lindqvist, Madelene Vagefi, Parsia A. Scully, Eileen P. Schildberg, Frank A. Altfeld, Marcus Walker, Bruce D. Kaufmann, Daniel E. Carroll, Michael C. PLoS Pathog Research Article Despite the success of antiretroviral therapy (ART), it does not cure Human Immunodeficiency Virus (HIV) and discontinuation results in viral rebound. Follicular dendritic cells (FDC) are in direct contact with CD4+ T cells and they retain intact antigen for prolonged periods. We found that human FDC isolated from patients on ART retain infectious HIV within a non-degradative cycling compartment and transmit infectious virus to uninfected CD4 T cells in vitro. Importantly, treatment of the HIV+ FDC with a soluble complement receptor 2 purges the FDC of HIV virions and prevents viral transmission in vitro. Our results provide an explanation for how FDC can retain infectious HIV for extended periods and suggest a therapeutic strategy to achieve cure in HIV-infected humans. Public Library of Science 2015-12-01 /pmc/articles/PMC4666623/ /pubmed/26623655 http://dx.doi.org/10.1371/journal.ppat.1005285 Text en © 2015 Heesters 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, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Heesters, Balthasar A.
Lindqvist, Madelene
Vagefi, Parsia A.
Scully, Eileen P.
Schildberg, Frank A.
Altfeld, Marcus
Walker, Bruce D.
Kaufmann, Daniel E.
Carroll, Michael C.
Follicular Dendritic Cells Retain Infectious HIV in Cycling Endosomes
title Follicular Dendritic Cells Retain Infectious HIV in Cycling Endosomes
title_full Follicular Dendritic Cells Retain Infectious HIV in Cycling Endosomes
title_fullStr Follicular Dendritic Cells Retain Infectious HIV in Cycling Endosomes
title_full_unstemmed Follicular Dendritic Cells Retain Infectious HIV in Cycling Endosomes
title_short Follicular Dendritic Cells Retain Infectious HIV in Cycling Endosomes
title_sort follicular dendritic cells retain infectious hiv in cycling endosomes
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4666623/
https://www.ncbi.nlm.nih.gov/pubmed/26623655
http://dx.doi.org/10.1371/journal.ppat.1005285
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