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A Common Path to Innate Immunity to HIV-1 Induced by Toll-Like Receptor Ligands in Primary Human Macrophages
Toll-like receptors (TLR) represent the best characterized receptor family transducing innate immune responses, the first line of defense against microbial invaders. This study was designed to investigate whether responses through TLR inhibit HIV-1 replication in its primary target cells. Primary hu...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2011
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3164183/ https://www.ncbi.nlm.nih.gov/pubmed/21904615 http://dx.doi.org/10.1371/journal.pone.0024193 |
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author | Wang, Xingyu Chao, Wei Saini, Manisha Potash, Mary Jane |
author_facet | Wang, Xingyu Chao, Wei Saini, Manisha Potash, Mary Jane |
author_sort | Wang, Xingyu |
collection | PubMed |
description | Toll-like receptors (TLR) represent the best characterized receptor family transducing innate immune responses, the first line of defense against microbial invaders. This study was designed to investigate whether responses through TLR inhibit HIV-1 replication in its primary target cells. Primary human macrophages and lymphocytes from several different donors and HIV-1 infection in tissue culture were used exclusively in this work. We report that ligands of three different TLR: LPS, R848, and double stranded RNA, induce a common antiviral response in macrophages as assayed by measurement of HIV-1 p24 protein, gag DNA, and entry into cells. HIV-1 infection is arrested after efficient entry but prior to reverse transcription. TLR-ligand activated cells secrete antiviral factors that induce a similar restriction. HIV-1 infection of lymphocytes is not affected by exposure to TLR ligands or to antiviral factors secreted by activated macrophages. TBK1, but neither NF-κB nor JAK-STAT activity, is required in macrophages to mount this antiviral response; the combination of p38 MAPK and JNK are partially required for induction of antiviral activity. Based on transcriptional induction and inhibition, the TLR-linked antiviral activity is different from APOBEC3 A or G, interferon-β, NAMPT, or p21(Cip1). The cell-type specificity, site of action, and requirement for signaling intermediates suggest that the TLR-linked antiviral activity is novel. |
format | Online Article Text |
id | pubmed-3164183 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-31641832011-09-08 A Common Path to Innate Immunity to HIV-1 Induced by Toll-Like Receptor Ligands in Primary Human Macrophages Wang, Xingyu Chao, Wei Saini, Manisha Potash, Mary Jane PLoS One Research Article Toll-like receptors (TLR) represent the best characterized receptor family transducing innate immune responses, the first line of defense against microbial invaders. This study was designed to investigate whether responses through TLR inhibit HIV-1 replication in its primary target cells. Primary human macrophages and lymphocytes from several different donors and HIV-1 infection in tissue culture were used exclusively in this work. We report that ligands of three different TLR: LPS, R848, and double stranded RNA, induce a common antiviral response in macrophages as assayed by measurement of HIV-1 p24 protein, gag DNA, and entry into cells. HIV-1 infection is arrested after efficient entry but prior to reverse transcription. TLR-ligand activated cells secrete antiviral factors that induce a similar restriction. HIV-1 infection of lymphocytes is not affected by exposure to TLR ligands or to antiviral factors secreted by activated macrophages. TBK1, but neither NF-κB nor JAK-STAT activity, is required in macrophages to mount this antiviral response; the combination of p38 MAPK and JNK are partially required for induction of antiviral activity. Based on transcriptional induction and inhibition, the TLR-linked antiviral activity is different from APOBEC3 A or G, interferon-β, NAMPT, or p21(Cip1). The cell-type specificity, site of action, and requirement for signaling intermediates suggest that the TLR-linked antiviral activity is novel. Public Library of Science 2011-08-31 /pmc/articles/PMC3164183/ /pubmed/21904615 http://dx.doi.org/10.1371/journal.pone.0024193 Text en Wang 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 Wang, Xingyu Chao, Wei Saini, Manisha Potash, Mary Jane A Common Path to Innate Immunity to HIV-1 Induced by Toll-Like Receptor Ligands in Primary Human Macrophages |
title | A Common Path to Innate Immunity to HIV-1 Induced by Toll-Like Receptor Ligands in Primary Human Macrophages |
title_full | A Common Path to Innate Immunity to HIV-1 Induced by Toll-Like Receptor Ligands in Primary Human Macrophages |
title_fullStr | A Common Path to Innate Immunity to HIV-1 Induced by Toll-Like Receptor Ligands in Primary Human Macrophages |
title_full_unstemmed | A Common Path to Innate Immunity to HIV-1 Induced by Toll-Like Receptor Ligands in Primary Human Macrophages |
title_short | A Common Path to Innate Immunity to HIV-1 Induced by Toll-Like Receptor Ligands in Primary Human Macrophages |
title_sort | common path to innate immunity to hiv-1 induced by toll-like receptor ligands in primary human macrophages |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3164183/ https://www.ncbi.nlm.nih.gov/pubmed/21904615 http://dx.doi.org/10.1371/journal.pone.0024193 |
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