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Interleukin 16 contributes to gammaherpesvirus pathogenesis by inhibiting viral reactivation
Gammaherpesviruses have evolved various strategies to take advantage of host cellular factors or signaling pathways to establish a lifelong latent infection. Like the human gammaherpesvirus Epstein-Barr virus, murine gammaherpesvirus 68 (MHV68) establishes and maintains latency in the memory B cells...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7423151/ https://www.ncbi.nlm.nih.gov/pubmed/32735617 http://dx.doi.org/10.1371/journal.ppat.1008701 |
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author | Liu, Shuai Lei, Zhangmengxue Li, Jie Wang, Liu Jia, Ran Liu, Zhongshun Jiang, Congwei Gao, Ying Liu, Mu Kuang, Linlin Qian, Zhikang Zhou, Dongming Speck, Samuel H. Liang, Xiaozhen |
author_facet | Liu, Shuai Lei, Zhangmengxue Li, Jie Wang, Liu Jia, Ran Liu, Zhongshun Jiang, Congwei Gao, Ying Liu, Mu Kuang, Linlin Qian, Zhikang Zhou, Dongming Speck, Samuel H. Liang, Xiaozhen |
author_sort | Liu, Shuai |
collection | PubMed |
description | Gammaherpesviruses have evolved various strategies to take advantage of host cellular factors or signaling pathways to establish a lifelong latent infection. Like the human gammaherpesvirus Epstein-Barr virus, murine gammaherpesvirus 68 (MHV68) establishes and maintains latency in the memory B cells during infection of laboratory mice. We have previously shown that MHV68 can immortalize fetal liver-derived B cells that induce lymphomas when injected into immunodeficient mice. Here we identify interleukin 16 (IL16) as a most abundantly expressed cytokine in MHV68-immortalized B cells and show that MHV68 infection elevates IL16 expression. IL16 is not important for MHV68 lytic infection but plays a critical role in MHV68 reactivation from latency. IL16 deficiency increases MHV68 lytic gene expression in MHV68-immortalized B cells and enhances reactivation from splenic latency. Correlatively, IL16 deficiency increases the frequency of MHV68-infected plasma cells that can be attributed to enhanced MHV68 reactivation. Furthermore, similar to TPA-mediated lytic replication of Kaposi's sarcoma-associated herpesvirus, IL16 deficiency markedly induces Tyr705 STAT3 de-phosphorylation and elevates p21 expression, which can be counteracted by the tyrosine phosphatase inhibitor orthovanadate. Importantly, orthovanadate strongly blocks MHV68 lytic gene expression mediated by IL16 deficiency. These data demonstrate that virus-induced IL16 does not directly participate in MHV68 lytic replication, but rather inhibits virus reactivation to facilitate latent infection, in part through the STAT3-p21 axis. |
format | Online Article Text |
id | pubmed-7423151 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-74231512020-08-20 Interleukin 16 contributes to gammaherpesvirus pathogenesis by inhibiting viral reactivation Liu, Shuai Lei, Zhangmengxue Li, Jie Wang, Liu Jia, Ran Liu, Zhongshun Jiang, Congwei Gao, Ying Liu, Mu Kuang, Linlin Qian, Zhikang Zhou, Dongming Speck, Samuel H. Liang, Xiaozhen PLoS Pathog Research Article Gammaherpesviruses have evolved various strategies to take advantage of host cellular factors or signaling pathways to establish a lifelong latent infection. Like the human gammaherpesvirus Epstein-Barr virus, murine gammaherpesvirus 68 (MHV68) establishes and maintains latency in the memory B cells during infection of laboratory mice. We have previously shown that MHV68 can immortalize fetal liver-derived B cells that induce lymphomas when injected into immunodeficient mice. Here we identify interleukin 16 (IL16) as a most abundantly expressed cytokine in MHV68-immortalized B cells and show that MHV68 infection elevates IL16 expression. IL16 is not important for MHV68 lytic infection but plays a critical role in MHV68 reactivation from latency. IL16 deficiency increases MHV68 lytic gene expression in MHV68-immortalized B cells and enhances reactivation from splenic latency. Correlatively, IL16 deficiency increases the frequency of MHV68-infected plasma cells that can be attributed to enhanced MHV68 reactivation. Furthermore, similar to TPA-mediated lytic replication of Kaposi's sarcoma-associated herpesvirus, IL16 deficiency markedly induces Tyr705 STAT3 de-phosphorylation and elevates p21 expression, which can be counteracted by the tyrosine phosphatase inhibitor orthovanadate. Importantly, orthovanadate strongly blocks MHV68 lytic gene expression mediated by IL16 deficiency. These data demonstrate that virus-induced IL16 does not directly participate in MHV68 lytic replication, but rather inhibits virus reactivation to facilitate latent infection, in part through the STAT3-p21 axis. Public Library of Science 2020-07-31 /pmc/articles/PMC7423151/ /pubmed/32735617 http://dx.doi.org/10.1371/journal.ppat.1008701 Text en © 2020 Liu 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 Liu, Shuai Lei, Zhangmengxue Li, Jie Wang, Liu Jia, Ran Liu, Zhongshun Jiang, Congwei Gao, Ying Liu, Mu Kuang, Linlin Qian, Zhikang Zhou, Dongming Speck, Samuel H. Liang, Xiaozhen Interleukin 16 contributes to gammaherpesvirus pathogenesis by inhibiting viral reactivation |
title | Interleukin 16 contributes to gammaherpesvirus pathogenesis by inhibiting viral reactivation |
title_full | Interleukin 16 contributes to gammaherpesvirus pathogenesis by inhibiting viral reactivation |
title_fullStr | Interleukin 16 contributes to gammaherpesvirus pathogenesis by inhibiting viral reactivation |
title_full_unstemmed | Interleukin 16 contributes to gammaherpesvirus pathogenesis by inhibiting viral reactivation |
title_short | Interleukin 16 contributes to gammaherpesvirus pathogenesis by inhibiting viral reactivation |
title_sort | interleukin 16 contributes to gammaherpesvirus pathogenesis by inhibiting viral reactivation |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7423151/ https://www.ncbi.nlm.nih.gov/pubmed/32735617 http://dx.doi.org/10.1371/journal.ppat.1008701 |
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