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PPM1G restricts innate immune signaling mediated by STING and MAVS and is hijacked by KSHV for immune evasion
The adaptor proteins, STING and MAVS, are components of critical pathogen-sensing pathways that induce innate immunity. Phosphorylation of either adaptor results in activation of the type I interferon pathway. How this phosphorylation is regulated and how it is manipulated by pathogens remain largel...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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American Association for the Advancement of Science
2020
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7679160/ https://www.ncbi.nlm.nih.gov/pubmed/33219031 http://dx.doi.org/10.1126/sciadv.abd0276 |
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author | Yu, Kuai Tian, Huabin Deng, Hongyu |
author_facet | Yu, Kuai Tian, Huabin Deng, Hongyu |
author_sort | Yu, Kuai |
collection | PubMed |
description | The adaptor proteins, STING and MAVS, are components of critical pathogen-sensing pathways that induce innate immunity. Phosphorylation of either adaptor results in activation of the type I interferon pathway. How this phosphorylation is regulated and how it is manipulated by pathogens remain largely unknown. Here, we identified host protein phosphatase, Mg(2+)/Mn(2+) dependent 1G (PPM1G) as a negative regulator of innate immune pathways and showed that this host system is hijacked by Kaposi’s sarcoma-associated herpesvirus (KSHV). Mechanistically, KSHV tegument protein ORF33 interacts with STING/MAVS and enhances recruitment of PPM1G to dephosphorylate p-STING/p-MAVS for immunosuppression. Inhibition of PPM1G expression improves the antiviral response against both DNA and RNA viruses. Collectively, our study shows that PPM1G restricts both cytosolic DNA– and RNA–sensing pathways to naturally balance the intensity of the antiviral response. Manipulation of PPM1G by KSHV provides an important strategy for immune evasion. |
format | Online Article Text |
id | pubmed-7679160 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | American Association for the Advancement of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-76791602020-11-25 PPM1G restricts innate immune signaling mediated by STING and MAVS and is hijacked by KSHV for immune evasion Yu, Kuai Tian, Huabin Deng, Hongyu Sci Adv Research Articles The adaptor proteins, STING and MAVS, are components of critical pathogen-sensing pathways that induce innate immunity. Phosphorylation of either adaptor results in activation of the type I interferon pathway. How this phosphorylation is regulated and how it is manipulated by pathogens remain largely unknown. Here, we identified host protein phosphatase, Mg(2+)/Mn(2+) dependent 1G (PPM1G) as a negative regulator of innate immune pathways and showed that this host system is hijacked by Kaposi’s sarcoma-associated herpesvirus (KSHV). Mechanistically, KSHV tegument protein ORF33 interacts with STING/MAVS and enhances recruitment of PPM1G to dephosphorylate p-STING/p-MAVS for immunosuppression. Inhibition of PPM1G expression improves the antiviral response against both DNA and RNA viruses. Collectively, our study shows that PPM1G restricts both cytosolic DNA– and RNA–sensing pathways to naturally balance the intensity of the antiviral response. Manipulation of PPM1G by KSHV provides an important strategy for immune evasion. American Association for the Advancement of Science 2020-11-20 /pmc/articles/PMC7679160/ /pubmed/33219031 http://dx.doi.org/10.1126/sciadv.abd0276 Text en Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). https://creativecommons.org/licenses/by-nc/4.0/ https://creativecommons.org/licenses/by-nc/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license (https://creativecommons.org/licenses/by-nc/4.0/) , which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited. |
spellingShingle | Research Articles Yu, Kuai Tian, Huabin Deng, Hongyu PPM1G restricts innate immune signaling mediated by STING and MAVS and is hijacked by KSHV for immune evasion |
title | PPM1G restricts innate immune signaling mediated by STING and MAVS and is hijacked by KSHV for immune evasion |
title_full | PPM1G restricts innate immune signaling mediated by STING and MAVS and is hijacked by KSHV for immune evasion |
title_fullStr | PPM1G restricts innate immune signaling mediated by STING and MAVS and is hijacked by KSHV for immune evasion |
title_full_unstemmed | PPM1G restricts innate immune signaling mediated by STING and MAVS and is hijacked by KSHV for immune evasion |
title_short | PPM1G restricts innate immune signaling mediated by STING and MAVS and is hijacked by KSHV for immune evasion |
title_sort | ppm1g restricts innate immune signaling mediated by sting and mavs and is hijacked by kshv for immune evasion |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7679160/ https://www.ncbi.nlm.nih.gov/pubmed/33219031 http://dx.doi.org/10.1126/sciadv.abd0276 |
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