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Noncanonical autophagy is a new strategy to inhibit HSV-1 through STING1 activation
STING1 (stimulator of interferon response cGAMP interactor 1) plays an essential role in immune responses for virus inhibition via inducing the production of type I interferon, inflammatory factors and macroautophagy/autophagy. In this study, we found that STING1 activation could induce not only can...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Taylor & Francis
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10621258/ https://www.ncbi.nlm.nih.gov/pubmed/37471002 http://dx.doi.org/10.1080/15548627.2023.2237794 |
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author | Zheng, Zhihua Zhao, Man Shan, Hao Fang, Dongmei Jin, Zuyi Tang, Jiuge Liu, Zhiping Hong, Liang Liu, Peiqing Li, Min |
author_facet | Zheng, Zhihua Zhao, Man Shan, Hao Fang, Dongmei Jin, Zuyi Tang, Jiuge Liu, Zhiping Hong, Liang Liu, Peiqing Li, Min |
author_sort | Zheng, Zhihua |
collection | PubMed |
description | STING1 (stimulator of interferon response cGAMP interactor 1) plays an essential role in immune responses for virus inhibition via inducing the production of type I interferon, inflammatory factors and macroautophagy/autophagy. In this study, we found that STING1 activation could induce not only canonical autophagy but also non-canonical autophagy (NCA) which is independent of the ULK1 or BECN1 complexes to form MAP1LC3/LC3-positive structures. Whether STING1-induced NCA has similar characters and physiological functions to canonical autophagy is totally unknown. Different from canonical autophagy, NCA could increase single-membrane structures and failed to degrade long-lived proteins, and could be strongly suppressed by interrupting vacuolar-type H(+)-translocating ATPase (V-ATPase) activity. Importantly, STING1-induced NCA could effectively inhibit DNA virus HSV-1 in cell model. Moreover, STING1 [1–340], a STING1 mutant lacking immunity and inflammatory response due to deletion of the tail end of STING1, could degrade virus through NCA alone, suggesting that the antiviral effect of activated STING1 could be separately mediated by inherent immunity, canonical autophagy, and NCA. In addition, the translocation and dimerization of STING1 do not rely on its immunity function and autophagy pathway. Similar to canonical autophagy, LC3-positive structures of NCA induced by STING1 could finally fuse with lysosomes, and the degradation of HSV-1 could be reverted by inhibition of lysosome function, suggesting that the elimination of DNA virus via NCA still requires the lysosome pathway. Collectively, we proved that besides its classical immunity function and canonical autophagy pathway, STING1-induced NCA is also an efficient antiviral pathway for the host cell. Abbreviations: ATG: autophagy related; Baf: bafilomycin A(1); CASM: conjugation of LC3 to a single membrane; CGAS: cyclic GMP-AMP synthase; cGAMP: cyclic GMP-AMP; CQ: chloroquine; CTD: C-terminal domain; CTT: C-terminal tail; ER: endoplasmic reticulum; ERGIC: ER-Golgi intermediate compartment; HSV-1: herpes simplex virus 1; IRF3: interferon regulatory factor 3; IFNs: interferons; LAMP1: lysosomal associated membrane protein 1; LAP: LC3-associated phagocytosis; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MOI: multiplicity of infection; RB1CC1/FIP200: RB1 inducible coiled-coil 1; STING1: stimulator of interferon response cGAMP interactor 1; TBK1: TANK binding kinase 1; TGOLN2/TGN46: trans-golgi network protein 2; ULK1: unc-51 like autophagy activating kinase 1; V-ATPase: vacuolar-type H(+)-translocating ATPase; VSV: vesicular stomatitis virus |
format | Online Article Text |
id | pubmed-10621258 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Taylor & Francis |
record_format | MEDLINE/PubMed |
spelling | pubmed-106212582023-11-03 Noncanonical autophagy is a new strategy to inhibit HSV-1 through STING1 activation Zheng, Zhihua Zhao, Man Shan, Hao Fang, Dongmei Jin, Zuyi Tang, Jiuge Liu, Zhiping Hong, Liang Liu, Peiqing Li, Min Autophagy Research Paper STING1 (stimulator of interferon response cGAMP interactor 1) plays an essential role in immune responses for virus inhibition via inducing the production of type I interferon, inflammatory factors and macroautophagy/autophagy. In this study, we found that STING1 activation could induce not only canonical autophagy but also non-canonical autophagy (NCA) which is independent of the ULK1 or BECN1 complexes to form MAP1LC3/LC3-positive structures. Whether STING1-induced NCA has similar characters and physiological functions to canonical autophagy is totally unknown. Different from canonical autophagy, NCA could increase single-membrane structures and failed to degrade long-lived proteins, and could be strongly suppressed by interrupting vacuolar-type H(+)-translocating ATPase (V-ATPase) activity. Importantly, STING1-induced NCA could effectively inhibit DNA virus HSV-1 in cell model. Moreover, STING1 [1–340], a STING1 mutant lacking immunity and inflammatory response due to deletion of the tail end of STING1, could degrade virus through NCA alone, suggesting that the antiviral effect of activated STING1 could be separately mediated by inherent immunity, canonical autophagy, and NCA. In addition, the translocation and dimerization of STING1 do not rely on its immunity function and autophagy pathway. Similar to canonical autophagy, LC3-positive structures of NCA induced by STING1 could finally fuse with lysosomes, and the degradation of HSV-1 could be reverted by inhibition of lysosome function, suggesting that the elimination of DNA virus via NCA still requires the lysosome pathway. Collectively, we proved that besides its classical immunity function and canonical autophagy pathway, STING1-induced NCA is also an efficient antiviral pathway for the host cell. Abbreviations: ATG: autophagy related; Baf: bafilomycin A(1); CASM: conjugation of LC3 to a single membrane; CGAS: cyclic GMP-AMP synthase; cGAMP: cyclic GMP-AMP; CQ: chloroquine; CTD: C-terminal domain; CTT: C-terminal tail; ER: endoplasmic reticulum; ERGIC: ER-Golgi intermediate compartment; HSV-1: herpes simplex virus 1; IRF3: interferon regulatory factor 3; IFNs: interferons; LAMP1: lysosomal associated membrane protein 1; LAP: LC3-associated phagocytosis; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MOI: multiplicity of infection; RB1CC1/FIP200: RB1 inducible coiled-coil 1; STING1: stimulator of interferon response cGAMP interactor 1; TBK1: TANK binding kinase 1; TGOLN2/TGN46: trans-golgi network protein 2; ULK1: unc-51 like autophagy activating kinase 1; V-ATPase: vacuolar-type H(+)-translocating ATPase; VSV: vesicular stomatitis virus Taylor & Francis 2023-07-25 /pmc/articles/PMC10621258/ /pubmed/37471002 http://dx.doi.org/10.1080/15548627.2023.2237794 Text en © 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License (http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) ), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited, and is not altered, transformed, or built upon in any way. The terms on which this article has been published allow the posting of the Accepted Manuscript in a repository by the author(s) or with their consent. |
spellingShingle | Research Paper Zheng, Zhihua Zhao, Man Shan, Hao Fang, Dongmei Jin, Zuyi Tang, Jiuge Liu, Zhiping Hong, Liang Liu, Peiqing Li, Min Noncanonical autophagy is a new strategy to inhibit HSV-1 through STING1 activation |
title | Noncanonical autophagy is a new strategy to inhibit HSV-1 through STING1 activation |
title_full | Noncanonical autophagy is a new strategy to inhibit HSV-1 through STING1 activation |
title_fullStr | Noncanonical autophagy is a new strategy to inhibit HSV-1 through STING1 activation |
title_full_unstemmed | Noncanonical autophagy is a new strategy to inhibit HSV-1 through STING1 activation |
title_short | Noncanonical autophagy is a new strategy to inhibit HSV-1 through STING1 activation |
title_sort | noncanonical autophagy is a new strategy to inhibit hsv-1 through sting1 activation |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10621258/ https://www.ncbi.nlm.nih.gov/pubmed/37471002 http://dx.doi.org/10.1080/15548627.2023.2237794 |
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