HSP27 Protein Dampens Encephalomyocarditis Virus Replication by Stabilizing Melanoma Differentiation-Associated Gene 5

Heat shock proteins (HSPs) are a protein family that respond to physiological stress, such as heat, starvation, and infection. As cellular protein chaperones, they play an important role in protein folding, assembly, and degradation. Though it is well known that HSP27 is involved in a range of viral...

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Autores principales:	Xiangrong Li, Ruixian Ma, Bei Wu, Yuhui Niu, Hongshan Li, Dianyu Li, Jingying Xie, Adi Idris, Ruofei Feng
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	HSP27 encephalomyocarditis virus MDA5 2Cpro 3Apro Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/9641f2d917b34d1096035b1ece4ba25b
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spelling	oai:doaj.org-article:9641f2d917b34d1096035b1ece4ba25b2021-12-01T08:23:21ZHSP27 Protein Dampens Encephalomyocarditis Virus Replication by Stabilizing Melanoma Differentiation-Associated Gene 51664-302X10.3389/fmicb.2021.788870https://doaj.org/article/9641f2d917b34d1096035b1ece4ba25b2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fmicb.2021.788870/fullhttps://doaj.org/toc/1664-302XHeat shock proteins (HSPs) are a protein family that respond to physiological stress, such as heat, starvation, and infection. As cellular protein chaperones, they play an important role in protein folding, assembly, and degradation. Though it is well known that HSP27 is involved in a range of viral infections, its role during an encephalomyocarditis virus (EMCV) infection is not known. Here, we report that EMCV degrades HSP27 and that EMCV proteins 2Cpro and 3Apro are primarily responsible for its degradation. Consequently, loss of cellular HSP27 augmented EMCV proliferation, an effect that could be reversed upon HSP27 overexpression. Importantly, we found that HSP27 positively regulated EMCV-triggered type I interferon (IFN) production. Moreover, overexpression of 2Cpro and 3Apro significantly blocked type I IFN production. We also found for the first time that HSP27, as a molecular chaperone, can specifically interact with MDA5 and stabilize the expression of MDA5. Collectively, this study shows that HSP27 dampens EMCV infectivity by positively regulating EMCV-triggered retinoic acid-inducible gene (RIG)-I-like receptor (RLR)/melanoma differentiation-associated gene 5 (MDA5) signal pathway, while EMCV proteins 2Cpro and 3Apro interact with HSP27 and degrade HSP27 protein expression to allow EMCV proliferation. Our findings provide further mechanistic evidence for EMCV partaking in immune escape mechanisms, and that 2Cpro and 3Apro could serve as potential antiviral targets.Xiangrong LiRuixian MaBei WuYuhui NiuHongshan LiDianyu LiJingying XieAdi IdrisRuofei FengFrontiers Media S.A.articleHSP27encephalomyocarditis virusMDA52Cpro3AproMicrobiologyQR1-502ENFrontiers in Microbiology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	HSP27 encephalomyocarditis virus MDA5 2Cpro 3Apro Microbiology QR1-502
spellingShingle	HSP27 encephalomyocarditis virus MDA5 2Cpro 3Apro Microbiology QR1-502 Xiangrong Li Ruixian Ma Bei Wu Yuhui Niu Hongshan Li Dianyu Li Jingying Xie Adi Idris Ruofei Feng HSP27 Protein Dampens Encephalomyocarditis Virus Replication by Stabilizing Melanoma Differentiation-Associated Gene 5
description	Heat shock proteins (HSPs) are a protein family that respond to physiological stress, such as heat, starvation, and infection. As cellular protein chaperones, they play an important role in protein folding, assembly, and degradation. Though it is well known that HSP27 is involved in a range of viral infections, its role during an encephalomyocarditis virus (EMCV) infection is not known. Here, we report that EMCV degrades HSP27 and that EMCV proteins 2Cpro and 3Apro are primarily responsible for its degradation. Consequently, loss of cellular HSP27 augmented EMCV proliferation, an effect that could be reversed upon HSP27 overexpression. Importantly, we found that HSP27 positively regulated EMCV-triggered type I interferon (IFN) production. Moreover, overexpression of 2Cpro and 3Apro significantly blocked type I IFN production. We also found for the first time that HSP27, as a molecular chaperone, can specifically interact with MDA5 and stabilize the expression of MDA5. Collectively, this study shows that HSP27 dampens EMCV infectivity by positively regulating EMCV-triggered retinoic acid-inducible gene (RIG)-I-like receptor (RLR)/melanoma differentiation-associated gene 5 (MDA5) signal pathway, while EMCV proteins 2Cpro and 3Apro interact with HSP27 and degrade HSP27 protein expression to allow EMCV proliferation. Our findings provide further mechanistic evidence for EMCV partaking in immune escape mechanisms, and that 2Cpro and 3Apro could serve as potential antiviral targets.
format	article
author	Xiangrong Li Ruixian Ma Bei Wu Yuhui Niu Hongshan Li Dianyu Li Jingying Xie Adi Idris Ruofei Feng
author_facet	Xiangrong Li Ruixian Ma Bei Wu Yuhui Niu Hongshan Li Dianyu Li Jingying Xie Adi Idris Ruofei Feng
author_sort	Xiangrong Li
title	HSP27 Protein Dampens Encephalomyocarditis Virus Replication by Stabilizing Melanoma Differentiation-Associated Gene 5
title_short	HSP27 Protein Dampens Encephalomyocarditis Virus Replication by Stabilizing Melanoma Differentiation-Associated Gene 5
title_full	HSP27 Protein Dampens Encephalomyocarditis Virus Replication by Stabilizing Melanoma Differentiation-Associated Gene 5
title_fullStr	HSP27 Protein Dampens Encephalomyocarditis Virus Replication by Stabilizing Melanoma Differentiation-Associated Gene 5
title_full_unstemmed	HSP27 Protein Dampens Encephalomyocarditis Virus Replication by Stabilizing Melanoma Differentiation-Associated Gene 5
title_sort	hsp27 protein dampens encephalomyocarditis virus replication by stabilizing melanoma differentiation-associated gene 5
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/9641f2d917b34d1096035b1ece4ba25b
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HSP27 Protein Dampens Encephalomyocarditis Virus Replication by Stabilizing Melanoma Differentiation-Associated Gene 5

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