Nonmuscle Myosin Heavy Chain IIA Recognizes Sialic Acids on Sialylated RNA Viruses To Suppress Proinflammatory Responses via the DAP12-Syk Pathway

ABSTRACT Viral infections induce proinflammatory signaling cascades and inflammatory cytokine production, which is precisely regulated for host benefits. In the current study, we unravel a previously unappreciated role of nonmuscle myosin heavy chain IIA (NMHC-IIA) as a negative regulator in inflamm...

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Autores principales:	Yingqi Liu, Rui Li, Xin-xin Chen, Yubao Zhi, Ruiguang Deng, En-min Zhou, Songlin Qiao, Gaiping Zhang
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	DAP12 NMHC-IIA negative modulation proinflammatory responses sialic acids sialylated RNA virus Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/1910a67c3a7b4f89a5ee6602a974ea91
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spelling	oai:doaj.org-article:1910a67c3a7b4f89a5ee6602a974ea912021-11-15T15:55:24ZNonmuscle Myosin Heavy Chain IIA Recognizes Sialic Acids on Sialylated RNA Viruses To Suppress Proinflammatory Responses via the DAP12-Syk Pathway10.1128/mBio.00574-192150-7511https://doaj.org/article/1910a67c3a7b4f89a5ee6602a974ea912019-06-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00574-19https://doaj.org/toc/2150-7511ABSTRACT Viral infections induce proinflammatory signaling cascades and inflammatory cytokine production, which is precisely regulated for host benefits. In the current study, we unravel a previously unappreciated role of nonmuscle myosin heavy chain IIA (NMHC-IIA) as a negative regulator in inflammatory responses. We identified that cell surface NMHC-IIA recognized sialic acids on sialylated RNA viruses during early infections and interacted with an immune adaptor DNAX activation protein of 12 kDa (DAP12) to recruit downstream spleen tyrosine kinase (Syk), leading to suppressed virus-triggered proinflammatory responses. More importantly, recognition of sialylated RNA viruses or sialic acid mimics by NMHC-IIA was shown to inhibit lipopolysaccharide (LPS)-induced proinflammatory responses via the DAP12-Syk pathway. These findings uncover a novel negative regulation mechanism of proinflammatory responses and provide a molecular basis to design anti-inflammatory drugs. IMPORTANCE NMHC-IIA, a subunit of nonmuscle myosin IIA (NM-IIA), takes part in diverse physiological processes, including cell movement, cell shape maintenance, and signal transduction. Recently, NMHC-IIA has been demonstrated to be a receptor or factor contributing to viral infections. Here, we identified that NMHC-IIA recognizes sialic acids on sialylated RNA viruses, vesicular stomatitis virus (VSV) and porcine reproductive and respiratory syndrome virus (PRRSV). Upon recognition, NMHC-IIA associates with the transmembrane region of DAP12 to recruit Syk. Activation of the DAP12-Syk pathway impairs the host antiviral proinflammatory cytokine production and signaling cascades. More importantly, sialic acid mimics and sialylated RNA viruses enable the antagonism of LPS-triggered proinflammatory responses through engaging the NMHC-IIA–DAP12-Syk pathway. These results actually support that NMHC-IIA is involved in negative modulation of the host innate immune system, which provides a molecular basis for prevention and control of the sialylated RNA viruses and treatment of inflammatory diseases.Yingqi LiuRui LiXin-xin ChenYubao ZhiRuiguang DengEn-min ZhouSonglin QiaoGaiping ZhangAmerican Society for MicrobiologyarticleDAP12NMHC-IIAnegative modulationproinflammatory responsessialic acidssialylated RNA virusMicrobiologyQR1-502ENmBio, Vol 10, Iss 3 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	DAP12 NMHC-IIA negative modulation proinflammatory responses sialic acids sialylated RNA virus Microbiology QR1-502
spellingShingle	DAP12 NMHC-IIA negative modulation proinflammatory responses sialic acids sialylated RNA virus Microbiology QR1-502 Yingqi Liu Rui Li Xin-xin Chen Yubao Zhi Ruiguang Deng En-min Zhou Songlin Qiao Gaiping Zhang Nonmuscle Myosin Heavy Chain IIA Recognizes Sialic Acids on Sialylated RNA Viruses To Suppress Proinflammatory Responses via the DAP12-Syk Pathway
description	ABSTRACT Viral infections induce proinflammatory signaling cascades and inflammatory cytokine production, which is precisely regulated for host benefits. In the current study, we unravel a previously unappreciated role of nonmuscle myosin heavy chain IIA (NMHC-IIA) as a negative regulator in inflammatory responses. We identified that cell surface NMHC-IIA recognized sialic acids on sialylated RNA viruses during early infections and interacted with an immune adaptor DNAX activation protein of 12 kDa (DAP12) to recruit downstream spleen tyrosine kinase (Syk), leading to suppressed virus-triggered proinflammatory responses. More importantly, recognition of sialylated RNA viruses or sialic acid mimics by NMHC-IIA was shown to inhibit lipopolysaccharide (LPS)-induced proinflammatory responses via the DAP12-Syk pathway. These findings uncover a novel negative regulation mechanism of proinflammatory responses and provide a molecular basis to design anti-inflammatory drugs. IMPORTANCE NMHC-IIA, a subunit of nonmuscle myosin IIA (NM-IIA), takes part in diverse physiological processes, including cell movement, cell shape maintenance, and signal transduction. Recently, NMHC-IIA has been demonstrated to be a receptor or factor contributing to viral infections. Here, we identified that NMHC-IIA recognizes sialic acids on sialylated RNA viruses, vesicular stomatitis virus (VSV) and porcine reproductive and respiratory syndrome virus (PRRSV). Upon recognition, NMHC-IIA associates with the transmembrane region of DAP12 to recruit Syk. Activation of the DAP12-Syk pathway impairs the host antiviral proinflammatory cytokine production and signaling cascades. More importantly, sialic acid mimics and sialylated RNA viruses enable the antagonism of LPS-triggered proinflammatory responses through engaging the NMHC-IIA–DAP12-Syk pathway. These results actually support that NMHC-IIA is involved in negative modulation of the host innate immune system, which provides a molecular basis for prevention and control of the sialylated RNA viruses and treatment of inflammatory diseases.
format	article
author	Yingqi Liu Rui Li Xin-xin Chen Yubao Zhi Ruiguang Deng En-min Zhou Songlin Qiao Gaiping Zhang
author_facet	Yingqi Liu Rui Li Xin-xin Chen Yubao Zhi Ruiguang Deng En-min Zhou Songlin Qiao Gaiping Zhang
author_sort	Yingqi Liu
title	Nonmuscle Myosin Heavy Chain IIA Recognizes Sialic Acids on Sialylated RNA Viruses To Suppress Proinflammatory Responses via the DAP12-Syk Pathway
title_short	Nonmuscle Myosin Heavy Chain IIA Recognizes Sialic Acids on Sialylated RNA Viruses To Suppress Proinflammatory Responses via the DAP12-Syk Pathway
title_full	Nonmuscle Myosin Heavy Chain IIA Recognizes Sialic Acids on Sialylated RNA Viruses To Suppress Proinflammatory Responses via the DAP12-Syk Pathway
title_fullStr	Nonmuscle Myosin Heavy Chain IIA Recognizes Sialic Acids on Sialylated RNA Viruses To Suppress Proinflammatory Responses via the DAP12-Syk Pathway
title_full_unstemmed	Nonmuscle Myosin Heavy Chain IIA Recognizes Sialic Acids on Sialylated RNA Viruses To Suppress Proinflammatory Responses via the DAP12-Syk Pathway
title_sort	nonmuscle myosin heavy chain iia recognizes sialic acids on sialylated rna viruses to suppress proinflammatory responses via the dap12-syk pathway
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/1910a67c3a7b4f89a5ee6602a974ea91
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Nonmuscle Myosin Heavy Chain IIA Recognizes Sialic Acids on Sialylated RNA Viruses To Suppress Proinflammatory Responses via the DAP12-Syk Pathway

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