Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) membrane (M) protein inhibits type I and III interferon production by targeting RIG-I/MDA-5 signaling

Zheng, Yi; Zhuang, Meng; Han, Lulu; Zhang, Jing; Mei, Nan; Zhan, Peng; Kang, Dongwei; Liu, Xinyong; Gao, Chengjiang; Wang, Pei‐Hui

doi:10.1038/s41392-020-00438-7

Cited by 259 publications

(235 citation statements)

References 48 publications

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“…It showed that N protein mainly involved in viral mRNA transcription and replication and cytoskeletal and immune regulation of host cells [58] . The M protein of SARS-CoV-2 can inhibit IFN-β promoter activation and participate in evading host anti-viral immunity [59] . E protein relates to the virus pathogenicity and may activate the host's inflammatory response.…”

Section: Discussionmentioning

confidence: 99%

Dependence of SARS-CoV-2 infection on cholesterol-rich lipid raft and endosomal acidification

Zhu

Fan

et al. 2021

Computational and Structural Biotechnology Journal

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Section: Discussionmentioning

confidence: 99%

Dependence of SARS-CoV-2 infection on cholesterol-rich lipid raft and endosomal acidification

Zhu

Fan

et al. 2021

Computational and Structural Biotechnology Journal

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“… 52 Membrane (M) protein inhibits type I and III IFN production by targeting RIG-I/MDA-5. 53 ORF6 is shown to inhibit both type I IFN production and downstream signaling. 54 , 55 Despite most of the recent identified SARS-CoV-2 viral proteins are shown to restrict host immune response, which is regarded as a common defense strategy that pathogenic viruses use to replicate and propagate in their host, our study revealed the SARS-CoV-2 N protein could positively regulate inflammatory responses through promoting NF-κB activation.…”

Section: Discussionmentioning

confidence: 99%

RNA-induced liquid phase separation of SARS-CoV-2 nucleocapsid protein facilitates NF-κB hyper-activation and inflammation

Cai

et al. 2021

Sig Transduct Target Ther

117

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The ongoing 2019 novel coronavirus disease (COVID-19) caused by SARS-CoV-2 has posed a worldwide pandemic and a major global public health threat. The severity and mortality of COVID-19 are associated with virus-induced dysfunctional inflammatory responses and cytokine storms. However, the interplay between host inflammatory responses and SARS-CoV-2 infection remains largely unknown. Here, we demonstrate that SARS-CoV-2 nucleocapsid (N) protein, the major structural protein of the virion, promotes the virus-triggered activation of NF-κB signaling. After binding to viral RNA, N protein robustly undergoes liquid–liquid phase separation (LLPS), which recruits TAK1 and IKK complex, the key kinases of NF-κB signaling, to enhance NF-κB activation. Moreover, 1,6-hexanediol, the inhibitor of LLPS, can attenuate the phase separation of N protein and restrict its regulatory functions in NF-κB activation. These results suggest that LLPS of N protein provides a platform to induce NF-κB hyper-activation, which could be a potential therapeutic target against COVID-19 severe pneumonia.

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“…The envelope (E) protein likely forms a viroporin, which is important for virus assembly and release, and is also a putative virulence determinant [ 23 ]. The membrane (M) protein is an abundantly expressed structural protein within the lipid envelope that is also important for viral morphogenesis and interferon suppression [ 24 ]. Finally, the nucleocapsid protein (N) stabilizes the RNA genome in a helical complex [ 25 ] and serves as a key target of adaptive immunity.…”

Section: Taxonomy Genomic Organization and Replication Cycle Of Sarmentioning

confidence: 99%

Lessons learned 1 year after SARS-CoV-2 emergence leading to COVID-19 pandemic

Sridhar

Chiu

et al. 2021

Emerging Microbes & Infections

270

189

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Without modern medical management and vaccines, the severity of the Coronavirus Disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome(SARS) coronavirus 2 (SARS-CoV-2) might approach the magnitude of 1894-plague (12 million deaths) and 1918-A(H1N1) influenza (50 million deaths) pandemics. The COVID-19 pandemic was heralded by the 2003 SARS epidemic which led to the discovery of human and civet SARS-CoV-1, bat SARS-related-CoVs, Middle East respiratory syndrome(MERS)-related bat CoV HKU4 and HKU5, and other novel animal coronaviruses. The suspected animal-to-human jumping of 4 betacoronaviruses including the human coronaviruses OC43(1890), SARS-CoV-1(2003), MERS-CoV(2012), and SARS-CoV-2(2019) indicates their significant pandemic potential. The presence of a large reservoir of coronaviruses in bats and other wild mammals, culture of mixing and selling them in urban markets with suboptimal hygiene, habit of eating exotic mammals in highly populated areas, and the rapid and frequent air traffic from these areas are perfect ingredients for brewing rapidly exploding epidemics. The possibility of emergence of a hypothetical SARS-CoV-3 or other novel viruses from animals or laboratories, and therefore needs for global preparedness should not be ignored. We reviewed representative publications on the epidemiology, virology, clinical manifestations, pathology, laboratory diagnostics, treatment, vaccination and infection control of COVID-19 as of 20 January 2021, which is one year after person-to-person transmission of SARS-CoV-2 was announced. The difficulties of mass testing, labour-intensive contact tracing, importance of compliance to universal masking, low efficacy of antiviral treatment for severe disease, possibilities of vaccine or antiviral-resistant virus variants and SARS-CoV-2 becoming another common cold coronavirus are discussed. The chronology of the pandemic An outbreak of acute community-acquired atypical pneumonia of unknown aetiology was reported in Wuhan, the capital of Hubei province in central China, in December 2019. The initial cluster of cases was related to the Huanan seafood wholesale market where wild game animals were also sold (1). During subsequent investigation, severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2) was detected in 33 out of 585 environmental samples taken from the market (2). However, 45% of the cases with onset before 1 January 2020 had no apparent link to this market (3). Retrospective molecular clock inference studies using phylogenetic analysis suggested that the earliest cases likely emerged between October and November 2019 (4, 5). The culprit virus was identified using next-generation sequencing on bronchoalveolar lavage fluids of three Wuhan patients (6). The complete genome sequences of SARS-CoV-2 clustered in a distinct clade from SARS-CoV within the genus Sarbecovirus. The draft genome sequence was released on 10 Jan 2020, 10 days after the outbreak was announced. As an escalating number of local cases was reported in Wuhan, a f...

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) membrane (M) protein inhibits type I and III interferon production by targeting RIG-I/MDA-5 signaling

Cited by 259 publications

References 48 publications

Dependence of SARS-CoV-2 infection on cholesterol-rich lipid raft and endosomal acidification

Dependence of SARS-CoV-2 infection on cholesterol-rich lipid raft and endosomal acidification

RNA-induced liquid phase separation of SARS-CoV-2 nucleocapsid protein facilitates NF-κB hyper-activation and inflammation

Lessons learned 1 year after SARS-CoV-2 emergence leading to COVID-19 pandemic

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