Middle East Respiratory Syndrome Coronavirus 4a Protein Is a Double-Stranded RNA-Binding Protein That Suppresses PACT-Induced Activation of RIG-I and MDA5 in the Innate Antiviral Response

Siu, Kam Leung; Yeung, Man Lung; Kok, Kin Hang; Yuen, Kit San; Kew, Chun; Lui, Pak-Yin; Chan, Chi-Ping; Tse, Herman; Woo, Patrick C. Y.; Yuen, Kwok Yung; Jin, Dong Yan

doi:10.1128/jvi.03649-13

Cited by 173 publications

(201 citation statements)

References 53 publications

(100 reference statements)

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“…Primers for EBER and the BamHI W region were as described previously (Lan et al, 2007;Choy et al, 2008a). qRT-PCR was performed using a SYBR Premix Ex Taq system (TaKaRa) as described previously (Kew et al, 2013;Siu et al, 2014).…”

Section: Methodsmentioning

confidence: 99%

CRISPR/Cas9-mediated genome editing of Epstein–Barr virus in human cells

Yuen

Chan

Wong

et al. 2015

Journal of General Virology

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153

114

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Section: Methodsmentioning

confidence: 99%

CRISPR/Cas9-mediated genome editing of Epstein–Barr virus in human cells

Yuen

Chan

Wong

et al. 2015

Journal of General Virology

Self Cite

153

114

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“…p3 and p4b have been predicted to each contain one transmembrane helix, whereas p5 has been proposed to comprise three such helices (Siu et al, 2014). p3 and p5 have been found in the ERGIC, whereas p4a and p4b display a diffuse cytoplasmic distribution and are also partly localized to the nucleus (Siu et al, 2014), although in another study, p4b was found to localize exclusively to the nucleus (Matthews et al, 2014). Both the p4a and the p4b protein of MERS coronavirus have been shown to be a type-I interferon antagonists (Siu et al, 2014;Matthews et al, 2014;Niemeyer et al, 2013).…”

Section: Accessory Proteins Of Other Betacoronavirusesmentioning

confidence: 99%

Accessory proteins of SARS-CoV and other coronaviruses

et al. 2014

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The huge RNA genome of SARS coronavirus comprises a number of open reading frames that code for a total of eight accessory proteins. Although none of these are essential for virus replication, some appear to have a role in virus pathogenesis. Notably, some SARS-CoV accessory proteins have been shown to modulate the interferon signaling pathways and the production of pro-inflammatory cytokines. The structural information on these proteins is also limited, with only two (p7a and p9b) having their structures determined by X-ray crystallography. This review makes an attempt to summarize the published knowledge on SARS-CoV accessory proteins, with an emphasis on their involvement in virus-host interaction. The accessory proteins of other coronaviruses are also briefly discussed. This paper forms part of a series of invited articles in Antiviral Research on "From SARS to MERS: 10 years of research on highly pathogenic human coronaviruses" (see Introduction by Hilgenfeld and Peiris (2013)).

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“…ORF4a encoded one of the accessory proteins that block IFN induction and works as a strong inhibitor of type 1 IFN by inhibiting dsRNA recognition by cellular RIG‐I and MDA5 (Niemeyer et al, ; Siu et al, ). MERS‐CoV 4a protein has a suppression effect on the PACT‐induced activation of RIG‐I and MDA5, however, this double‐stranded RNA‐binding protein has no effect on the activity of downstream effectors such as RIG‐I, MDA5, MAVS, TBK1, and IRF3 (Siu, Yeung et al, ).…”

Section: Innate Immunementioning

confidence: 99%

Modulation of the immune response by Middle East respiratory syndrome coronavirus

Shokri

Mahmoudvand

Taherkhani

et al. 2018

Journal Cellular Physiology

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Coronavirus (CoV) infections are commonly associated with respiratory and enteric disease in humans and animals. In 2012, a new human disease called Middle East respiratory syndrome (MERS) emerged in the Middle East. MERS was caused by a virus that was originally called human coronavirus-Erasmus Medical Center/2012 but was later renamed as Middle East respiratory syndrome coronavirus (MERS-CoV). MERS-CoV causes high fever, cough, acute respiratory tract infection, and multiorgan dysfunction that may eventually lead to the death of the infected individuals. The exact origin of MERS-CoV remains unknown, but the transmission pattern and evidence from virological studies suggest that dromedary camels are the major reservoir host, from which human infections may sporadically occur through the zoonotic transmission. Human to human transmission also occurs in healthcare facilities and communities. Recent studies on Middle Eastern respiratory continue to highlight the need for further understanding the virus-host interactions that govern disease severity and infection outcome. In this review, we have highlighted the major mechanisms of immune evasion strategies of MERS-CoV. We have demonstrated that M, 4a, 4b proteins and Plppro of MERS-CoV inhibit the type I interferon (IFN) and nuclear factor-κB signaling pathways and therefore facilitate innate immune evasion. In addition, nonstructural protein 4a (NSP4a), NSP4b, and NSP15 inhibit double-stranded RNA sensors. Therefore, the mentioned proteins limit early induction of IFN and cause rapid apoptosis of macrophages. MERS-CoV strongly inhibits the activation of T cells with downregulation of antigen presentation. In addition, uncontrolled secretion of interferon ɣ-induced protein 10 and monocyte chemoattractant protein-1 can suppress proliferation of human myeloid progenitor cells.

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Middle East Respiratory Syndrome Coronavirus 4a Protein Is a Double-Stranded RNA-Binding Protein That Suppresses PACT-Induced Activation of RIG-I and MDA5 in the Innate Antiviral Response

Abstract: Middle East respiratory syndrome coronavirus (MERS-CoV

Cited by 173 publications

References 53 publications

CRISPR/Cas9-mediated genome editing of Epstein–Barr virus in human cells

CRISPR/Cas9-mediated genome editing of Epstein–Barr virus in human cells

Accessory proteins of SARS-CoV and other coronaviruses

Modulation of the immune response by Middle East respiratory syndrome coronavirus

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