p53 Degradation by a Coronavirus Papain-like Protease Suppresses Type I Interferon Signaling

Lin, Yuan; Chen, Zhongbin; Song, Shanshan; Wang, Shan; Tian, Chunyan; Xing, Guichun; Chen, Xiaojuan; Xiao, Zhi‐Xiong Jim; He, Fuchu; Zhang, Lingqiang

doi:10.1074/jbc.m114.619890

Cited by 109 publications

(119 citation statements)

References 33 publications

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“…In 2015, Yuan et al . found that p53 can upregulate the transcription of IRF7. HCoV‐NL63 PL2 pro deubiquitinates and stabilizes MDM2, a p53 degradation stimulator, thus causing p53 degradation and blocking the p53–IRF7–IFNβ signaling pathway (Fig.…”

Section: Rna‐virus Proteases Interfering With the Host Innate Immunementioning

confidence: 95%

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RNA‐virus proteases counteracting host innate immunity

Lei

Hilgenfeld

2017

FEBS Letters

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Virus invasion triggers host immune responses, in particular, innate immune responses. Pathogen‐associated molecular patterns of viruses (such as dsRNA, ssRNA, or viral proteins) released during virus replication are detected by the corresponding pattern‐recognition receptors of the host, and innate immune responses are induced. Through production of type‐I and type‐III interferons as well as various other cytokines, the host innate immune system forms the frontline to protect host cells and inhibit virus infection. Not surprisingly, viruses have evolved diverse strategies to counter this antiviral system. In this review, we discuss the multiple strategies used by proteases of positive‐sense single‐stranded RNA viruses of the families Picornaviridae, Coronaviridae, and Flaviviridae, when counteracting host innate immune responses.

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Section: Rna‐virus Proteases Interfering With the Host Innate Immunementioning

confidence: 95%

“…HCoV‐NL63 PL2 pro deubiquitinates and stabilizes MDM2, a p53 degradation stimulator, thus causing p53 degradation and blocking the p53–IRF7–IFNβ signaling pathway (Fig. A) . p53 also inhibits SARS‐CoV replication .…”

Section: Rna‐virus Proteases Interfering With the Host Innate Immunementioning

confidence: 99%

RNA‐virus proteases counteracting host innate immunity

Lei

Hilgenfeld

2017

FEBS Letters

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“…In addition, the HCoV-NL63 PL2 pro was shown to block the p53-IRF7-IFNβ signaling pathway (Yuan et al, 2015). p53 can induce type-I interferon production via IRF7 (interferon regulatory factor 7; Yuan et al, 2015).…”

Section: Papain-like Protease 2 (Pl2 Pro )mentioning

confidence: 99%

Nsp3 of coronaviruses: Structures and functions of a large multi-domain protein

2018

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The multi-domain non-structural protein 3 (Nsp3) is the largest protein encoded by the coronavirus (CoV) genome, with an average molecular mass of about 200 kD. Nsp3 is an essential component of the replication/transcription complex. It comprises various domains, the organization of which differs between CoV genera, due to duplication or absence of some domains. However, eight domains of Nsp3 exist in all known CoVs: the ubiquitin-like domain 1 (Ubl1), the Glu-rich acidic domain (also called "hypervariable region"), a macrodomain (also named "X domain"), the ubiquitin-like domain 2 (Ubl2), the papain-like protease 2 (PL2), the Nsp3 ectodomain (3Ecto, also called "zinc-finger domain"), as well as the domains Y1 and CoV-Y of unknown functions. In addition, the two transmembrane regions, TM1 and TM2, exist in all CoVs. The three-dimensional structures of domains in the N-terminal two thirds of Nsp3 have been investigated by X-ray crystallography and/or nuclear magnetic resonance (NMR) spectroscopy since the outbreaks of Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) in 2003 as well as Middle-East Respiratory Syndrome coronavirus (MERS-CoV) in 2012. In this review, the structures and functions of these domains of Nsp3 are discussed in depth.

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“…On the other hand, many viruses have also developed strategies to manipulate host p53 signalling pathways to increase virus replication (Casavant et al, ; Royds et al, ). For example, coronavirus inhibited p53‐mediated host apoptosis to ensure viral growth in infected cells (Yuan et al, ). In our study, RGNNV infection reduced the expression of Ljp53 at 48 hpi, which at least partially inhibited the host cell apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Comparative transcriptome analysis reveals the role of p53 signalling pathway during red‐spotted grouper nervous necrosis virus infection in Lateolabrax japonicus brain cells

Xiang

Jia

Liu

et al. 2019

Journal of Fish Diseases

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Nervous necrosis virus (NNV) is one of the fish pathogens that have caused mass mortalities of many marine and freshwater fishes in the world. To better comprehend the molecular immune mechanism of sea perch (Lateolabrax japonicus) against NNV infection, the comparative transcriptome analysis of red‐spotted grouper nervous necrosis virus (RGNNV)‐infected or mock‐infected L. japonicus brain (LJB) cells was performed via RNA sequencing technology. Here, 1,969 up‐regulated genes and 9,858 down‐regulated genes, which were widely implicated in immune response pathways, were identified. Furthermore, we confirmed that p53 signalling pathway was repressed at 48 hr post‐RGNNV infection, as indicated by up‐regulation of Mdm2 and down‐regulation of p53 and its downstream target genes, including Bax, Casp8 and CytC. Overexpression of L. japonicus p53 (Ljp53) significantly inhibited RGNNV replication and up‐regulated the expression of apoptosis‐related genes, whereas the down‐regulation caused by pifithrin‐α led to the opposite effect, suggesting Ljp53 might promote cell apoptosis to repress virus replication. Luciferase assay indicated that Ljp53 could enhance the promoter activities of zebrafish interferon (IFN)1, indicating that Ljp53 could exert its anti‐RGNNV activities by enforcing the type I IFN response. This study revealed the potential antiviral role of p53 during NNV infection.

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p53 Degradation by a Coronavirus Papain-like Protease Suppresses Type I Interferon Signaling

Cited by 109 publications

References 33 publications

RNA‐virus proteases counteracting host innate immunity

RNA‐virus proteases counteracting host innate immunity

Nsp3 of coronaviruses: Structures and functions of a large multi-domain protein

Comparative transcriptome analysis reveals the role of p53 signalling pathway during red‐spotted grouper nervous necrosis virus infection in Lateolabrax japonicus brain cells

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