SARS-CoV-1 N protein binds TRIM25

Stable Identifier
Reaction [binding]
Homo sapiens
Related Species
Human SARS coronavirus
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Antiviral innate immune response receptor RIG-I (also known as retinoic acid-inducible gene I protein RIG-1 or DDX58) directly recognizes and binds to viral 5′-PPP RNA and short dsRNA, which are found in cells infected with a variety of RNA viruses, through its helicase and repressor domain (Kato H et al. 2006). After recognition, the N-terminal caspase recruitment domains (CARDs) of DDX58 (RIG-1) are modified by ubiquitin. The ubiquitination is mediated by the E3 ubiquitin ligase tripartite motif protein 25 (TRIM25). The severe acute respiratory syndrome coronavirus type 1 (SARS-CoV-1) N protein binds to the SPla and the ryanodine receptor (SPRY) domain of TRIM25 in human embryonic kidney 293T (HEK293T) cells expressing Flag-TRIM25 and green fluorescent protein (GFP)-tagged full-length or truncated viral N protein (Hu Y et al. 2017). The viral N protein inhibited TRIM25-mediated DDX58 ubiquitination upon coexpression in HEK293T cells in a dose-dependent manner (Hu Y et al. 2017). Further, an in situ proximity ligation assay (PLA) followed by confocal microscopy demonstrated that the interaction between endogenous DDX58 and TRIM25 was decreased by exogenous SARS-CoV-1 N protein expressed in HeLa cells. SARS-CoV-1 N protein suppressed type I IFN production in Sendai virus (SeV)-infected human alveolar basal epithelial (A549) and HEK293T cells. Further, SARS-CoV-1 replication in A549 and human bronchial epithelium Calu-3 cells was increased by overexpression of the full-length N protein but not the N-terminal amino acids 1 to 361, which could not interact with TRIM25. Middle East respiratory syndrome CoV (MERS-CoV) N protein also interacted with TRIM25 and inhibited RIG-I signaling (Hu Y et al. 2017). These data suggest that SARS-CoV-1 N protein interferes with the association between TRIM25 and DDX58 (RIG-1) to suppress type I IFN production.
Literature References
PubMed ID Title Journal Year
28148787 The Severe Acute Respiratory Syndrome Coronavirus Nucleocapsid Inhibits Type I Interferon Production by Interfering with TRIM25-Mediated RIG-I Ubiquitination

Cao, C, Gao, T, Li, W, Ma, Q, Liu, X, Li, P, Jin, Y, Cui, Y, Hu, Y

J. Virol. 2017
Name Identifier Synonyms
severe acute respiratory syndrome DOID:2945 SARS-CoV infection, SARS
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