PMID:19369340

Citation	Frieman, M, Ratia, K, Johnston, RE, Mesecar, AD and Baric, RS (2009) Severe acute respiratory syndrome coronavirus papain-like protease ubiquitin-like domain and catalytic domain regulate antagonism of IRF3 and NF-kappaB signaling. J. Virol. 83:6689-705
Abstract	The outcome of a viral infection is regulated in part by the complex coordination of viral and host interactions that compete for the control and optimization of virus replication. Severe acute respiratory syndrome coronavirus (SARS-CoV) intimately engages and regulates the host innate immune responses during infection. Using a novel interferon (IFN) antagonism screen, we show that the SARS-CoV proteome contains several replicase, structural, and accessory proteins that antagonize the IFN pathway. In this study, we focus on the SARS-CoV papain-like protease (PLP), which engages and antagonizes the IFN induction and NF-kappaB signaling pathways. PLP blocks these pathways by affecting activation of the important signaling proteins in each pathway, IRF3 and NF-kappaB. We also show that the ubiquitin-like domain of PLP is necessary for pathway antagonism but not sufficient by itself to block these pathways regardless of the enzymatic activity of the protease. The potential mechanism of PLP antagonism and its role in pathogenesis are discussed.
Links	PubMed PMC2698564 Online version:10.1128/JVI.02220-08
Keywords	Cell Line; Cysteine Endopeptidases/metabolism; Humans; I-kappa B Proteins/metabolism; Interferon Regulatory Factor-3/metabolism; Interferons/antagonists & inhibitors; NF-kappa B/metabolism; Phosphorylation; SARS Virus/enzymology; Viral Proteins/metabolism
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
CVHSA:R1AB	involved_in	GO:0039548: suppression by virus of host IRF3 activity	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete
CVHSA:R1AB	involved_in	GO:0039644: suppression by virus of host NF-kappaB transcription factor activity	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete
CVHSA:R1AB	involved_in	GO:0039502: suppression by virus of host type I interferon-mediated signaling pathway	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete

References

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