期刊
ONCOTARGET
卷 8, 期 30, 页码 49655-49670出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.17912
关键词
coronavirus; nucleocapsid protein; innate immunity evasion; type I interferon; PACT
资金
- National Key RD Plan of China [2016YFD0500103]
- Key Technology R&D Program of China [2015BAD12B02]
- National Natural Science Foundation of China [31672569]
- Natural Science Foundation of Hubei Province [2014CFA009]
- PhD Candidate Research Innovation Project of Huazhong Aricultural University [2014bs16]
Coronaviruses (CoVs) are a huge threat to both humans and animals and have evolved elaborate mechanisms to antagonize interferons (IFNs). Nucleocapsid (N) protein is the most abundant viral protein in CoV-infected cells, and has been identified as an innate immunity antagonist in several CoVs, including mouse hepatitis virus (MHV) and severe acute respiratory syndrome (SARS)-CoV. However, the underlying molecular mechanism(s) remain unclear. In this study, we found that MHV N protein inhibited Sendai virus and poly(I:C)-induced IFN-beta production by targeting a molecule upstream of retinoic acid-induced gene I (RIG-I) and melanoma differentiation gene 5 (MDA5). Further studies showed that both MHV and SARS-CoV N proteins directly interacted with protein activator of protein kinase R (PACT), a cellular dsRNA-binding protein that can bind to RIG-I and MDA5 to activate IFN production. The N-PACT interaction sequestered the association of PACT and RIG-I/MDA5, which in turn inhibited IFN-beta production. However, the N proteins from porcine epidemic diarrhea virus (PEDV) and porcine reproductive and respiratory syndrome virus (PRRSV), which are also classified in the order Nidovirales, did not interact and counteract with PACT. Taken together, our present study confirms that both MHV and SARS-CoV N proteins can perturb the function of cellular PACT to circumvent the innate antiviral response. However, this strategy does not appear to be used by all CoVs N proteins.
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