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Activation and evasion of type I interferon responses by SARS-CoV-2.

Xiaobo LeiXiaojing DongRuiyi MaWenjing WangXia XiaoZhongqin TianConghui WangYing WangLi LiLili RenFei GuoZhendong ZhaoZhuo ZhouZichun XiangJianwei Wang
Published in: Nature communications (2020)
The pandemic of COVID-19 has posed an unprecedented threat to global public health. However, the interplay between the viral pathogen of COVID-19, SARS-CoV-2, and host innate immunity is poorly understood. Here we show that SARS-CoV-2 induces overt but delayed type-I interferon (IFN) responses. By screening 23 viral proteins, we find that SARS-CoV-2 NSP1, NSP3, NSP12, NSP13, NSP14, ORF3, ORF6 and M protein inhibit Sendai virus-induced IFN-β promoter activation, whereas NSP2 and S protein exert opposite effects. Further analyses suggest that ORF6 inhibits both type I IFN production and downstream signaling, and that the C-terminus region of ORF6 is critical for its antagonistic effect. Finally, we find that IFN-β treatment effectively blocks SARS-CoV-2 replication. In summary, our study shows that SARS-CoV-2 perturbs host innate immune response via both its structural and nonstructural proteins, and thus provides insights into the pathogenesis of SARS-CoV-2.
Keyphrases
  • sars cov
  • immune response
  • dendritic cells
  • respiratory syndrome coronavirus
  • public health
  • gene expression
  • dna methylation
  • coronavirus disease
  • toll like receptor
  • endothelial cells
  • amino acid
  • inflammatory response