Nonstructural Protein 1 of Variant PEDV Plays a Key Role in Escaping Replication Restriction by Complement C3

Baochao Fan, Qi Peng, Shiying Song, Danyi Shi, Xue Zhang, Weilu Guo, Yunchuan Li, Jinzhu Zhou, Xuejiao Zhu, Yongxiang Zhao, Rongli Guo, Kongwang He, Huiying Fan, Siyuan Ding, Bin Li

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Zoonotic coronaviruses represent an ongoing threat to public health. The classical porcine epidemic diarrhea virus (PEDV) first appeared in the early 1970s. Since 2010, outbreaks of highly virulent PEDV variants have caused great economic losses to the swine industry worldwide. However, the strategies by which PEDV variants escape host immune responses are not fully understood. Complement component 3 (C3) is considered a central component of the three complement activation pathways and plays a crucial role in preventing viral infection. In this study, we found that C3 significantly inhibited PEDV replication in vitro, and both variant and classical PEDV strains induced high levels of interleukin-1β (IL-1β) in Huh7 cells. However, the PEDV variant strain reduces C3 transcript and protein levels induced by IL-1β compared with the PEDV classical strain. Examination of key molecules of the C3 transcriptional signaling pathway revealed that variant PEDV reduced C3 by inhibiting CCAAT/ enhancer-βinding protein β (C/EBP-β) phosphorylation. Mechanistically, PEDV nonstructural protein 1 (NSP1) inhibited C/EBP-β phosphorylation via amino acid residue 50. Finally, we constructed recombinant PEDVs to verify the critical role of amino acid 50 of NSP1 in the regulation of C3 expression. In summary, we identified a novel antiviral role of C3 in inhibiting PEDV replication and the viral immune evasion strategies of PEDV variants. Our study reveals new information on PEDV-host interactions and furthers our understanding of the pathogenic mechanism of this virus.

Original languageEnglish
JournalJournal of virology
Volume96
Issue number18
DOIs
StatePublished - Sep 2022

Keywords

  • C/EBP-β
  • NSP1
  • PEDV
  • complement C3
  • replication

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