Frontiers in Microbiology (Nov 2021)

DHAV-1 Blocks the Signaling Pathway Upstream of Type I Interferon by Inhibiting the Interferon Regulatory Factor 7 Protein

  • Yalan Lai,
  • Yalan Lai,
  • Yalan Lai,
  • Xiaoyan Xia,
  • Xiaoyan Xia,
  • Xiaoyan Xia,
  • Anchun Cheng,
  • Anchun Cheng,
  • Anchun Cheng,
  • Mingshu Wang,
  • Mingshu Wang,
  • Mingshu Wang,
  • Xumin Ou,
  • Xumin Ou,
  • Xumin Ou,
  • Sai Mao,
  • Sai Mao,
  • Sai Mao,
  • Di Sun,
  • Di Sun,
  • Di Sun,
  • Shaqiu Zhang,
  • Shaqiu Zhang,
  • Shaqiu Zhang,
  • Qiao Yang,
  • Qiao Yang,
  • Qiao Yang,
  • Ying Wu,
  • Ying Wu,
  • Ying Wu,
  • Dekang Zhu,
  • Dekang Zhu,
  • Renyong Jia,
  • Renyong Jia,
  • Renyong Jia,
  • Shun Chen,
  • Shun Chen,
  • Shun Chen,
  • Mafeng Liu,
  • Mafeng Liu,
  • Mafeng Liu,
  • Xin-Xin Zhao,
  • Xin-Xin Zhao,
  • Xin-Xin Zhao,
  • Juan Huang,
  • Juan Huang,
  • Juan Huang,
  • Qun Gao,
  • Qun Gao,
  • Qun Gao,
  • Bin Tian,
  • Bin Tian,
  • Yunya Liu,
  • Yunya Liu,
  • Yunya Liu,
  • Yanling Yu,
  • Yanling Yu,
  • Yanling Yu,
  • Ling Zhang,
  • Ling Zhang,
  • Ling Zhang,
  • Leichang Pan,
  • Leichang Pan

DOI
https://doi.org/10.3389/fmicb.2021.700434
Journal volume & issue
Vol. 12

Abstract

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Duck hepatitis A virus (DHAV), which mainly infects 1- to 4-week-old ducklings, has a fatality rate of 95% and poses a huge economic threat to the duck industry. However, the mechanism by which DHAV-1 regulates the immune response of host cells is rarely reported. This study examined whether DHAV-1 contains a viral protein that can regulate the innate immunity of host cells and its specific regulatory mechanism, further exploring the mechanism by which DHAV-1 resists the host immune response. In the study, the dual-luciferase reporter gene system was used to screen the viral protein that regulates the host innate immunity and the target of this viral protein. The results indicate that the DHAV-1 3C protein inhibits the pathway upstream of interferon (IFN)-β by targeting the interferon regulatory factor 7 (IRF7) protein. In addition, we found that the 3C protein inhibits the nuclear translocation of the IRF7 protein. Further experiments showed that the 3C protein interacts with the IRF7 protein through its N-terminus and that the 3C protein degrades the IRF7 protein in a caspase 3-dependent manner, thereby inhibiting the IFN-β-mediated antiviral response to promote the replication of DHAV-1. The results of this study are expected to serve as a reference for elucidating the mechanisms of DHAV-1 infection and pathogenicity.

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