Jiyu Zhang,Hongyan Shi,Liaoyuan Zhang,Tingshuai Feng,Jianfei Chen,Xin Zhang,Zhaoyang Ji,Zhaoyang Jing,Xiaoyuan Zhu,Dakai Liu,Xiaoman Yang,Miaomiao Zeng,Da Shi,Li Feng

Vet Res.2024 Apr 8;55(1):44.doi: 10.1186/s13567-024-01303-z.

Abstract

Swine acute diarrhea syndrome coronavirus (SADS-CoV), an emerging Alpha-coronavirus, brings huge economic loss in swine industry. Interferons (IFNs) participate in a frontline antiviral defense mechanism triggering the activation of numerous downstream antiviral genes. Here, we demonstrated that TRIM25 overexpression significantly inhibited SADS-CoV replication, whereas TRIM25 deficiency markedly increased viral yield. We found that SADS-CoV N protein suppressed interferon-beta (IFN-β) production induced by Sendai virus (SeV) or poly(I:C). Moreover, we determined that SADS-CoV N protein interacted with RIG-I N-terminal two caspase activation and recruitment domains (2CARDs) and TRIM25 coiled-coil dimerization (CCD) domain. The interaction of SADS-CoV N protein with RIG-I and TRIM25 caused TRIM25 multimerization inhibition, the RIG-I-TRIM25 interaction disruption, and consequent the IRF3 and TBK1 phosphorylation impediment. Overexpression of SADS-CoV N protein facilitated the replication of VSV-GFP by suppressing IFN-β production. Our results demonstrate that SADS-CoV N suppresses the host IFN response, thus highlighting the significant involvement of TRIM25 in regulating antiviral immune defenses.

Keywords: RIG-I; Swine acute diarrhea syndrome coronavirus; TRIM25; interferon; nucleocapsid.