2. Academic Validation
  3. Replication of Porcine Astrovirus Type 1-Infected PK-15 Cells In Vitro Affected by RIG-I and MDA5 Signaling Pathways

Replication of Porcine Astrovirus Type 1-Infected PK-15 Cells In Vitro Affected by RIG-I and MDA5 Signaling Pathways

  • Microbiol Spectr. 2023 May 4;e0070123. doi: 10.1128/spectrum.00701-23.
Qinting Dong 1 2 3 4,  Xinyue Zhu 1 2 3 4,  Leping Wang 1,  Wenchao Zhang 1 2 3 4,  Lifei Lu 1 2 3 4,  Jun Li 5 6,  Shuhong Zhong 5 6,  Chunxia Ma 5 6,  Kang Ouyang 1 2 3 4,  Ying Chen 1 2 3 4,  Zuzhang Wei 1 2 3 4,  Yifeng Qin 1 2 3 4,  Hao Peng 5 6,  Weijian Huang 1 2 3 4
Affiliations

Affiliations

  • 1 Laboratory of Animal Infectious Diseases and Molecular Immunology, College of Animal Science and Technology, Guangxi University, Nanning, China.
  • 2 Guangxi Zhuang Autonomous Region Engineering Research Center of Veterinary Biologics, Nanning, China.
  • 3 Guangxi Key Laboratory of Animal Reproduction, Breeding and Disease Control, Nanning, China.
  • 4 Guangxi Colleges and Universities Key Laboratory of Prevention and Control for Animal Disease, Nanning, China.
  • 5 Guangxi Key Laboratory of Veterinary Biotechnology, Guangxi Veterinary Research Institute, Nanning, Guangxi, China.
  • 6 Key Laboratory of China (Guangxi)-ASEAN Cross-Border Animal Disease Prevention and Control, Ministry of Agriculture and Rural Affairs of China, Nanning, China.
PMID: 37140381 DOI: 10.1128/spectrum.00701-23
Abstract

The interferon (IFN) system is an extremely powerful Antiviral response in animal cells. The subsequent effects caused by porcine astrovirus type 1 (PAstV1) IFN activation are important for the host's response to viral infections. Here, we show that this virus, which causes mild diarrhea, growth retardation, and damage of the villi of the small intestinal mucosa in piglets, induces an IFN response upon Infection of PK-15 cells. Although IFN-β mRNA was detected within infected cells, this response usually occurs during the middle stages of Infection, after genome replication has taken place. Treatment of PAstV1-infected cells with the interferon regulatory factor 3 (IRF3) inhibitor BX795 decreased IFN-β expression, whereas the nuclear factor kappa LIGHT chain enhancer of activated B cells (NF-κB) inhibitor BAY11-7082 did not. These findings indicate that PAstV induced the production of IFN-β via IRF3-mediated rather than NF-κB-mediated signaling pathways in PK-15 cells. Moreover, PAstV1 increased the protein expression levels of retinoic acid-inducible gene I (RIG-I) and melanoma differentiation-associated protein 5 (MDA5) in PK-15 cells. The knockdown of RIG-I and MDA5 decreased the expression levels of IFN-β and the viral loads and increased the infectivity of PAstV1. In conclusion, PAstV1 induced the production of IFN-β via the RIG-I and MDA5 signaling pathways, and the IFN-β produced during PAstV1 Infection inhibited viral replication. These results will help provide new evidence that PAstV1-induced IFNs may protect against PAstV replication and pathogenesis. IMPORTANCE Astroviruses (AstVs) are widespread and can infect multiple species. Porcine astroviruses produce mainly gastroenteritis and neurological diseases in pigs. However, astrovirus-host interactions are less well studied, particularly with respect to their antagonism of IFN. Here, we report that PAstV1 acts via IRF3 transcription pathway activation of IFN-β. In addition, the knockdown of RIG-I and MDA5 attenuated the production of IFN-β induced by PAstV1 in PK-15 cells and increased efficient viral replication in vitro. We believe that these findings will help us to better understand the mechanism of how AstVs affect the host IFN response.

Keywords

MDA5; PAstV; RIG-I; interferon; viral replication.

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