2. Academic Validation
  3. Non-cytopathic bovine viral diarrhea virus (BVDV) inhibits innate immune responses via induction of mitophagy

Non-cytopathic bovine viral diarrhea virus (BVDV) inhibits innate immune responses via induction of mitophagy

  • Vet Res. 2024 Mar 5;55(1):27. doi: 10.1186/s13567-024-01284-z.
Zhijun Li # 1 2,  Ying Zhang # 1 2,  Bao Zhao 1 3,  Qinghong Xue 4,  Chunjiang Wang 5,  Siyu Wan 1 2,  Jingyu Wang 1 2,  Xiwen Chen 6,  Xuefeng Qi 7 8
Affiliations

Affiliations

  • 1 College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, China.
  • 2 Key Laboratory of Ruminant Disease Prevention and Control (West), Ministry of Agriculture and Rural Affairs, Xi'an, China.
  • 3 Shaanxi Animal Disease Control Center, Xi'an, China.
  • 4 China Institute of Veterinary Drug Control, Beijing, China.
  • 5 Hebei Veyong Pharmaceutical Co., Ltd, Shijiazhuang, China.
  • 6 Animal Disease Prevention and Control & Healthy Breeding Engineering Technology Research Center, Mianyang Normal University, Mianyang, Sichuan, China. xwch05@163.com.
  • 7 College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, China. yxyan2002@163.com.
  • 8 Key Laboratory of Ruminant Disease Prevention and Control (West), Ministry of Agriculture and Rural Affairs, Xi'an, China. yxyan2002@163.com.
  • # Contributed equally.
PMID: 38443986 DOI: 10.1186/s13567-024-01284-z
Abstract

Bovine viral diarrhea virus (BVDV) belongs to the genus Pestivirus within the family Flaviviridae. Mitophagy plays important roles in virus-host interactions. Here, we provide evidence that non-cytopathic (NCP) BVDV shifts the balance of mitochondrial dynamics toward fission and induces Mitophagy to inhibit innate immune responses. Mechanistically, NCP BVDV triggers the translocation of dynamin-related protein (Drp1) to mitochondria and stimulates its phosphorylation at Ser616, leading to mitochondrial fission. In parallel, NCP BVDV-induced complete Mitophagy via Parkin-dependent pathway contributes to eliminating damaged mitochondria to inhibit MAVS- and mtDNA-cGAS-mediated innate immunity responses, mtROS-mediated inflammatory responses and Apoptosis initiation. Importantly, we demonstrate that the LIR motif of ERNS is essential for Mitophagy induction. In conclusion, this study is the first to show that NCP BVDV-induced Mitophagy plays a central role in promoting cell survival and inhibiting innate immune responses in vitro.

Keywords

BVDV; MAVS; PINK1-Parkin; cGAS; innate immunity; mitophagy; persistent infection.

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