2. Academic Validation
  3. CyHV-2 infection triggers mitochondrial-mediated apoptosis in GiCF cells by upregulating the pro-apoptotic gene ccBAX

CyHV-2 infection triggers mitochondrial-mediated apoptosis in GiCF cells by upregulating the pro-apoptotic gene ccBAX

  • Fish Shellfish Immunol. 2024 Jan 20:109400. doi: 10.1016/j.fsi.2024.109400.
Wenjie Cheng 1,  Yilin Ren 1,  Chenwei Yu 1,  Tianqi Zhou 1,  Ye Zhang 1,  Liqun Lu 1,  Yanli Liu 2,  Dan Xu 3
Affiliations

Affiliations

  • 1 National Pathogen Collection Center for Aquatic Animals, Shanghai Ocean University, Shanghai 201306, China; National Demonstration Center for Experimental Fisheries Science Education, Shanghai Ocean University, Shanghai 201306, China; Key Laboratory of Freshwater Aquatic Genetic Resources, Ministry of Agriculture, Shanghai Ocean University, Shanghai 201306, China.
  • 2 State Key Laboratory of NBC Protection for Civilian, Beijing 102205, China. Electronic address: liu3062023@163.com.
  • 3 National Pathogen Collection Center for Aquatic Animals, Shanghai Ocean University, Shanghai 201306, China; National Demonstration Center for Experimental Fisheries Science Education, Shanghai Ocean University, Shanghai 201306, China; Key Laboratory of Freshwater Aquatic Genetic Resources, Ministry of Agriculture, Shanghai Ocean University, Shanghai 201306, China. Electronic address: dxu@shou.edu.cn.
PMID: 38253137 DOI: 10.1016/j.fsi.2024.109400
Abstract

Apoptosis is a physiological cell death phenomenon, representing one of the fundamental physiological mechanisms for maintaining homeostasis in living organisms. Previous studies have observed typical apoptotic features in Carassius auratus gibelio caudal fin cell (GiCF) infected with Cyprinid herpesvirus 2 (CyHV-2), and found a significant up-regulation of ccBAX expression in these infected cells. However, the specific apoptotic mechanism involved remains unclear. In this study, we utilized the GiCF cell line to investigate the apoptotic mechanism during CyHV-2 Infection. Immunofluorescence staining revealed translocation of ccBAX into mitochondria upon CyHV-2 Infection. Flow cytometry analysis demonstrated that overexpression of ccBAX expedited virus-induced Apoptosis, characterized by heightened mitochondrial depolarization, increased transcriptional levels of Cytochrome c (Cyto c) in both the cytoplasm and mitochondria, and augmented Caspase 3/7 Enzyme activity. Bax Inhibitor peptide V5 (BIP-V5), an inhibitor interfering with the function of Bax proteins, inhibited Bax-mediated apoptotic events through the mitochondrial pathway and attenuated Apoptosis induced by CyHV-2. In this study, it was identified for the first time that CyHV-2 induces Apoptosis via the mitochondrial pathway in GiCF cells, bridging an important gap in our understanding regarding cell death mechanisms induced by herpesvirus infections in fish species. These findings provide a theoretical basis for comprehending viral apoptotic regulation mechanisms and the prevention and control of cellular pathologies caused by CyHV-2 Infection.

Keywords

Apoptosis; Cyprinid herpesvirus 2 (CyHV-2); Cytochrome c (cyto c); Mitochondria; ccBAX.

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