Duck Circovirus genotype 2 ORF3 protein induces apoptosis through the mitochondrial pathway

Juan Huang; Yanting Zhang; Anchun Cheng; Mingshu Wang; Mafeng Liu; Dekang Zhu; Shun Chen; Xinxin Zhao; Qiao Yang; Ying Wu; Shaqiu Zhang; Xumin Ou; Sai Mao; Qun Gao; Di Sun; Bin Tian; Zhongqiong Yin; Renyong Jia

Poultry Science (Apr 2023)

Duck Circovirus genotype 2 ORF3 protein induces apoptosis through the mitochondrial pathway

Juan Huang,
Yanting Zhang,
Anchun Cheng,
Mingshu Wang,
Mafeng Liu,
Dekang Zhu,
Shun Chen,
Xinxin Zhao,
Qiao Yang,
Ying Wu,
Shaqiu Zhang,
Xumin Ou,
Sai Mao,
Qun Gao,
Di Sun,
Bin Tian,
Zhongqiong Yin,
Renyong Jia

Affiliations

Juan Huang: Research Center of Avian Disease, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan, 611130, China; Institute of Preventive Veterinary Medicine, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan, 611130, China; Key Laboratory of Animal Disease and Human Health of Sichuan Province, Chengdu, Sichuan, 611130, China
Yanting Zhang: Research Center of Avian Disease, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan, 611130, China; Institute of Preventive Veterinary Medicine, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan, 611130, China
Anchun Cheng: Research Center of Avian Disease, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan, 611130, China; Institute of Preventive Veterinary Medicine, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan, 611130, China; Key Laboratory of Animal Disease and Human Health of Sichuan Province, Chengdu, Sichuan, 611130, China
Mingshu Wang: Research Center of Avian Disease, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan, 611130, China; Institute of Preventive Veterinary Medicine, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan, 611130, China; Key Laboratory of Animal Disease and Human Health of Sichuan Province, Chengdu, Sichuan, 611130, China
Mafeng Liu: Research Center of Avian Disease, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan, 611130, China; Institute of Preventive Veterinary Medicine, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan, 611130, China; Key Laboratory of Animal Disease and Human Health of Sichuan Province, Chengdu, Sichuan, 611130, China
Dekang Zhu: Research Center of Avian Disease, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan, 611130, China; Institute of Preventive Veterinary Medicine, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan, 611130, China; Key Laboratory of Animal Disease and Human Health of Sichuan Province, Chengdu, Sichuan, 611130, China
Shun Chen: Research Center of Avian Disease, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan, 611130, China; Institute of Preventive Veterinary Medicine, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan, 611130, China; Key Laboratory of Animal Disease and Human Health of Sichuan Province, Chengdu, Sichuan, 611130, China
Xinxin Zhao: Research Center of Avian Disease, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan, 611130, China; Institute of Preventive Veterinary Medicine, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan, 611130, China; Key Laboratory of Animal Disease and Human Health of Sichuan Province, Chengdu, Sichuan, 611130, China
Qiao Yang: Research Center of Avian Disease, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan, 611130, China; Institute of Preventive Veterinary Medicine, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan, 611130, China; Key Laboratory of Animal Disease and Human Health of Sichuan Province, Chengdu, Sichuan, 611130, China
Ying Wu: Research Center of Avian Disease, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan, 611130, China; Institute of Preventive Veterinary Medicine, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan, 611130, China; Key Laboratory of Animal Disease and Human Health of Sichuan Province, Chengdu, Sichuan, 611130, China
Shaqiu Zhang: Research Center of Avian Disease, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan, 611130, China; Institute of Preventive Veterinary Medicine, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan, 611130, China; Key Laboratory of Animal Disease and Human Health of Sichuan Province, Chengdu, Sichuan, 611130, China
Xumin Ou: Research Center of Avian Disease, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan, 611130, China; Institute of Preventive Veterinary Medicine, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan, 611130, China; Key Laboratory of Animal Disease and Human Health of Sichuan Province, Chengdu, Sichuan, 611130, China
Sai Mao: Research Center of Avian Disease, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan, 611130, China; Institute of Preventive Veterinary Medicine, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan, 611130, China; Key Laboratory of Animal Disease and Human Health of Sichuan Province, Chengdu, Sichuan, 611130, China
Qun Gao: Research Center of Avian Disease, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan, 611130, China; Institute of Preventive Veterinary Medicine, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan, 611130, China; Key Laboratory of Animal Disease and Human Health of Sichuan Province, Chengdu, Sichuan, 611130, China
Di Sun: Research Center of Avian Disease, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan, 611130, China; Institute of Preventive Veterinary Medicine, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan, 611130, China; Key Laboratory of Animal Disease and Human Health of Sichuan Province, Chengdu, Sichuan, 611130, China
Bin Tian: Research Center of Avian Disease, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan, 611130, China; Institute of Preventive Veterinary Medicine, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan, 611130, China; Key Laboratory of Animal Disease and Human Health of Sichuan Province, Chengdu, Sichuan, 611130, China
Zhongqiong Yin: Key Laboratory of Animal Disease and Human Health of Sichuan Province, Chengdu, Sichuan, 611130, China
Renyong Jia: Research Center of Avian Disease, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan, 611130, China; Institute of Preventive Veterinary Medicine, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan, 611130, China; Key Laboratory of Animal Disease and Human Health of Sichuan Province, Chengdu, Sichuan, 611130, China; Corresponding author:

Journal volume & issue: Vol. 102, no. 4
p. 102533

Abstract

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ABSTRACT: Duck circovirus genotype 2 (DuCV2) belongs to the genus Circovirus, family Circoviridae. It can generally cause lymphocyte atrophy and necrosis in ducks, which leads to immunosuppression. The function of the DuCV2 open reading frame 3 (ORF3) protein in viral pathogenesis in host cells remains unclear. Therefore, a series of studies based on ORF3 of the isolate DuCV GH01 strain (belonging to DuCV2) were carried out in duck embryo fibroblasts (DEFs) in this study. The results showed that the ORF3 protein could induce nuclear shrinkage and fragmentation in DEFs. Chromosomal DNA breakage was observed by TUNEL assay. The expression levels of caspase-related genes showed that ORF3 primarily promoted caspase 3 and caspase 9 expression. Furthermore, the protein expression levels of cleaved caspase 3 and cleaved caspase 9 in DEFs were enhanced by ORF3. Thus, ORF3 may activate the mitochondrial apoptosis pathway. When the 20 amino acid residues at the C-terminus of ORF3 (ORF3ΔC20) were deleted, the apoptosis rates were decreased. Moreover, compared to ORF3, ORF3ΔC20 downregulated the mRNA levels of cytochrome c (Cyt c), poly ADP-ribose polymerase (PARP) and apoptosis protease activating factor 1 (Apaf-1), which are the key molecules in the mitochondrial apoptotic pathway. Further study showed that ORF3ΔC20 could reduce the mitochondrial membrane potential (MMP). This study suggested that the DuCV2 ORF3 protein may primarily activate apoptosis through the mitochondrial pathway in DEFs, and this function is ORF3 C20 dependent.

Published in Poultry Science

ISSN: 0032-5791 (Print); 1525-3171 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Agriculture: Animal culture
Website: https://www.journals.elsevier.com/poultry-science

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