Duck Circovirus genotype 2 ORF3 protein induces apoptosis through the mitochondrial pathway
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 rema...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-04-01
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| Series: | Poultry Science |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0032579123000573 |
| _version_ | 1797854334816354304 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Juan Huang |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-09T20:05:25Z |
| format | Article |
| id | doaj.art-7b351ee67f8a426bb1d36fa4bf6ab734 |
| institution | Directory Open Access Journal |
| issn | 0032-5791 |
| language | English |
| last_indexed | 2024-04-09T20:05:25Z |
| publishDate | 2023-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Poultry Science |
| spelling | doaj.art-7b351ee67f8a426bb1d36fa4bf6ab7342023-04-02T06:10:54ZengElsevierPoultry Science0032-57912023-04-011024102533Duck Circovirus genotype 2 ORF3 protein induces apoptosis through the mitochondrial pathwayJuan Huang0Yanting Zhang1Anchun Cheng2Mingshu Wang3Mafeng Liu4Dekang Zhu5Shun Chen6Xinxin Zhao7Qiao Yang8Ying Wu9Shaqiu Zhang10Xumin Ou11Sai Mao12Qun Gao13Di Sun14Bin Tian15Zhongqiong Yin16Renyong Jia17Research 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, ChinaResearch 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, ChinaResearch 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, ChinaResearch 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, ChinaResearch 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, ChinaResearch 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, ChinaResearch 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, ChinaResearch 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, ChinaResearch 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, ChinaResearch 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, ChinaResearch 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, ChinaResearch 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, ChinaResearch 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, ChinaResearch 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, ChinaResearch 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, ChinaResearch 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, ChinaKey Laboratory of Animal Disease and Human Health of Sichuan Province, Chengdu, Sichuan, 611130, ChinaResearch 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: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.http://www.sciencedirect.com/science/article/pii/S0032579123000573duck circovirus genotype 2ORF3 proteinDEFapoptosismitochondrial apoptosis pathway |
| spellingShingle | 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 Duck Circovirus genotype 2 ORF3 protein induces apoptosis through the mitochondrial pathway Poultry Science duck circovirus genotype 2 ORF3 protein DEF apoptosis mitochondrial apoptosis pathway |
| title | Duck Circovirus genotype 2 ORF3 protein induces apoptosis through the mitochondrial pathway |
| title_full | Duck Circovirus genotype 2 ORF3 protein induces apoptosis through the mitochondrial pathway |
| title_fullStr | Duck Circovirus genotype 2 ORF3 protein induces apoptosis through the mitochondrial pathway |
| title_full_unstemmed | Duck Circovirus genotype 2 ORF3 protein induces apoptosis through the mitochondrial pathway |
| title_short | Duck Circovirus genotype 2 ORF3 protein induces apoptosis through the mitochondrial pathway |
| title_sort | duck circovirus genotype 2 orf3 protein induces apoptosis through the mitochondrial pathway |
| topic | duck circovirus genotype 2 ORF3 protein DEF apoptosis mitochondrial apoptosis pathway |
| url | http://www.sciencedirect.com/science/article/pii/S0032579123000573 |
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