Porcine Parvovirus Infection Causes Pig Placenta Tissue Damage Involving Nonstructural Protein 1 (NS1)-Induced Intrinsic ROS/Mitochondria-Mediated Apoptosis
Porcine parvovirus (PPV) is an important pathogen causing reproductive failure in pigs. PPV-induced cell apoptosis has been recently identified as being involved in PPV-induced placental tissue damages resulting in reproductive failure. However, the molecular mechanism was not fully elucidated. Here...
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MDPI AG
2019-04-01
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author | Jianlou Zhang Jinghui Fan Yan Li Shuang Liang Shanshan Huo Xing Wang Yuzhu Zuo Dan Cui Wenyan Li Zhenyu Zhong Fei Zhong |
author_facet | Jianlou Zhang Jinghui Fan Yan Li Shuang Liang Shanshan Huo Xing Wang Yuzhu Zuo Dan Cui Wenyan Li Zhenyu Zhong Fei Zhong |
author_sort | Jianlou Zhang |
collection | DOAJ |
description | Porcine parvovirus (PPV) is an important pathogen causing reproductive failure in pigs. PPV-induced cell apoptosis has been recently identified as being involved in PPV-induced placental tissue damages resulting in reproductive failure. However, the molecular mechanism was not fully elucidated. Here we demonstrate that PPV nonstructural protein 1 (NS1) can induce host cell apoptosis and death, thereby indicating the NS1 may play a crucial role in PPV-induced placental tissue damages and reproductive failure. We have found that NS1-induced apoptosis was significantly inhibited by caspase 9 inhibitor, but not caspase 8 inhibitor, and transfection of NS1 gene into PK-15 cells significantly inhibited mitochondria-associated antiapoptotic molecules Bcl-2 and Mcl-1 expressions and enhanced proapoptotic molecules Bax, P21, and P53 expressions, suggesting that NS1-induced apoptosis is mainly through the mitochondria-mediated intrinsic apoptosis pathway. We also found that both PPV infection and NS1 vector transfection could cause host DNA damage resulting in cell cycle arrest at the G1 and G2 phases, trigger mitochondrial ROS accumulation resulting in mitochondria damage, and therefore, induce the host cell apoptosis. This study provides a molecular basis for elucidating PPV-induced cell apoptosis and reproductive failure. |
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spelling | doaj.art-1ca07220061544e58a6fa1b1c10e55362022-12-22T03:04:49ZengMDPI AGViruses1999-49152019-04-0111438910.3390/v11040389v11040389Porcine Parvovirus Infection Causes Pig Placenta Tissue Damage Involving Nonstructural Protein 1 (NS1)-Induced Intrinsic ROS/Mitochondria-Mediated ApoptosisJianlou Zhang0Jinghui Fan1Yan Li2Shuang Liang3Shanshan Huo4Xing Wang5Yuzhu Zuo6Dan Cui7Wenyan Li8Zhenyu Zhong9Fei Zhong10Laboratory of Molecular Virology and Immunology, College of Animal Science and Technology/College of Veterinary Medicine, Hebei Agricultural University, Hebei Engineering and Technology Research Center of Veterinary Biotechnology, Baoding 071000, ChinaLaboratory of Molecular Virology and Immunology, College of Animal Science and Technology/College of Veterinary Medicine, Hebei Agricultural University, Hebei Engineering and Technology Research Center of Veterinary Biotechnology, Baoding 071000, ChinaLaboratory of Molecular Virology and Immunology, College of Animal Science and Technology/College of Veterinary Medicine, Hebei Agricultural University, Hebei Engineering and Technology Research Center of Veterinary Biotechnology, Baoding 071000, ChinaDepartment of Immunology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9093, USALaboratory of Molecular Virology and Immunology, College of Animal Science and Technology/College of Veterinary Medicine, Hebei Agricultural University, Hebei Engineering and Technology Research Center of Veterinary Biotechnology, Baoding 071000, ChinaLaboratory of Molecular Virology and Immunology, College of Animal Science and Technology/College of Veterinary Medicine, Hebei Agricultural University, Hebei Engineering and Technology Research Center of Veterinary Biotechnology, Baoding 071000, ChinaLaboratory of Molecular Virology and Immunology, College of Animal Science and Technology/College of Veterinary Medicine, Hebei Agricultural University, Hebei Engineering and Technology Research Center of Veterinary Biotechnology, Baoding 071000, ChinaLaboratory of Molecular Virology and Immunology, College of Animal Science and Technology/College of Veterinary Medicine, Hebei Agricultural University, Hebei Engineering and Technology Research Center of Veterinary Biotechnology, Baoding 071000, ChinaDepartment of Biology, School of Medicine, Hebei University, Baoding 071000, ChinaDepartment of Immunology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9093, USALaboratory of Molecular Virology and Immunology, College of Animal Science and Technology/College of Veterinary Medicine, Hebei Agricultural University, Hebei Engineering and Technology Research Center of Veterinary Biotechnology, Baoding 071000, ChinaPorcine parvovirus (PPV) is an important pathogen causing reproductive failure in pigs. PPV-induced cell apoptosis has been recently identified as being involved in PPV-induced placental tissue damages resulting in reproductive failure. However, the molecular mechanism was not fully elucidated. Here we demonstrate that PPV nonstructural protein 1 (NS1) can induce host cell apoptosis and death, thereby indicating the NS1 may play a crucial role in PPV-induced placental tissue damages and reproductive failure. We have found that NS1-induced apoptosis was significantly inhibited by caspase 9 inhibitor, but not caspase 8 inhibitor, and transfection of NS1 gene into PK-15 cells significantly inhibited mitochondria-associated antiapoptotic molecules Bcl-2 and Mcl-1 expressions and enhanced proapoptotic molecules Bax, P21, and P53 expressions, suggesting that NS1-induced apoptosis is mainly through the mitochondria-mediated intrinsic apoptosis pathway. We also found that both PPV infection and NS1 vector transfection could cause host DNA damage resulting in cell cycle arrest at the G1 and G2 phases, trigger mitochondrial ROS accumulation resulting in mitochondria damage, and therefore, induce the host cell apoptosis. This study provides a molecular basis for elucidating PPV-induced cell apoptosis and reproductive failure.https://www.mdpi.com/1999-4915/11/4/389Porcine parvovirusNS1 proteinapoptosis reactive oxygen speciesmitochondria damageintrinsic pathway |
spellingShingle | Jianlou Zhang Jinghui Fan Yan Li Shuang Liang Shanshan Huo Xing Wang Yuzhu Zuo Dan Cui Wenyan Li Zhenyu Zhong Fei Zhong Porcine Parvovirus Infection Causes Pig Placenta Tissue Damage Involving Nonstructural Protein 1 (NS1)-Induced Intrinsic ROS/Mitochondria-Mediated Apoptosis Viruses Porcine parvovirus NS1 protein apoptosis reactive oxygen species mitochondria damage intrinsic pathway |
title | Porcine Parvovirus Infection Causes Pig Placenta Tissue Damage Involving Nonstructural Protein 1 (NS1)-Induced Intrinsic ROS/Mitochondria-Mediated Apoptosis |
title_full | Porcine Parvovirus Infection Causes Pig Placenta Tissue Damage Involving Nonstructural Protein 1 (NS1)-Induced Intrinsic ROS/Mitochondria-Mediated Apoptosis |
title_fullStr | Porcine Parvovirus Infection Causes Pig Placenta Tissue Damage Involving Nonstructural Protein 1 (NS1)-Induced Intrinsic ROS/Mitochondria-Mediated Apoptosis |
title_full_unstemmed | Porcine Parvovirus Infection Causes Pig Placenta Tissue Damage Involving Nonstructural Protein 1 (NS1)-Induced Intrinsic ROS/Mitochondria-Mediated Apoptosis |
title_short | Porcine Parvovirus Infection Causes Pig Placenta Tissue Damage Involving Nonstructural Protein 1 (NS1)-Induced Intrinsic ROS/Mitochondria-Mediated Apoptosis |
title_sort | porcine parvovirus infection causes pig placenta tissue damage involving nonstructural protein 1 ns1 induced intrinsic ros mitochondria mediated apoptosis |
topic | Porcine parvovirus NS1 protein apoptosis reactive oxygen species mitochondria damage intrinsic pathway |
url | https://www.mdpi.com/1999-4915/11/4/389 |
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