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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Main Authors: Jianlou Zhang, Jinghui Fan, Yan Li, Shuang Liang, Shanshan Huo, Xing Wang, Yuzhu Zuo, Dan Cui, Wenyan Li, Zhenyu Zhong, Fei Zhong
Format: Article
Language:English
Published: MDPI AG 2019-04-01
Series:Viruses
Subjects:
Online Access:https://www.mdpi.com/1999-4915/11/4/389
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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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