Abstract
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.
Highlights
Porcine parvovirus (PPV) is one of the most important pathogens causing reproductive failure in sows, characterized by infertility, abortion, stillbirth, malformed fetus and mummification
We present evidence to indicate that the PPV-encoded nonstructural protein 1 (NS1) contributes to PPV-induced apoptosis, which is mainly involved in the mitochondria-mediated intrinsic apoptosis pathway
PPV-induced aborted placenta tissues and normal labored placenta tissues were histologically sectioned, the histopathological changes were analyzed by hematoxylin-eosin staining, and the apoptosis was detected by TUNEL staining
Summary
Porcine parvovirus (PPV) is one of the most important pathogens causing reproductive failure in sows, characterized by infertility, abortion, stillbirth, malformed fetus and mummification. Parvovirus of the family Parvoviridae, with a single-stranded DNA genome of ~5 kb encoding three capsid proteins (VP1, VP2, and VP3) and three nonstructural proteins (NS1, NS2, and NS3) [3]. Viruses 2019, 11, 389 the major component of the capsid proteins, possessing strong antigenicity to stimulate host immune responses [4,5] and mediating virus infection by interaction with the PPV receptor. VP1 is the minor component of the virus capsid, and is involved in viral replication [6]. NS1 is an important nonstructural protein participating in viral genome replication, transcriptional regulation, and host cell pathogenicity [7]. NS2 has been identified to be involved in capsid assembly and nuclear export [8]
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