Porcine parvovirus infection causes pig placenta tissue damage involving nonstructural protein 1 (NS1)-induced intrinsic ROS/mitochondria-mediated apoptosis

Jianlou Zhang, Jinghui Fan, Yan Li, Shuang Liang, Shanshan Huo, Xing Wang, Yuzhu Zuo, Dan Cui, Wenyan Li, Zhenyu Zhong, Fei Zhong

Research output: Contribution to journalArticle

2 Scopus citations

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.

Original languageEnglish (US)
Article number389
JournalViruses
Volume11
Issue number4
DOIs
StatePublished - Apr 2019

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Keywords

  • Apoptosis reactive oxygen species
  • Intrinsic pathway
  • Mitochondria damage
  • NS1 protein
  • Porcine parvovirus

ASJC Scopus subject areas

  • Infectious Diseases
  • Virology

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