Autophagy Promotes Porcine Parvovirus Replication and Induces Non-Apoptotic Cell Death in Porcine Placental Trophoblasts.

Xiujuan Zhang,Jie Zhang,Zhenyu Wang,Yingli Xiong,Dewen Tong,Bichen Miao,Songbiao Chen,Qian Du,Ting Shao,Yong Huang

doi:10.3390/v12010015

Xiujuan Zhang, Jie Zhang + Show 8 more

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https://doi.org/10.3390/v12010015

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Journal: Viruses	Publication Date: Dec 20, 2019
Citations: 16	License type: CC BY 4.0

Affiliation: North West Agriculture and Forestry University

Abstract

Autophagy plays important roles in the infection and pathogenesis of many viruses, yet the regulatory roles of autophagy in the process of porcine parvovirus (PPV) infection remain unclear. Herein, we show that PPV infection induces autophagy in porcine placental trophoblasts (PTCs). Induction of autophagy by rapamycin (RAPA) inhibited the occurrence of apoptotic cell death, yet promoted viral replication in PPV-infected cells; inhibition of autophagy by 3-MA or ATG5 knockdown increased cellular apoptosis and reduced PPV replication. Interestingly, we found that in the presence of caspase-inhibitor zVAD-fmk, PPV induces non-apoptotic cell death that was characterized by lysosomal damage and associated with autophagy. Induction of complete autophagy flux by RAPA markedly promoted PPV replication compared with incomplete autophagy induced by RAPA plus bafilomycin (RAPA/BAF) in the early phase of PPV infection (24 h.p.i.). Meanwhile, induction of complete autophagy with RAPA increased lysosomal damage and non-apoptotic cell death in the later phase of PPV infection. Therefore, our data suggest that autophagy can enhance PPV replication and promote the occurrence of lysosomal-damage-associated non-apoptotic cell death in PPV-infected porcine placental trophoblasts.

Highlights

Porcine parvovirus (PPV), belongs to the genus Protoparvovirus of the family Parvoviridae, and is one of the major pathogens causing reproductive disorders in sow [1,2]
24 h.p.i.; LC3-II levels markedly increased in porcine placenta trophoblast cells (PTCs) compared to mock-infected cells at 12 h and remained constant for 24 h, whereas the levels of LC3-I decreased with the increase of infection time (Figure 1A,B), suggesting that autophagosome formation cumulatively increases as porcine parvovirus (PPV) infection progresses
We demonstrated that PPV infection induces cell autophagy, apoptosis and non-apoptotic cell death

Summary

Introduction

Porcine parvovirus (PPV), belongs to the genus Protoparvovirus of the family Parvoviridae, and is one of the major pathogens causing reproductive disorders in sow [1,2]. PPV is characterized as a small non-enveloped virus with a single-stranded DNA genome of about 5000 bases that contains the encoding genes of three major non-structural proteins (NS1, NS2, NS3), three structural proteins (VP1, VP2, VP3) and a late nonstructural protein (SAT) [3,4,5]. PPV structural proteins are responsible for the packaging of single-stranded viral progeny DNA to form infectious progeny virions [6,7,8], while non-structural proteins participate in the regulation of viral replication and its pathogenic process [9,10]. As a dynamic, ubiquitous catabolic process to maintain cellular homeostasis and produce recycling energy, emerges as an important mechanism to regulate virus-host interaction when cells are faced with external stress stimuli [13,14].

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