title: The viral non-structural protein 1 alpha (Nsp1α) inhibits p53 apoptosis activity by increasing murine double minute 2 (mdm2) expression in porcine reproductive and respiratory syndrome virus (PRRSV) early-infected cells.
abstract: Apoptosis is one of the most important mechanisms of pathogenesis in porcine reproductive and respiratory syndrome virus (PRRSV)-infected cells. The tumor suppressor p53 plays a critical role in apoptotic induction in viral infections. In the present study, we found that p53 activity was inhibited at the early stage of PRRSV infection in both the highly pathogenic (HP) and lowly pathogenic (LP) PRRSV isolates. Bax expression showed a similar change pattern to that of p53. Murine double minute 2 (mdm2) expressed higher in PRRSV-infected cells than in uninfected cells at the early stage of infection and promoted p53 degradation. We show for the first time that the non-structural protein 1 alpha (Nsp1α) of PRRSV is a negative regulator of p53 activity through increasing mdm2 expression and p53 ubiquitination, while p53 is inhibitory to PRRSV replication at the early stage of infection. We conclude that PRRSV manipulates the host factors mdm2 and p53 via its Nsp1α for increased replication at the early stage of infection. These provide a novel perspective to understand the interaction between apoptosis and replication of PRRSV.
authors: College of Animal Science and Technology, Zhejiang A&F University, Lin'an, China. Electronic address: xiaoduwang@163.com.
authors: Xiaodu
authors: X
authors: Wang
authors: College of Animal Science and Technology, Zhejiang A&F University, Lin'an, China. Electronic address: cyshao0101@163.com.
authors: Chunyan
authors: C
authors: Shao
authors: College of Animal Science and Technology, Zhejiang A&F University, Lin'an, China. Electronic address: luyanhankesi@sina.com.
authors: Luyan
authors: L
authors: Wang
authors: College of Animal Science and Technology, Zhejiang A&F University, Lin'an, China. Electronic address: 646089770@qq.com.
authors: Qunjing
authors: Q
authors: Li
authors: College of Animal Science and Technology, Zhejiang A&F University, Lin'an, China. Electronic address: songhh@zafu.edu.cn.
authors: Houhui
authors: H
authors: Song
authors: College of Animal Science and Technology, Zhejiang A&F University, Lin'an, China; Zhejiang University Institute of Preventive Veterinary Medicine, Zhejiang Province Key Laboratory of Preventive Veterinary Medicine, Hangzhou, China. Electronic address: whfang@zju.edu.cn.
authors: Weihuan
authors: W
authors: Fang
mesh_terms: D000818:Animals; D017209:Apoptosis; D002460:Cell Line; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D005786:Gene Expression Regulation; D019318:Porcine Reproductive and Respiratory Syndrome / Q000503:physiopathology*; D019316:Porcine respiratory and reproductive syndrome virus / Q000502:physiology*; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics*; D013552:Swine; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D054875:Ubiquitination; D017361:Viral Nonstructural Proteins / Q000378:metabolism*; D014779:Virus Replication / Q000502:physiology; D051028:bcl-2-Associated X Protein / Q000235:genetics
chemical_list: D016159:Tumor Suppressor Protein p53; D017361:Viral Nonstructural Proteins; D051028:bcl-2-Associated X Protein; D051736:Proto-Oncogene Proteins c-mdm2
keywords: Apoptosis; Porcine reproductive and respiratory syndrome virus; mdm2; p53