PMID- 26854347 OWN - NLM STAT- MEDLINE DCOM- 20161011 LR - 20191210 IS - 1873-2542 (Electronic) IS - 0378-1135 (Linking) VI - 184 DP - 2016 Feb 29 TI - The viral non-structural protein 1 alpha (Nsp1alpha) inhibits p53 apoptosis activity by increasing murine double minute 2 (mdm2) expression in porcine reproductive and respiratory syndrome virus (PRRSV) early-infected cells. PG - 73-9 LID - S0378-1135(16)30009-8 [pii] LID - 10.1016/j.vetmic.2016.01.009 [doi] AB - 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 (Nsp1alpha) 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 Nsp1alpha for increased replication at the early stage of infection. These provide a novel perspective to understand the interaction between apoptosis and replication of PRRSV. CI - Copyright (c) 2016 Elsevier B.V. All rights reserved. FAU - Wang, Xiaodu AU - Wang X AD - College of Animal Science and Technology, Zhejiang A&F University, Lin'an, China. Electronic address: xiaoduwang@163.com. FAU - Shao, Chunyan AU - Shao C AD - College of Animal Science and Technology, Zhejiang A&F University, Lin'an, China. Electronic address: cyshao0101@163.com. FAU - Wang, Luyan AU - Wang L AD - College of Animal Science and Technology, Zhejiang A&F University, Lin'an, China. Electronic address: luyanhankesi@sina.com. FAU - Li, Qunjing AU - Li Q AD - College of Animal Science and Technology, Zhejiang A&F University, Lin'an, China. Electronic address: 646089770@qq.com. FAU - Song, Houhui AU - Song H AD - College of Animal Science and Technology, Zhejiang A&F University, Lin'an, China. Electronic address: songhh@zafu.edu.cn. FAU - Fang, Weihuan AU - Fang W AD - 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. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20160114 PL - Netherlands TA - Vet Microbiol JT - Veterinary microbiology JID - 7705469 RN - 0 (Tumor Suppressor Protein p53) RN - 0 (Viral Nonstructural Proteins) RN - 0 (bcl-2-Associated X Protein) RN - EC 2.3.2.27 (Proto-Oncogene Proteins c-mdm2) SB - IM MH - Animals MH - *Apoptosis MH - Cell Line MH - Cells, Cultured MH - Chlorocebus aethiops MH - *Gene Expression Regulation MH - Porcine Reproductive and Respiratory Syndrome/*physiopathology MH - Porcine respiratory and reproductive syndrome virus/*physiology MH - Proto-Oncogene Proteins c-mdm2/*genetics MH - Swine MH - Tumor Suppressor Protein p53/*metabolism MH - Ubiquitination MH - Viral Nonstructural Proteins/*metabolism MH - Virus Replication/physiology MH - bcl-2-Associated X Protein/genetics OTO - NOTNLM OT - Apoptosis OT - Porcine reproductive and respiratory syndrome virus OT - mdm2 OT - p53 EDAT- 2016/02/09 06:00 MHDA- 2016/10/12 06:00 CRDT- 2016/02/09 06:00 PHST- 2015/08/13 00:00 [received] PHST- 2016/01/09 00:00 [revised] PHST- 2016/01/11 00:00 [accepted] PHST- 2016/02/09 06:00 [entrez] PHST- 2016/02/09 06:00 [pubmed] PHST- 2016/10/12 06:00 [medline] AID - S0378-1135(16)30009-8 [pii] AID - 10.1016/j.vetmic.2016.01.009 [doi] PST - ppublish SO - Vet Microbiol. 2016 Feb 29;184:73-9. doi: 10.1016/j.vetmic.2016.01.009. Epub 2016 Jan 14.