PMID- 27718457 OWN - NLM STAT- MEDLINE DCOM- 20170615 LR - 20171219 IS - 1096-0341 (Electronic) IS - 0042-6822 (Linking) VI - 499 DP - 2016 Dec TI - Nuclear export signal of PRRSV NSP1alpha is necessary for type I IFN inhibition. PG - 278-287 LID - S0042-6822(16)30176-3 [pii] LID - 10.1016/j.virol.2016.07.008 [doi] AB - The nonstructural protein 1alpha (NSP1alpha) of porcine reproductive and respiratory syndrome virus (PRRSV) is a nucleo-cytoplasmic protein that suppresses the production of type I interferon (IFN). In this study, we investigated the relationship between the subcellular distribution of NSP1alpha and its inhibition of type I IFN. NSP1alpha was found to contain the classical nuclear export signal (NES) and NSP1alpha nuclear export was CRM-1-mediated. NSP1alpha was shuttling between the nucleus and cytoplasm. We also showed that the nuclear export of NSP1alpha was necessary for its ability for type I IFN inhibition. NSP1alpha was also found to interact with CBP, which implies a possible mechanism of CBP degradation by NSP1alpha. Taken together, our results describe a novel mechanism of PRRSV NSP1alpha for type I IFN inhibition and suppression of the host innate antiviral response. CI - Copyright (c) 2016. Published by Elsevier Inc. FAU - Chen, Zhi AU - Chen Z AD - Shandong Key Laboratory of Animal Disease Control and Breeding, Institute of Animal Science and Veterinary Medicine, Shandong Academy of Agricultural Sciences, Sangyuan Road No. 8, Jinan 250100, China. FAU - Liu, Shaoning AU - Liu S AD - Shandong Key Laboratory of Animal Disease Control and Breeding, Institute of Animal Science and Veterinary Medicine, Shandong Academy of Agricultural Sciences, Sangyuan Road No. 8, Jinan 250100, China; Shandong Institute of Veterinary Drug Quality Inspection, Shandong Key Laboratory for Quality Safety Monitoring and Risk Assessment of Animal Products, Huaicun Street No. 68, Jinan 250722, Shandong Province, China. FAU - Sun, Wenbo AU - Sun W AD - Shandong Key Laboratory of Animal Disease Control and Breeding, Institute of Animal Science and Veterinary Medicine, Shandong Academy of Agricultural Sciences, Sangyuan Road No. 8, Jinan 250100, China. FAU - Chen, Lei AU - Chen L AD - Shandong Key Laboratory of Animal Disease Control and Breeding, Institute of Animal Science and Veterinary Medicine, Shandong Academy of Agricultural Sciences, Sangyuan Road No. 8, Jinan 250100, China. FAU - Yoo, Dongwan AU - Yoo D AD - Department of Pathobiology, University of Illinois at Urbana-Champaign, 2001 South Lincoln Ave, Urbana, IL 61802, USA. FAU - Li, Feng AU - Li F AD - Department of Biology and Microbiology, Department of Veterinary and Biomedical Sciences, South Dakota State University, Brookings, SD 57007, USA. FAU - Ren, Sufang AU - Ren S AD - Shandong Key Laboratory of Animal Disease Control and Breeding, Institute of Animal Science and Veterinary Medicine, Shandong Academy of Agricultural Sciences, Sangyuan Road No. 8, Jinan 250100, China. FAU - Guo, Lihui AU - Guo L AD - Shandong Key Laboratory of Animal Disease Control and Breeding, Institute of Animal Science and Veterinary Medicine, Shandong Academy of Agricultural Sciences, Sangyuan Road No. 8, Jinan 250100, China. FAU - Cong, Xiaoyan AU - Cong X AD - Shandong Key Laboratory of Animal Disease Control and Breeding, Institute of Animal Science and Veterinary Medicine, Shandong Academy of Agricultural Sciences, Sangyuan Road No. 8, Jinan 250100, China. FAU - Li, Jun AU - Li J AD - Shandong Key Laboratory of Animal Disease Control and Breeding, Institute of Animal Science and Veterinary Medicine, Shandong Academy of Agricultural Sciences, Sangyuan Road No. 8, Jinan 250100, China. FAU - Zhou, Shun AU - Zhou S AD - College of marine science and engineering, Qingdao Agricultural University, Changcheng Road No. 700, Qingdao 266109, China. FAU - Wu, Jiaqiang AU - Wu J AD - Shandong Key Laboratory of Animal Disease Control and Breeding, Institute of Animal Science and Veterinary Medicine, Shandong Academy of Agricultural Sciences, Sangyuan Road No. 8, Jinan 250100, China. Electronic address: wujiaqiang2000@sina.com. FAU - Du, Yijun AU - Du Y AD - Shandong Key Laboratory of Animal Disease Control and Breeding, Institute of Animal Science and Veterinary Medicine, Shandong Academy of Agricultural Sciences, Sangyuan Road No. 8, Jinan 250100, China. Electronic address: duyijun0916@163.com. FAU - Wang, Jinbao AU - Wang J AD - Shandong Key Laboratory of Animal Disease Control and Breeding, Institute of Animal Science and Veterinary Medicine, Shandong Academy of Agricultural Sciences, Sangyuan Road No. 8, Jinan 250100, China. Electronic address: wangjb@saas.ac.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20161006 PL - United States TA - Virology JT - Virology JID - 0110674 RN - 0 (Nuclear Export Signals) RN - 0 (Viral Nonstructural Proteins) RN - 77238-31-4 (Interferon-beta) RN - EC 2.3.1.48 (CREB-Binding Protein) SB - IM MH - Active Transport, Cell Nucleus MH - Animals MH - CREB-Binding Protein/genetics/metabolism MH - Cell Nucleus/genetics/metabolism/virology MH - Cytoplasm/genetics/metabolism/virology MH - Interferon-beta/*genetics/metabolism MH - *Nuclear Export Signals MH - Porcine Reproductive and Respiratory Syndrome/genetics/*metabolism/virology MH - Porcine respiratory and reproductive syndrome virus/chemistry/genetics/*metabolism MH - Promoter Regions, Genetic MH - Protein Binding MH - Proteolysis MH - Swine MH - Viral Nonstructural Proteins/chemistry/genetics/*metabolism OTO - NOTNLM OT - NSP1alpha OT - Nuclear export signal (NES) OT - PRRSV OT - Type I IFN EDAT- 2016/10/09 06:00 MHDA- 2017/06/16 06:00 CRDT- 2016/10/09 06:00 PHST- 2016/03/16 00:00 [received] PHST- 2016/07/04 00:00 [revised] PHST- 2016/07/06 00:00 [accepted] PHST- 2016/10/09 06:00 [pubmed] PHST- 2017/06/16 06:00 [medline] PHST- 2016/10/09 06:00 [entrez] AID - S0042-6822(16)30176-3 [pii] AID - 10.1016/j.virol.2016.07.008 [doi] PST - ppublish SO - Virology. 2016 Dec;499:278-287. doi: 10.1016/j.virol.2016.07.008. Epub 2016 Oct 6.