PMID- 29325778 OWN - NLM STAT- MEDLINE DCOM- 20180420 LR - 20210109 IS - 1096-0341 (Electronic) IS - 0042-6822 (Print) IS - 0042-6822 (Linking) VI - 517 DP - 2018 Apr TI - Nonstructural proteins nsp2TF and nsp2N of porcine reproductive and respiratory syndrome virus (PRRSV) play important roles in suppressing host innate immune responses. PG - 164-176 LID - S0042-6822(17)30422-1 [pii] LID - 10.1016/j.virol.2017.12.017 [doi] AB - Recently, we identified a unique -2/-1 ribosomal frameshift mechanism in PRRSV, which yields two truncated forms of nonstructural protein (nsp) 2 variants, nsp2TF and nsp2N. Here, in vitro expression of individual PRRSV nsp2TF and nsp2N demonstrated their ability to suppress cellular innate immune responses in transfected cells. Two recombinant viruses were further analyzed, in which either nsp2TF was C-terminally truncated (vKO1) or expression of both nsp2TF and nsp2N was knocked out (vKO2). Host cellular mRNA profiling showed that a panel of cellular immune genes, in particular those involved in innate immunity, was upregulated in cells infected with vKO1 and vKO2. Compared to the wild-type virus, vKO1 and vKO2 expedited the IFN-alpha response and increased NK cell cytotoxicity, and subsequently enhanced T cell immune responses in infected pigs. Our data strongly implicate nsp2TF/nsp2N in arteriviral immune evasion and demonstrate that nsp2TF/nsp2N-deficient PRRSV is less capable of counteracting host innate immune responses. CI - Copyright (c) 2017 The Authors. Published by Elsevier Inc. All rights reserved. FAU - Li, Y AU - Li Y AD - Department of Diagnostic Medicine and Pathobiology, Kansas State Veterinary Diagnostic Laboratory, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506, USA. FAU - Shang, P AU - Shang P AD - Department of Diagnostic Medicine and Pathobiology, Kansas State Veterinary Diagnostic Laboratory, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506, USA. FAU - Shyu, D AU - Shyu D AD - Food Animal Health Research Program (FAHRP), Veterinary Preventive Medicine, The Ohio State University, Wooster, OH 44691, USA. FAU - Carrillo, C AU - Carrillo C AD - Physical & Life Sciences Directorate, Lawrence Livermore National Laboratory, Livermore, CA 94550, USA. FAU - Naraghi-Arani, P AU - Naraghi-Arani P AD - Physical & Life Sciences Directorate, Lawrence Livermore National Laboratory, Livermore, CA 94550, USA. FAU - Jaing, Crystal J AU - Jaing CJ AD - Physical & Life Sciences Directorate, Lawrence Livermore National Laboratory, Livermore, CA 94550, USA. FAU - Renukaradhya, G J AU - Renukaradhya GJ AD - Food Animal Health Research Program (FAHRP), Veterinary Preventive Medicine, The Ohio State University, Wooster, OH 44691, USA. FAU - Firth, A E AU - Firth AE AD - Department of Pathology, University of Cambridge, Cambridge CB2 1QP, United Kingdom. FAU - Snijder, E J AU - Snijder EJ AD - Molecular Virology Laboratory, Department of Medical Microbiology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands. FAU - Fang, Y AU - Fang Y AD - Department of Diagnostic Medicine and Pathobiology, Kansas State Veterinary Diagnostic Laboratory, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506, USA. Electronic address: yfang@vet.k-state.edu. LA - eng GR - WT_/Wellcome Trust/United Kingdom GR - 106207/WT_/Wellcome Trust/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20180108 PL - United States TA - Virology JT - Virology JID - 0110674 RN - 0 (RNA, Messenger) RN - 0 (Viral Nonstructural Proteins) SB - IM MH - Animals MH - Cell Line MH - Chlorocebus aethiops MH - Gene Expression Regulation/immunology MH - Immunity, Innate MH - Porcine Reproductive and Respiratory Syndrome/*immunology/virology MH - Porcine respiratory and reproductive syndrome virus/immunology/*metabolism MH - RNA, Messenger/genetics/metabolism MH - Swine MH - Up-Regulation MH - Viral Nonstructural Proteins/*immunology/metabolism PMC - PMC5884420 OTO - NOTNLM OT - Innate immune response OT - PRRSV OT - Ribosomal frameshift OT - nsp2N OT - nsp2TF EDAT- 2018/01/13 06:00 MHDA- 2018/04/21 06:00 PMCR- 2018/04/01 CRDT- 2018/01/13 06:00 PHST- 2017/10/03 00:00 [received] PHST- 2017/12/14 00:00 [revised] PHST- 2017/12/15 00:00 [accepted] PHST- 2018/01/13 06:00 [pubmed] PHST- 2018/04/21 06:00 [medline] PHST- 2018/01/13 06:00 [entrez] PHST- 2018/04/01 00:00 [pmc-release] AID - S0042-6822(17)30422-1 [pii] AID - 10.1016/j.virol.2017.12.017 [doi] PST - ppublish SO - Virology. 2018 Apr;517:164-176. doi: 10.1016/j.virol.2017.12.017. Epub 2018 Jan 8.