PMID- 28235682 OWN - NLM STAT- MEDLINE DCOM- 20170526 LR - 20201027 IS - 1096-0341 (Electronic) IS - 0042-6822 (Print) IS - 0042-6822 (Linking) VI - 505 DP - 2017 May TI - Nuclear imprisonment of host cellular mRNA by nsp1beta protein of porcine reproductive and respiratory syndrome virus. PG - 42-55 LID - S0042-6822(17)30036-3 [pii] LID - 10.1016/j.virol.2017.02.004 [doi] AB - Positive-strand RNA genomes function as mRNA for viral protein synthesis which is fully reliant on host cell translation machinery. Competing with cellular protein translation apparatus needs to ensure the production of viral proteins, but this also stifles host innate defense. In the present study, we showed that porcine reproductive and respiratory syndrome virus (PRRSV), whose replication takes place in the cytoplasm, imprisoned host cell mRNA in the nucleus, which suggests a novel mechanism to enhance translation of PRRSV genome. PRRSV nonstructural protein (nsp) 1beta was identified as the nuclear protein playing the role for host mRNA nuclear retention and subversion of host protein synthesis. A SAP (SAF-A/B, Acinus, and PIAS) motif was identified in nsp1beta with the consensus sequence of (126)-LQxxLxxxGL-(135). In situ hybridization unveiled that SAP mutants were unable to cause nuclear retention of host cell mRNAs and did not suppress host protein synthesis. In addition, these SAP mutants reverted PRRSV-nsp1beta-mediated suppression of interferon (IFN) production, IFN signaling, and TNF-alpha production pathway. Using reverse genetics, a series of SAP mutant PRRS viruses, vK124A, vL126A, vG134A, and vL135A were generated. No mRNA nuclear retention was observed during vL126A and vL135A infections. Importantly, vL126A and vL135A did not suppress IFN production. For other arteriviruses, mRNA nuclear accumulation was also observed for LDV-nsp1beta and SHFV-nsp1beta. EAV-nsp1 was exceptional and did not block the host mRNA nuclear export. CI - Copyright (c) 2017 Elsevier Inc. All rights reserved. FAU - Han, Mingyuan AU - Han M AD - Department of Pathobiology, University of Illinois at Urbana-Champaign, 2001 South Lincoln Avenue, Urbana, IL 61802, USA. Electronic address: hanming@umich.edu. FAU - Ke, Hanzhong AU - Ke H AD - Department of Pathobiology, University of Illinois at Urbana-Champaign, 2001 South Lincoln Avenue, Urbana, IL 61802, USA. FAU - Zhang, Qingzhan AU - Zhang Q AD - Department of Pathobiology, University of Illinois at Urbana-Champaign, 2001 South Lincoln Avenue, Urbana, IL 61802, USA. FAU - Yoo, Dongwan AU - Yoo D AD - Department of Pathobiology, University of Illinois at Urbana-Champaign, 2001 South Lincoln Avenue, Urbana, IL 61802, USA. Electronic address: dyoo@illinois.edu. LA - eng PT - Journal Article DEP - 20170220 PL - United States TA - Virology JT - Virology JID - 0110674 RN - 0 (RNA, Messenger) RN - 0 (Viral Nonstructural Proteins) RN - 9008-11-1 (Interferons) SB - IM MH - Active Transport, Cell Nucleus/*physiology MH - Animals MH - Cell Line, Tumor MH - Cell Nucleus/genetics MH - Chlorocebus aethiops MH - HeLa Cells MH - Host-Pathogen Interactions MH - Humans MH - Immunity, Innate/immunology MH - Interferons/biosynthesis/metabolism MH - Mice MH - Porcine respiratory and reproductive syndrome virus/*genetics/*physiology MH - Protein Biosynthesis/*genetics MH - RNA, Messenger/*genetics MH - Signal Transduction MH - Viral Nonstructural Proteins/genetics/*metabolism MH - Virus Replication/*physiology PMC - PMC7111332 OTO - NOTNLM OT - Arterivirus OT - Interferon suppression OT - MRNA nuclear export OT - Nsp1 OT - PRRSV OT - Pathogenesis OT - SAP motif EDAT- 2017/02/27 06:00 MHDA- 2017/05/27 06:00 PMCR- 2017/02/20 CRDT- 2017/02/26 06:00 PHST- 2016/11/16 00:00 [received] PHST- 2017/02/03 00:00 [revised] PHST- 2017/02/08 00:00 [accepted] PHST- 2017/02/27 06:00 [pubmed] PHST- 2017/05/27 06:00 [medline] PHST- 2017/02/26 06:00 [entrez] PHST- 2017/02/20 00:00 [pmc-release] AID - S0042-6822(17)30036-3 [pii] AID - 10.1016/j.virol.2017.02.004 [doi] PST - ppublish SO - Virology. 2017 May;505:42-55. doi: 10.1016/j.virol.2017.02.004. Epub 2017 Feb 20.