PMID- 20701940 OWN - NLM STAT- MEDLINE DCOM- 20101005 LR - 20100913 IS - 1096-0341 (Electronic) IS - 0042-6822 (Linking) VI - 406 IP - 2 DP - 2010 Oct 25 TI - Porcine reproductive and respiratory syndrome virus non-structural protein 1 suppresses tumor necrosis factor-alpha promoter activation by inhibiting NF-kappaB and Sp1. PG - 270-9 LID - 10.1016/j.virol.2010.07.016 [doi] AB - The objective of this study was to identify porcine reproductive and respiratory syndrome virus (PRRSV)-encoded proteins that are responsible for the inhibition of TNF-alpha expression and the mechanism(s) involved in this phenomenon. Using a TNF-alpha promoter reporter system, the non-structural protein 1 (Nsp1) was found to strongly suppress the TNF-alpha promoter activity. Such inhibition takes place especially at the promoter's proximal region. Both Nsp1alpha and Nsp1beta, the two proteolytic fragments of Nsp1, were shown to be involved in TNF-alpha promoter suppression. Furthermore, using reporter plasmids specific for transcription factors (TFs) that bind to TNF-alpha promoter, Nsp1alpha and Nsp1beta were demonstrated to inhibit the activity of the TFs that bind CRE-kappaB(3) and Sp1 elements respectively. Subsequent analyses showed that Nsp1alpha moderately inhibits NF-kappaB activation and that Nsp1beta completely abrogates the Sp1 transactivation. These findings reveal one of the important mechanisms underlying the innate immune evasion by PRRSV during infection. CI - Copyright (c) 2010 Elsevier Inc. All rights reserved. FAU - Subramaniam, Sakthivel AU - Subramaniam S AD - School of Veterinary Medicine & Biomedical Sciences, University of Nebraska-Lincoln, NE 68583, USA. FAU - Kwon, Byungjoon AU - Kwon B FAU - Beura, Lalit K AU - Beura LK FAU - Kuszynski, Charles A AU - Kuszynski CA FAU - Pattnaik, Asit K AU - Pattnaik AK FAU - Osorio, Fernando A AU - Osorio FA LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20100811 PL - United States TA - Virology JT - Virology JID - 0110674 RN - 0 (NF-kappa B) RN - 0 (Sp1 Transcription Factor) RN - 0 (Tumor Necrosis Factor-alpha) RN - 0 (Viral Nonstructural Proteins) SB - IM MH - Animals MH - Base Sequence MH - Cell Line MH - *Down-Regulation MH - Mice MH - Molecular Sequence Data MH - NF-kappa B/genetics/*metabolism MH - Porcine Reproductive and Respiratory Syndrome/*genetics/metabolism MH - Porcine respiratory and reproductive syndrome virus/genetics/*metabolism MH - *Promoter Regions, Genetic MH - Protein Binding MH - Sp1 Transcription Factor/genetics/*metabolism MH - Swine MH - Transcriptional Activation MH - Tumor Necrosis Factor-alpha/*genetics/metabolism MH - Viral Nonstructural Proteins/genetics/*metabolism EDAT- 2010/08/13 06:00 MHDA- 2010/10/06 06:00 CRDT- 2010/08/13 06:00 PHST- 2010/06/04 00:00 [received] PHST- 2010/07/10 00:00 [accepted] PHST- 2010/08/13 06:00 [entrez] PHST- 2010/08/13 06:00 [pubmed] PHST- 2010/10/06 06:00 [medline] AID - S0042-6822(10)00456-3 [pii] AID - 10.1016/j.virol.2010.07.016 [doi] PST - ppublish SO - Virology. 2010 Oct 25;406(2):270-9. doi: 10.1016/j.virol.2010.07.016. Epub 2010 Aug 11.