PMID- 20850164
OWN - NLM
STAT- MEDLINE
DCOM- 20101104
LR  - 20231213
IS  - 1096-0341 (Electronic)
IS  - 0042-6822 (Linking)
VI  - 407
IP  - 2
DP  - 2010 Nov 25
TI  - Nonstructural protein 1alpha subunit-based inhibition of NF-kappaB activation and 
      suppression of interferon-beta production by porcine reproductive and respiratory 
      syndrome virus.
PG  - 268-80
LID - 10.1016/j.virol.2010.08.025 [doi]
AB  - Induction of type I interferon (IFN-alpha/beta) is an early antiviral response of the 
      host, and porcine reproductive and respiratory syndrome virus (PRRSV) has been 
      reported to downregulate the IFN response during infection in cells and pigs. We 
      report that the PRRSV nonstructural protein 1alpha (Nsp1alpha) subunit of Nsp1 is a 
      nuclear-cytoplasmic protein distributed to the nucleus and contains a strong 
      suppressive activity for IFN-beta production that is mediated through the retinoic 
      acid-inducible gene I (RIG-I) signaling pathway. Nsp1alpha suppressed the activation 
      of nuclear factor (NF)-kappaB when stimulated with dsRNA or tumor necrosis factor 
      (TNF)-alpha, and NF-kappaB suppression was RIG-I-dependent. The suppression of NF-kappaB 
      activation was associated with the poor production of IFN-beta during PRRSV 
      infection. The C-terminal 14 amino acids of the Nsp1alpha subunit were critical in 
      maintaining immunosuppressive activity of Nsp1alpha for both IFN-beta and NF-kappaB, 
      suggesting that the newly identified zinc finger configuration comprising of 
      Met180 may be crucial for inhibitory activities. Nsp1alpha inhibited IkappaB 
      phosphorylation and as a consequence NF-kappaB translocation to the nucleus was 
      blocked, leading to the inhibition of NF-kappaB stimulated gene expression. Our 
      results suggest that PRRSV Nsp1alpha is a multifunctional nuclear protein 
      participating in the modulation of the host IFN system.
CI  - Copyright (c) 2010 Elsevier Inc. All rights reserved.
FAU - Song, Cheng
AU  - Song C
AD  - Department of Pathobiology, University of Guelph, Guelph, Ontario, Canada N1G 
      2W1.
FAU - Krell, Peter
AU  - Krell P
FAU - Yoo, Dongwan
AU  - Yoo D
LA  - eng
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20100917
PL  - United States
TA  - Virology
JT  - Virology
JID - 0110674
RN  - 0 (NF-kappa B)
RN  - 0 (Receptors, Immunologic)
RN  - 0 (Viral Nonstructural Proteins)
RN  - 77238-31-4 (Interferon-beta)
RN  - EC 3.6.1.- (RIGI protein, human)
RN  - EC 3.6.4.13 (DEAD Box Protein 58)
RN  - EC 3.6.4.13 (DEAD-box RNA Helicases)
SB  - IM
MH  - Animals
MH  - Cell Line
MH  - DEAD Box Protein 58
MH  - DEAD-box RNA Helicases/genetics/metabolism
MH  - Down-Regulation/*drug effects
MH  - HeLa Cells
MH  - Humans
MH  - Interferon-beta/*drug effects/genetics/metabolism
MH  - NF-kappa B/*drug effects/genetics/metabolism
MH  - Porcine respiratory and reproductive syndrome 
      virus/genetics/metabolism/*pathogenicity
MH  - Receptors, Immunologic
MH  - Signal Transduction
MH  - Swine
MH  - Viral Nonstructural Proteins/genetics/metabolism/*pharmacology
EDAT- 2010/09/21 06:00
MHDA- 2010/11/05 06:00
CRDT- 2010/09/21 06:00
PHST- 2010/05/14 00:00 [received]
PHST- 2010/06/22 00:00 [revised]
PHST- 2010/08/20 00:00 [accepted]
PHST- 2010/09/21 06:00 [entrez]
PHST- 2010/09/21 06:00 [pubmed]
PHST- 2010/11/05 06:00 [medline]
AID - S0042-6822(10)00555-6 [pii]
AID - 10.1016/j.virol.2010.08.025 [doi]
PST - ppublish
SO  - Virology. 2010 Nov 25;407(2):268-80. doi: 10.1016/j.virol.2010.08.025. Epub 2010 
      Sep 17.