PMID- 20540975
OWN - NLM
STAT- MEDLINE
DCOM- 20101104
LR  - 20100802
IS  - 1872-7492 (Electronic)
IS  - 0168-1702 (Linking)
VI  - 152
IP  - 1-2
DP  - 2010 Sep
TI  - Porcine reproductive and respiratory syndrome virus replication is suppressed by 
      inhibition of the extracellular signal-regulated kinase (ERK) signaling pathway.
PG  - 50-8
LID - 10.1016/j.virusres.2010.06.002 [doi]
AB  - Viruses are known to develop the ability to manipulate a variety of host cell 
      signal transduction pathways in order to facilitate successful virus survival. 
      However, to date, little is known about the intracellular signaling mechanisms 
      involved in porcine reproductive and respiratory syndrome virus (PRRSV) 
      replication. The extracellular signal-regulated kinase (ERK) pathway that 
      transduces signals to modulate a wide range of cellular functions has been shown 
      to regulate a number of viral infections. The present study therefore aimed to 
      determine the role of this pathway during PRRSV infection in porcine alveolar 
      macrophages. We found that the PRRSV infection induces early robust but transient 
      activation of ERK1/2 by 6h postinfection and thereafter the progressive decrease 
      of its phosphorylation. However, the maximal induction of phosphorylated ERK1/2 
      seen at 6h postinfection was inconsistent with synthesis of a viral nucleocapsid 
      protein that was first evident by 12h postinfection. These results indicate that 
      ERK1/2 activation is mediated independently of viral gene expression during PRRSV 
      replication. Notably, infection with UV-irradiated, inactivated virus, which is 
      capable of receptor binding and internalization but prevents viral gene 
      synthesis, was sufficient to trigger ERK1/2 phosphorylation, suggesting that the 
      viral entry process may be responsible for early ERK activation. Treatment of 
      cells with U0126, a selective ERK1/2 inhibitor, markedly diminished PRRSV 
      infection and its inhibitory effect on PRRSV replication was exerted at the early 
      stage in virus infection. Furthermore, inhibition of ERK activation resulted in 
      significant suppression of subgenomic RNA transcription, viral protein 
      translation, and progeny virus production. Taken together, the findings in this 
      study suggest that the ERK signaling pathway plays an important role in postentry 
      steps of the PRRSV replication cycle and beneficially contributes to viral 
      infection.
CI  - Copyright (c) 2010 Elsevier B.V. All rights reserved.
FAU - Lee, Yoo Jin
AU  - Lee YJ
AD  - Department of Microbiology, College of Natural Sciences, Kyungpook National 
      University, 1370 Sankyuk-dong, Buk-gu, Daegu, South Korea.
FAU - Lee, Changhee
AU  - Lee C
LA  - eng
PT  - Journal Article
DEP - 20100609
PL  - Netherlands
TA  - Virus Res
JT  - Virus research
JID - 8410979
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3)
SB  - IM
MH  - Animals
MH  - Cell Line, Transformed
MH  - *Down-Regulation
MH  - Enzyme Activation
MH  - *MAP Kinase Signaling System
MH  - Mice
MH  - Mitogen-Activated Protein Kinase 1/genetics/*metabolism
MH  - Mitogen-Activated Protein Kinase 3/genetics/*metabolism
MH  - Phosphorylation
MH  - Porcine Reproductive and Respiratory Syndrome/*enzymology/virology
MH  - Porcine respiratory and reproductive syndrome virus/genetics/*physiology
MH  - Swine
MH  - *Virus Replication
EDAT- 2010/06/15 06:00
MHDA- 2010/11/05 06:00
CRDT- 2010/06/15 06:00
PHST- 2010/02/25 00:00 [received]
PHST- 2010/05/28 00:00 [revised]
PHST- 2010/06/01 00:00 [accepted]
PHST- 2010/06/15 06:00 [entrez]
PHST- 2010/06/15 06:00 [pubmed]
PHST- 2010/11/05 06:00 [medline]
AID - S0168-1702(10)00186-3 [pii]
AID - 10.1016/j.virusres.2010.06.002 [doi]
PST - ppublish
SO  - Virus Res. 2010 Sep;152(1-2):50-8. doi: 10.1016/j.virusres.2010.06.002. Epub 2010 
      Jun 9.