PMID- 21255624
OWN - NLM
STAT- MEDLINE
DCOM- 20111103
LR  - 20211020
IS  - 1872-7492 (Electronic)
IS  - 0168-1702 (Print)
IS  - 0168-1702 (Linking)
VI  - 156
IP  - 1-2
DP  - 2011 Mar
TI  - Regulation of STAT signaling in mouse bone marrow derived dendritic cells by 
      respiratory syncytial virus.
PG  - 127-33
LID - 10.1016/j.virusres.2011.01.007 [doi]
AB  - BACKGROUND/AIMS: Dendritic cells (DCs) act as a portal for virus invasion as well 
      as potent antigen-presenting cells (APCs) involved in the antiviral host 
      response. Interferons (IFNs) are produced in response to bacterial and viral 
      infection and activate innate immune responses to efficiently counteract and 
      remove pathogenic invaders. Respiratory syncytial virus (RSV) could inhibit 
      IFN-mediated signaling pathway in epithelial cells; however, the effects of RSV 
      on IFN signaling in the dendritic cells (DCs) are still unknown. METHODS: Mouse 
      bone marrow derived DCs (BMDCs) were mock or infected with RSV at different 
      multiplicity of infection (MOI) for 24h, and then treated with different 
      cytokines such as interferon-beta (IFN-beta), IFN-gamma or interleukin-10 (IL-10). The mRNA 
      expression of RSV nonstructural protein-1 (NS-1) and NS-2 was detected by RT-PCR. 
      The expression of Janus family kinase-signal transducer and activator of 
      transcription (JAK/STAT) signaling proteins was assessed by immunoblotting 
      assays. The nuclear localization of specific signaling proteins was determined by 
      immunofluorescence assay. RESULTS: Increasing amounts of NS-1 or NS-2 mRNA 
      expression in BMDCs were observed with infected RSV at increasing MOI, suggesting 
      BMDCs were permissive for viral gene expression. Further examination of the IFN-beta 
      signaling cascade showed RSV infection increased the total cellular levels of 
      STAT1 and STAT2 in BMDCs, but impaired the IFN-beta-dependent phosphorylation and 
      nuclear localization of STAT1 and STAT2. The inhibitory effects of RSV on STAT1 
      and STAT2 phosphorylation and translocation were abolished by UV inactivation. In 
      contrast, RSV did not inhibit the IFN-gamma-stimulated STAT1 phosphorylation and 
      nuclear localization. IL-10-stimulated STAT3 phosphorylation was also unaffected 
      by RSV. CONCLUSIONS: As well as RSV inhibiting STAT protein levels through 
      degradation mechanisms in epithelial cells, these findings demonstrate that RSV 
      also can specifically inhibit the type I interferon response in BMDCs through 
      regulation of STAT1 and STAT2 phosphorylation and nuclear translocation.
CI  - Copyright (c) 2011 Elsevier B.V. All rights reserved.
FAU - Jie, Zhijun
AU  - Jie Z
AD  - Infectious Diseases Program, Lovelace Respiratory Research Institute, 
      Albuquerque, NM 87108, USA. jiezjlxh@gmail.com
FAU - Dinwiddie, Darrell L
AU  - Dinwiddie DL
FAU - Senft, Albert P
AU  - Senft AP
FAU - Harrod, Kevin S
AU  - Harrod KS
LA  - eng
GR  - K22 HL066994/HL/NHLBI NIH HHS/United States
GR  - R01 HL066964/HL/NHLBI NIH HHS/United States
GR  - HL-66994/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20110119
PL  - Netherlands
TA  - Virus Res
JT  - Virus research
JID - 8410979
RN  - 0 (STAT Transcription Factors)
RN  - 130068-27-8 (Interleukin-10)
RN  - 9008-11-1 (Interferons)
SB  - IM
MH  - Animals
MH  - Bone Marrow Cells/immunology
MH  - Cell Nucleus/metabolism
MH  - Cells, Cultured
MH  - Dendritic Cells/cytology/*immunology/*metabolism/virology
MH  - Interferons/metabolism
MH  - Interleukin-10/metabolism
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Respiratory Syncytial Viruses/*immunology
MH  - STAT Transcription Factors/*metabolism
MH  - *Signal Transduction
MH  - Virus Replication/genetics
PMC - PMC3726278
MID - NIHMS387765
EDAT- 2011/01/25 06:00
MHDA- 2011/11/04 06:00
PMCR- 2013/07/29
CRDT- 2011/01/25 06:00
PHST- 2010/10/07 00:00 [received]
PHST- 2011/01/11 00:00 [revised]
PHST- 2011/01/13 00:00 [accepted]
PHST- 2011/01/25 06:00 [entrez]
PHST- 2011/01/25 06:00 [pubmed]
PHST- 2011/11/04 06:00 [medline]
PHST- 2013/07/29 00:00 [pmc-release]
AID - S0168-1702(11)00023-2 [pii]
AID - 10.1016/j.virusres.2011.01.007 [doi]
PST - ppublish
SO  - Virus Res. 2011 Mar;156(1-2):127-33. doi: 10.1016/j.virusres.2011.01.007. Epub 
      2011 Jan 19.