PMID- 16002711
OWN - NLM
STAT- MEDLINE
DCOM- 20050927
LR  - 20191210
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 175
IP  - 2
DP  - 2005 Jul 15
TI  - Critical role for the oligoadenylate synthetase/RNase L pathway in response to 
      IFN-beta during acute ocular herpes simplex virus type 1 infection.
PG  - 1100-6
AB  - We previously demonstrated that IFN-beta transgene treatment protects mouse 
      trigeminal ganglia (TG) cells from acute HSV-1 infection in vitro. However, 
      IFN-alpha6 transgene treatment does not provide protection against acute HSV-1 
      infection in vitro, even though equivalent levels of IFN are expressed with both 
      transgene treatments. In the present study we show that IFN-beta transgene 
      treatment before acute ocular HSV-1 infection protects mice from HSV-1-mediated 
      mortality, whereas IFN-alpha6 transgene treatment does not reduce mortality. 
      Treatment with the IFN-beta and IFN-alpha6 transgenes was associated with 
      increased expression of oligoadenylate synthetase (OAS)1a mRNA in the eye. 
      However, protein kinase R mRNA was not up-regulated in the eye. In TG, only 
      IFN-beta transgene treatment reduced infectious virus levels. Furthermore, in the 
      absence of a functional OAS pathway, corneal HSV-1 Ag expression was more 
      widespread, and the ability of IFN-beta transgene treatment to reduce infectious 
      HSV-1 in eyes and TG was lost. Along with selective up-regulation of OAS1a mRNA 
      expression in TG from IFN-beta transgene-treated mice, we found increased levels 
      of phospho-STAT1. Likewise, p38 MAPK phosphorylation was increased in TG from 
      IFN-beta transgene-treated mice, compared with both IFN-alpha6 and vector-treated 
      mice. We also observed a time-dependent increase in JNK phosphorylation in TG 
      from IFN-beta transgene-treated vs IFN-alpha6 and vector-treated mice. Our 
      results demonstrate that IFN-beta is a potent antiviral cytokine that exerts 
      protection against ocular HSV-1 infection via selective up-regulation of OAS1a 
      mRNA in TG and by altering the phosphorylation of proteins in antiviral signaling 
      cascades.
FAU - Austin, Bobbie Ann
AU  - Austin BA
AD  - Department of Ophthalmology, University of Oklahoma Health Sciences Center, 
      Biomedical Sciences Building, 608 Stanton L. Young Boulevard, Oklahoma City, OK 
      73104, USA.
FAU - James, Cassandra
AU  - James C
FAU - Silverman, Robert H
AU  - Silverman RH
FAU - Carr, Daniel J J
AU  - Carr DJ
LA  - eng
GR  - AI 053108/AI/NIAID NIH HHS/United States
GR  - CA 44059/CA/NCI NIH HHS/United States
GR  - EY 12190/EY/NEI NIH HHS/United States
GR  - R01 AI053108-03/AI/NIAID NIH HHS/United States
GR  - R01 CA044059-20/CA/NCI NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Interferon-alpha)
RN  - 0 (STAT1 Transcription Factor)
RN  - 0 (Stat1 protein, mouse)
RN  - 0 (Trans-Activators)
RN  - 77238-31-4 (Interferon-beta)
RN  - EC 2.7.11.1 (eIF-2 Kinase)
RN  - EC 2.7.7.84 (2',5'-Oligoadenylate Synthetase)
RN  - EC 3.1.- (Endoribonucleases)
RN  - EC 3.1.26.- (2-5A-dependent ribonuclease)
SB  - IM
MH  - 2',5'-Oligoadenylate Synthetase/biosynthesis/deficiency/genetics/*physiology
MH  - Acute Disease
MH  - Animals
MH  - Chlorocebus aethiops
MH  - DNA-Binding Proteins/biosynthesis
MH  - Endoribonucleases/deficiency/genetics/*physiology
MH  - Herpesvirus 1, Human/*immunology
MH  - Interferon-alpha/genetics
MH  - Interferon-beta/administration & dosage/genetics/*physiology
MH  - Keratitis, Herpetic/*enzymology/*immunology/mortality/prevention & control
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Inbred ICR
MH  - Mice, Knockout
MH  - Phosphorylation
MH  - STAT1 Transcription Factor
MH  - Signal Transduction/genetics/*immunology
MH  - Trans-Activators/biosynthesis
MH  - Transfection
MH  - *Transgenes
MH  - Trigeminal Ganglion/metabolism/virology
MH  - Up-Regulation/immunology
MH  - Vero Cells
MH  - Viral Load
MH  - eIF-2 Kinase/deficiency/genetics/metabolism
EDAT- 2005/07/09 09:00
MHDA- 2005/09/28 09:00
CRDT- 2005/07/09 09:00
PHST- 2005/07/09 09:00 [pubmed]
PHST- 2005/09/28 09:00 [medline]
PHST- 2005/07/09 09:00 [entrez]
AID - 175/2/1100 [pii]
AID - 10.4049/jimmunol.175.2.1100 [doi]
PST - ppublish
SO  - J Immunol. 2005 Jul 15;175(2):1100-6. doi: 10.4049/jimmunol.175.2.1100.