PMID- 17404299
OWN - NLM
STAT- MEDLINE
DCOM- 20070521
LR  - 20231213
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 178
IP  - 8
DP  - 2007 Apr 15
TI  - Oligoadenylate synthetase/protein kinase R pathways and alphabeta TCR+ T cells 
      are required for adenovirus vector: IFN-gamma inhibition of herpes simplex 
      virus-1 in cornea.
PG  - 5166-72
AB  - An adenoviral (Ad) vector containing the murine IFN-gamma transgene 
      (Ad:IFN-gamma) was evaluated for its capacity to inhibit HSV-1. To measure 
      effectiveness, viral titers were analyzed in cornea and trigeminal ganglia (TG) 
      during acute ocular HSV-1 infection. Ad:IFN-gamma potently suppressed HSV-1 
      replication in a dose-dependent fashion, requiring IFN-gamma receptor. Moreover, 
      Ad:IFN-gamma was effective when delivered -72 and -24 h before infection as well 
      as 24 h postinfection. Associated with antiviral opposition, TG from 
      Ad:IFN-gamma-transduced mice harbored fewer T cells. Also related to T cell 
      involvement, Ad:IFN-gamma was effective but attenuated in TG from alphabeta 
      TCR-deficient mice. In corneas, alphabeta TCR(+) T cells were obligatory for 
      protection against viral multiplication. Type I IFN involvement amid antiviral 
      efficacy of Ad:IFN-gamma was further investigated because types I and II IFN 
      pathways have synergistic anti-HSV-1 activity. Ad:IFN-gamma inhibited viral 
      reproduction in corneas and TG from alphabeta IFNR-deficient (CD118(-/-)) mice, 
      although viral titers were 2- to 3-fold higher in cornea and TG compared with 
      wild-type mice. The absence of IFN-stimulated antiviral proteins, 2'-5' 
      oligoadenylate synthetase/RNase L, and dsRNA-dependent protein kinase R 
      completely eliminated the antiviral effectiveness of Ad:IFN-gamma. Collectively, 
      the results demonstrate the following: 1) nonexistence of type I IFN receptor 
      does not abolish defense of Ad:IFN-gamma against HSV-1; 2) antiviral pathways 
      oligoadenylate synthetase-RNase L and protein kinase R are mandatory; and 3) 
      alphabeta TCR(+) T cells are compulsory for Ad:IFN-gamma effectiveness against 
      HSV-1 in cornea but not in TG.
FAU - Austin, Bobbie Ann
AU  - Austin BA
AD  - Department of Ophthalmology, University of Oklahoma Health Sciences Center, 
      Oklahoma City, OK 73104, USA.
FAU - Halford, William P
AU  - Halford WP
FAU - Williams, Bryan R G
AU  - Williams BR
FAU - Carr, Daniel J J
AU  - Carr DJ
LA  - eng
GR  - R01 AI053108/AI/NIAID NIH HHS/United States
GR  - R01 AI051414-04/AI/NIAID NIH HHS/United States
GR  - P30 EY012190/EY/NEI NIH HHS/United States
GR  - EY12190/EY/NEI NIH HHS/United States
GR  - R01 AI051414/AI/NIAID NIH HHS/United States
GR  - AI053108/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Leukemia Inhibitory Factor Receptor alpha Subunit)
RN  - 0 (Receptors, Antigen, T-Cell, alpha-beta)
RN  - 0 (Receptors, Interferon)
RN  - 82115-62-6 (Interferon-gamma)
RN  - EC 2.7.11.1 (eIF-2 Kinase)
RN  - EC 2.7.7.84 (2',5'-Oligoadenylate Synthetase)
SB  - IM
MH  - 2',5'-Oligoadenylate Synthetase/*physiology
MH  - Adenoviridae/*genetics
MH  - Animals
MH  - Cornea/*virology
MH  - Dose-Response Relationship, Drug
MH  - Genetic Vectors
MH  - Herpesvirus 1, Human/*drug effects
MH  - Interferon-gamma/*pharmacology
MH  - Killer Cells, Natural/physiology
MH  - Leukemia Inhibitory Factor Receptor alpha Subunit/physiology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Receptors, Antigen, T-Cell, alpha-beta/*physiology
MH  - Receptors, Interferon/physiology
MH  - T-Lymphocytes/*physiology
MH  - Trigeminal Ganglion/virology
MH  - eIF-2 Kinase/*physiology
MH  - Interferon gamma Receptor
PMC - PMC1865505
MID - NIHMS16539
COIS- Disclosures The authors have no financial conflict of interest.
EDAT- 2007/04/04 09:00
MHDA- 2007/05/22 09:00
PMCR- 2008/04/15
CRDT- 2007/04/04 09:00
PHST- 2007/04/04 09:00 [pubmed]
PHST- 2007/05/22 09:00 [medline]
PHST- 2007/04/04 09:00 [entrez]
PHST- 2008/04/15 00:00 [pmc-release]
AID - 178/8/5166 [pii]
AID - 10.4049/jimmunol.178.8.5166 [doi]
PST - ppublish
SO  - J Immunol. 2007 Apr 15;178(8):5166-72. doi: 10.4049/jimmunol.178.8.5166.