Oligoadenylate synthetase/protein kinase R pathways and αβ TCR+ T cells are required for adenovirus vector:: IFN-γ inhibition of herpes simplex virus-1 in cornea

被引:10
作者
Austin, Bobbie Ann
Halford, William P.
Williams, Bryan R. G.
Carr, Daniel J. J.
机构
[1] Univ Oklahoma, Hlth Sci Ctr, Dept Microbiol & Immunol, Dean A McGee Eye Inst, Oklahoma City, OK 73104 USA
[2] Univ Oklahoma, Hlth Sci Ctr, Dept Ophthalmol, Oklahoma City, OK 73104 USA
[3] Montana State Univ, Bozeman, MT 59718 USA
[4] Monash Univ, Med Ctr, Monash Inst Med Res, Clayton, Vic 3168, Australia
关键词
D O I
10.4049/jimmunol.178.8.5166
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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 alpha beta TCR-delicient mice. In corneas, alpha beta TCR+ T cells were obligatory for projection 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 alpha beta 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) alpha beta TCR+ T cells are compulsory for Ad:IFN-gamma effectiveness against HSV-1 in cornea but not in TG.
引用
收藏
页码:5166 / 5172
页数:7
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