Persistent LCMV Infection Is Controlled by Blockade of Type I Interferon Signaling

被引：598

作者：

Teijaro, John R. ^{[1
]}

Cherie Ng ^{[1
]}

Lee, Andrew M. ^{[1
]}

Sullivan, Brian M. ^{[1
]}

Sheehan, Kathleen C. F. ^{[2
]}

Welch, Megan ^{[1
]}

Schreiber, Robert D. ^{[2
]}

de la Torre, Juan Carlos ^{[1
]}

Oldstone, Michael B. A. ^{[1
]}

机构：

[1] Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA

[2] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA

来源：

SCIENCE | 2013年 / 340卷 / 6129期

关键词：

LYMPHOCYTIC CHORIOMENINGITIS VIRUS; VIRAL PERSISTENCE; DENDRITIC CELLS; IMMUNE ACTIVATION; GENOMIC ANALYSIS; T-CELLS; IMMUNOSUPPRESSION; MICE; VIVO; GLYCOPROTEIN;

D O I：

10.1126/science.1235214

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

During persistent viral infections, chronic immune activation, negative immune regulator expression, an elevated interferon signature, and lymphoid tissue destruction correlate with disease progression. We demonstrated that blockade of type I interferon (IFN-I) signaling using an IFN-I receptor neutralizing antibody reduced immune system activation, decreased expression of negative immune regulatory molecules, and restored lymphoid architecture in mice persistently infected with lymphocytic choriomeningitis virus. IFN-I blockade before and after establishment of persistent virus infection resulted in enhanced virus clearance and was CD4 T cell-dependent. Hence, we demonstrate a direct causal link between IFN-I signaling, immune activation, negative immune regulator expression, lymphoid tissue disorganization, and virus persistence. Our results suggest that therapies targeting IFN-I may help control persistent virus infections.

引用

页码：207 / 211

页数：6

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