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Science 340 (6129): 202-207

Copyright © 2013 by the American Association for the Advancement of Science

Blockade of Chronic Type I Interferon Signaling to Control Persistent LCMV Infection

Elizabeth B. Wilson,1 Douglas H. Yamada,1 Heidi Elsaesser,1 Jonathan Herskovitz,1 Jane Deng,2 Genhong Cheng,1 Bruce J. Aronow,3 Christopher L. Karp,4,* David G. Brooks1,{dagger}

Abstract: Type I interferons (IFN-I) are critical for antiviral immunity; however, chronic IFN-I signaling is associated with hyperimmune activation and disease progression in persistent infections. We demonstrated in mice that blockade of IFN-I signaling diminished chronic immune activation and immune suppression, restored lymphoid tissue architecture, and increased immune parameters associated with control of virus replication, ultimately facilitating clearance of the persistent infection. The accelerated control of persistent infection induced by blocking IFN-I signaling required CD4 T cells and was associated with enhanced IFN-{gamma} production. Thus, we demonstrated that interfering with chronic IFN-I signaling during persistent infection redirects the immune environment to enable control of infection.

1 Department of Microbiology, Immunology and Molecular Genetics and the UCLA AIDS Institute, David Geffen School of Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA 90095, USA.
2 Division of Pulmonary and Critical Care Medicine, David Geffen School of Medicine, UCLA, Los Angeles, CA 90095, USA.
3 Division of Biomedical Informatics and Division of Developmental Biology, Cincinnati Children’s Hospital Research Foundation and the University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA.
4 Division of Molecular Immunology, Cincinnati Children’s Hospital Research Foundation and the University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA.

* Present address: The Bill and Melinda Gates Foundation, Seattle, WA 98109, USA.

{dagger} Corresponding author. E-mail: dbrooks{at}microbio.ucla.edu


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