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Science 340 (6129): 207-211

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

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

John R. Teijaro,1,* Cherie Ng,1,* Andrew M. Lee,1,{dagger} Brian M. Sullivan,1 Kathleen C. F. Sheehan,2 Megan Welch,1 Robert D. Schreiber,2 Juan Carlos de la Torre,1 Michael B. A. Oldstone1,{ddagger}

Abstract: 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.

1 Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.
2 Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.

* These authors contributed equally to this work.

{dagger} Present address: Center for Genetics of Host Defense, Immunology, University of Texas Southwestern, Dallas, TX 75390–8505, USA.

{ddagger} Corresponding author. E-mail: mbaobo{at}scripps.edu


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