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Persistent LCMV Infection Is Controlled by Blockade of Type I Interferon Signaling
John R. Teijaro,1,*
Andrew M. Lee,1,
Brian M. Sullivan,1
Kathleen C. F. Sheehan,2
Robert D. Schreiber,2
Juan Carlos de la Torre,1
Michael B. A. Oldstone1,
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.
Present address: Center for Genetics of Host Defense, Immunology, University of Texas Southwestern, Dallas, TX 75390–8505, USA.
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