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Science. 2013 Apr 12;340(6129):207-11. doi: 10.1126/science.1235214.

Persistent LCMV infection is controlled by blockade of type I interferon signaling.

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1
Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.

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.

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PMID:
23580529
PMCID:
PMC3640797
DOI:
10.1126/science.1235214
[Indexed for MEDLINE]
Free PMC Article

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