Toll-like receptor 7 is required for effective adaptive immune responses that prevent persistent virus infection |
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Authors: | Walsh Kevin B Teijaro John R Zuniga Elina I Welch Megan J Fremgen Daniel M Blackburn Shawn D von Tiehl Karl F Wherry E John Flavell Richard A Oldstone Michael B A |
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Affiliation: | Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA. |
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Abstract: | TLR7 is an innate signaling receptor that recognizes single-stranded viral RNA and is activated by viruses that cause persistent infections. We show that TLR7 signaling dictates either clearance or establishment of life-long chronic infection by lymphocytic choriomeningitis virus (LCMV) Cl 13 but does not affect clearance of the acute LCMV Armstrong 53b strain. TLR7(-/-) mice infected with LCMV Cl 13 remained viremic throughout life from defects in the adaptive antiviral immune response-notably, diminished T?cell function, exacerbated T?cell exhaustion, decreased plasma cell maturation, and negligible antiviral antibody production. Adoptive transfer of TLR7(+/+) LCMV immune memory cells that enhanced clearance of persistent LCMV Cl 13 infection in TLR7(+/+) mice failed to purge LCMV Cl 13 infection in TLR7(-/-) mice, demonstrating that a TLR7-deficient environment renders antiviral responses ineffective. Therefore, methods that promote TLR7 signaling are promising treatment strategies for chronic viral infections. |
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