Journal
IMMUNITY
Volume 47, Issue 4, Pages 723-+Publisher
CELL PRESS
DOI: 10.1016/j.immuni.2017.09.017
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Funding
- NIH/NIDDK [T32-DK007066, P30DK050306, K08-DK097301]
- NIH [U01-AI-095608, U19 AI AI082630, P01 AI AI112521, U19-AI109725]
- German Research Foundation Fellowship [BE5496/1-1]
- NCI Comprehensive Cancer Center Support Grant [P30 CA016520]
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Noroviruses can establish chronic infections with active viral shedding in healthy humans but whether persistence is associated with adaptive immune dysfunction is unknown. We used genetically engineered strains of mouse norovirus (MNV) to investigate CD8(+) T cell differentiation during chronic infection. We found that chronic infection drove MNV-specific tissue-resident memory (Trm) CD8(+) T cells to a differentiation state resembling inflationary effector responses against latent cytomegalovirus with only limited evidence of exhaustion. These MNV-specific Trm cells remained highly functional yet appeared ignorant of ongoing viral replication. Pre-existing MNV-specific Trm cells provided partial protection against chronic infection but largely ceased to detect virus within 72 hours of challenge, demonstrating rapid sequestration of viral replication away from T cells. Our studies revealed a strategy of immune evasion by MNV via the induction of a CD8(+) T cell program normally reserved for latent pathogens and persistence in an immune-privileged enteric niche.
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