Differentiation and Protective Capacity of Virus-Specific CD8+ T Cells Suggest Murine Norovirus Persistence in an Immune-Privileged Enteric Niche

Vesselin T. Tomov, Olesya Palko, Chi Wai Lau, Ajinkya Pattekar, Yuhang Sun, Ralitza Tacheva, Bertram Bengsch, Sasikanth Manne, Gabriela L. Cosma, Laurence C. Eisenlohr, Timothy Nice, Herbert W. Virgin, E. John Wherry

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

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. Chronic infections often cause T cell dysfunction, but how noroviruses (NV) evade immunity is unknown. Tomov et al. show that gut-resident T cells against NV remain functional but ignorant of chronic viral replication, suggesting that NV persists in an immune-privileged enteric niche.

Original languageEnglish (US)
JournalImmunity
DOIs
StateAccepted/In press - 2017

Fingerprint

Norovirus
Viruses
T-Lymphocytes
Infection
Virus Shedding
Immune Evasion
Cytomegalovirus
Cell Differentiation
Immunity

Keywords

  • Enteric viral persistence
  • Norovirus
  • T cell exhaustion
  • T cell inflation
  • Tissue-resident memory T cells

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

Cite this

Differentiation and Protective Capacity of Virus-Specific CD8+ T Cells Suggest Murine Norovirus Persistence in an Immune-Privileged Enteric Niche. / Tomov, Vesselin T.; Palko, Olesya; Lau, Chi Wai; Pattekar, Ajinkya; Sun, Yuhang; Tacheva, Ralitza; Bengsch, Bertram; Manne, Sasikanth; Cosma, Gabriela L.; Eisenlohr, Laurence C.; Nice, Timothy; Virgin, Herbert W.; Wherry, E. John.

In: Immunity, 2017.

Research output: Contribution to journalArticle

Tomov, VT, Palko, O, Lau, CW, Pattekar, A, Sun, Y, Tacheva, R, Bengsch, B, Manne, S, Cosma, GL, Eisenlohr, LC, Nice, T, Virgin, HW & Wherry, EJ 2017, 'Differentiation and Protective Capacity of Virus-Specific CD8+ T Cells Suggest Murine Norovirus Persistence in an Immune-Privileged Enteric Niche', Immunity. https://doi.org/10.1016/j.immuni.2017.09.017
Tomov, Vesselin T. ; Palko, Olesya ; Lau, Chi Wai ; Pattekar, Ajinkya ; Sun, Yuhang ; Tacheva, Ralitza ; Bengsch, Bertram ; Manne, Sasikanth ; Cosma, Gabriela L. ; Eisenlohr, Laurence C. ; Nice, Timothy ; Virgin, Herbert W. ; Wherry, E. John. / Differentiation and Protective Capacity of Virus-Specific CD8+ T Cells Suggest Murine Norovirus Persistence in an Immune-Privileged Enteric Niche. In: Immunity. 2017.
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AU - Manne, Sasikanth

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AB - 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. Chronic infections often cause T cell dysfunction, but how noroviruses (NV) evade immunity is unknown. Tomov et al. show that gut-resident T cells against NV remain functional but ignorant of chronic viral replication, suggesting that NV persists in an immune-privileged enteric niche.

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