Tuft-cell-intrinsic and -extrinsic mediators of norovirus tropism regulate viral immunity

Madison S. Strine, Mia Madel Alfajaro, Vincent R. Graziano, Jaewon Song, Leon L. Hsieh, Ryan Hill, Jun Guo, Kelli L. VanDussen, Robert C. Orchard, Megan T. Baldridge, Sanghyun Lee, Craig B. Wilen

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Murine norovirus (MNoV) is a model for human norovirus and for interrogating mechanisms of viral tropism and persistence. We previously demonstrated that the persistent strain MNoVCR6 infects tuft cells, which are dispensable for the non-persistent strain MNoVCW3. We now show that diverse MNoV strains require tuft cells for chronic enteric infection. We also demonstrate that interferon-λ (IFN-λ) acts directly on tuft cells to cure chronic MNoVCR6 infection and that type I and III IFNs signal together via STAT1 in tuft cells to restrict MNoVCW3 tropism. We then develop an enteroid model and find that MNoVCR6 and MNoVCW3 similarly infect tuft cells with equal IFN susceptibility, suggesting that IFN derived from non-epithelial cells signals on tuft cells in trans to restrict MNoVCW3 tropism. Thus, tuft cell tropism enables MNoV persistence and is determined by tuft cell-intrinsic factors (viral receptor expression) and -extrinsic factors (immunomodulatory signaling by non-epithelial cells).

Original languageEnglish
Article number111593
JournalCell Reports
Volume41
Issue number6
DOIs
StatePublished - Nov 8 2022

Keywords

  • CP: Immunology
  • CP: Microbiology
  • immune evasion
  • interferon
  • mucosal immunity
  • norovirus
  • tuft cells
  • viral persistence
  • viral tropism

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