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Cell Host Microbe. 2017 Oct 11;22(4):449-459.e4. doi: 10.1016/j.chom.2017.08.021. Epub 2017 Sep 28.

Norovirus Cell Tropism Is Determined by Combinatorial Action of a Viral Non-structural Protein and Host Cytokine.

Author information

1
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.
2
Department of Pediatrics, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, MO, USA.
3
Department of Medicine, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, MO, USA.
4
Department of Molecular Microbiology and Immunology, Oregon Health and Science University, Portland, OR, USA.
5
Department of Medicine, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, MO, USA. Electronic address: mbaldridge@wustl.edu.
6
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA. Electronic address: virgin@wustl.edu.

Abstract

Cellular tropism during persistent viral infection is commonly conferred by the interaction of a viral surface protein with a host receptor complex. Norovirus, the leading global cause of gastroenteritis, can be persistently shed during infection, but its in vivo cellular tropism and tropism determinants remain unidentified. Using murine norovirus (MNoV), we determine that a small number of intestinal epithelial cells (IECs) serve as the reservoir for fecal shedding and persistence. The viral non-structural protein NS1, rather than a viral surface protein, determines IEC tropism. Expression of NS1 from a persistent MNoV strain is sufficient for an acute MNoV strain to target IECs and persist. In addition, interferon-lambda (IFN-λ) is a key host determinant blocking MNoV infection in IECs. The inability of acute MNoV to shed and persist is rescued in Ifnlr1-/- mice, suggesting that NS1 evades IFN-λ-mediated antiviral immunity. Thus, NS1 and IFN-λ interactions govern IEC tropism and persistence of MNoV.

KEYWORDS:

interferon-lambda; norovirus; persistence; reservoir; tropism

Comment in

PMID:
28966054
PMCID:
PMC5679710
DOI:
10.1016/j.chom.2017.08.021
[Indexed for MEDLINE]
Free PMC Article

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