Abstract
Noroviruses are understudied because these important enteric pathogens have not been cultured to date. We found that the norovirus murine norovirus 1 (MNV-1) infects macrophage-like cells in vivo and replicates in cultured primary dendritic cells and macrophages. MNV-1 growth was inhibited by the interferon-alphabeta receptor and STAT-1, and was associated with extensive rearrangements of intracellular membranes. An amino acid substitution in the capsid protein of serially passaged MNV-1 was associated with virulence attenuation in vivo. This is the first report of replication of a norovirus in cell culture. The capacity of MNV-1 to replicate in a STAT-1-regulated fashion and the unexpected tropism of a norovirus for cells of the hematopoietic lineage provide important insights into norovirus biology.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Antibodies, Monoclonal / metabolism
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Blotting, Northern
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Brain / metabolism
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Cell Line
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Cell Lineage
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Cell Membrane / metabolism
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Cells, Cultured
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Dendritic Cells / virology*
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Enzyme-Linked Immunosorbent Assay
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Fibroblasts / metabolism
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Hematopoietic Stem Cells / cytology
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Hybridomas / metabolism
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Immunohistochemistry
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Macrophages / virology*
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Membrane Proteins / metabolism
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Mice
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Mice, Transgenic
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Microscopy, Electron
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Norovirus / metabolism
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Norovirus / physiology*
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RNA / metabolism
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RNA, Viral / metabolism
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Receptor, Interferon alpha-beta
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Receptors, Interferon / metabolism
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STAT1 Transcription Factor / metabolism
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Spleen / metabolism
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Tropism
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Virulence
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Virus Replication*
Substances
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Antibodies, Monoclonal
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Membrane Proteins
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RNA, Viral
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Receptors, Interferon
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STAT1 Transcription Factor
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Stat1 protein, mouse
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Receptor, Interferon alpha-beta
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RNA