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
- Research Support, N.I.H., Extramural
- Research Support, U.S. Gov't, P.H.S.
MeSH terms
- Animals
- Antibodies, Monoclonal / metabolism
- Blotting, Northern
- Brain / metabolism
- Cell Line
- Cell Lineage
- Cell Membrane / metabolism
- Cells, Cultured
- Dendritic Cells / virology*
- Enzyme-Linked Immunosorbent Assay
- Fibroblasts / metabolism
- Hematopoietic Stem Cells / cytology
- Hybridomas / metabolism
- Immunohistochemistry
- Macrophages / virology*
- Membrane Proteins / metabolism
- Mice
- Mice, Transgenic
- Microscopy, Electron
- Norovirus / metabolism
- Norovirus / physiology*
- RNA / metabolism
- RNA, Viral / metabolism
- Receptor, Interferon alpha-beta
- Receptors, Interferon / metabolism
- STAT1 Transcription Factor / metabolism
- Spleen / metabolism
- Tropism
- Virulence
- Virus Replication*
Substances
- Antibodies, Monoclonal
- Membrane Proteins
- RNA, Viral
- Receptors, Interferon
- STAT1 Transcription Factor
- Stat1 protein, mouse
- Receptor, Interferon alpha-beta
- RNA