Replication of Norovirus in cell culture reveals a tropism for dendritic cells and macrophages.
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.
Wobus
Christiane E
CE
Department of Pathology and Immunology, Washington University School of Medicine St. Louis, Missouri, USA.
Karst
Stephanie M
SM
Thackray
Larissa B
LB
Chang
Kyeong-Ok
KO
Sosnovtsev
Stanislav V
SV
Belliot
Gaël
G
Krug
Anne
A
Mackenzie
Jason M
JM
Green
Kim Y
KY
Virgin
Herbert W
HW
D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D015152:Blotting, Northern; D001921:Brain / Q000378:metabolism; D002460:Cell Line; D019070:Cell Lineage; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000821:virology*; D004797:Enzyme-Linked Immunosorbent Assay; D005347:Fibroblasts / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000166:cytology; D006825:Hybridomas / Q000378:metabolism; D007150:Immunohistochemistry; D008264:Macrophages / Q000821:virology*; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D008854:Microscopy, Electron; D029322:Norovirus / Q000378:metabolism / Q000502:physiology*; D012313:RNA / Q000378:metabolism; D012367:RNA, Viral / Q000378:metabolism; D053633:Receptor, Interferon alpha-beta; D017471:Receptors, Interferon / Q000378:metabolism; D050794:STAT1 Transcription Factor / Q000378:metabolism; D013154:Spleen / Q000378:metabolism; D018523:Tropism; D014774:Virulence; D014779:Virus Replication
D000911:Antibodies, Monoclonal; D008565:Membrane Proteins; D012367:RNA, Viral; D017471:Receptors, Interferon; D050794:STAT1 Transcription Factor; C494080:Stat1 protein, mouse; D053633:Receptor, Interferon alpha-beta; D012313:RNA