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PMID: 15562321 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, U.S. Gov't, P.H.S.

Replication of Norovirus in cell culture reveals a tropism for dendritic cells and macrophages.

PLoS biology ·Vol. 2 ·No. 12 ·2004-12-00 ·Pages e432

Wobus CE, Karst SM, Thackray LB, Chang KO, Sosnovtsev SV, Belliot G, Krug A, Mackenzie JM, Green KY, Virgin HW

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.

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,physiology RNA/metabolism RNA, Viral/metabolism Receptor, Interferon alpha-beta Receptors, Interferon/metabolism STAT1 Transcription Factor/metabolism Spleen/metabolism Tropism Virulence Virus Replication
Chemicals
Antibodies, Monoclonal Membrane Proteins RNA, Viral Receptors, Interferon STAT1 Transcription Factor Stat1 protein, mouse Receptor, Interferon alpha-beta RNA
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Wobus Christiane E
Department of Pathology and Immunology, Washington University School of Medicine St. Louis, Missouri, USA.
Karst Stephanie M
Thackray Larissa B
Chang Kyeong-Ok
Sosnovtsev Stanislav V
Belliot Gaël
Krug Anne
Mackenzie Jason M
Green Kim Y
Virgin Herbert W
Conflict of Interest

The authors have declared that no conflicts of interest exist.

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Article Info
Journal
PLoS biology
Abbr.
PLoS Biol
ISSN
1545-7885
DOI
10.1371/journal.pbio.0020432
Published
2004-12-00
Epub
2004-00-30
Pages
e432
Language
English
Region
United States
NLM ID
101183755
PMCID
PMC532393
Subset
IM
Grants
NIAID NIH HHS · T32-AI07163 · United States
NIAID NIH HHS · R01 AI54483 · United States
NIAID NIH HHS · R01 AI054483 · United States
NCI NIH HHS · T32 CA009547 · United States
NIAID NIH HHS · T32 AI007163 · United States
NCI NIH HHS · T32-CA09547 · United States
NIAID NIH HHS · AI007163 · United States
External Links
PubMed source DOI: 10.1371/journal.pbio.0020432 PMC Full Text View journal details
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