The norovirus NS3 protein is a dynamic lipid- and microtubule-associated protein involved in viral RNA replication

Cotton, Ben T., Hyde, Jennifer L., Sarvestani, Soroush T., Sosnovtsev, Stanislav V., Green, Kim Y., White, Peter A. and Mackenzie, Jason M. (2017) The norovirus NS3 protein is a dynamic lipid- and microtubule-associated protein involved in viral RNA replication. Journal of Virology, 91 3: . doi:10.1128/JVI.02138-16

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Author Cotton, Ben T.
Hyde, Jennifer L.
Sarvestani, Soroush T.
Sosnovtsev, Stanislav V.
Green, Kim Y.
White, Peter A.
Mackenzie, Jason M.
Title The norovirus NS3 protein is a dynamic lipid- and microtubule-associated protein involved in viral RNA replication
Journal name Journal of Virology   Check publisher's open access policy
ISSN 1098-5514
0022-538X
Publication date 2017-02-01
Year available 2016
Sub-type Article (original research)
DOI 10.1128/JVI.02138-16
Open Access Status File (Publisher version)
Volume 91
Issue 3
Total pages 19
Place of publication Washington, DC, United States
Publisher American Society for Microbiology
Collection year 2017
Language eng
Formatted abstract
Norovirus (NoV) infections are a significant health burden to society, yet the lack of reliable tissue culture systems has hampered the development of appropriate antiviral therapies. Here we show that the NoV NS3 protein, derived from murine NoV (MNV), is intimately associated with the MNV replication complex and the viral replication intermediate double-stranded RNA (dsRNA). We observed that when expressed individually, MNV NS3 and NS3 encoded by human Norwalk virus (NV) induced the formation of distinct vesicle-like structures that did not colocalize with any particular protein markers to cellular organelles but localized to cellular membranes, in particular those with a high cholesterol content. Both proteins also showed some degree of colocalization with the cytoskeleton marker β-tubulin. Although the distribution of MNV and NV NS3s were similar, NV NS3 displayed a higher level of colocalization with the Golgi apparatus and the endoplasmic reticulum (ER). However, we observed that although both proteins colocalized in membranes counterstained with filipin, an indicator of cholesterol content, MNV NS3 displayed a greater association with flotillin and stomatin, proteins known to associate with sphingolipid- and cholesterol-rich microdomains. Utilizing time-lapse epifluorescence microscopy, we observed that the membrane-derived vesicular structures induced by MNV NS3 were highly motile and dynamic in nature, and their movement was dependent on intact microtubules. These results begin to interrogate the functions of NoV proteins during virus replication and highlight the conserved properties of the NoV NS3 proteins among the seven Norovirus genogroups.
Keyword Cellular lipids
Cytoskeleton
Norovirus
Virus replication
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
School of Chemistry and Molecular Biosciences
 
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