Inhibition of hepatitis C virus RNA replication by ISG15 does not require its conjugation to protein substrates by the HERC5 E3 ligase

Domingues, P., Bamford, C. G.G., Boutell, C. and McLauchlan, J. (2015) Inhibition of hepatitis C virus RNA replication by ISG15 does not require its conjugation to protein substrates by the HERC5 E3 ligase. Journal of General Virology, 96(11), pp. 3236-3242. (doi:10.1099/jgv.0.000283) (PMID:26361997)

[img]
Preview
Text
114875.pdf - Published Version
Available under License Creative Commons Attribution.

280kB

Abstract

Chronic infection of the liver by hepatitis C virus (HCV) induces a range of host factors including IFN-stimulated genes such as ISG15. ISG15 functions as an antiviral factor that limits virus replication. Previous studies have suggested that ISG15 could influence HCV replication in both a positive and a negative manner. In this report, we determined the effect of ISG15 on HCV RNA replication in two independent cell lines that support viral genome synthesis by inhibiting ISG15 expression through small interfering RNA, short-hairpin RNA and CRISPR/Cas9 gene knockout approaches. Our results demonstrated that ISG15 impairs HCV RNA replication in both the presence and absence of IFN stimulation, consistent with an antiviral role for ISG15 during HCV infection. ISG15 conjugation to protein substrates typically requires the E3 ligase, HERC5. Our results showed that the inhibitory effect of ISG15 on HCV RNA replication does not require its conjugation to substrates by HERC5.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Domingues, Miss Patricia and Boutell, Dr Chris and McLauchlan, Professor John and Bamford, Dr Connor
Authors: Domingues, P., Bamford, C. G.G., Boutell, C., and McLauchlan, J.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Journal of General Virology
Publisher:Microbiology Society
ISSN:0022-1317
ISSN (Online):1465-2099
Copyright Holders:Copyright © 2015 The Authors
First Published:First published in Journal of General Virology 96(11):3236-3243
Publisher Policy:Reproduced under a Creative Commons licence

University Staff: Request a correction | Enlighten Editors: Update this record