Bamford, C. G.C., Aranday-Cortes, E. , Sanchez-Velazquez, R., Mullan, C., Kohl, A. , Patel, A. H. , Wilson, S. J. and McLauchlan, J. (2022) A human and rhesus macaque interferon-stimulated gene screen shows that over-expression of ARHGEF3/XPLN inhibits replication of hepatitis C virus and other flavivirids. Viruses, 14(8), 1655. (doi: 10.3390/v14081655) (PMID:36016278) (PMCID:PMC9414520)
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Abstract
Natural hepatitis C virus (HCV) infection is restricted to humans, whereas other primates such as rhesus macaques are non-permissive for infection. To identify human and rhesus macaque genes that differ or share the ability to inhibit HCV replication, we conducted a medium-throughput screen of lentivirus-expressed host genes that disrupt replication of HCV subgenomic replicon RNA expressing secreted Gaussia luciferase. A combined total of >800 interferon-stimulated genes (ISGs) were screened. Our findings confirmed established anti-HCV ISGs, such as IRF1, PKR and DDX60. Novel species–specific inhibitors were also identified and independently validated. Using a cell-based system that recapitulates productive HCV infection, we identified that over-expression of the ‘Rho Guanine Nucleotide Exchange Factor 3’ gene (ARHGEF3) from both species inhibits full-length virus replication. Additionally, replication of two mosquito-borne flaviviruses, yellow fever virus (YFV) and Zika virus (ZIKV), were also reduced in cell lines over-expressing ARHGEF3 compared to controls. In conclusion, we ascribe novel antiviral activity to the cellular gene ARHGEF3 that inhibits replication of HCV and other important human viral pathogens belonging to the Flaviviridae, and which is conserved between humans and rhesus macaques.
Item Type: | Articles |
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Status: | Published |
Refereed: | Yes |
Glasgow Author(s) Enlighten ID: | Sanchez Velazquez, Ricardo and Aranday-Cortes, Dr Elihu and Wilson, Professor Sam and Mullan, Catrina and Patel, Professor Arvind and Bamford, Dr Connor and Kohl, Professor Alain and McLauchlan, Professor John |
Authors: | Bamford, C. G.C., Aranday-Cortes, E., Sanchez-Velazquez, R., Mullan, C., Kohl, A., Patel, A. H., Wilson, S. J., and McLauchlan, J. |
College/School: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research |
Journal Name: | Viruses |
Publisher: | MDPI |
ISSN: | 1999-4915 |
ISSN (Online): | 1999-4915 |
Published Online: | 28 July 2022 |
Copyright Holders: | Copyright © 2022 The Authors |
First Published: | First published in Viruses 14(8): 1655 |
Publisher Policy: | Reproduced under a Creative Commons License |
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