Mankouri, J orcid.org/0000-0002-4325-3687, Walter, C, Stewart, H et al. (6 more authors) (2016) Release of Infectious Hepatitis C Virus from Huh7 Cells Occurs via a trans-Golgi Network-to-Endosome Pathway Independent of Very-Low-Density Lipoprotein Secretion. Journal of Virology, 90 (16). pp. 7159-7170. ISSN 0022-538X
Abstract
The release of infectious hepatitis C virus (HCV) particles from infected cells remains poorly characterized. We previously demonstrated that virus release is dependent on the endosomal sorting complex required for transport (ESCRT). Here, we show a critical role of trans-Golgi network (TGN)-endosome trafficking during the assembly, but principally the secretion, of infectious virus. This was demonstrated by both small interfering RNA (siRNA)-mediated silencing of TGN-associated adaptor proteins and a panel of dominant negative (DN) Rab GTPases involved in TGN-endosome trafficking steps. Importantly, interfering with factors critical for HCV release did not have a concomitant effect on secretion of triglycerides, ApoB, or ApoE, indicating that particles are likely released from Huh7 cells via pathways distinct from that of very-low-density lipoprotein (VLDL). Finally, we show that HCV NS2 perturbs TGN architecture, redistributing TGN membranes to closely associate with HCV core protein residing on lipid droplets. These findings support the notion that HCV hijacks TGN-endosome trafficking to facilitate particle assembly and release. Moreover, although essential for assembly and infectivity, the trafficking of mature virions is seemingly independent of host lipoproteins.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2016 Mankouri et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license. |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Molecular and Cellular Biology (Leeds) The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Leeds Institute of Cancer and Pathology (LICAP) > Oncology and Cancer Research - Labs (Leeds) |
Funding Information: | Funder Grant number Wellcome Trust 082812/Z/07/Z Royal Society UF100419 Wellcome Trust 096670/Z/11/Z Royal Society RG110306 Royal Society Not Known British Lung Foundation PPRG15-17 |
Depositing User: | Symplectic Publications |
Date Deposited: | 27 May 2016 13:39 |
Last Modified: | 15 Feb 2018 22:39 |
Published Version: | http://dx.doi.org/10.1128/JVI.00826-16 |
Status: | Published |
Publisher: | American Society for Microbiology |
Identification Number: | 10.1128/JVI.00826-16 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:100196 |