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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

Mankouri, Jamel; Walter, Cheryl; Stewart, Hazel; Bentham, Matthew; Park, Wei Sun; Heo, Won Do; Fukuda, Mitsunori; Griffin, Stephen; Harris, Mark

Authors

Jamel Mankouri

Cheryl Walter

Hazel Stewart

Matthew Bentham

Wei Sun Park

Won Do Heo

Mitsunori Fukuda

Stephen Griffin

Mark Harris



Contributors

M. S. Diamond
Editor

Abstract

© 2016 Mankouri et al. 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.

Journal Article Type Article
Publication Date Aug 15, 2016
Journal Journal of Virology
Print ISSN 0022-538X
Electronic ISSN 1098-5514
Publisher American Society for Microbiology
Peer Reviewed Peer Reviewed
Volume 90
Issue 16
Pages 7159-7170
APA6 Citation Mankouri, J., Walter, C., Stewart, H., Bentham, M., Park, W. S., Heo, W. D., …Harris, M. (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), 7159-7170. doi:10.1128/jvi.00826-16
DOI https://doi.org/10.1128/jvi.00826-16
Publisher URL http://jvi.asm.org/content/90/16/7159
Related Public URLs http://eprints.whiterose.ac.uk/100196/
Copyright Statement Copyright © 2016 Mankouri et al.
This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.

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Copyright Statement
Copyright © 2016 Mankouri et al.
This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.



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