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

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.

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. https://doi.org/10.1128/jvi.00826-16

• Journal Article Type: Article
• Acceptance Date: May 23, 2016
• Online Publication Date: May 25, 2016
• Publication Date: Aug 15, 2016
• Deposit Date: Jul 2, 2018
• Publicly Available Date: Jul 12, 2018
• 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
• DOI: https://doi.org/10.1128/jvi.00826-16
• Public URL: https://hull-repository.worktribe.com/output/906253
• Publisher URL: http://jvi.asm.org/content/90/16/7159
• Related Public URLs: http://eprints.whiterose.ac.uk/100196/