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Bayer, K. ; Banning, C.* ; Bruss, V. ; Wiltzer-Bach, L.* ; Schindler, M.

Hepatitis C virus is released via a non-canonical secretory route.

J. Virol. 90, 10558-10573 (2016)
Verlagsversion Postprint DOI PMC
Open Access Green
We analyzed HCV morphogenesis using viral genomes encoding for a mCherry-tagged E1 glycoprotein. HCV-E1-mCherry polyprotein expression, intracellular localization and replication kinetics were comparable to untagged HCV and E1-mCherry tagged viral particles were assembled and released into cell culture supernatants. Expression and localization of structural E1 and non-structural NS5A followed a tempo-spatial pattern with succinct decrease in replication complexes and the appearance of E1-mCherry punctae. Interaction of the structural proteins E1, Core and E2 increased at E1-mCherry punctae in a time-dependent manner, indicating that E1-mCherry punctae represent assembled or assembling virions. E1-mCherry did not colocalize with Golgi markers. Furthermore, the bulk of viral glycoproteins within released particles revealed an EndoH-sensitive glycosylation pattern, indicating absence of viral glycoprotein processing by the Golgi. In contrast, HCV-E1-mCherry trafficked with Rab9-positive compartments and inhibition of endosomes specifically suppressed HCV release. Our data suggests that assembled HCV particles are released via a non-canonical secretory route involving the endosomal compartment. IMPORTANCE STATEMENT: The goal of this study was to shed light on the poorly understood trafficking and release routes of hepatitis C virus (HCV). For this, we generated novel HCV genomes which result in the production of fluorescently labeled viral particles. We used live cell microscopy and other imaging techniques to follow up on the temporal dynamics of virus particle formation and trafficking in HCV-expressing liver cells. While viral particles and viral structural protein were found in endosomal compartments, no overlap with Golgi structures could be observed. Furthermore, biochemical and inhibitor-based experiments support a HCV release route which is distinguishable from canonical Golgi-mediated secretion. Since viruses hijack cellular pathways to generate viral progeny, our results point towards the possible existence of a not yet described cellular secretion route.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Nonstructural Protein 5a; Core Protein; Lipid Droplets; Endoplasmic-reticulum; Viral Replication; Living Cells; Glycoprotein Complexes; Envelope Glycoproteins; Transmembrane Domain; Fluorescent Protein
ISSN (print) / ISBN 0022-538X
e-ISSN 1098-5514
Zeitschrift Journal of Virology
Quellenangaben Band: 90, Heft: 23, Seiten: 10558-10573 Artikelnummer: , Supplement: ,
Verlag American Society for Microbiology (ASM)
Verlagsort Washington
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Virology (VIRO)