Please use this identifier to cite or link to this item: https://hdl.handle.net/2440/103605
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Type: Journal article
Title: Calsyntenin-1 mediates hepatitis C virus replication
Author: Awan, Z.
Tay, E.
Eyre, N.
Wu, L.
Beard, M.
Boo, I.
Drummer, H.
George, J.
Douglas, M.
Citation: Journal of General Virology, 2016; 97(8):1877-1887
Publisher: Microbiology Society
Issue Date: 2016
ISSN: 0022-1317
1465-2099
Statement of
Responsibility: 
Zunaira Awan, Enoch S. E. Tay, Nicholas S. Eyre, Lindsay E. Wu, Michael R. Beard, Irene Boo, Heidi E. Drummer, Jacob George and Mark W. Douglas
Abstract: The hepatitis C virus (HCV) RNA genome of 9.6 kb encodes only 10 proteins, and so is highly dependent on host hepatocyte factors to facilitate replication. We aimed to identify host factors involved in the egress of viral particles. By screening the supernatant of HCV-infected Huh7 cells using SILAC-based proteomics, we identified the transmembrane protein calsyntenin-1 as a factor specifically secreted by infected cells. Calsyntenin-1 has previously been shown to mediate transport of endosomes along microtubules in neurons, through interactions with kinesin light chain-1. Here we demonstrate for the first time, we believe, a similar role for calsyntenin-1 in Huh7 cells, mediating intracellular transport of endosomes. In HCV-infected cells we show that calsyntenin-1 contributes to the early stages of the viral replication cycle and the formation of the replication complex. Importantly, we demonstrate in our model that silencing calsyntenin-1 disrupts the viral replication cycle, confirming the reliance of HCV on this protein as a host factor. Characterizing the function of calsyntenin-1 will increase our understanding of the HCV replication cycle and pathogenesis, with potential application to other viruses sharing common pathways.
Keywords: Cell Line
Hepatocytes
Humans
Hepacivirus
Calcium-Binding Proteins
Virus Replication
Host-Pathogen Interactions
Rights: © 2016 The Authors
DOI: 10.1099/jgv.0.000511
Grant ID: http://purl.org/au-research/grants/nhmrc/1003767
http://purl.org/au-research/grants/nhmrc/1047417
http://purl.org/au-research/grants/nhmrc/1053206
http://purl.org/au-research/grants/nhmrc/1020175
http://purl.org/au-research/grants/nhmrc/1041897
Appears in Collections:Aurora harvest 7
Molecular and Biomedical Science publications

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