title: Calsyntenin-1 mediates hepatitis C virus replication.
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.
authors.affiliation: Storr Liver Centre, The Westmead Millennium Institute for Medical Research, The University of Sydney at Westmead Hospital, 176 Hawkesbury Rd, Westmead NSW 2145, Australia.
authors.forename: Zunaira
authors.initials: Z
authors.lastname: Awan
authors.affiliation: Storr Liver Centre, The Westmead Millennium Institute for Medical Research, The University of Sydney at Westmead Hospital, 176 Hawkesbury Rd, Westmead NSW 2145, Australia.
authors.forename: Enoch S E
authors.initials: ESE
authors.lastname: Tay
authors.affiliation: Hepatitis C Virus Research Laboratory, School of Molecular and Biomedical Science, University of Adelaide, Adelaide, Australia.
authors.forename: Nicholas S
authors.initials: NS
authors.lastname: Eyre
authors.affiliation: University of New South Wales, Sydney NSW 2052, Australia.
authors.forename: Lindsay E
authors.initials: LE
authors.lastname: Wu
authors.affiliation: Hepatitis C Virus Research Laboratory, School of Molecular and Biomedical Science, University of Adelaide, Adelaide, Australia.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Beard
authors.affiliation: Centre for Biomedical Research, Burnet Institute, 85 Commercial Rd, Melbourne VIC 3004, Australia.
authors.forename: Irene
authors.initials: I
authors.lastname: Boo
authors.affiliation: Centre for Biomedical Research, Burnet Institute, 85 Commercial Rd, Melbourne VIC 3004, Australia.|Department of Microbiology, 19 Innovation Walk, Monash University, Victoria, Australia.|Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.
authors.forename: Heidi E
authors.initials: HE
authors.lastname: Drummer
authors.affiliation: Storr Liver Centre, The Westmead Millennium Institute for Medical Research, The University of Sydney at Westmead Hospital, 176 Hawkesbury Rd, Westmead NSW 2145, Australia.
authors.forename: Jacob
authors.initials: J
authors.lastname: George
authors.affiliation: Storr Liver Centre, The Westmead Millennium Institute for Medical Research, The University of Sydney at Westmead Hospital, 176 Hawkesbury Rd, Westmead NSW 2145, Australia.|Centre for Infectious Diseases and Microbiology, Marie Bashir Institute for Infectious Diseases and Biosecurity, University of Sydney at Westmead Hospital, Westmead NSW 2145, Australia.
authors.forename: Mark W
authors.initials: MW
authors.lastname: Douglas
mesh_terms: D002135:Calcium-Binding Proteins / Q000378:metabolism*; D002460:Cell Line; D016174:Hepacivirus / Q000502:physiology*; D022781:Hepatocytes / Q000821:virology; D054884:Host-Pathogen Interactions; D006801:Humans; D014779:Virus Replication
chemical_list: C503225:CLSTN1 protein, human; D002135:Calcium-Binding Proteins