RT Journal Article SR Electronic(1) A1 Awan, Zunaira A1 Tay, Enoch S. E. A1 Eyre, Nicholas S. A1 Wu, Lindsay E. A1 Beard, Michael R. A1 Boo, Irene A1 Drummer, Heidi E. A1 George, Jacob A1 Douglas, Mark W.YR 2016 T1 Calsyntenin-1 mediates hepatitis C virus replication JF Journal of General Virology, VO 97 IS 8 SP 1877 OP 1887 DO https://doi.org/10.1099/jgv.0.000511 PB Microbiology Society, SN 1465-2099, AB 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., UL https://www.microbiologyresearch.org/content/journal/jgv/10.1099/jgv.0.000511