Calsyntenin-1 mediates hepatitis C virus replication

Zunaira Awan, Enoch S.E. Tay, Nicholas S. Eyre, Lindsay E. Wu, Michael R. Beard, Irene Boo, Heidi E. Drummer, Jacob George, Mark W. Douglas

Research output: Contribution to journalArticle

1 Citation (Scopus)

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.

Original languageEnglish
Article number000511
Pages (from-to)1877-1887
Number of pages11
JournalJournal of General Virology
Volume97
Issue number8
DOIs
Publication statusPublished - Aug 2016
Externally publishedYes

Keywords

  • Calsyntenin-1
  • Hepatitis C virus
  • Replication

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  • Cite this

    Awan, Z., Tay, E. S. E., Eyre, N. S., Wu, L. E., Beard, M. R., Boo, I., Drummer, H. E., George, J., & Douglas, M. W. (2016). Calsyntenin-1 mediates hepatitis C virus replication. Journal of General Virology, 97(8), 1877-1887. [000511]. https://doi.org/10.1099/jgv.0.000511