Publication

Hepatoma polarization limits CD81 and hepatitis C virus dynamics

Harris, H. J., Clerte, C., Farquhar, M. J., Goodall, M., Hu, K., Rassam, P., Dosset, P., Wilson, G. K., Balfe, P., IJzendoorn, S. C., Milhiet, P. E. & McKeating, J. A., Mar-2013, In : Cellular Microbiology. 15, 3, p. 430-445 16 p.

Research output: Contribution to journalArticleAcademicpeer-review

  • H. J. Harris
  • C. Clerte
  • M. J. Farquhar
  • M. Goodall
  • K. Hu
  • P. Rassam
  • P. Dosset
  • G. K. Wilson
  • P. Balfe
  • S. C. IJzendoorn
  • P. E. Milhiet
  • J. A. McKeating

Many viruses target the polarized epithelial apex during host invasion. In contrast, hepatitis C virus (HCV) engages receptors at the basal surface of hepatocytes in the polarized liver parenchyma. Hepatocyte polarization limits HCV entry by undefined mechanism(s). Given the recent reports highlighting a role for receptor mobility in pathogen entry, we studied the effect(s) of hepatocyte polarization on viral receptor and HCV pseudoparticle (HCVpp) dynamics using real-time fluorescence recovery after photobleaching and single particle tracking. Hepatoma polarization reduced CD81 and HCVpp dynamics at the basal membrane. Since cell polarization is accompanied by changes in the actin cytoskeleton and CD81 links to actin via its C-terminus, we studied the dynamics of a mutant CD81 lacking a C-terminal tail (CD81C) and its effect(s) on HCVpp mobility and infection. CD81C showed an increased frequency of confined trajectories and a reduction of Brownian diffusing molecules compared to wild-type protein in non-polarized cells. However, these changes were notobserved in polarized cells. HCVpp showed a significant reduction in Brownian diffusion and infection of CD81C expressing non-polarized cells. In summary, these data highlight the dynamic nature of CD81 and demonstrate a role for CD81 lateral diffusion to regulate HCV infection in a polarization-dependent manner.

Original languageEnglish
Pages (from-to)430-445
Number of pages16
JournalCellular Microbiology
Volume15
Issue number3
Publication statusPublished - Mar-2013

    Keywords

  • RECEPTOR CLASS-B, SINGLE-PARTICLE TRACKING, SCAVENGER RECEPTOR, EPITHELIAL-CELLS, TETRASPANIN WEB, SR-BI, QUANTITATIVE COLOCALIZATION, TYROSINE PHOSPHORYLATION, ACTIN CYTOSKELETON, SURFACE DOMAINS

ID: 5793184