Hepatoma polarization limits CD81 and hepatitis C virus dynamics

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

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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 (CD81ΔC) and its effect(s) on HCVpp mobility and infection. CD81ΔC 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 not observed in polarized cells. HCVpp showed a significant reduction in Brownian diffusion and infection of CD81ΔC 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
JournalCellular Microbiology
Issue number3
Early online date20 Nov 2012
Publication statusPublished - 1 Mar 2013


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