1887

Abstract

The major cell type supporting hepatitis C virus (HCV) infection is the hepatocyte; however, most reports studying viral entry and replication utilize transformed hepatoma cell lines. We demonstrate that HCV pseudoparticles (HCVpp) infect primary hepatocytes with comparable rates to hepatoma cells, demonstrating the limited variability in donor hepatocytes to support HCV receptor-glycoprotein-dependent entry. In contrast, we observed a 2-log range in viral replication between the same donor hepatocytes. We noted that cell proliferation augments pseudoparticle reporter activity and arresting hepatoma cells yields comparable levels of infection to hepatocytes. This study demonstrates comparable rates of HCVpp entry into primary hepatocytes and hepatoma cells, validating the use of transformed cells as a model system to study HCV entry.

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2015-06-01
2024-04-19
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References

  1. Alter M. J. 2007; Epidemiology of hepatitis C virus infection. World J Gastroenterol 13:2436–2441 [View Article][PubMed]
    [Google Scholar]
  2. Baumert T. F., Meredith L., Ni Y., Felmlee D. J., McKeating J. A., Urban S. 2014; Entry of hepatitis B and C viruses – recent progress and future impact. Curr Opin Virol 4:58–65 [View Article][PubMed]
    [Google Scholar]
  3. Blight K. J., McKeating J. A., Marcotrigiano J., Rice C. M. 2003; Efficient replication of hepatitis C virus genotype 1a RNAs in cell culture. J Virol 77:3181–3190 [View Article][PubMed]
    [Google Scholar]
  4. Farquhar M. J., McKeating J. A. 2008; Primary hepatocytes as targets for hepatitis C virus replication. J Viral Hepat 15:849–854 [View Article][PubMed]
    [Google Scholar]
  5. Farquhar M. J., Hu K., Harris H. J., Davis C., Brimacombe C. L., Fletcher S. J., Baumert T. F., Rappoport J. Z., Balfe P., McKeating J. A. 2012; Hepatitis C virus induces CD81 and claudin-1 endocytosis. J Virol 86:4305–4316 [View Article][PubMed]
    [Google Scholar]
  6. Fofana I., Krieger S. E., Grunert F., Glauben S., Xiao F., Fafi-Kremer S., Soulier E., Royer C., Thumann C. et al. 2010; Monoclonal anti-claudin 1 antibodies prevent hepatitis C virus infection of primary human hepatocytes. Gastroenterology 139:953–964, e1–e4 [View Article][PubMed]
    [Google Scholar]
  7. Hsu M., Zhang J., Flint M., Logvinoff C., Cheng-Mayer C., Rice C. M., McKeating J. A. 2003; Hepatitis C virus glycoproteins mediate pH-dependent cell entry of pseudotyped retroviral particles. Proc Natl Acad Sci U S A 100:7271–7276 [View Article][PubMed]
    [Google Scholar]
  8. Jensen T. B., Gottwein J. M., Scheel T. K., Hoegh A. M., Eugen-Olsen J., Bukh J. 2008; Highly efficient JFH1-based cell-culture system for hepatitis C virus genotype 5a: failure of homologous neutralizing-antibody treatment to control infection. J Infect Dis 198:1756–1765 [View Article][PubMed]
    [Google Scholar]
  9. Li K., Lemon S. M. 2013; Innate immune responses in hepatitis C virus infection. Semin Immunopathol 35:53–72 [View Article][PubMed]
    [Google Scholar]
  10. Liang Y., Shilagard T., Xiao S. Y., Snyder N., Lau D., Cicalese L., Weiss H., Vargas G., Lemon S. M. 2009; Visualizing hepatitis C virus infections in human liver by two-photon microscopy. Gastroenterology 137:1448–1458 [View Article][PubMed]
    [Google Scholar]
  11. Lupberger J., Zeisel M. B., Xiao F., Thumann C., Fofana I., Zona L., Davis C., Mee C. J., Turek M. et al. 2011; EGFR and EphA2 are host factors for hepatitis C virus entry and possible targets for antiviral therapy. Nat Med 17:589–595 [View Article][PubMed]
    [Google Scholar]
  12. Marukian S., Jones C. T., Andrus L., Evans M. J., Ritola K. D., Charles E. D., Rice C. M., Dustin L. B. 2008; Cell culture-produced hepatitis C virus does not infect peripheral blood mononuclear cells. Hepatology 48:1843–1850 [View Article][PubMed]
    [Google Scholar]
  13. Marukian S., Andrus L., Sheahan T. P., Jones C. T., Charles E. D., Ploss A., Rice C. M., Dustin L. B. 2011; Hepatitis C virus induces interferon-λ and interferon-stimulated genes in primary liver cultures. Hepatology 54:1913–1923 [View Article][PubMed]
    [Google Scholar]
  14. Meredith L. W., Wilson G. K., Fletcher N. F., McKeating J. A. 2012; Hepatitis C virus entry: beyond receptors. Rev Med Virol 22:182–193 [View Article][PubMed]
    [Google Scholar]
  15. Mitry R. R. 2009; Isolation of human hepatocytes. Methods Mol Biol 481:17–23 [View Article][PubMed]
    [Google Scholar]
  16. Park H., Serti E., Eke O., Muchmore B., Prokunina-Olsson L., Capone S., Folgori A., Rehermann B. 2012; IL-29 is the dominant type III interferon produced by hepatocytes during acute hepatitis C virus infection. Hepatology 56:2060–2070 [View Article][PubMed]
    [Google Scholar]
  17. Ploss A., Evans M. J. 2012; Hepatitis C virus host cell entry. Curr Opin Virol 2:14–19 [View Article][PubMed]
    [Google Scholar]
  18. Podevin P., Carpentier A., Pène V., Aoudjehane L., Carrière M., Zaïdi S., Hernandez C., Calle V., Méritet J. F. et al. 2010; Production of infectious hepatitis C virus in primary cultures of human adult hepatocytes. Gastroenterology 139:1355–1364, 1364.e6 [View Article][PubMed]
    [Google Scholar]
  19. Régeard M., Trotard M., Lepère C., Gripon P., Le Seyec J. 2008; Entry of pseudotyped hepatitis C virus into primary human hepatocytes depends on the scavenger class B type I receptor. J Viral Hepat 15:865–870 [View Article][PubMed]
    [Google Scholar]
  20. Sainz B. Jr, Barretto N., Martin D. N., Hiraga N., Imamura M., Hussain S., Marsh K. A., Yu X., Chayama K. et al. 2012a). Identification of the Niemann–Pick C1-like 1 cholesterol absorption receptor as a new hepatitis C virus entry factor. Nat Med 18:281–285 [View Article][PubMed]
    [Google Scholar]
  21. Sainz B. Jr, Barretto N., Yu X., Corcoran P., Uprichard S. L. 2012b). Permissiveness of human hepatoma cell lines for HCV infection. Virol J 9:30 [View Article][PubMed]
    [Google Scholar]
  22. Scheel T. K., Rice C. M. 2013; Understanding the hepatitis C virus life cycle paves the way for highly effective therapies. Nat Med 19:837–849 [View Article][PubMed]
    [Google Scholar]
  23. Schwarz A. K., Grove J., Hu K., Mee C. J., Balfe P., McKeating J. A. 2009; Hepatoma cell density promotes claudin-1 and scavenger receptor BI expression and hepatitis C virus internalization. J Virol 83:12407–12414 [View Article][PubMed]
    [Google Scholar]
  24. Taub R. 2004; Liver regeneration: from myth to mechanism. Nat Rev Mol Cell Biol 5:836–847 [View Article][PubMed]
    [Google Scholar]
  25. Wilson G. K., Stamataki Z. 2012; In vitro systems for the study of hepatitis C virus infection. Int J Hepatol 2012:292591 [View Article][PubMed]
    [Google Scholar]
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