{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T06:56:54Z","timestamp":1791874614168,"version":"4.3.4"},"reference-count":25,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":2403,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2009,2]]},"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>\n                      Six major hepatitis C virus (HCV) genotypes and numerous subtypes have been described, and recently a seventh major genotype was discovered. Genotypes show significant molecular and clinical differences, such as differential response to combination therapy with interferon-\u03b1 and ribavirin. Recently, HCV research has been accelerated by cell culture systems based on the unique growth capacity of strain JFH1 (genotype 2a). By development of JFH1-based intergenotypic recombinants containing Core, envelope protein 1 and 2 (E1, E2), p7, and nonstructural protein 2 (NS2) of genotype 6a and 7a strains, as well as subtype 1b and 2b strains, we have completed a panel of culture systems for all major HCV genotypes. Efficient growth in Huh7.5 cells depended on adaptive mutations for HK6a\/JFH1 (6a\/2a, in E1 and E2) and J4\/JFH1 (1b\/2a, in NS2 and NS3); viability of J8\/JFH1 (2b\/2a) and QC69\/JFH1 (7a\/2a) did not require adaptation. To facilitate comparative studies, we generated virus stocks of genotype 1\u20137 recombinants with infectivity titers of 10\n                      <jats:sup>3.7<\/jats:sup>\n                      to 10\n                      <jats:sup>5.2<\/jats:sup>\n                      50% tissue culture infectious dose\/mL and HCV RNA titers of 10\n                      <jats:sup>7.0<\/jats:sup>\n                      to 10\n                      <jats:sup>7.9<\/jats:sup>\n                      IU\/mL. Huh7.5 cultures infected with genotype 1\u20136 viruses had similar spread kinetics, intracellular Core, NS5A, and lipid amounts, and colocalization of Core and NS5A with lipids. Treatment with interferon-\u03b12b but not ribavirin or amantadine showed a significant antiviral effect. Infection with all genotypes could be blocked by specific antibodies against the putative coreceptors CD81 and scavenger receptor class B type I in a dose-dependent manner. Finally, neutralizing antibodies in selected chronic phase HCV sera had differential effects against genotype 1\u20137 viruses.\n                      <jats:italic toggle=\"yes\">Conclusion:<\/jats:italic>\n                      We completed and characterized a panel of JFH1-based cell culture systems of all seven major HCV genotypes and important subtypes and used these viruses in comparative studies of antivirals, HCV receptor interaction, and neutralizing antibodies. 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