title: Patient-derived hepatitis C virus and JFH-1 clones differ in their ability to infect human hepatoma cells and lymphocytes.
abstract: Hepatitis C virus (HCV) is a hepatotropic virus that also infects cells of the immune system. HCV clones cultivated in human hepatoma Huh-7.5 cells have significantly advanced our understanding of HCV replication and candidate hepatocyte receptors. However, naturally occurring patient-derived HCV, in contrast to the HCV JFH-1 clone, is unable to infect Huh-7.5 cells, while it can replicate in human primary T-cells and selected T-cell lines. To better understand this incongruity, we examined the susceptibility of primary T-cells, PBMCs and T-cell lines to infection with patient-derived HCV, the classical HCV JFH-1 and a cell culture-adapted JFH1(T) known to be highly infectious to Huh-7.5 cells. We also tested whether Huh-7.5 cells are prone to virus readily infecting T-lymphocytes. The results revealed that while primary T-cells and Molt4 and Jurkat T-cell lines were susceptible to patient-derived HCV, they were resistant to infection with either JFH1(T) or JFH-1. However, the JFH1(T) clone interacted more firmly, although non-productively, with the cells than JFH-1. Further, Huh-7.5 cells robustly supported replication of JFH1(T) but not patient-derived, wild-type virus, despite using highly sensitive detection assays. In conclusion, JFH-1 and JFH1(T) clones were unable to establish productive infection in human primary T-cells, PBMCs and T-cell lines known to be prone to infection by patient-derived HCV, while Huh-7.5 cells were resistant to infection with naturally occurring virus infecting immune cells. The data showed that the ability to infect lymphocytes is a characteristic of native virus but not laboratory HCV clones.
authors.affiliation: Molecular Virology and Hepatology Research Group, Division of BioMedical Sciences, Faculty of Medicine, Health Sciences Center, Memorial University, St John's, Newfoundland and Labrador, Canada.
authors.forename: Mohammed A
authors.initials: MA
authors.lastname: Sarhan
authors.affiliation: Molecular Virology and Hepatology Research Group, Division of BioMedical Sciences, Faculty of Medicine, Health Sciences Center, Memorial University, St John's, Newfoundland and Labrador, Canada.
authors.forename: Annie Y
authors.initials: AY
authors.lastname: Chen
authors.affiliation: Immunology and Infectious Disease Group, Division of BioMedical Sciences, Faculty of Medicine, Health Sciences Center, Memorial University, St John's, Newfoundland and Labrador, Canada.
authors.forename: Rodney S
authors.initials: RS
authors.lastname: Russell
authors.affiliation: Immunology and Infectious Disease Group, Division of BioMedical Sciences, Faculty of Medicine, Health Sciences Center, Memorial University, St John's, Newfoundland and Labrador, Canada.|Molecular Virology and Hepatology Research Group, Division of BioMedical Sciences, Faculty of Medicine, Health Sciences Center, Memorial University, St John's, Newfoundland and Labrador, Canada.
authors.forename: Tomasz I
authors.initials: TI
authors.lastname: Michalak
mesh_terms: D000328:Adult; D006528:Carcinoma, Hepatocellular / Q000821:virology*; D045744:Cell Line, Tumor; D018076:DNA, Complementary; D005838:Genotype; D016174:Hepacivirus / Q000145:classification* / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000821:virology*; D006801:Humans; D008113:Liver Neoplasms / Q000821:virology*; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000821:virology*; D056189:Viral Tropism; D014779:Virus Replication
chemical_list: D018076:DNA, Complementary; D012367:RNA, Viral