title: Transmission in vitro of hepatitis C virus from persistently infected human B-cells to hepatoma cells by cell-to-cell contact.
abstract: Virus cell-to-cell spread has been reported for many different viruses and may contribute to pathogenesis of viral disease. The role played by cell-to-cell contact in hepatitis C virus (HCV) transmission was studied in vitro by cell co-cultivation experiments. A human lymphoblastoid B-cell line, infected persistently with HCV in vitro (TO.FE(HCV)), was used as HCV donor [Serafino et al., 2003]; recipient cells were the human hepatoma HepG2 cell line. Both cell types were co-cultured for 48 hr to allow the cell-to-cell contacts. The hepatoma HepG2 cells are not permissive to free-virus infection, but they were infected successfully using TO.FE(HCV) cells as source of virus. The kinetics of viral RNA synthesis and the percentage of infected cells were compared in cell-mediated-and cell-free-viral infection. After co-cultivation, a consistent proportion of hepatoma cells replicated HCV and stably expressed viral antigens. Virus produced was infectious as demonstrated by the ability to reinfect fresh B-cells. This cell model shows that permissiveness to HCV infection can be achieved in vitro in non-permissive hepatoma cells by direct cell-to-cell contacts with infected human B-cells. This mechanism of virus spread may also play a pathogenic role in vivo.
authors.affiliation: Institute of Neurobiology and Molecular Medicine, National Research Council (CNR), Area di Ricerca CNR TorVergata, Roma, Italy.
authors.forename: Maria Beatrice
authors.initials: MB
authors.lastname: Valli
authors.forename: Annalucia
authors.initials: A
authors.lastname: Serafino
authors.forename: Annalisa
authors.initials: A
authors.lastname: Crema
authors.forename: Luisa
authors.initials: L
authors.lastname: Bertolini
authors.forename: Aldo
authors.initials: A
authors.lastname: Manzin
authors.forename: Giulia
authors.initials: G
authors.lastname: Lanzilli
authors.forename: Cesare
authors.initials: C
authors.lastname: Bosman
authors.forename: Silvia
authors.initials: S
authors.lastname: Iacovacci
authors.forename: Sergio
authors.initials: S
authors.lastname: Giunta
authors.forename: Antonio
authors.initials: A
authors.lastname: Ponzetto
authors.forename: Massimo
authors.initials: M
authors.lastname: Clementi
authors.forename: Guido
authors.initials: G
authors.lastname: Carloni
mesh_terms: D001402:B-Lymphocytes / Q000502:physiology / Q000821:virology*; D006528:Carcinoma, Hepatocellular / Q000523:psychology / Q000821:virology*; D002450:Cell Communication; D002460:Cell Line; D018920:Coculture Techniques; D016174:Hepacivirus / Q000378:metabolism / Q000502:physiology*; D006526:Hepatitis C / Q000821:virology; D006801:Humans; D014776:Virus Cultivation; D014779:Virus Replication