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.FEHCV), 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.FEHCV 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. J. Med. Virol. 78:192–201, 2006.