Molecular and Cellular Determinants of Cell-to-Cell Transmission of HCV In Vitro.

It was reported previously that HCV can be transmitted from persistently infected human bone-marrow-derived B-lymphoblastoid cells (TO.FE(HCV)) to human hepatoma cells by cell-to-cell contact. The present study confirms and characterize further such type of HCV infection in vitro. TO.FE(HCV) cells were co-cultured with 2.2.15 hepatoma cells, that are not susceptible to cell-free infection by sera containing HCV of 1b genotype. By this co-cultivation system it was demonstrated that HCV transmission to recipient cells requires de novo virus RNA replication. Several factors may favor HCV-transmission, evidence is provided that TO.FE(HCV) cells were able to select HCV-quasispecies. 5'-UTR and core sequence analysis revealed differences in the HCV-quasispecies composition in serum inoculum and in infected TO.FE B-cells at 4 months post-inoculation. It is considered that the latter may be more successful in replicating HCV in vitro and used to express surface molecules which may be involved in cell-to-cell contact. In TO.FE(HCV) cells replicate distinct, or few close related, HCV-variants correlated with those of serum inoculum. Comparative analysis of tetra-spans and integrins expression