Cellular changes associated with persistent hepatitis A infection in vitro.

The rate of division, morphology and ultrastructure of BSC-1 cells, persistently infected with hepatitis A virus (HAV), were compared with uninfected cells for 60 days after splitting of the cells. Both control and infected cells showed a biphasic growth pattern marked firstly by increasing cell density and high mitotic rate (exponential phase) and then high constant cell density and little mitosis (stationary phase). Immunoperoxidase studies showed that hepatitis A antigen (HAAg) appeared as cytoplasmic granules approximately one third of the way through the exponential phase in infected cells. The percentage of cells with HAAg rose until the early stationary phase when virtually all cells contained antigen. Radioimmunoassay demonstrated an increase in HAAg per cell in the stationary phase. Radioimmunofocus assay and immune electron microscopy confirmed the presence of HAV in infected cells in the stationary phase. Thin sectioning electron microscopy showed cytoplasmic annulate lamellae in infected cells of both phases but not in control cells.