Ultrastructural features of fetal erythroid precursors infected with parvovirus B19 in vitro: evidence of cell death by apoptosis.

Human parvovirus B19 cannot be cultured in standard cell lines and relatively little is known about the intracellular life-cycle of the virus. In this study, ultrastructural features of B19 infection were examined using haemopoietic cell suspension cultures derived from human fetal liver. Erythroblasts from infected cultures frequently contained crystalline arrays of both full and empty virus-like particles. The number and size of these arrays increased with the duration of culture, and their location changed from exclusively nuclear at 24 h post-infection to both nuclear and cytoplasmic at 3 days post-infection. Arrays were occasionally found in cytoplasmic protuberances which appeared to be pinching off from the cell. The location of the arrays corresponded to the distribution of viral capsid protein determined by immunolabelling at the light microscope level. Cells containing viral crystalline arrays also exhibited nucleolar degeneration, extreme margination of the nuclear heterochromatin, and cytoplasmic vacuolation. These features are typical of cells undergoing individual programmed cell death or 'apoptosis'. The triggering of apoptosis in erythroid precursors by parvovirus B19 may help to explain the apparent lack of a strong inflammatory response to fetal B19 infection and may have implications for understanding the mechanisms of viral spread throughout the host.