Persistent poliovirus infection: Establishment and maintenance involve distinct mechanisms

Abstract

Mutants of poliovirus (PV) with highly modified biological properties can be selected in vitro in cells of neural origin. Mutations accumulate in the genome of type 1 PV strains selected in human neuroblastoma cells, modifying cell specificity and conferring to the virus the ability to persist in such nonneural cells as HEp-2c (Pelletier et al., Virology 180, 729 1991). With this cell system, we have both parent lytic strains and persistent PV mutants; these were used to study the mechanisms of the establishment and maintenance of the persistent infection. We found that a persistent infection was established when the lytic potential of the virus was reduced; this involved both an early and a late event of the virus cycle for the type 1 mutants. In contrast, maintenance of the infection did not correlate with the reduced lytic potential of the viruses, but rather with the selection of mutant cell populations of various phenotypes. Two cell lines, representative of two phenotypes, were studied in greater detail. In the first one, HEp-S32 (c17), the PV receptor was not detected by cytofluorometry and viral genomes were detected by in situ hybridization in 2% of the cells. In the second cell line, HEp-S31 (cl18), 97% of the cells expressed the PV receptor, viral genomes were detected in 9–10% of the cells, and viral antigens in 5–10% of the cells. With this cell line, the cure of the culture or, alternatively, the lysis of the majority of cells, could be induced under specific culture conditions. We propose a model involving an equilibrium between an abortive and a lytic infection to explain the properties of cells persistently infected with PV.