Initiation and maintenance of persistent infection by respiratory syncytial virus

Abstract

Propagation of cells infected with temperature-sensitive (ts) mutants of respiratory syncytial (RS) virus at nonpermissive temperature (39.degree. c) resulted in cytolytic, abortive or persistent infection, depending on the mutant used to initiate infection. Five mutants from complementation group B produced cytolytic or abortive infections, but a single mutant (ts1) from group D and a noncomplementing mutant produced persistent infections. The persistently infected culture initiated by mutant ts1 (RS ts1/BS-C-1) was maintained in serial culture for > 100 transfers, and infectious-center assays and immunofluorescent staining indicated that all cells harbored the RS virus genome. RS ts/BS-C-1 cultures were resistant to superinfection by homologous and some heterologous viruses, and interferon-like activity against some heterologous viruses was present in the culture medium. Small amounts (0.002-0.2 PFU[plaque forming units]/cell) of infectious virus were present in the culture fluid, but autointerfering defective particles were not detected. This released virus formed small plaques and produced persistent infection of [African green monkey kidney] BS-C-1 cells at 37.degree. C. The RS ts1/BS-C-1 cells contained abundant RS virus antigen internally, but little at the surface, although the cells showed enhanced agglutinability by concanavalin A. Nucleocapsids and the 41,000 MW nucleoprotein were present in extracts of both nucleated and enucleated cells. No infectious RS virus was obtained by transfection of DNA from RS tts1/BS-C-1 cells to susceptible BS-C-1 or feline embryo cells under conditions allowing efficient transfection of a foamy virus proviral DNA. Persistent infection was apparently maintained in part by a non-ts variant of RS virus partially defective in maturation. The karyotype of the RS sts1/BS-C-1 culture differed from that of uninfected cells.