Conditional lethal mutants of vesicular stomatitis virus III. Host range properties, interfering capacity, and complementation patterns of specific hr mutants

Abstract

A group of host-restricted ( hr) mutants of VSV-Indiana that was previously shown to be defective for virus-directed RNA synthesis in nonpermissive HEp-2 cells has been further characterized. Thirty animal cell lines tested for their ability to support productive infections with mutant or wild-type virus showed that complete or partial restriction of mutant virus was the dominant phenotype. Certain cell lines such as BHK-21 were highly permissive for both wild-type and hr virus, whereas a gradient of restriction for mutant virus replication was observed among other cell types which was most pronounced with cells of human origin. Homotypic interference against VSV-Indiana and heterotypic interference against VSV-New Jersey could be demonstrated in HEp-2 cells abortively infected with certain hr mutants. Mixed infection of nonpermissive HEp-2 cells with pairwise combinations of 10 hr mutants demonstrated weak complementation between certain pairs resulting in enhanced virus yields. No hr + recombinants were detected. Final assignment of these mutants to distinct complementation groups is not yet advocated since it is suggested that complementation may occur at the intragenic level based on the relatively low efficiency observed and the high probability that most of the hr mutants will be found to involve genetic lesions occurring in the cistron coding for the L (transcriptase) protein of VSV. The general findings of this study emphasize the importance of unidentified host factors which appear to be essential for the replication of this rhabdovirus.