Altered replicase specificity is responsible for resistance to defective interfering particle interference of an Sdi- mutant of vesicular stomatitis virus.

The in vitro resistance of an Sdi- mutant of vesicular stomatitis virus to interference by wild-type defective interfering (DI) particles was expressed quantitatively in a cell-free replication system derived from mutant-infected cells. Added wild-type DI particle templates were replicated very poorly by extracts of Sdi- mutant-infected cells. However, the addition of purified viral polymerase (a complex of L and NS proteins) from wild-type vesicular stomatitis virus allowed efficient replication of wild-type DI particle genomes in these cell extracts. Added wild-type NS protein alone did not complement DI particle genome replication in these cell extracts, but it did complement a defect in the in vitro transcriptional activity of Sdi- mutant virus. These results clearly implicate the vesicular stomatitis virus polymerase complex in the inability of Sdi- mutants to replicate DI particles and in the quantitative escape from DI particle interference in evolving virus populations.