The isolation of interferon-inducing mutants of vesicular stomatitis virus with altered viral P function for the inhibition of total protein synthesis

Abstract

We have previously reported that T1026, a temperature-sensitive ( ts) noncytocidal mutant of VSV, and its ts revenant, T1026-R1, are nonconditional mutants in the VSV function “P” for the inhibition of total protein synthesis (viral plus cellular) in infected cells ( C. P. Stanners, A. M. Francoeur, and T. Lam, 1977, Cell 11, 273–281 ; C. P. Stanners, S. Kennedy, and L. Poliquin, 1987, Virology 160, 255–258 ). We have also shown that P − mutants such as these are superior interferon inducers relative to their parental P + wild-type virus, HR, and that P − mutants may be distinguished from P + virus using the plaque interferon production or PIF assay ( A. M. Francoeur, T. Lam, and C. P. Stanners, 1980, Virology 105, 526–536 ). In order to carry the analysis of VSV P function further, a number of independent mutants in the VSV P function are required. We show here that the PIF assay may be used to isolate spontaneously occurring interferon-inducing mutants (PIF + mutants) from wild-type VSV (PIF − virus) populations. About one-half of the PIF + mutants isolated with the PIF assay were found to have alterations in the VSV P function. As well as mutants that were defective for the inhibition of total protein synthesis, the assay yielded a new class of VSV P function mutants which appear to inhibit protein synthesis more severely than does P + virus. The majority of newly isolated PIF + mutants was also found to be temperature sensitive for growth. The ts phenotype, however, could be reverted for most PIF + mutants with little effect on the PIF or P phenotype. These findings show that interferon induction and P function are related functions of VSV; this fact has allowed the isolation of a repertoire of mutants with widely varying P function.