Interferon induction by viruses. XVII. Non-temperature-sensitive mutations regulate interferon induction by vesicular stomatitis virus.
Wild-type (wt) strains of vesicular stomatitis virus (VSV) strain Indiana are poor to non-inducers of interferon (IFN) which express IFN induction-suppressing activity. At non-permissive temperatures, temperature-sensitive (ts) mutants of this virus are either like their wt parents, or they are good to excellent inducers of IFN. IFN inducibility and IFN induction-suppressing activity are mutually exclusive phenotypes in VSV-Indiana. With one exception, all Orsay ts mutants derived by A. Flamand (CNRS, Gif-sur-Yvette, France), representing the five complementation groups, were poor to non-inducers of IFN and were also capable of suppressing IFN induction by other viruses. In contrast, all Glasgow ts mutants derived by C. R. Pringle (University of Warwick, Coventry, U.K.) were excellent inducers of IFN. We demonstrate that this difference in acquisition of IFN inducibility relates primarily to the origin of the mutations; spontaneous for Orsay, and mutagen-derived for Glasgow. Tests with newly generated spontaneous and mutagen-derived mutants, and temperature-stable revertants of IFN-inducing ts mutants indicate that IFN inducibility results from non-ts, multiple mutations rarely acquired spontaneously, but generated frequently upon mutagenesis with 5-fluorouracil. The capacity of VSV-Indiana to induce IFN is considered intrinsic to the virus, but is only manifested when the dominant IFN induction-suppressing phenotype is lost through mutagenesis. Thus, non-ts mutations appear to regulate the expression of the IFN induction-suppressing phenotype, and hence the IFN inducibility of VSV-Indiana.
Sekellick
M J
MJ
Department of Molecular and Cell Biology, University of Connecticut, Storrs 06268.
Marcus
P I
PI
D000818:Animals; D005472:Fluorouracil / Q000494:pharmacology; D005814:Genes, Viral / Q000187:drug effects; D005816:Genetic Complementation Test; D007372:Interferons / Q000032:analysis / Q000096:biosynthesis*; D009154:Mutation; D010641:Phenotype; D013696:Temperature; D014721:Vesicular stomatitis Indiana virus / Q000187:drug effects / Q000235:genetics* / Q000302:isolation & purification; D014776:Virus Cultivation
D007372:Interferons; D005472:Fluorouracil