Spontaneous mutation of RNA tumour viruses

Abstract

There are 2 categories of spontaneously occurring avian and mammalian RNA tumour virus mutants: conditional and non-conditional. 1) Conditional mutants are able to replicate in or transform cells only under certain physiological conditions or in certain cells. RNA tumour virus temperature-sensitive mutants, focus-morphology mutants, and host range mutants are spontaneously formed. Some of these conditional mutants probably arise by point mutations in the viral genome. 2) Non-conditional mutants have genetic lesions that render them inactive under all conditions. There are non-conditional spontaneous RNA tumour virus mutants that are missing either the virion envelope glycoprotein or both the envelope glycoprotein and the virion DNA polymerase. These mutants cannot replicate or transform cells. Other spontaneous non-conditional mutants can replicate but are defective in their ability to transform fibroblastoid cells. These spontaneous transformation-defective mutants can have deletions in 10-20% of the genomic RNA. Conditional mutants with an altered host range occur at a high rate of approximately 1 mutation/50 infected cell generations during DNA-to-DNA information transfer. This type of conditional mutation requires cell replication but does not occur frequently either during the original synthesis of viral DNA (RNA-to-DNA information transfer) or during the transcription of progeny viral RNA from the (RNA-to-DNA information transfer) or during the transcription of progeny viral RNA from the DNA (DNA-to-RNA information transfer). Temperature-sensitive and focus-morphology mutants also have a high rate of spontaneous formation. Non-conditional mutants missing the viral envelope glycoprotein, DNA polymerase, or transformation gene, also appear to be spontaneously formed at a high rate. Normal avian and mammalian cells contain RNA tumour virus-related genes in their DNA. It is hypothesized that these endogenous RNA tumour virus-related genes in normal cells also have a high rate of spontaneous mutation and are involved in neoplastic processes.