A MODEL SYSTEM FOR NONHOMOLOGOUS RECOMBINATION BETWEEN RETROVIRAL ANDCELLULAR RNA

A current model for the generation of transforming retroviruses propos es that read-through RNAs, containing both viral and cellular sequence s, are copackaged with viral genomic RNA. It is, however, possible tha t a cellular mRNA is occasionally encapsidated into a retroviral parti cle, even though viral packaging sequences are absent. We have generat ed recombinant proviruses following copackaging of an avian leukosis v iral genomic RNA and a neo-containing RNA completely devoid of retrovi ral sequences. In these studies, we used the packaging cell line SE21Q 1b, which has the unique ability to randomly package cellular mRNA int o retroviral particles. We describe 10 recombinants obtained following copackaging of nonhomologous RNAs. Our data show that recombination i s not occurring at the DNA level in the parental SE21Q1b cells but is occurring at the RNA level, during reverse transcription. These data f urther suggest that reverse transcriptase can preferentially jump betw een templates at short stretches of homology in otherwise unrelated RN As. We conclude that retroviral sequences are not required for package d mRNA to be reverse transcribed and to be included in integrated prov iruses.