A model system for nonhomologous recombination between retroviral and cellular RNA

A current model for the generation of transforming retroviruses proposes that read-through RNAs, containing both viral and cellular sequences, are copackaged with viral genomic RNA. It is, however, possible that a cellular mRNA is occasionally encapsidated into a retroviral particle, even though viral packaging sequences are absent. We have generated recombinant proviruses following copackaging of an avian leukosis viral genomic RNA and a neo-containing RNA completely devoid of retroviral sequences. In these studies, we used the packaging cell line SE21Q1b, which has the unique ability to randomly package cellular mRNA into retroviral particles. We describe 10 recombinants obtained following copackaging of nonhomologous RNAs. Our data show that recombination is not occurring at the DNA level in the parental SE21Q1b cells but is occurring at the RNA level, during reverse transcription. These data further suggest that reverse transcriptase can preferentially jump between templates at short stretches of homology in otherwise unrelated RNAs. We conclude that retroviral sequences are not required for packaged mRNA to be reverse transcribed and to be included in integrated proviruses.