Rapid reversion of a deletion mutation in Moloney murine leukemia virus by recombination with a closely related endogenous provirus

Abstract

During abortive infection of mouse cells, defective retroviruses carrying deletions in essential functions can recombine with endogenous retroviral sequences to form viable, replication-competent viruses. We have examined the reversion of a mutant Moloney murine leukemia virus with a deletion in the protease domain of the pol gene after infection of NIH/3T3 cells. In this system revertants arise quickly, only 2 weeks after infection. Analysis of DNA clones of the revertant viral genomes showed that they were derived by recombination with a long sequence of gag and pol exhibiting 95% sequence identity to Moloney virus. One such cloned recombinant was fully infectious, indicating that the repertoire of viral sequences in the NIH/3T3 genome must include substantial stretches of functional viral genes. Examination of the viral DNAs very early in the infection revealed the presence of defective genomes, formed by nonhomologous crossovers between the two parental sequences. We suggest that these may serve as intermediates in the eventual formation of the viable revertant genomes.