Mutational analysis of the sequences at the termini of the Moloney murine leukemia virus DNA required for integration

Abstract

The insertion of retroviral DNA into the genome of the infected cell to form the integrated provirus requires the presence of short inverted repeat (IR) sequences at the viral DNA termini. To examine the sequence requirements at the IRs for integration of the Moloney murine leukemia virus, we generated a series of mutants with deletion and substitution mutations and tested their ability to replicate and form proviruses in vivo. The experiments did not detect evidence of a requirement for sequences outside the IRs, and only a very loose requirement for the IR sequences, with many point mutations well tolerated. Examination of the mutants suggests that bases very near the terminus and those approximately one turn of the DNA helix away from the terminus are important for recognition by the integrase function.