Mutations in gag proteins P12 and P15 of Moloney murine leukemia virus block early stages of infection.
A collection of mutants of Moloney murine leukemia virus with deletions in the gag gene was generated by restriction enzyme site-directed mutagenesis of a cloned proviral DNA. The mutants all contained deletions of the NarI site in the P12 region, and some contained deletions extending into the adjacent P15 region. The deletions did not significantly affect the assembly or release of viral particles. Examination of endogenous reverse transcription products demonstrated normal synthesis of minus- and plus-strand strong-stop DNAs, indicating that the RNA genome was packaged and that reverse transcription in detergent-permeabilized virions was not impaired. The virion particles contained high levels of an abnormal protein which corresponded to a P15-P12 fusion protein; proteolytic processing of this abnormal protein was completely blocked by all the mutations. The infectivity of the particles was dramatically reduced. Analysis of the low-molecular-weight DNA in infected NIH/3T3 cells indicated that the mutant virions could not carry out viral DNA synthesis. These data suggest that the P12 and P15 proteins may not be critical for virion assembly but do play an important role in early steps of viral infection.
D000818:Animals; D002872:Chromosome Deletion; D004279:DNA, Viral / Q000096:biosynthesis; D015683:Gene Products, gag; D051379:Mice; D008979:Moloney murine leukemia virus / Q000235:genetics* / Q000472:pathogenicity; D009154:Mutation; D012367:RNA, Viral / Q000378:metabolism; D014764:Viral Proteins / Q000235:genetics*; D014771:Virion / Q000235:genetics / Q000378:metabolism
D004279:DNA, Viral; D015683:Gene Products, gag; D012367:RNA, Viral; D014764:Viral Proteins