Nonconditional replication mutants of type C and type D retroviruses defective in gag gene-coded polyprotein post-translational processing

Abstract

A rapid method for the isolation of nonconditional replication-defective mutants of type C retroviruses of primate and nonprimate origin and a representative type D retrovirus is described. By this means, six RD114, three M7-baboon, four Rauscher-murine leukemia virus (R-MuLV), and nine squirrel monkey retrovirus (SMRV) mutant clones were isolated. Although defective for virus production, all but two of the mutant clones isolated were characterized by relatively high levels of gag and env gene-coded protein expression. While expression of gag and env gene translational products was coordinate in most of the R-MuLV and SMRV mutant clones, certain clones nonproductively infected with either RD114 or M7 baboon virus showed noncoordinate synthesis. Further analysis of representative mutant clones indicated impaired gag gene-coded polyprotein post-translational processing. This latter observation made possible identification of the component structural proteins of both RD114 and SMRV gag gene-coded precursor polyproteins. The susceptibility of many of the clones to superinfection by wild-type virus indicated that the defect in virus production was due to mutation in the viral, rather than host, genome. Several nonproductively-infected clones, on the other hand, were resistant to superinfection. The demonstration of greater cross-interference to superinfection between M7, RD114, and SMRV than between any of these viruses and the amphotropic murine type C virus isolate, 4070-A, corroborates the presence of shared envelope glycoprotein determinants between primate-derived type C and type D viruses.