A small region of the ecotropic murine leukemia virus (MuLV) gag gene profoundly influences the types of polytropic MuLVs generated in mice

Abstract

The vast majority of recombinant polytropic murine leukemia viruses (MuLVs) generated in mice after infection by ecotropic MuLVs can be classified into two major antigenic groups based on their reactivities to two monoclonal antibodies (MAbs) termed Hy 7 and 516. These groups very likely correspond to viruses formed by recombination of the ecotropic MuLV with two distinct sets of polytropic env genes present in the genomes of inbred mouse strains. We have found that nearly all polytropic MuLVs identified in mice infected with a substrain of Friend MuLV (F-MuLV 57 ) are reactive with Hy 7, whereas mice infected with Moloney MuLV (Mo-MuLV) generate major populations of both Hy 7-and 516-reactive polytropic MuLVs. We examined polytropic MuLVs generated in NFS/N mice after inoculation with Mo-MuLV-F-MuLV 57 chimeras to determine which regions of the viral genome influence this difference between the two ecotropic MuLVs. These studies identified a region of the MuLV genome which encodes the nucleocapsid protein and a portion of the viral protease as the only region that influenced the difference in polytropic-MuLV generation by Mo-MuLV and F-MuLV 57 .

Introduction of acis-Acting Mutation in the Capsid-Coding Gene of Moloney Murine Leukemia Virus Extends Its Leukemogenic Properties

“…Leukemias developing following insertional mutagenesis of replicationcompetent MuLV can be associated either with the original ecotropic inoculum or with polytropic MCF viruses (39). It is therefore important to note that the prototypic thymoma-inducing Moloney MuLV and the erythroleukemogenic Friend MuLV differ in the endogenous envelope loci that are used to generate in vivo spreading of MCF viruses (14,30). Genetic mapping of these differences includes gag sequences at the 3Ј end of the capsid gene, downstream of the mutations introduced in MSD1 (30).…”

“…It is therefore important to note that the prototypic thymoma-inducing Moloney MuLV and the erythroleukemogenic Friend MuLV differ in the endogenous envelope loci that are used to generate in vivo spreading of MCF viruses (14,30). Genetic mapping of these differences includes gag sequences at the 3Ј end of the capsid gene, downstream of the mutations introduced in MSD1 (30). Therefore, it remains conceivable that the mutations present in MSD1 modulate the types of MCF recombinant MuLVs that are generated with new pseudotyping envelopes, allowing extended cell lineages to be targeted (29).…”