Characterization of epitopes defining two major subclasses of polytropic murine leukemia viruses (MuLVs) which are differentially expressed in mice infected with different ecotropic MuLVs

Abstract

Polytropic murine leukemia viruses (MuLVs) arise in mice by recombination of ecotropic MuLVs with endogenous retroviral envelope genes and have been implicated in the induction of hematopoietic proliferative diseases. Inbred mouse strains contain many endogenous sequences which are homologous to the polytropic env genes; however, the extent to which particular sequences participate in the generation of the recombinants is unknown. Previous studies have established antigenic heterogeneity among the env genes of polytropic MuLVs, which may reflect recombination with distinct endogenous genes. In the present study, we have examined many polytropic MuLVs and found that nearly all isolates fall into two mutually exclusive antigenic subclasses on the basis of the ability of their SU proteins to react with one of two monoclonal antibodies, termed Hy 7 and MAb 516. Epitope-mapping studies revealed that reactivity to the two antibodies is dependent on the identity of a single amino acid residue encoded in a variable region of the receptor-binding domain of the env gene. This indicated that the two antigenic subclasses of MuLVs arose by recombination with distinct sets of endogenous genes. Evaluation of polytropic MuLVs in mice revealed distinctly different ratios of the two subclasses after inoculation of different ecotropic MuLVs, suggesting that individual ecotropic MuLVs preferentially recombine with distinct sets of endogenous polytropic env genes.

A multistep process of leukemogenesis in Moloney murine leukemia virus-infected mice that is modulated by retroviral pseudotyping and interference

“…It is clear, however, that polytropic MuLVs exhibit a great deal of heterogeneity in their in vitro infectivities, with mouse-to-mink infectivity ratios ranging from 10 Ϫ3 in the case of a group of recombinant viruses isolated from F-MuLV-infected mice (21) to 10 3 in the case of class II polytropic MuLVs from AKR mice (20,25). We have recently reported the occurrence of two antigenic subclasses of polytropic MuLVs in M-MuLV-infected NFS/N mice defined by the MAbs 516 and Hy 7 (32). Preliminary evidence suggests that the Hy 7-reactive polytropic MuLVs from M-MuLV-infected mice are variable in their in vitro tropisms and are frequently much less infectious for mink cells than for mouse cells.…”

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

“…The NCPR region of a second F-MuLV, FB29, is nearly identical to that of F-MuLV 57 (34). Infection of NFS/N mice with FB29 frequently results in a higher proportion of Hy 7-reactive than 516-reactive recombinants in the spleen; however, more MAb 516-reactive polytropic MuLVs are detected in FB29-infected mice than in mice infected with F-MuLV 57 (26). It is possible that regions of the genome other than the NCPR region in other ecotropic MuLVs may influence the types of polytropic MuLVs generated.…”

“…We have previously reported that nearly all polytropic MuLV isolates can be classified as members of two major antigenic subclasses defined by their reactivity with two monoclonal antibodies (MAbs) termed Hy 7 and 516 (26). These two MAbs react with mutually exclusive epitopes, both of which have been mapped to the same amino acid in the first third of the SU protein and very likely reflect the existence of two discrete families of endogenous polytropic sequences.…”

“…To define more closely the sequences of FMU5G which influence the generation of the two subclasses of polytropic MuLVs, chimeric viruses containing smaller substitutions within the U5G region were examined ( Mice were inoculated neonatally and sacrificed at 4 to 8 weeks of age. IC assays were conducted on thymocytes and splenocytes as previously described (26). For determination of the percentage of polytropic MuLVs reactive with MAb Hy 7, the total polytropic MuLV population was taken to be the sum of Hy 7-reactive and 516-reactive polytropic MuLVs.…”