CHARACTERIZATION OF EPITOPES DEFINING 2 MAJOR SUBCLASSES OF POLYTROPIC MURINE LEUKEMIA VIRUSES (MULVS) WHICH ARE DIFFERENTIALLY EXPRESSED IN MICE INFECTED WITH DIFFERENT ECOTROPIC MULVS

Polytropic murine leukemia viruses (MuLVs) arise in mice by recombinat ion of ecotropic MuLVs with endogenous retroviral envelope genes and h ave been implicated in the induction of hematopoietic proliferative di seases. Inbred mouse strains contain many endogenous sequences which a re homologous to the polytropic env genes; however, the extent to whic h particular sequences participate in the generation of the recombinan ts is unknown, Previous studies have established antigenic heterogenei ty among the env genes of polytropic MuLVs, which may reflect recombin ation with distinct endogenous genes. In the present study, we have ex amined many polytropic MuLVs and found that nearly all isolates fall i nto two mutually exclusive antigenic subclasses on the basis of the ab ility of their SU proteins to react with one of two monoclonal antibod ies, termed Hy 7 and MAb 516. Epitope-mapping studies revealed that re activity to the two antibodies is dependent on the identity of a singl e amino acid residue encoded in a variable region of the receptor-bind ing domain of the env gene. This indicated that the two antigenic subc lasses of MuLVs arose by recombination with distinct sets of endogenou s genes. Evaluation of polytropic MuLVs in mice revealed distinctly di fferent ratios of the two subclasses after inoculation of different ec otropic MuLVs, suggesting that individual ecotropic MuLVs preferential ly recombine with distinct sets of endogenous polytropic env genes.