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Characterization of epitopes defining two major subclasses of polytropic murine leukemia viruses (MuLVs) which are
M Lavignon1, J L Walker, S M Perryman
1Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, Hamilton, Montana 59840.
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.
Insights
Polytropic murine leukemia viruses (MuLVs) with distinct antigenic properties arise from recombination events. Different ecotropic MuLVs preferentially recombine with specific endogenous polytropic env genes, influencing disease induction.
Area of Science:
- Virology
- Molecular Biology
- Immunology
Background:
- Polytropic murine leukemia viruses (MuLVs) are linked to hematopoietic diseases in mice.
- These viruses emerge through recombination between ecotropic MuLVs and endogenous retroviral envelope genes.
- The specific endogenous sequences involved in generating polytropic MuLVs remain largely uncharacterized.
Purpose of the Study:
- To investigate the antigenic diversity of polytropic MuLV envelope (env) genes.
- To determine the genetic basis for antigenic heterogeneity among polytropic MuLVs.
- To explore the preferential recombination of specific ecotropic MuLVs with endogenous polytropic env genes.
Main Methods:
- Antigenic characterization of polytropic MuLV isolates using monoclonal antibodies (Hy 7 and MAb 516).
- Epitope-mapping of the SU protein to identify key residues responsible for antibody reactivity.
- In vivo evaluation of polytropic MuLV subclass ratios following inoculation with different ecotropic MuLVs.
Main Results:
- Nearly all polytropic MuLV isolates segregated into two distinct antigenic subclasses based on SU protein reactivity.
- Reactivity differences were attributed to a single amino acid substitution in a variable region of the env gene's receptor-binding domain.
- Inoculation with different ecotropic MuLVs resulted in significantly different ratios of these two polytropic MuLV subclasses in mice.
Conclusions:
- The two antigenic subclasses of polytropic MuLVs likely arise from recombination with distinct sets of endogenous genes.
- Specific ecotropic MuLV strains exhibit a preference for recombining with particular endogenous polytropic env gene sequences.
- This preferential recombination influences the generation of polytropic MuLVs and their potential role in disease pathogenesis.