Loss of antigenic epitopes as the result of env gene recombination in retrovirus-induced leukemia in immunocompetent mice

The murine leukemia virus, E-55⁺ virus, induces a thymic lymphoma/leukemia in 100% of BALB.K mice infected as adults after a latent period of 4 months or more (Pozsgay et al., Virology 173, 330-334, 1989). Two molecular clones of virus designated E-55⁺ and E-55— based on their ability to encode the E-55 epitope detected by the monoclonal antibody 55 (mAb 55) were isolated from a leukemic BALB.K mouse inoculated with a biologically cloned E-55⁺ virus (Chesebro et al., Virology 112, 131-144, 1981). Env gene sequence analysis of E-55⁺ and E-55— clones showed that the E-55— virus was generated from the E-55⁺ virus as the result of a recombination between E-55⁺ virus and the endogenous ecotropic virus, emv-1, carried in the genome of the BALB.K mouse strain. The recombinant E-55— virus is replication competent. This recombination event and the consequential expression of E-55— virus consistently occur in immunocompetent BALB.K mice inoculated with the E-55⁺ virus and appear to play a role in the loss of epitopes recognized by virus neutralizing antibodies. The loss of these epitopes apparently allows the virus to evade the host immune response.