In vivo generation of antigenic variants of murine retroviruses

Inoculation of adult BALB/c-H-2k (BALB.K) mice with both Gross murine leukemia virus (GV) and a biological clone derived from this virus resulted in the recovery of variant viruses which differ from GV with respect to the expression of specific epitopes associated with the env gene product, gp70. The loss of these epitopes correlated with the failure of antiserum raised in BALB.K mice against GV to neutralize variant virus although this antiserum neutralized GV. In contrast, BALB/c-H-2b (BALB.B) mice, immunized with GV, produced antibodies which neutralized both GV and the variant virus, indicating that BALB.B mice respond to epitopes distinct from those recognized by BALB.K mice. These results suggest that the selection of variant viruses resulting from in vivo passage may be related to the immunoselective pressures exerted in mice which express particular alleles of certain major histocompatibility complex (MHC)-linked genes.