The mouse H-2A region influences the envelope gene structure of tumor-associated murine leukemia viruses.
C57BL/10 (B10) strains congenic at the mouse major histocompatibility locus (H-2) were injected with a modified ecotropic SL3-3 murine leukemia virus (MuLV) to determine the effect of the H-2 genes on the envelope gene structure of recombinant MuLVs. All tested strains rapidly developed T-cell lymphomas, and recombinant proviruses were detected in the tumor DNAs by Southern blot. The B10.D2 (H-2d), B10.Br (H-2k), B10.Q (H-2q), and B10.RIII (H-2r) strains exhibited a TI phenotype in which almost all tumors contained type I recombinants. These recombinants characteristically acquire envelope gene sequences from the endogenous polytropic viruses but retain the 5' p15E (TM) gene sequences from the ecotropic virus. The parental B10 (H-2b) strain, however, had a novel phenotype that was designated NS for nonselective. Only 30% of the B10 tumors had detectable type I recombinants, whereas a proportion of the others appeared to contain type II recombinants that lacked the type I-specific ecotropic p15E gene sequences. Studies of other B10 congenic strains with hybrid H-2 loci and selected F1 animals revealed that the NS phenotype was regulated by a dominant gene(s) that mapped to the A region of H-2b. These results demonstrate that a host gene within the major histocompatibility complex can influence the genetic evolution of pathogenic retroviruses in vivo.
Nuckols
J D
JD
Department of Pathology, Duke University Medical Center, Durham, North Carolina 27705, USA.
Thomas
C Y
CY
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D004279:DNA, Viral; D005814:Genes, Viral; D006183:H-2 Antigens / Q000235:genetics*; D009052:Leukemia Virus, Murine / Q000235:genetics*; D016399:Lymphoma, T-Cell / Q000821:virology; D051379:Mice; D008969:Molecular Sequence Data; D010641:Phenotype; D011995:Recombination, Genetic; D015682:Retroviridae Proteins, Oncogenic / Q000235:genetics; D012689:Sequence Homology, Nucleic Acid; D014759:Viral Envelope Proteins / Q000235:genetics*
D004279:DNA, Viral; D006183:H-2 Antigens; C108513:H-2A antigen; D015682:Retroviridae Proteins, Oncogenic; D014759:Viral Envelope Proteins; C078678:p15E protein, Murine leukemia virus