BOTH THE CHANGES OF 6 AMINO-ACIDS AND THE C-TERMINAL TRUNCATION CAUSED BY A ONE-BASE INSERTION IN THE DEFECTIVE ENV GENE OF FRIEND SPLEEN FOCUS-FORMING VIRUS SIGNIFICANTLY AFFECT THE PATHOGENIC ACTIVITY OF THEENCODED LEUKEMOGENIC MEMBRANE GLYCOPROTEIN (GP55)

Friend spleen focus-forming virus (F-SFFV) causes acute erythroleukemi a in mice and encodes in its defective env gene an Env-like membrane g lycoprotein (gp55). The F-SFFV env gene has three characteristic struc tures compared with that of ecotropic murine leukemia viruses (MuLVs): substitution by the polytropic MuLV env sequence, a 585-bp deletion, and a I-bp insertion. All of these characteristic structures are essen tial for the leukemogenic potential of gp55 of polycythemia-inducing i solates of F-SFFV (F-SFFVp). The I-bp insertion causes changes of six amino acids and truncation by 34 amino acids at the C terminus. In thi s study, we constructed 12 mutant F-SFFV genomes starting from the wil d-type F-SFFVp and examined the effect of the C-terminal truncation an d the six altered amino acids on the pathogenic activity of gp55. The results indicated that at least 18 to 24 amino acids must be deleted f rom the C terminus for the env product to be pathogenically active. We also found that the six altered amino acids contributed significantly to the pathogenic activity of gp55. Analyses of the cellular processi ng of these mutant gp55s supported a correlation between the pathogeni c activity of gp55 and its efficiency in overall cellular processing.