A SPONTANEOUS POINT MUTATION IN THE HUMAN T-CELL LEUKEMIA-VIRUS TYPE-1 PX GENE LEADS TO EXPRESSION OF A NOVEL DOUBLY SPLICED PX-MESSENGER-RNA THAT ENCODES A 25-KD, AMINO-TERMINAL DELETED REX PROTEIN

Primary RNA transcripts of the human T-cell leukemia virus type 1 (HTL V-1) are processed into mature mRNA by a complex series of splicing ev ents. In this paper, we report the finding of a novel doubly spliced p X mRNA in two out of eight HTLV-1-infected cell lines and in one out o f 13 peripheral blood mononuclear cells from HTLV-1-infected individua ls. The second splicing for this novel pX mRNA is different from that for the known doubly spliced pX mRNA. A novel acceptor site in this sp licing was generated by a single point mutation (G to A) at nucleotide 7,337 of the pX gene. This mRNA contained a Complete open reading fra me that encodes an amino-terminal truncated p27rex protein with 189 am ino acids. A new 25-kD protein was detected in the cell lines expressi ng the novel pX mRNA by an antibody against the carboxy-terminal pepti de of p27rex and was termed p25rex. Although the function of p25rex is not clear, we clarified that p25rex is a cytoplasmic phosphoprotein a nd its function is different from the transcriptional regulator functi on of p27rex. The possibility that the mutated virus is replicable onl y in cells coinfected with the wild type HTLV-1 may explain why the in cidence of the mutants observed here is low.