A spontaneous point mutation in the human T-cell leukemia virus type 1 pX gene leads to expression of a novel doubly spliced pX-mRNA that encodes a 25-kD, amino-terminal deleted rex protein.
Primary RNA transcripts of the human T-cell leukemia virus type 1 (HTLV-1) are processed into mature mRNA by a complex series of splicing events. In this paper, we report the finding of a novel doubly spliced pX mRNA in two out of eight HTLV-1-infected cell lines and in one out of 13 peripheral blood mononuclear cells from HTLV-1-infected individuals. 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 splicing 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 frame that encodes an amino-terminal truncated p27rex protein with 189 amino acids. A new 25-kD protein was detected in the cell lines expressing the novel pX mRNA by an antibody against the carboxy-terminal peptide of p27rex and was termed p25rex. Although the function of p25rex is not clear, we clarified that p25rex is a cytoplasmic phosphoprotein and its function is different from the transcriptional regulator function of p27rex. The possibility that the mutated virus is replicable only in cells coinfected with the wild type HTLV-1 may explain why the incidence of the mutants observed here is low.
Shionogi Institute for Medical Science, Osaka, Japan.
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S
Orita
H
H
Kobayashi
A
A
Saiga
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R
Kubota
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M
Osame
H
H
Igarashi
D000595:Amino Acid Sequence; D001483:Base Sequence; D002460:Cell Line; D004279:DNA, Viral; D016370:Gene Products, rex / Q000235:genetics*; D016356:Gene Products, tax / Q000235:genetics; D015490:HTLV-I Infections / Q000382:microbiology; D015368:Human T-lymphotropic virus 1 / Q000235:genetics*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000382:microbiology; D008969:Molecular Sequence Data; D017354:Point Mutation; D012326:RNA Splicing; D012333:RNA, Messenger / Q000235:genetics*; D012367:RNA, Viral / Q000235:genetics*
D004279:DNA, Viral; D016370:Gene Products, rex; D016356:Gene Products, tax; D012333:RNA, Messenger; D012367:RNA, Viral