Identification of HTLV-I gag protease and its sequential processing of the gag gene product.
The full-length provirus of human T-cell leukemia virus type I (HTLV-I) was isolated from MT-2, a lymphoid cell line producing HTLV-I. In transfected cells, structural proteins of HTLV-I, the gag and env products, were formed and processed in the same manner as observed in MT-2 cells. The nucleotide sequence was determined for a region between the gag and pol genes of the proviral DNA clone containing an open-reading frame. The deduced amino acid sequences show that this open-reading frame encodes a putative HTLV-I protease. The protease gene (pro) of HTLV-I was investigated using a vaccinia virus expression vector. Processing of 53k gag precursor polyprotein into mature p19, p24, and p15 gag structural proteins was detectable with a recombinant plasmid harboring the entire gag- and protease-coding sequence. We demonstrated that the protease processed the gag precursor polyprotein in a trans-action. A change in the sequence Asp(64)-Thr-Gly, the catalytic core sequence among aspartyl proteases, to Gly-Thr-Gly was shown to abolish correct processing, suggesting that HTLV-I protease may belong to the aspartyl protease group. The 76k gag-pro precursor polyprotein was identified, implying that a cis-acting function of HTLV-I protease may be necessary to trigger the initial cleavage event for its own release from a precursor protein, followed by the release of p53 gag precursor protein. The p53 gag precursor protein is then processed by the trans-action of the released protease to form p19, p24, and p15.
Hatanaka
M
M
Institute for Virus Research, Kyoto University, Japan.
Nam
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D000595:Amino Acid Sequence; D001483:Base Sequence; D015153:Blotting, Western; D004279:DNA, Viral / Q000235:genetics; D010450:Endopeptidases / Q000032:analysis* / Q000096:biosynthesis / Q000235:genetics; D016333:HIV Protease; D006868:Hydrolysis; D008969:Molecular Sequence Data; D014162:Transfection; D014764:Viral Proteins / Q000032:analysis
D004279:DNA, Viral; D014764:Viral Proteins; D010450:Endopeptidases; D016333:HIV Protease