Mutational analysis of human T-cell leukemia virus type I Tax: regions necessary for function determined with 47 mutant proteins.
We have made 47 mutations that span the length of the human T-cell leukemia virus type I (HTLV-I) Tax open reading frame. Of the 47 mutations, 38 were substitutions of single amino acids, 5 were missense changes in two or more amino acids, and 4 were deletions. A subset of these mutations includes individual changes of all 26 naturally occurring serines to alanines. By assaying each mutant protein separately on the HTLV-I long terminal repeat (LTR) and the human immunodeficiency virus type 1 (HIV-1) LTR in parallel, we were able to identify regions of Tax selectively necessary for each promoter. A small region in the carboxyl terminus, amino acids 315 to 325, was found to be selectively important for activation of the HTLV-I LTR. Three changes at serine 113, serine 160, and serine 258 were found to specifically affect function on the HIV-1 LTR. Surprisingly, we found that the great preponderance of missense changes (32 of 42) in Tax did not affect function.
Semmes
O J
OJ
Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892.
Jeang
K T
KT
D000818:Animals; D002460:Cell Line; D004279:DNA, Viral / Q000235:genetics / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D016356:Gene Products, tax / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D016355:Genes, pX; D016325:HIV Long Terminal Repeat; D015368:Human T-lymphotropic virus 1 / Q000235:genetics* / Q000378:metabolism*; D016297:Mutagenesis, Site-Directed; D012091:Repetitive Sequences, Nucleic Acid; D017384:Sequence Deletion; D013347:Subcellular Fractions / Q000378:metabolism; D015533:Transcriptional Activation; D014162:Transfection
D004279:DNA, Viral; D016356:Gene Products, tax