PMID- 11159527 OWN - NLM STAT- MEDLINE DCOM- 20010412 LR - 20210216 IS - 0006-4971 (Print) IS - 0006-4971 (Linking) VI - 97 IP - 4 DP - 2001 Feb 15 TI - Existence of escape mutant in HTLV-I tax during the development of adult T-cell leukemia. PG - 987-93 AB - Although Tax protein is the main target of cytotoxic T lymphocyte (CTL) on human T-cell lymphotropic virus type I (HTLV-I)-infected cells, and Tax peptide 11 through 19 binding to HLA-A*02 has been shown to elicit a strong CTL response, there are patients with adult T-cell leukemia (ATL) bearing HLA-A*02. To explore whether there is genetic variation in HTLV-I tax that can escape CTL recognition during the development of ATL, the HTLV-I tax gene was sequenced in 55 patients with ATL, 61 patients with HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP), and 62 healthy carriers, and it was correlated with the presence of HLA-A*02. First, a premature stop codon in the 5' half of the tax gene that looses transactivation activity on the viral enhancer was observed in 3 patients with acute and 1 patient with chronic ATL. This stop codon was revealed to emerge after the viral transmission to the patient from sequence analysis in family members with ATL. Second, amino acid change in Tax peptide 11-19 was observed in 3 patients with ATL. CTL assays demonstrated that this altered Tax 11-19 peptide, observed in ATL patients with HLA-A*02, was not recognized by Tax 11-19-specific CTL. Two patients with ATL had large deletions in tax by sequencing, and 5 patients with ATL had deletions in HTLV-I by Southern blotting. These findings suggest that at some stage of ATL development, HTLV-I-infected cells that can escape the host immune system are selected and have a chance to accumulate genetic alterations for further malignant transformation, leading to acute ATL. FAU - Furukawa, Y AU - Furukawa Y AD - Third Department of Internal Medicine and the Center for Chronic Viral Diseases, Faculty of Medicine, Kagoshima University, Kagoshima, Japan. furukawy@m2.kufm.kagoshima-u.ac.jp FAU - Kubota, R AU - Kubota R FAU - Tara, M AU - Tara M FAU - Izumo, S AU - Izumo S FAU - Osame, M AU - Osame M LA - eng SI - GENBANK/AB036372 SI - GENBANK/AB036373 SI - GENBANK/AB036374 SI - GENBANK/AB036375 SI - GENBANK/AB036376 SI - GENBANK/AB036377 SI - GENBANK/AB036378 SI - GENBANK/AB036379 SI - GENBANK/AB036380 SI - GENBANK/AB036381 SI - GENBANK/AB036382 SI - GENBANK/AB036383 SI - GENBANK/AB045399 SI - GENBANK/AB045400 SI - GENBANK/AB045401 SI - GENBANK/AB045402 SI - GENBANK/AB045403 SI - GENBANK/AB045404 SI - GENBANK/AB045405 SI - GENBANK/AB045406 SI - GENBANK/AB045407 SI - GENBANK/AB045408 SI - GENBANK/AB045409 SI - GENBANK/AB045410 SI - GENBANK/AB045411 SI - GENBANK/AB045412 SI - GENBANK/AB045413 SI - GENBANK/AB045414 SI - GENBANK/AB045415 SI - GENBANK/AB045416 SI - GENBANK/AB045417 SI - GENBANK/AB045418 SI - GENBANK/AB045419 SI - GENBANK/AB045420 SI - GENBANK/AB045421 SI - GENBANK/AB045422 SI - GENBANK/AB045423 SI - GENBANK/AB045424 SI - GENBANK/AB045425 SI - GENBANK/AB045426 SI - GENBANK/AB045427 SI - GENBANK/AB045428 SI - GENBANK/AB045429 SI - GENBANK/AB045430 SI - GENBANK/AB045431 SI - GENBANK/AB045432 SI - GENBANK/AB045433 SI - GENBANK/AB045434 SI - GENBANK/AB045435 SI - GENBANK/AB045436 SI - GENBANK/AB045437 SI - GENBANK/AB045438 SI - GENBANK/AB045439 SI - GENBANK/AB045440 SI - GENBANK/AB045441 PT - Comparative Study PT - Journal Article PL - United States TA - Blood JT - Blood JID - 7603509 RN - 0 (Codon, Terminator) RN - 0 (Epitopes) RN - 0 (Gene Products, tax) RN - 0 (HLA-A2 Antigen) SB - IM CIN - Blood. 2001 Feb 15;97(4):833. PMID: 11159502 MH - *Codon, Terminator MH - DNA Mutational Analysis MH - Enhancer Elements, Genetic MH - Epitopes/genetics MH - Female MH - Gene Products, tax/chemistry/immunology MH - *Genes, pX MH - HLA-A2 Antigen/genetics/immunology MH - HTLV-I Infections/virology MH - Human T-lymphotropic virus 1/*genetics MH - Humans MH - *Immunologic Surveillance MH - Leukemia-Lymphoma, Adult T-Cell/immunology/*virology MH - Male MH - Molecular Sequence Data MH - Proviruses/genetics MH - Sequence Deletion MH - T-Lymphocytes, Cytotoxic/immunology MH - Time Factors MH - Transcriptional Activation EDAT- 2001/02/13 11:00 MHDA- 2001/04/17 10:01 CRDT- 2001/02/13 11:00 PHST- 2001/02/13 11:00 [pubmed] PHST- 2001/04/17 10:01 [medline] PHST- 2001/02/13 11:00 [entrez] AID - S0006-4971(20)56309-X [pii] AID - 10.1182/blood.v97.4.987 [doi] PST - ppublish SO - Blood. 2001 Feb 15;97(4):987-93. doi: 10.1182/blood.v97.4.987.