title: HTLV-1 subgroups associated with the risk of HAM/TSP are related to viral and host gene expression in peripheral blood mononuclear cells, independent of the transactivation functions of the viral factors.
abstract: Among human T cell leukemia virus type 1 (HTLV-1)-infected individuals, the risk of developing HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) across lifetime differs between ethnic groups. There is an association between HTLV-1 tax gene subgroups (subgroup-A or subgroup-B) and the risk of HAM/TSP in the Japanese population. In this study, we investigated the full-length proviral genome sequences of various HTLV-1-infected cell lines and patient samples. The functional differences in the viral transcriptional regulators Tax and HTLV-1 bZIP factor (HBZ) between each subgroup and the relationships between subgroups and the clinical and laboratory characteristics of HAM/TSP patients were evaluated. The results of these analyses indicated the following: (1) distinct nucleotide substitutions corresponding to each subgroup were associated with nucleotide substitutions in viral structural, regulatory, and accessory genes; (2) the HBZ messenger RNA (mRNA) expression in HTLV-1-infected cells was significantly higher in HAM/TSP patients with subgroup-B than in those with subgroup-A; (3) a positive correlation was observed between the expression of HBZ mRNA and its target Foxp3 mRNA in HAM/TSP patients with subgroup-B, but not in patients with subgroup-A; (4) no clear differences were noted in clinical and laboratory characteristics between HAM/TSP patients with subgroup-A and subgroup-B; and (5) no functional differences were observed in Tax and HBZ between each subgroup based on reporter gene assays. Our results indicate that although different HTLV-1 subgroups are characterized by different patterns of viral and host gene expression in HAM/TSP patients via independent mechanisms of direct transcriptional regulation, these differences do not significantly affect the clinical and laboratory characteristics of HAM/TSP patients.
authors.affiliation: Laboratory of Virus Control, Institute for Virus Research, Kyoto University, Kyoto, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Yasuma
authors.affiliation: Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
authors.forename: Toshio
authors.initials: T
authors.lastname: Matsuzaki
authors.affiliation: Department of Rare Diseases Research, Institute of Medical Science, St. Marianna University School of Medicine, Kanagawa, Japan.
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Yamano
authors.affiliation: Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Takashima
authors.affiliation: Laboratory of Virus Control, Institute for Virus Research, Kyoto University, Kyoto, Japan.
authors.forename: Masao
authors.initials: M
authors.lastname: Matsuoka
authors.affiliation: Department of Microbiology, Kawasaki Medical School, 577 Matsushima, Kurashiki, Okayama, 701-0192, Japan. mineki@med.kawasaki-m.ac.jp.
authors.forename: Mineki
authors.initials: M
authors.lastname: Saito
mesh_terms: D000328:Adult; D044466:Asian People; D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics* / Q000378:metabolism; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D016356:Gene Products, tax / Q000235:genetics* / Q000378:metabolism; D015490:HTLV-I Infections / Q000150:complications / Q000235:genetics / Q000473:pathology / Q000821:virology*; D054884:Host-Pathogen Interactions; D015368:Human T-lymphotropic virus 1 / Q000145:classification* / Q000235:genetics / Q000254:growth & development / Q000472:pathogenicity; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000473:pathology / Q000821:virology; D008297:Male; D008875:Middle Aged; D058889:Molecular Typing; D015493:Paraparesis, Tropical Spastic / Q000150:complications / Q000235:genetics / Q000473:pathology / Q000821:virology*; D020641:Polymorphism, Single Nucleotide; D011533:Proviruses / Q000145:classification* / Q000235:genetics / Q000254:growth & development / Q000472:pathogenicity; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012191:Retroviridae Proteins / Q000235:genetics* / Q000378:metabolism; D012306:Risk; D015398:Signal Transduction; D019562:Viral Load
chemical_list: D050976:Basic-Leucine Zipper Transcription Factors; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D016356:Gene Products, tax; C479751:HBZ protein, human T-cell leukemia virus type I; D012333:RNA, Messenger; D012191:Retroviridae Proteins; C514970:tax protein, Human T-lymphotrophic virus 1
keywords: Foxp3; HAM/TSP; HBZ; HTLV-1; Tax; Virus subgroup