Up-regulation of human T lymphotropic virus type 1 (HTLV-1) tax/rex mRNA in infected lung tissues.
HTLV-1 has been implicated in certain pulmonary diseases. We previously demonstrated that expression of HTLV-1 tax/rex mRNA, encoding the transcriptional transactivator Tax, was closely associated with infiltration of activated T lymphocytes into lung tissue. To explore mechanisms of tax/rex expression in the lung, tax/rex mRNA expression and proviral DNA load were compared between peripheral blood mononuclear cells (PBMC) and bronchoalveolar lavage cells (BALC) from four patients with HTLV-1-associated myelopathy (HAM/TSP) and 13 carriers with various pulmonary symptoms. Semiquantitative detection of tax/rex mRNA strongly suggested that the lung was a preferential site for its expression. Proviral DNA loads in non-HAM/TSP carriers were variable but correlated well between PBMC and BALC in each individual, and revealed no relationship with tax/rex mRNA expression. In contrast, both cell groups from four HAM/TSP patients expressed detectable tax/rex mRNA accompanied by high proviral DNA load. The ratio of tax/rex mRNA expression to proviral DNA load was higher in BALC than in PBMC in three of four carriers and in three of four HAM/TSP patients, suggesting up-regulation of tax/rex mRNA in infected lung tissue. To analyse differences in distribution of HTLV-1 quasispecies between the two tissues, phylogenetic analysis was performed for sequence sets of the proviral tax open reading frame (ORF: 1059 bp) derived from PBMC and BALC of two infected individuals. Sequences derived from the two tissues distributed similarly to branches of phylogenetic trees, and there was no evidence of selective distribution of certain quasispecies in the lung. Our results suggest the presence of tissue-specific conditions that activate viral expression in infected cells in the lung. Constitutive exposure of this tissue to foreign antigens leading to up-regulation of basal viral promoter activity is likely to be one such mechanism.
Seki
M
M
Second Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki, Japan.
Higashiyama
Y
Y
Mizokami
A
A
Kadota
J
J
Moriuchi
R
R
Kohno
S
S
Suzuki
Y
Y
Takahashi
K
K
Gojobori
T
T
Katamine
S
S
D000293:Adolescent; D000328:Adult; D000368:Aged; D001483:Base Sequence; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D015967:Gene Expression Regulation, Viral; D016370:Gene Products, rex / Q000235:genetics*; D016356:Gene Products, tax / Q000235:genetics*; D015490:HTLV-I Infections / Q000235:genetics*; D015368:Human T-lymphotropic virus 1 / Q000235:genetics*; D006801:Humans; D008168:Lung / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000378:metabolism; D015854:Up-Regulation
D016370:Gene Products, rex; D016356:Gene Products, tax; D012333:RNA, Messenger