M. Seki et al., Up-regulation of human T lymphotropic virus type 1 (HTLV-1) tax/rex mRNA in infected lung tissues, CLIN EXP IM, 120(3), 2000, pp. 488-498
HTLV-1 has been implicated in certain pulmonary diseases. We previously dem
onstrated that expression of HTLV-1 tax/rex mRNA, encoding the transcriptio
nal transactivator Tax, was closely associated with infiltration of activat
ed T lymphocytes into lung tissue. To explore mechanisms of tax/rex express
ion in the lung, tax/rex mRNA expression and proviral DNA load were compare
d between peripheral blood mononuclear cells (PBMC) and bronchoalveolar lav
age cells (BALC) from four patients with HTLV-1-associated myelopathy (HAM/
TSP) and 13 carriers with various pulmonary symptoms. Semiquantitative dete
ction of tax/rex mRNA strongly suggested that the lung was a preferential s
ite for its expression. Proviral DNA loads in non-HAM/TSP carriers were var
iable but correlated well between PBMC and BALC in each individual, and rev
ealed no relationship with tax/rex mRNA expression. In contrast, both cell
groups from four HAM/TSP patients expressed detectable tax/rex mRNA accompa
nied by high proviral DNA load. The ratio of tax/rex mRNA expression to pro
viral DNA load was higher in BALC than in PBMC in three of four carriers an
d in three of four HAM/TSP patients, suggesting up-regulation of tax/rex mR
NA 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) de
rived from PBMC and BALC of two infected individuals. Sequences derived fro
m 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 condition
s that activate viral expression in infected cells in the lung. Constitutiv
e exposure of this tissue to foreign antigens leading to up-regulation of b
asal viral promoter activity is likely to be one such mechanism.