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 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.