Temporal dynamics of human T-lymphotropic virus type I tax mRNA and proviral DNA load in peripheral blood mononuclear cells of human T-lymphotropic virus type I-associated myelopathy patients

Abstract

Human T-cell lymphotropic virus type I (HTLV-I) is the etiologic agent of HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). High HTLV-I provirus load and tax mRNA level have been suggested as predictors of disease progression in patients with HAM/TSP, but little is known about the temporal variation in patients. To clarify the role of high proviral and tax mRNA loads and their fluctuations in the pathogenesis of HAM/TSP, we measured proviral load and tax mRNA in serially collected peripheral blood mononuclear cells (PBMCs) from nine patients with HAM/TSP during a long-term follow-up, by use of real-time polymerase chain reaction using tax primers. The real-time PCR quantitation revealed a wide range of variation of proviral loads (7.82-97.13 copies per 100 PBMCs) and tax mRNA (0.20-245.30 copies) among HAM/TSP patients. Patients showed three different patterns of HTLV-I tax mRNA loads during the course of the disease. Tax mRNA load showed a separate evolution with respect to the disease. The dynamic patterns of proviral load and mRNA Tax expression suggest that only the permanent presence of a basal level of tax mRNA, rather than the tax mRNA load, is related to the development of HAM/TSP. To our knowledge, this is the first longitudinal study to determine tax mRNA expression at different clinical stages.