Fluctuation of HTLV-I proviral DNA in peripheral blood mononuclear cells of HTLV-I-associated myelopathy

Abstract

To assess the immunopathological significance of the increased replication of human T-cell leukemia virus type I (HTLV-I) in HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) we investigated the dynamics of HTLV-I proviral DNA in peripheral blood mononuclear cells (PBMC) of HAM/TSP patients at different clinical stages. We compared the dynamics to those of asymptomatic HTLV-I carriers (AC). The estimation of the amount of HTLV-I proviral DNA was carried out by quantitative polymerase chain reaction of serially diluted DNA samples where it was feasible to titrate 0.04-80 copies per 100 PBMC. The proviral DNA quantified in six patients with HAM/TSP was 2-20 copies per 100 PBMC, while that in eight cases of AC was 0.04-8 copies per 100 PBMC. Thus, the amount of HTLV-I proviral DNA in HAM/TSP patients was 3-50 times as high as that of AC. When we followed up HAM/TSP patients for 1-3 years, the amount of HTLV-I proviral DNA fluctuated from 4 to 10-fold. These data suggest that the rate of HTLV-I replication increases in HAM/TSP and the amount of HTLV-I proviral DNA fluctuates in their clinical course. Fluctuation in the amount of HTLV-I proviral DNA may reflect dynamics of HTLV-I infected cell proliferation and immunological suppression in vivo in HAM/TSP patients.