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.