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In Vivo Proviral Burden and Viral Rna Expression in T Cell Subsets of Patients with Human T Lymphotropic Virus Type-1-Associated Myelopathy/Tropical Spastic Paraparesis

We used in situ hybridization combined with immunocytochemistry, cell sorting, and the polymerase chain reaction (PCR) to investigate clinical events in three asymptomatic carriers of human T lymphotrophic virus type-1 (HTLV-1) and ten patients with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The objective was to determine which T cell subset of peripheral blood mononuclear cells (PBMC), CD4 or CD8, were infected by HTLV-1 and the manner in which HTLV-1 proviral DNA was expressed at the level of the single cell. Both CD4-positive and CD8-positive cells of the PBMC from five patients with HAM/TSP were infected with HTLV-1. The proportion of HTLV-1-infected cells was 2.5–40% in the CD4-positive subset and 1.0–65% in the CD8-positive subset, when quantified by PCR using HTLV-1-infected MT2 cells as a positive standard. Proviral DNA of HTLV-1 was expressed in both CD4-positive cells and CD8-positive cells of the PBMC from six patients with HAM/TSP and three asymptomatic HTLV-1 carriers. In patients with HAM/TSP, the proportion of the cells expressing HTLV-1 proviral DNA was 0.02–0.1% in both subsets. In asymptomatic carriers, the expression of HTLV-1 proviral DNA was 0.01–0.02% in the CD4-positive subset and 0.01% in the CD8-positive subset. Therefore, HTLV-1 possessed similar in vivo cellular tropism for both CD4-positive cells and CD8-positive cells and HTLV-1 proviral DNA was expressed in vivo in both circulating T cell subsets. These results suggest that the immunologic states of patients with HAM/TSP are modulated by the viral gene expression in both T cell subsets.

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