In vivo cellular tropism of human T-lymphotropic virus type II is not restricted to CD8+ cells

We have examined the in vivo and in vitro susceptibility of lymphocyte subpopulations to human T-lymphotropic virus type II (HTLV-II) to determine the cellular tropism for this virus. Monoclonal antibodies to T-cell subsets were used to separate highly purified CD4+ and CD8+ cells from peripheral blood lymphocytes of 35 individuals previously shown to be infected with HTLV-II. The purified T-cell subsets were analyzed for HTLV-II provirus (pol and tax gene sequences) by polymerase chain reaction (PCR) and cultured to determine virus expression by p24gag antigen detection. On the basis of PCR amplification in the pol and tax gene regions, both CD8+ subsets (89 to 91%) and CD4+ subsets (54 to 80%) from most infected subjects demonstrated HTLV-II provirus, irrespective of the viral genotype. Analysis of cultured lymphocytes demonstrated a higher spontaneous lymphocyte proliferation (17,986 +/- 4675 cpm) and p24gag antigen production (median 115 pg/ml; range 14-1360 pg/ml) in CD8+ cells compared to CD4+ cells (2333 +/- 826 cpm; p24gag antigen; 9 pg/ml; 2-250 pg/ml), suggesting a higher proviral load in CD8 cells. Limiting cell-dilution PCR analysis indicated that the CD8+ subset carried a higher HTLV-II provirus burden than the CD4+ subset. In vitro infection of purified CD4+ and CD8+ lymphocytes with irradiated HTLV-II cell lines resulted in productive infection of both subsets. Cell sorting and PCR analysis of lymphocyte subsets from 4 HTLV-II-infected subjects further demonstrated that in addition to CD4+ and CD8+ subsets, both CD45RO+ and CD45RO- and non-T-cells (CD14, CD16, and CD19) carried HTLV-II provirus. Taken together, these data suggest that HTLV-II possesses a broad tropism for peripheral blood mononuclear cells.