IN-VIVO CELLULAR TROPISM OF HUMAN T-LYMPHOTROPIC VIRUS TYPE-II IS NOTRESTRICTED 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 det ermine 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 s hown to be infected with HTLV-II. The purified T-cell subsets were ana lyzed for HTLV-II provirus (pol and tax gene sequences) by polymerase chain reaction (PCR) and cultured to determine virus expression by p24 (gag) antigen detection. On the basis of PCR amplification in the pol and tax gene regions, both CD8(+) subsets (89 to 91%) and CD4(+) subse ts (54 to 80%) from most infected subjects demonstrated HTLV-II provir us, irrespective of the Viral genotype. Analysis of cultured lymphocyt es demonstrated a higher spontaneous lymphocyte proliferation (17986 /- 4675 cpm) and p24(gag) antigen production (median 115 pg/ml; range 14-1360 pg/ml) in CD8(+) cells compared to CD4(+) cells (2333 +/- 826 cpm; p24(gag) antigen: 9 pg/ml; 2-250 pg/ml), suggesting a higher prov iral load in CD8 cells. Limiting cell-dilution PCR analysis indicated that the CD8(+) subset carried a higher HTLV-II provirus burden than t he CD4(+) subset in vitro infection of purified CD4(+) and CD8(+) lymp hocytes with irradiated HTLV-II cell lines resulted in productive infe ction of both subsets. Cell sorting and PCR analysis of lymphocyte sub sets from 4 HTLV-II-infected subjects further demonstrated that in add ition to CD4(+) and CD8(+) subsets, both CD45RO(+) and CD45RO(-) and n on-T-cells (CD14, CD16, and CD19) carried HTLV-II provirus. Taken toge ther, these data suggest that HTLV-II possesses a broad tropism for pe ripheral blood mononuclear cells. (C) 1995 Academic Press, Inc.