EVOLUTION IN A CHRONIC RNA VIRUS-INFECTION - SELECTION ON HTLV-I TAX PROTEIN DIFFERS BETWEEN HEALTHY CARRIERS AND PATIENTS WITH TROPICAL SPASTIC PARAPARESIS

HTLV-I causes T-cell leukemia and tropical spastic paraparesis (TSP) i n a minority of infected people, whereas the majority remain healthy. The virus differs little in sequence between isolates but has been sho wn to have a quasispecies structure. Using the Nei and Gojobori algori thm, we have shown that the proportion of nonsynonymous to synonymous changes in HTLV-I proviral tax gene sequences from healthy seropositiv e subjects (Dn/Ds = 0.9 to 1.3) is significantly higher than those fro m TSP patients (Dn/Ds = 0.3 to 0.6). Here we show that the distinction between healthy seropositives and TSP patients can only be seen with proviral tax sequences, but not with cDNA, the aminoterminal or carbox y-terminal half of tax, or the rex gene, The Dn/Ds ratio of proviral t ax sequences was used to analyze two TSP patients with atypical featur es and to investigate the influence of cytotoxic T cells (CTL) on the viral quasispecies.