GENETIC AND PHYLOGENETIC ANALYSES OF HUMAN T-CELL LYMPHOTROPIC VIRUS TYPE-I VARIANTS FROM MELANESIANS WITH AND WITHOUT SPASTIC MYELOPATHY

Molecular variants of human T-cell lymphotropic virus type I (HTLV-I) have been isolated recently from lifelong residents of remote Melanesi an populations, including a Solomon Islander with tropical spastic par aparesis/HTLV-I-associated myelopathy (TSP/HAM) or HTLV-I myeloneuropa thy. To clarify the genetic heterogeneity and molecular epidemiology o f disease-associated strains of HTLV-I, we enzymatically amplified, th en directly sequenced representative regions of the gag, pol, env, and pX genes of HTLV-I strains from Melanesians with and without TSP/HAM, and aligned and compared these sequences with those of HTLV-I strains from patients with TSP/HAM or adult T-cell leukemia/lymphoma and from asymptomatic carriers from widely separated and culturally disparate populations. Overall, the HTLV-I variant from the Solomon Islander wit h TSP/HAM, like HTLV-I strains from asymptomatically infected Melanesi ans, diverged by approx 7% from cosmopolitan HTLV-I strain. No disease -specific viral sequences were found. Gene phylogenies, as determined by the unweighted pair-group method of assortment and by the maximum p arsimony method, indicated that the Melanesian and cosmopolitan strain s of HTLV-I have evolved along separate geographically dependent linea ges, one comprised of HTLV-I strains from Papua New Guinea and the Sol omon Islands, and the other composed of virus strains from Japan, Indi a, the Caribbean, Polynesia, the Americas, and Africa. The total absen ce of nonhuman primates in Papua New Guinea and the Solomon Islands pr ecludes any possibility that the Melanesian HTLV-I strains have evolve d recently from the simian homolog of HTLV-I.