PHYLOGENETIC CLASSIFICATION OF HUMAN T-CELL LEUKAEMIA LYMPHOMA VIRUS TYPE-I GENOTYPES IN 5 MAJOR MOLECULAR AND GEOGRAPHICAL SUBTYPES/

Proviral DNA was obtained from ex vivo peripheral blood mononuclear ce lls of 75 human T cell leukaemia/lymphoma virus type I (HTLV-I)-infect ed individuals who were either asymptomatic or had adult T cell leukae mia or tropical spastic paraparesis/HTLV-I-associated myelopathy. Ampl ified long terminal repeats (LTRs) were analysed for restriction fragm ent length polymorphisms (RFLPs). The results, together with previousl y published LTR data (a total of 180 specimens analysed), showed the p resence of 12 different RFLP profiles with four major molecular subtyp es. Furthermore, a fragment of 313 bp (nucleotides 22 to 434) of the U 3/R region was sequenced for 12 new HTLV-I specimens originating from Central and West Africa (8 cases), Iran (1 case), Caribbean (2 cases) and Reunion Island (1 case). Phylogenetic analysis using three differe nt techniques (maximum parsimony, neighbour joining and UPGMA) compari ng these 12 strains (including four new African HTLV-I variants) with the 30 published partial HTLV-I LTR sequences (nt 120 to 434) showed t he existence of clusters of molecular variants in discrete geographica l areas. The topology of the phylogenetic trees is thought to reflect HTLV-I evolution and the migrations of virally infected populations in the recent or distant past. Furthermore, there was a nearly perfect c oncordance between the clustering based on the LTR sequence homologies and the LTR RFLP subtypes suggesting that this rapid and simple techn ique is well suited to the investigation of HTLV-I molecular epidemiol ogy. These results allow a new phylogenetic classification of HTLV-I g enotypes into five major molecular subtypes: Cosmopolitan (C) subtype widespread all over the world, Japanese (J) subtype, West African (WA) subtype, Central African (CA) subtype and Melanesian (M) subtype.