MOLECULAR EPIDEMIOLOGY OF 58 NEW AFRICAN HUMAN T-CELL LEUKEMIA-VIRUS TYPE-1 (HTLV-1) STRAINS - IDENTIFICATION OF A NEW AND DISTINCT HTLV-1 MOLECULAR SUBTYPE IN CENTRAL-AFRICA AND IN PYGMIES

To gain new insights on the origin, evolution, and modes of disseminat ion of human T-cell leukemia virus type 1 (HTLV-1), we performed a mol ecular analysis of 58 new African HTLV-1 strains (18 from West Africa, 36 from Central Africa, and 4 from South Africa) originating from 13 countries. Of particular interest were eight strains from Pygmies of r emote areas of Cameroon and the Central African Republic (CAR), consid ered to be the oldest inhabitants of these regions. Eight long-term ac tivated T-cell lines producing HTLV-1 gag and env antigens were establ ished from peripheral blood mononuclear cell cultures of HTLV-1 seropo sitive individuals, including three from Pygmies. A fragment of the en v gene encompassing most of the gp21 transmembrane legion was sequence d for the 58 new strains, while the complete long terminal repeat (LTR ) region was sequenced for 9 strains, including 4 from Pygmies. Compar ative sequence analyses and phylogenetic studies performed on both the env and LTR regions by the neighbor-joining and DNA parsimony methods demonstrated that all 22 strains from West and South Africa belong to the widespread cosmopolitan subtype (also called HTLV-1 subtype A). W ithin or alongside the previously described Zairian cluster (HTLV-1 su btype B), we discovered a number of new HTLV-1 variants forming differ ent subgroups corresponding mainly to the geographical origins of the infected persons, Cameroon, Gabon, and Zaire. Six of the eight Pygmy s trains clustered together within this Central African subtype, suggest ing a common origin. Furthermore, three new strains (two originating f rom Pygmies from Cameroon and the CAR, respectively, and one from a Ga bonese individual) were particularly divergent and formed a distinct n ew phylogenetic cluster, characterized by specific mutations and occup ying in most analyses a unique phylogenetic position between the large Central African genotype (HTLV 1 subtype B) and the Melanesian subtyp e (HTLV-1 subtype C). We have tentatively named this new HTLV 1 genoty pe HTLV-1 subtype D. While the HTLV-1 subtype D strains were not close ly related to any known African strain of simian T-cell leukemia virus type 1 (STLV-1), other Pygmy strains and some of the new Cameroonian and Gabonese HTLV-1 strains were very similar (>98% nucleotide identit y) to chimpanzee STLV-1 strains, reinforcing the hypothesis of intersp ecies transmission between humans and monkeys in Central Africa.