MOLECULAR EPIDEMIOLOGY OF HTLV TYPE-I IN JAPAN - EVIDENCE FOR 2 DISTINCT ANCESTRAL LINEAGES WITH A PARTICULAR GEOGRAPHICAL-DISTRIBUTION

Japan is one of the highest endemic areas of the world for human T cel l leukemia-lymphoma virus type I (HTLV-I). To gain new insight as to t he origin of this virus in Japan and especially in the southern island s of the archipelago, we investigated the long terminal repeat (LTR) o f 67 newly isolated HTLV-I proviral DNAs from peripheral blood mononuc lear cells of HTLV-I-infected individuals for their restriction fragme nt length polymorphism (RFLP). The specimens were from Japanese living in different geographical areas (Hokkaido, Honshu, Kyushu, or the Ryu kyu Islands) of Japan (59 cases) or Americans of Japanese ancestry liv ing in Hawaii (8 cases). The analysis of the results, together with da ta for the 19 previously published LTR sequences, demonstrated the exi stence of 2 subtypes of HTLV-I in Japan. The first, which we propose t o name Japanese subtype (previously named subtype III), is more freque nt (67 of 86: 78%) than the second, the cosmopolitan subtype (previous ly named subtype II) (19 of 86: 22%). In parallel, a fragment of 413 b ase pairs of the U3/R region (nucleotide 22 to 434) was cloned and seq uenced from 10 of the new Japanese samples. The alignment of these seq uences and their comparison and phylogenetic analysis with previously published LTR HTLV-I sequences, demonstrated clearly the existence of the two distinct molecular subtypes of HTLV-I in Japan, diverging in t his LTR region by about 1.6%. Furthermore, the study of the geographic al distribution of the 2 subtypes among the 80 samples from patients w hose place of residence in Japan was known showed an uneven distributi on. While the Japanese subtype was present in all parts of Japan, the cosmopolitan subtype seemed to cluster in the southern islands of the archipelago (i.e., Kyushu and the Ryukyu Islands) as well as in immigr ants from those areas who had lived in Hawaii for decades. These new m olecular data raise questions and suggest hypotheses, discussed here, concerning the origin and means of dissemination of these human retrov irus subtypes in Japan.