Molecular Epidemiology of HTLV Type I in Japan: Evidence for Two Distinct Ancestral Lineages with a Particular Geographical Distribution

Abstract

Japan is one of the highest endemic areas of the world for human T cell leukemia-lymphoma virus type I (HTLV-I). To gain new insight as to the origin of this virus in Japan and especially in the southern islands of the archipelago, we investigated the long terminal repeat (LTR) of 67 newly isolated HTLV-I proviral DNAs from peripheral blood mononuclear cells of HTLV-I-infected individuals for their restriction fragment length polymorphism (RFLP). The specimens were from Japanese living in different geographical areas (Hokkaido, Honshu, Kyushu, or the Ryukyu Islands) of Japan (59 cases) or Americans of Japanese ancestry living in Hawaii (8 cases). The analysis of the results, together with data for the 19 previously published LTR sequences, demonstrated the existence of 2 subtypes of HTLV-I in Japan. The first, which we propose to name Japanese subtype (previously named subtype III), is more frequent (67 of 86: 78%) than the second, the cosmopolitan subtype (previously named subtype II) (19 of 86: 22%). In parallel, a fragment of 413 base pairs of the U3/R region (nucleotide 22 to 434) was cloned and sequenced from 10 of the new Japanese samples. The alignment of these sequences 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 this LTR region by about 1.6%. Furthermore, the study of the geographical distribution of the 2 subtypes among the 80 samples from patients whose place of residence in Japan was known showed an uneven distribution. 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 immigrants from those areas who had lived in Hawaii for decades. These new molecular data raise questions and suggest hypotheses, discussed here, concerning the origin and means of dissemination of these human retrovirus subtypes in Japan.

Community-Based Molecular Epidemiology of HTLV Type I in Taiwan and Kinmen: Implication of the Origin of the Cosmopolitan Subtype in Northeast Asia

“…2). 13 Judging by the geographic closeness and historic interactions between Taiwan and Japan (Taiwan had been occupied by the Japanese between A.D. 1895 and 1945), it is logical to speculate that the predominant HTLV-I in Taiwan would also be group b (Japanese). On the contrary, as shown in Fig.…”

“…In Cosmopolitan subtype A, TSP1 (Caribbean), 22 CRI (Caribbean), 23 CH (Caribbean), 24 DJ16 (Japan), 13 and AINU (Japan) 9 belong to group a; DJ9 (Japan), 13 ATK (Japan), 25 H5 (Japan), 26 and ATM (Japan) 27 belong to group b; 1010/3 (Caribbean) and HS35 (Caribbean) 28 belong to group c; and BO (Algeria) 29 and Pr144 (Morocco) 29 belong to group d. In addition, EL (Zaire), 9 MWMG (Zaire), 9 H24 (Cameroon), 8 and PH236 (Gabon) 8 belong to subtype B; MEL5 (Solomon Islands) 30 and H23 (Cameroon) 8 are subtype C and subtype D, respectively. MEL5 was used as the outgroup to transform unrooted trees to rooted trees.…”

“…12 Previously, Ureta Vidal et al reported that in Japan, the Japanese subtype (subtype A, group b) is more prevalent than the Cosmopolitan subtype (subtype A, group a) and that the latter clusters in the southern islands of the archipelago, including Kyushu and Ryukyu islands. 13 On the basis of the finding of the north-to-south gradient of the HTLV-I subtype A distribution in Japan and Okinawa, Gessain et al hypothesized that there was migration of HTLV-I transcontinental group a-infected peopled from the south toward the north in East Asia. 12 However, its origin and the extent of the dissemination in East Asia needed to be determined.…”

Tax is Involved in Up-regulation of HMGB1 Expression Levels by Interaction with C/EBP

“…Adult T cell leukemia (ATL), an aggressive T-cell malignancy without an effective cure (Yoshida et al, 1982), is found to be caused by human T-cell leukemia virus type I (HTLV-I) infection and occurs in HTLV-I-endemic areas, such as southwestern Japan, Central and South America, the Caribbean islands, Middle East, Aboriginal regions in Australia, and Intertropical Africa (Uchiyama et al, 1977;Vidal et al, 1994). The prognosis is poor, with less than 1 year survival for patients (Goncalves et al, 2010).…”

Human T‐lymphotropic virus type 1 (HTLV‐1) genetic typing in Kakeroma Island, an island at the crossroads of the ryukyuans and Wajin in Japan, providing further insights into the origin of the virus in Japan

“…The cosmopolitan subtype is further divided into three subgroups: A, B, and C, which correspond to the Transcontinental subgroup, the Japanese subgroup, and the West African subgroup, respectively. The Transcontinental subgroup is widely distributed throughout South America, the Caribbean basin and Japan [Gallo et al, 1983;Ishida and Hinuma, 1986;Miura et al, 1994;Vidal et al, 1994]. Although this distribution pattern of HTLV-1 may reflect global population movements during the prehistoric period, as well as more recently, the origin of HTLV-1 in Japan is still hotly disputed [Suzuki and Gojobori, 1998;Verdonck et al, 2007].…”