Peripheral blood samples were collected from 23 human T-lymphotropic virus type-1 (HTLV-1) carriers residing in Kakeroma Island, Japan (Kagoshima Prefecture, Oshima County, Setouchi Town), one of the most highly endemic areas in Japan. The samples were subjected to amplification by PCR and sequencing of the Long Terminal Repeat in order to reconstruct a phylogenetic tree of HTLV-1 isolates. Restriction Fragment Length Polymorphism (RFLP) analysis of env region was also conducted for subgrouping of HTLV-1. Although one sample could not be amplified by PCR, and three more could not be sequenced due to the existence of conspicuous nonspecific bands or repeated sequences, the phylogenetic analysis revealed that the remaining 19 isolates obtained from Kakeroma Island belonged to either the Transcontinental or the Japanese subgroups of the Cosmopolitan subtype, one of the three major subtypes. The RFLP data corresponded closely with the typing data throughout the sequencing. The proportion of the Transcontinental subgroup among the isolates was 26.3% (5 of 19) by sequence analysis and 27.3% (6 of 22) by RFLP. Unlike in Taiwan, China and Okinawa, the Japanese subgroup was dominant in Kakeroma Island. The analysis would also suggest that the Japanese subgroup seems not to have derived from the Transcontinental subgroup, but rather that the Transcontinental subgroup came to Japan first and was followed later by the Japanese one.
Our research into the biogeography of HTLV-1 in Japan has led us to the hypothesis that the virus was introduced to Japan in the prehistoric era by the Jomon people. Later, in the Yayoi period (ca.300 BC-ca.300 AD), a mass migration of non-carriers (the Yayoi people) reached Japan from northeastern Asia, and these people became dominant by virtue of their proficiency in advanced technologies such as agriculture and iron works [1]. As a result, aggregations of HTLV-1 carriers gradually disappeared from central Japan, where today HTLV-1 remains only in remote areas along the coast and adjacent islands. In order to test this hypothesis, we conducted an experimental study which aimed to identify the relationship between HTLV-1 carrier status and the nucleotide substitution 538G A (rc 17822931) in ABCC11, a marker of the earwax type, which represents an inherited trait from either the Jomon or Yayoi people. Our results revealed that the proportion of wet earwax among HTLV-1 carriers was 28.6% (10/35), whereas that among non-carriers was only 5% (1/20). The difference was statistically significant (Kai square=4.42, p<0.05). This suggests that the HTLV-1 carrier population inherited a genetic trait from the Jomon people and lends support to the theory that it was the Jomon people who brought HTLV-1 into Japan. Although the process of introduction of HTLV-1 to Japan and its establishment there remain hotly disputed, two major hypotheses, i.e. the "European-trade" and "prehistoric" hypotheses, have been proposed [2, 3]. To date, however, no direct or tangible evidence has been available to
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