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The Nivkhi are a native people isolated in the Nogliki region of Sakhalin, Far East Russia, where our group recently recognized human T-cell lymphoma virus type I (HTLV-I) infection. In order to trace the Nivkhi's ethnic background and the HTLV-I carriers, we investigated HLA class I and II allele types of 53 Nivkhi (including four HTLV-I carriers). Major HLA class I alleles of the Nivkhi were A*24, A*02, B*40, B*48, B*27, B*35 with allele frequencies similar to the Orochon, a native people isolated in Northeast China. Major Nivkhi class II alleles were DRB1*0901, DRB1*1401, DRB1*1201, DRB1*1106 with allele frequencies similar to the Ainu in Hokkaido, Japan, but dissimilar to other Asian Mongoloids, including the general Japanese population. The same HLA class I and II allele frequencies are found in both Nivkhi HTLV-I carriers and the background population. A dendrogram of HLA class I alleles showed that the Nivkhi were closely related to the Orochon and Yakut, and remotely related to the Japanese, Ainu and other Asian Mongoloids. Interestingly, the Nivkhi were intermediately related to the Amerindians (Inuit, Tlingit and Andeans), a relationship closer than to the Japanese and Asian Mongoloids. These results suggested the Nivkhi might be related to some genetic group of Northeast Asian Mongoloids like the Orochon and Yakut, being infected with HTLV-I in the distant past before diverging into the current major Mongoloid ethnic groups.

In an effort to delineate the origin and evolution of HTLV-I/STLV-I, we have been conducting phylogenetic analyses on LTR sequences of this virus group. HTLV-I isolates newly analyzed in the present study were from Iran, South Africa, Cameroon, Sakhalin and Brazil where little is known concerning the genetic features of HTLV-I. In addition, STLV-I isolates were obtained from non-human primates in Africa and Asia including an isolate from orangutans in Indonesia. Proviral LTR sequences were amplified by nested PCR, and then sequenced. Phylogenetic trees were constructed by the neighbor joining method. The results obtained are: 1) African STLV-I isolates formed one large cluster together with the Central African group of HTLV-I in the tree; 2) Asian STLV-I isolates including that of an orangutan in Indonesia were highly divergent from African STLV-I and the Cosmopolitan group of HTLV-I, but not so closely related to each other and to the Melanesian group of HTLV-I; 3) An HTLV-I isolate of Cameroon Pygmy was related to African STLV-I isolates, but distinct from the Central African group of HTLV-I; 4) The majority of HTLV-I isolates belonged to subgroup A which is the most widespread subgroup of the Cosmopolitan group of HTLV-I, while some Brazilian isolates from descendants of Japanese immigrants belonged to subgroup B which mainly consists of HTLV-I isolates from Japan. 5) In the phylogenetic tree, several HTLV-I isolates of subgroup A from the same areas appear to form monophyletic clusters such as a subcluster of Brazilian and Colombian isolates and that of Iranian isolates.

The geographic distribution of human T-cell lymphotropic/leukemia virus type I (HTLV-I) was initially believed to be limited to southwestern Japan, the Caribbean basin, and Africa. However, extensive searches in recent years have discovered its existence in other areas of the world as well as in isolated, ethnic populations such as South Amerindians, Australo-Melanesian aborigines, religiously segregated Jews, and Pygmies. Previous genetic analyses indicated that HTLV-I can be phylogenetically classified into three major lineages: Melanesian, Central African, and Cosmopolitan groups. Recently, more detailed characterization using long terminal repeat sequences (the most variable genomic region) has revealed that the Cosmopolitan group consists of four subtypes: (A) Transcontinental, (B) Japanese, (C) West African, and (D) North African. Most HTLV-I isolates of the same ethnic group from distant locations and those from different groups inhabiting the same area showed phylogenetic similarities. These observations indicate the present distribution of this virus should be interpreted from the anthropological backgrounds of the virus-possessing populations as well as spatial contact among them. Thus, the molecular epidemiology of HTLV-I and its simian counterpart, STLV-I, provides us with important clues for understanding not only the origin and dissemination of this retrovirus but past human movements over the globe.