Phylogenetic relationships of HTLV-I/STLV-I in the world.

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.

Molecular phylogeny of human T-cell leukemia virus type I and II of Amerindians in Colombia and Chile.

Six human T-cell leukemia virus type I (HTLV-I) and eight human T-cell leukemia virus type II (HTLV-II) cases newly isolated from the South American countries of Colombia and Chile were analyzed together with the two Amerindian HTLV-I isolates previously reported. All of the HTLV-I isolates belonged to the transcontinental subgroup of the "cosmopolitan" group, and Colombian isolates, including those from native Amerindians and Negroes, formed a single tight cluster within this subgroup. The transcontinental subgroup consisted of isolates from various regions such as the Caribbean basin, India, Iran, South Africa, Sakhalin, and Japan, and included isolates from the "Ainu" and "Okinawa" people, regarded as relatively pure Japanese descended from the prehistoric "Jomon" period which began more than 10,000 years ago. This implied a dissemination of the subgroup associated with the movement of human beings in ancient times. On the other hand, all of the HTLV-II isolates from native Amerindians in Colombia and Chile belonged to the HTLV-IIb subtype which has previously been reported to be mainly endemic in certain populations of native Amerindians. The southernmost isolate from Chile, showing wide distribution of the IIb subtype in native South Amerindians and largest heterogeneity of the subtype in Colombian isolates, supported the idea that the HTLV-IIb subtype has been endemic for a long time in native Indians of South America.

Molecular epidemiology of HTLV-I in the world.

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.

HTLV-I from Iranian Mashhadi Jews in Israel is phylogenetically related to that of Japan, India, and South America rather than to that of Africa and Melanesia.

A new endemic focus of human T-lymphotropic virus type I (HTLV-I) was recently reported among Mashhadi Jews, a group of immigrants from northeastern Iran to Israel. We extracted DNAs from fresh peripheral blood mononuclear cells (PBMCs) and/or gargle mouthwash from 10 HTLV-I carriers, who consisted of members of one family, and HTLV-I-associated myelopathy (HAM) and adult T-cell leukemia (ATL) patients. Long terminal repeat (LTR) regions of proviral DNAs were sequenced and analyzed phylogenetically. In a phylogenetic tree, all the Mashhadi HTLV-I isolates belonged to subtype A, one of the three subtypes of the cosmopolitan type of HTLV-I, and made a tight cluster distinct from the other isolates of subtype A from Japan, India, the Caribbean Basin, and South America. Although a few nucleotide substitutions were observed among the clones sequenced, no characteristic sequence variation was found in different disease manifestations, even in one family or different sources of DNA preparation.

Phylogenetic subtypes of human T-lymphotropic virus type I and their relations to the anthropological background.

Isolates of human T-lymphotropic virus type I (HTLV-I) were phylogenetically analyzed from native inhabitants in India and South America (Colombia and Chile) and from Ainu (regarded as pure Japanese descendants from the preagricultural "Jomon" period). Their genomes were partially sequenced together with isolates from Gabon in central Africa and from Ghana in West Africa. The phylogenetic tree was constructed from the sequence data obtained and those of previously reported HTLV-I isolates and simian T-lymphotropic virus type I (STLV-I) isolates. The heterogeneity of HTLV-I was recently recognized, and one major type, generally called the "cosmopolitan" type, contained Japanese, Caribbean, and West African isolates. The phylogenetic tree constructed in the present study has shown that this cosmopolitan type can be further grouped into three lineages (subtypes A, B, and C). Subtype A consists of some Caribbean, two South American, and some Japanese isolates, including that from the Ainu, in addition to an Indian isolate, and subtype B consists of other Japanese isolates in addition to another Indian isolate, suggesting that there might be at least two ancestral lineages of the Japanese HTLV-I. Subtype A implies a close connection of the Caribbean and South American natives with the Japanese and thereby a possible migration of the lineage to the American continent via Beringia in the Paleolithic era. Subtype C consists of the West African and other Caribbean isolates, indicating that not all but part of the Caribbean strains directly originated from West Africa probably during the period of slave trade. The tree also has shown that the HTLV-I isolate from Gabon in central Africa forms a cluster with STLV-I from a chimpanzee, suggesting a possible interspecies transmission between man and the chimpanzee in the past. No specific clustering was observed in the tree in relation to manifestations of the disease such as adult T-cell leukemia and HTLV-I-related neurological disorders. Thus, the topology of the phylogenetic tree reflects the movement of people carrying the virus in the past.