GENETIC-VARIABILITY AND MOLECULAR EPIDEMIOLOGY OF HUMAN AND SIMIAN T-CELL LEUKEMIA LYMPHOMA VIRUS TYPE-I/

In the past few years, numerous investigators have demonstrated that h uman T cell leukemia/lymphoma virus type I (HTLV-I) possesses a great genetic stability, and recent data indicate that viral amplification v ia clonal expansion of infected cells, rather than by reverse transcri ption, could explain this remarkable genetic stability. In parallel, t he molecular epidemiology of HTLV-I proviruses showed that the few nuc leotide changes observed between isolates were specific for the geogra phical origin of the patients but not for the type of the associated p athologies (adult T cell leukemia/lymphoma, topical spastic paraparesi s/HTLV-I-associated myelopathy). Thus, based on sequence and/or restri ction fragment length polymorphism analysis of more than 250 HTLV-I is olates originating from the main viral endemic areas, three major mole cular geographical subtypes (or genotypes) emerged, strongly supported by phylogenetic analysis (high bootstrap values). Each of these genot ypes (Cosmopolitan, Central African, and Melanesian) appeared to arise from ancient. interspecies transmission between monkeys infected with simian T cell leukemia/lymphoma virus type I and humans. Furthermore, careful sequences analyses indicate that, within (or alongside) these three main genotypes, there are molecular subgroups defined clearly b y several specific mutations hut not always supported by phylogenetic analyses. Thus in Japan, there is evidence for two ancestral HTLV-I li neages: the classical Cosmopolitan genotype, representing similar to 2 5% of the HTLV-I present in Japan and clustering in the southern islan ds; and a related subgroup that we called the Japanese group. Similarl y, within the Central African cluster, there are molecular subgroups d efined by specific substitutions in either the env or the long termina l repeat. Furthermore, recent data from our laboratory indicate the pr esence of a new molecular phylogenetic group (fourth genotype) found a mong inhabitants of Central Africa, particularly in Pygmies. While geo graphical subtypes vary from 2 to 8% between themselves, HTLV-I quasi- species present within an individual appear to be much lower, with a v ariability of <0.5%.