Genetic variability and molecular epidemiology of human and simian T cell leukemia/lymphoma virus type I

Abstract

In the past few years, numerous investigators have demonstrated that human T cell leukemia/lymphoma virus type I (HTLV-I) possesses a great genetic stability, and recent data indicate that viral amplification via clonal expansion of infected cells, rather than by reverse transcription, could explain this remarkable genetic stability. In parallel, the molecular epidemiology of HTLV-I proviruses showed that the few nucleotide changes observed between isolates were specific for the geographical origin of the patients but not for the type of the associated pathologies (adult T cell leukemia/lymphoma, tropical spastic paraparesis/HTLV-I-associated myelopathy). Thus, based on sequence and/or restriction fragment length polymorphism analysis of more than 250 HTLV-I isolates originating from the main viral endemic areas, three major molecular geographical subtypes (or genotypes) emerged, strongly supported by phylogenetic analysis (high bootstrap values). Each of these genotypes (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 by several specific mutations but not always supported by phylogenetic analyses. Thus in Japan, there is evidence for two ancestral HTLV-I lineages: the classical Cosmopolitan genotype, representing approximately 25% of the HTLV-I present in Japan and clustering in the southern islands; and a related subgroup that we called the Japanese group. Similarly, within the Central African cluster, there are molecular subgroups defined by specific substitutions in either the env or the long terminal repeat. Furthermore, recent data from our laboratory indicate the presence of a new molecular phylogenetic group (fourth genotype) found among inhabitants of Central Africa, particularly in Pygmies. While geographical subtypes vary from 2 to 8% between themselves, HTLV-I quasi-species present within an individual appear to be much lower, with a variability of < 0.5%.