Evolutionary Rate and Genetic Heterogeneity of Human T-Cell Lymphotropic Virus Type II (HTLV-II) Using Isolates from European Injecting Drug Users

Abstract

Seven new Italian and two new British HTLV-II isolates were obtained from injecting drug users and the entire long terminal repeat (LTR) region was sequenced. Restriction analysis showed that all the Italian isolates are of the IIb subtype, whereas the British isolates are of the IIa subtype. To understand whether the further differentiation of each two principal HTLV-II subtypes in several subgroups could be statistically supported by phylogenetic analysis, the neighbor-joining, parsimony, and maximum likelihood methods were used. The separation between IIa and IIb is very well supported by all three methods. At least two phylogenetic subgroups exist within the HTLV-IIa and at least three within the HTLV-IIb subtype. In the present analysis, no statistical support was obtained for additional phylogroups. Two particular subgroups seem interesting because they include all European and North American injecting drug user strains within the IIa and IIb subtypes, respectively. These data confirm that European HTLV-II infection among drug users is probably derived from North America. They also suggest that though a certain differentiation by restriction analysis in different subgroups is possible, carefully interpreted phylogenetic analyses remain necessary. Using the likelihood ratio test, a molecular clock for the drug user strains was calibrated. A fixation rate between 1.08 x 10(-4) and 2.7 x 10(-5) nucleotide substitutions per site per year was calculated for the IIa and IIb injecting drug user strains. This is the lowest fixation rate so far reported for RNA viruses, including for HIV, which typically range between 10(-2) and 10(-4).

Different population dynamics of human T cell lymphotropic virus type II in intravenous drug users compared with endemically infected tribes

“…nucleotide substitutions per site per year in the long terminal repeat (LTR) (35). However, a general molecular clock for all the HTLV-II strains does not exist, implying that non-IDU strains evolve at a different rate (35).…”

“…However, a general molecular clock for all the HTLV-II strains does not exist, implying that non-IDU strains evolve at a different rate (35).…”

“…An HTLV-IIb strain has been isolated from Bakola pygmies living in Cameroon (15). It has been suggested that HTLV-II was brought into the Americas some 15,000-35,000 years ago during one or more migrations of HTLV-II-infected Asian populations over the Bering land bridge (13,18,33,34) and that HTLV-II among IDUs originated from Amerindians with at least two separate introductions during this century: one for the IIb subtype and another one for the IIa subtype (35). HTLV-II among IDUs seems to evolve at a constant rate.…”

New Insights into Prevalence, Genetic Diversity, and Proviral Load of Human T-Cell Leukemia Virus Types 1 and 2 in Pregnant Women in Gabon in Equatorial Central Africa

“…HTLV-2 has been shown to be endemic in various American Indian populations (4,53) and has also been endemic for the past 15 to 25 years among intravenous drug users in Europe and North America (41,50). Furthermore, since 1991, sporadic cases of HTLV-2 infection have been detected in west and central Africa, where the presence of this infection in isolated rural populations, including some Pygmies, suggests an ancient presence of HTLV-2 (17).…”

High Seroprevalence of Human T-Cell Lymphotropic Virus Type 1 in Blood Donors in Guyana and Molecular and Phylogenetic Analysis of New Strains in the Guyana Shelf (Guyana, Suriname, and French Guiana)

“…The overall prevalence of severe HTLV-1-associated disease is 2 to 8% among HTLV-1-infected persons, estimated to represent 15 million to 25 million individuals worldwide. HTLV-2 has been shown to be endemic in various American Indian populations (2,3,33,41,43,44) and has also been endemic for the past 10 to 20 years among intravenous drug users in Europe and North America (32,39,40). In populations in which these viruses are endemic, HTLV-1 and HTLV-2 are transmitted between sexual partners and from mother to child during breast-feeding.…”