ANALYSIS OF THE SIMIAN ORIGIN OF THE HTLV-I SUBTYPES

Abstract

P170 The topology of the primate T-cell lymphotropic virus type I (PTLV-I) tree reveals that HTLV-I clades are interspersed with STLV-I clades. Moreover simian strains are clustering closely with at least 4 of the human subtypes (-Ib, -Id, -Ie and -If), suggesting several interspecies transmissions between simians and humans. We have sequenced and phylogenetically analysed the LTR and env region of 3 new STLV-I strains, two isolates from drills (Mandrillus leucophaeus) of Cameroon, ML3 and ML4, and one from an Indonesian orang-utan (Pongo pygmaeus) OU-KA. We also performed molecular clock analyses on the African HTLV-I subtypes, and tried to date the presumed interspecies transmissions. Furthermore we determined the kind of selective pressure on PTLV-I as a result of inter- or intraspecies transmissions. OU-KA lies on a distinct branch with respect to the other Asian strains but is closely related to INA004, a STLV-I strain from the same simian genus and geographic origin. In the env region, using STLV-L and HTLV-II as outgroups, the oldest lineage is Marc-1 isolated from a Macaca arctoides with OU-KA being the next lineage diverging before the other Asian strains. ML3 and ML4 clustered within the human HTLV-Id subtype with bootstrap support above 70% in the LTR region and above 65% in the env region, suggesting that the mandrill genus is the simian reservoir for HTLV-Id. From our analyses it was also clear that the HTLV-Ib clusters with STLV-I strains from Pan troglodytes, -Ie with strains from Papio and Cercopythecus spp, and -If with a strain from a Mandrillus sphinx. We succeeded in estimating a time frame for the interspecies transmissions of all the African HTLV-I subtypes, including the cosmopolitan HTLV-Ia. Based on the topology of the FITCH tree using combined LTR and env sequences, we could conclude that interspecies transmission resulting in these HTLV-I subtypes occured between less than 300 years ago (for HTLV-If) to up to 10000 years ago (for HTLV-Ia, -Ib, -Id and -Ie). The synonymous versus non-synonymous substitution ratios suggested a tendency for purifying selection when the PTLV-I virus is transmitted from non-human primates to humans or reversed and also when it is evolving within the human host.