Isolation and characterization of a new simian T-cell leukemia virus type 1 from naturally infected celebes macaques (Macaca tonkeana): complete nucleotide sequence and phylogenetic relationship with the Australo-Melanesian human T-cell leukemia virus type 1

Abstract

A study of simian T-cell leukemia virus type 1 (STLV-1) infection in a captive colony of 23 Macaca tonkeana macaques indicated that 17 animals had high human T-cell leukemia virus type 1 (HTLV-1) antibody titers. Genealogical analysis suggested mainly a mother-to-offspring transmission of this STLV-1. Three long-term T-cell lines, established from peripheral blood mononuclear cell cultures from three STLV-1-seropositive monkeys, produced HTLV-1 Gag and Env antigens and retroviral particles. The first complete nucleotide sequence of an STLV-1 (9,025 bp), obtained for one of these isolates, indicated an overall genetic organization similar to that of HTLV-1 but with a nucleotide variability for the structural genes ranging from 7.8 to 13.1% compared with the HTLV-1 ATK and STLV-1 PTM3 Asian prototypes. The Tax and Rex regulatory proteins were well conserved, while the pX region, known to encode new proteins in HTLV-1 (open reading frames I and II), was more divergent than that in the ATK strain. Furthermore, a fragment of 522 bp of the gp21 env gene from uncultured peripheral blood mononuclear cell DNAs from five of the STLV-1-infected monkeys was sequenced. Phylogenetic trees constructed with the long terminal repeat and env (gp46 and gp21) regions demonstrated that this new STLV-1 occupies a unique position within the Asian STLV-1 and HTLV-1 isolates, being, by most analyses, related more to the Australo-Melanesian HTLV-1 topotype than to any other Asian STLV-1. These data raise new hypotheses on the possible interspecies viral transmission between monkeys carrying STLV-1 and early Australoid settlers, ancestors of the present day Australo-Melanesian inhabitants, during their migrations from the Southeast Asian land mass to the greater Australian continent.

Molecular epidemiology of 58 new African human T-cell leukemia virus type 1 (HTLV-1) strains: identification of a new and distinct HTLV-1 molecular subtype in Central Africa and in Pygmies

“…This conclusion is also supported by the fact that these individuals lived in widely separated areas of the western part of Central Africa without any evidence of recent contact. Recent studies (28,42,47,48,65,80) have suggested that the present world repartition of HTLV-1 genotypes is the result of at least three independent events, interspecies transmission of STLV-1 to humans (as in the case of chimpanzees in Central Africa), independent evolution of the virus in some remote areas (as in Melanesia), and migrations of infected populations (as, for example, during the slave trade). We therefore hypothesize that the presently described new HTLV-1 genotype (subtype D) may have taken its origin in interspecies transmission from monkeys to humans in Central Africa and that there exists or existed in Central Africa an STLV-1 closely related to this HTLV-1 subtype D genotype.…”

“…PCR. PCR was carried out as previously described (25,29,42). Briefly, highmolecular-weight DNA was extracted from PBMCs before or during cell culture by a classical phenol-chloroform technique.…”

“…In the phylogenetic analysis (based on 124 HTLV-1 and STLV-1 sequences) including all the 31 available STLV-1 env sequences (42,47), the four HTLV-1 geographically related clades were mixed and interspersed between several STLV-1 clades (Fig. 3B).…”

“…LTR analysis. For LTR analysis, two phylogenetic studies using either the complete LTR (3,10,12,17,24,39,42,44,48,52,63,72,75,78,79,80) including 38 and 54 HTLV-1 and STLV-1 strains, respectively, were done. This allowed the inclusion of the 11 African strains for which only partial sequences were available in the literature.…”

“…Based upon sequence and/or restriction fragment length polymorphism data from the pol and env genes and/or the long terminal repeat (LTR) of more than 250 different strains, there are three major geographical subtypes (or genotypes) (25,27,28,48,55,67,76,78,83) strongly supported by high bootstrap values in phylogenetic analysis. Each of these genotypes (cosmopolitan, HTLV-1 subtype A; Central African, HTLV-1 subtype B; and Melanesian, HTLV-1 subtype C) appears to have arisen from interspecies transmission between simian T-cell leukemia virus type 1 (STLV-1)-infected monkeys and humans followed by variable periods of evolution in the human host (28,42,47,48,65,78).…”