Emergence of unique primate T-lymphotropic viruses among central African bushmeat hunters

Abstract

The human T-lymphotropic viruses (HTLVs) types 1 and 2 originated independently and are related to distinct lineages of simian T-lymphotropic viruses (STLV-1 and STLV-2, respectively). These facts, along with the finding that HTLV-1 diversity appears to have resulted from multiple cross-species transmissions of STLV-1, suggest that contact between humans and infected nonhuman primates (NHPs) may result in HTLV emergence. We investigated the diversity of HTLV among central Africans reporting contact with NHP blood and body fluids through hunting, butchering, and keeping primate pets. We show that this population is infected with a wide variety of HTLVs, including two previously unknown retroviruses: HTLV-4 is a member of a phylogenetic lineage that is distinct from all known HTLVs and STLVs; HTLV-3 falls within the phylogenetic diversity of STLV-3, a group not previously seen in humans. We also document human infection with multiple STLV-1-like viruses. These results demonstrate greater HTLV diversity than previously recognized and suggest that NHP exposure contributes to HTLV emergence. Our discovery of unique and divergent HTLVs has implications for HTLV diagnosis, blood screening, and potential disease development in infected persons. The findings also indicate that cross-species transmission is not the ratelimiting step in pandemic retrovirus emergence and suggest that it may be possible to predict and prevent disease emergence by surveillance of populations exposed to animal reservoirs and interventions to decrease risk factors, such as primate hunting.retrovirus ͉ zoonosis ͉ simian ͉ exposures ͉ diversity

The tax protein from the primate T-cell lymphotropic virus type 3 is expressed in vivo and is functionally related to HTLV-1 Tax rather than HTLV-2 Tax

“…HTLV-3, the human counterpart of STLV-3 was discovered very recently (Calattini et al, 2005;Wolfe et al, 2005). In all phylogenetic analyses, STLV-3 and HTLV-3 cluster in a highly supported clade, indicating an evolutionary lineage independent from PTLV-1 and PTLV-2 (Meertens et al, 2002;Calattini et al, 2005;Wolfe et al, 2005).…”

“…Together with their related simian counterparts, HTLVs form the primate T-cell lymphotropic viruses (PTLV) lineages (Guo et al, 1984;Hunsmann et al, 1984). So far, four types of PTLVs have been discovered in primates (Slattery et al, 1999;Van Brussel et al, 1999;Calattini et al, 2005;Wolfe et al, 2005). While three of them, that is, PTLV-1, PTLV-2 and PTLV-3, comprise human and simian viruses (HTLV-1, HTLV-2, HTLV-3 and STLV-1, STLV-2, STLV-3 respectively) (Calattini et al, 2005), the fourth type (HTLV-4) consists only of one human strain (Wolfe et al, 2005).…”

“…So far, four types of PTLVs have been discovered in primates (Slattery et al, 1999;Van Brussel et al, 1999;Calattini et al, 2005;Wolfe et al, 2005). While three of them, that is, PTLV-1, PTLV-2 and PTLV-3, comprise human and simian viruses (HTLV-1, HTLV-2, HTLV-3 and STLV-1, STLV-2, STLV-3 respectively) (Calattini et al, 2005), the fourth type (HTLV-4) consists only of one human strain (Wolfe et al, 2005). Isolated for the first time shortly after HTLV-1 (Miyoshi et al, 1982), STLV-1 is highly prevalent in a large variety of old world monkey species (Slattery et al, 1999), and cases of ATLL-like diseases, with clonal integration of the STLV-1 provirus in the tumor cells described in several simian species (Blakeslee et al, 1987).…”

“…Sequence comparisons of STLV-3 fulllength proviruses indicated that these strains are highly divergent from HTLV-1 (60% nucleotide similarity), HTLV-2 (62%) or STLV-2 (62%) prototype sequences (Van Brussel et al, 1996;Meertens et al, 2002). HTLV-3, the human counterpart of STLV-3 was discovered very recently (Calattini et al, 2005;Wolfe et al, 2005). In all phylogenetic analyses, STLV-3 and HTLV-3 cluster in a highly supported clade, indicating an evolutionary lineage independent from PTLV-1 and PTLV-2 (Meertens et al, 2002;Calattini et al, 2005;Wolfe et al, 2005).…”

“…Interestingly, even if it possesses an ORF corresponding to the tax gene, the STLV-3 pX region organization is different from that of PTLV-1 and PTLV-2, with the absence of ORFs that would be equivalent to p12, p13 and p30 (Van Brussel et al, 1996;Meertens et al, 2002). At the amino-acid level, the available putative human HTLV-3 Tax protein sequence (Tax3 H ) possesses only 75 and 79% similarity with HTLV-1 and HTLV-2 Tax proteins (Tax1 and Tax2) (Wolfe et al, 2005), but 97% identity with the putative simian STLV-3 602 Tax protein. Given the recent discovery of HTLV-3 (Calattini et al, 2005;Wolfe et al, 2005), the large and increasing number of simian species infected with STLV-3 and the known transactivating ability of Tax proteins (Jeang et al, 2004), the Tax3 molecular properties needed to be investigated.…”