Discovery of a new human T-cell lymphotropic virus (HTLV-3) in Central Africa

Abstract

Human T-cell Leukemia virus type 1 (HTLV-1) and type 2 (HTLV-2) are pathogenic retroviruses that infect humans and cause severe hematological and neurological diseases. Both viruses have simian counterparts (STLV-1 and STLV-2). STLV-3 belongs to a third group of lymphotropic viruses which infect numerous African monkeys species. Among 240 Cameroonian plasma tested for the presence of HTLV-1 and/or HTLV-2 antibodies, 48 scored positive by immunofluorescence. Among those, 27 had indeterminate western-blot pattern. PCR amplification of pol and tax regions, using HTLV-1, -2 and STLV-3 highly conserved primers, demonstrated the presence of a new human retrovirus in one DNA sample. tax (180 bp) and pol (318 bp) phylogenetic analyses demonstrated the strong relationships between the novel human strain (Pyl43) and STLV-3 isolates from Cameroon. The virus, that we tentatively named HTLV-3, originated from a 62 years old Bakola Pygmy living in a remote settlement in the rain forest of Southern Cameroon. The plasma was reactive on MT2 cells but was negative on C19 cells. The HTLV 2.4 western-blot exhibited a strong reactivity to p19 and a faint one to MTA-1. On the INNO-LIA strip, it reacted faintly with the generic p19 (I/II), but strongly to the generic gp46 (I/II) and to the specific HTLV-2 gp46. The molecular relationships between Pyl43 and STLV-3 are thus not paralleled by the serological results, as most of the STLV-3 infected monkeys have an "HTLV-2 like" WB pattern. In the context of the multiple interspecies transmissions which occurred in the past, and led to the present-day distribution of the PTLV-1, it is thus very tempting to speculate that this newly discovered human retrovirus HTLV-3 might be widespread, at least in the African continent. Findings

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).…”

“…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. The aims of the present study were therefore to assess the Tax3 protein for (a) expression in vivo, (b) transactivation ability through the NF-kB and Cyclic AMP Response Element Binding (CREB) pathways and further transformation of human and simian cells in vivo, (c) mediation capacity for transcription of the autologous LTR in spite of lacking the distal TRE sequence (Van Brussel et al, 1997;Meertens et al, 2002Van Dooren et al, 2004).…”