1 Unité d'Epidémiologie et Physiopathologie des Virus Oncogènes, Département d'Ecosystème et Epidémiologie des Maladies Infectieuses, Batiment Lwoff, Institut Pasteur, 2528 rue du Dr Roux, 75724 Paris Cedex 15, France
2 HIV and Retrovirology Branch, Division of AIDS, STD, and TB Laboratory Research, National Center for Infectious Diseases, Centers for Disease Control and Prevention, 1600 Clifton Rd, MS G-19, Atlanta, GA 30333, USA
3 Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Disease, National Institutes of Health, Rockville, MD 20852, USA
4 Cercopan, Calabar, CRS, Nigeria
Correspondence
William M. Switzer
bis3{at}cdc.gov.
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ABSTRACT |
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The genome sequence of STLV-3/CTO-NG409 has been deposited in GenBank, accession no. AY222339.
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MAIN TEXT |
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Recently, 13 red-capped mangabeys (rcm) from a monkey sanctuary in Nigeria were tested for retroviral infections (Beer et al., 2001). Twelve of these animals were captured in the wild and came to the sanctuary as orphans. While in captivity, all red-capped mangabeys were housed together in enclosures separated from other monkeys. Blood specimens were obtained on an opportunistic basis as part of the monkeys initial or annual physical examinations in accordance with the animal use and care committee at this institution. Two orphaned monkeys were found to be infected with SIVrcm, and one was also seropositive for STLV antibodies. We present here the characterization of the STLV found in this animal, which appears to be a novel and unique STLV-3.
Serologically, the plasma of this animal reacted in an immunofluorescence assay in an equivalent manner to the HTLV-1- and HTLV-2-producing cell lines, MT2 and C19, respectively, with antibody titres of 1/320. However, by Western blot (WB) analysis, this plasma specimen exhibited an HTLV-2 like pattern showing strong reactivities to GD21, p24 and K55 by using the HTLV blot version 2.4 (Genelabs Diagnostics, Singapore) (Fig. 1). This WB profile is very similar to the findings present in most other known STLV-3s. Total DNA was extracted from uncultured peripheral blood lymphocytes of this animal, and an STLV-3-like infection was confirmed by using a PCR assay that differentiates the PTLVs by using generic tax gene primers and type-specific probes as described previously (data not shown) (Busch et al., 2000
). The complete proviral sequence of this STLV was then obtained by PCR amplification and sequence analysis of overlapping genomic regions as previously described (Meertens et al., 2002
). The entire genome of this novel STLV-3 (called STLV-3/CTO-NG409) was 8920 bp (GenBank accession no. AY222339) in length. STLV-3/CTO-NG409 had a genomic organization very similar to that of other PTLVs and included the structural, enzymatic and regulatory proteins. Interestingly, as with other PTLV-3s, the LTR (698 bp) was smaller than in PTLV-1 (756 bp) and PTLV-2 (764 bp) by having two and not three of the 21 bp repeats (Meertens et al., 2002
). Comparison of the complete genome of STLV-3/CTO-NG409 showed a nucleotide sequence similarity of only 61 % to both HTLV-1/ATK and HTLV-2/Mo. In contrast, this new STLV-3 was closer genetically to other STLV-3s but still highly divergent with nucleotide identities of only 88·7 % with STLV-3/CTO-604, 86·5 % with STLV-3/PHA-PH969 and 92·4 % with STLV-3/PPA-F3. Nonetheless, the LTR of STLV-3/CTO-NG409 was 1114 % divergent from the three other STLV-3s, further demonstrating the uniqueness of this new virus.
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This study reports the characterization of a novel STLV-3 in a C. torquatus from Nigeria, CTO-NG409 and is the second demonstration that STLV-3 can infect this species in the wild. Interestingly, these two CTO strains show 11·2 % and 13·8 % divergence over their complete genomes and LTRs, respectively. This finding agrees completely with the divergence of 8·9 % in the LTRs of the different STLV-3 strains infecting P. hamadryas strains from Ethiopia and Eritrea (Takemura et al., 2002). Nevertheless, in phylogenetic trees, these STLV-3 strains cluster together in highly supported clades corresponding to their geographical origin rather than by their host phylogeny as described for most of the PTLV-1s (Slattery et al., 1999
).
Evidence for multiple interspecies transmissions among the PTLV-1s (Meertens et al., 2001; Nerrienet et al., 2001
), along with the widespread distribution of STLV-3 across Africa and its probable ancient existence, raises questions about whether humans are infected with STLV-3-like viruses. The presence of such viruses in red-capped mangabeys, which are intensely hunted in both Nigeria and Cameroon, may support this possibility. So far, limited studies of 24 Africans and 325 non-Africans with HTLV seroindeterminate WB results have not detected any STLV-3-like infection in humans (Busch et al., 2000
; Vandamme et al., 1997
). Additional studies of larger numbers of human samples, especially from different areas of Africa, with not only indeterminate but also HTLV-2-like WB profiles, will be necessary to assess the rate of infection with STLV-3. The development and use of STLV-3-specific diagnostic reagents will facilitate screening for STLV-3-like infections in both humans and nonhuman primates.
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ACKNOWLEDGEMENTS |
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Use of trade names is for identification only and does not imply endorsement by the U.S. Department of Health and Human Services, the Public Health Service, or the Centers for Disease Control and Prevention.
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Received 25 March 2003;
accepted 3 July 2003.