Centre Pasteur du Cameroun, BP 1274, Yaoundé, Cameroon1
Unité dEpidémiologie et Physiopathologie des Virus Oncogènes, Département du SIDA et des Rétrovirus, Institut Pasteur, 2528 rue du Dr Roux, 75724 Paris Cedex 15, France2
Author for correspondence: Antoine Gessain. Fax +33 1 40 61 34 65, e-mail agessain{at}pasteur.fr
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Abstract |
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The origin of most HTLV-1 geographical subtypes appears to be linked with multiple episodes of interspecies transmission between STLV-1-infected monkeys and humans, followed by variable periods of evolution in the human host (Salemi et al., 2000 ; Slattery et al., 1999
; Van Dooren et al., 2001
; Watanabe et al., 1985
). However, clear evidence of interspecies transmission consists only of a described affiliation between HTLV-1 subtype B and subtype D from Central African inhabitants and few STLV-1 isolates from chimpanzees and mandrills respectively (Koralnik et al., 1994
; Mahieux et al., 1998a
; Voevodin et al., 1997b
). Furthermore, one STLV-1 strain, from a mandrill from Gabon (MSP-Mnd9), was recently found to be closely related to the Lib2 strain supporting the notion of interspecies transmission (Mahieux et al., 1998a
).
Sub-Saharan Africa is considered the largest HTLV-1 endemic area. Regarding STLV-1, serological studies have demonstrated that several African monkey and ape (sub)species are infected by STLV-1, including different subspecies of Papio, Chlorocebus aethiops, Cercopithecus, Erythrocebus patas, Miopithecus talapoin, Pan troglodytes, Mandrillus sphinx, Mandrillus leucophaeus and Cercocebus atys. However, only about 50 African STLV-1 strains have been molecularly partially characterized (Englebrecht et al., 1996 ; Koralnik et al., 1994
; Mahieux et al., 1998a
, b
, 2000
; Nerrienet et al., 1998
; Saksena et al., 1993
, 1994
; van Rensburg et al., 1999
; Voevodin et al., 1996a
, 1997a
, b
; Watanabe et al., 1986
), either in a small portion (120 bp) of the pol gene and/or in fragments (300 to 600 bp) of the LTR and/or of the env gene (300 to 522 bp). Some of these STLV-1 strains originate from monkeys or apes kept in captivity, a situation which is known to be associated with some nosocomial interspecies transmissions (Voevodin et al., 1996b
). Furthermore, several of the other strains originate from monkeys living in South or East Africa. Thus, the data regarding African wild-caught monkeys and Apes remain rare, especially from the Western part of Central Africa (Cameroon, Congo, Gabon) where the still-present deep rain forest represents a very important focus and sanctuary for wildlife biodiversity. Thus, our goal was to look for STLV-1 in a wild-caught population of several species/subspecies of monkeys and apes from Cameroon in order to gain new insights into the natural distribution and frequency of the STLV-1 molecular subtypes in such an ecosystem and their relationships with the HTLV-1 present in the same area.
The studied series comprised 102 plasma samples from 15 monkey and apes species or subspecies (Table 1) originating from the Mvog-betsi Zoo, Yaoundé. These animals originated from different areas of Cameroon (mostly the south), where most of them were initially kept as pets for a variable period of time, after their mothers were killed by hunters. They were confiscated by the Ministry of Environment and Forestry (MINEF), and then gathered in the Zoo. For some of these (sub)species (as Cercocebus agilis, Cercopithecus neglectus, C. nictitans or C. cephus cephus) no data were available regarding the presence of STLV-1 infection.
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PCR was performed on high molecular mass DNA extracted from the peripheral blood mononuclear cells or buffy coats of these four animals and from several controls. Two genomic fragments were amplified and sequenced, the complete LTR (755 bp) and a 522 bp fragment of the env gene (Mahieux et al., 1997 ). The seven new LTR and env sequences determined herein were deposited in the National Center for Biotechnology Information database. The GenBank accession numbers are AF38466 to AF38472.
A comparison of the aligned 522 bp fragments of the gp21 env gene obtained for the four STLV-1-seropositive animals indicated that these sequences exhibited no deletions nor insertions as compared to the ATK HTLV-1 reference strain. Furthermore, genetic comparison of these four new sequences with the other published STLV-1 env sequences indicated close similarities between some of them. The two new sequences from Mandrillus sphinx (MSP-BET.854 and MSP-SAN.855), which exhibited only 1 bp difference, were closely related (99% similarity) to three sequences from Mandrillus sphinx from Gabon (Mnd13, 15, 18). The sequence from the Cercocebus agilis isolate (CAG-DJA.853) exhibited only 2·5% (509/522) nucleotide divergence from an STLV-1 strain obtained from another Mandrillus sphinx strain (Mnd9) also originating from Gabon. Lastly, the new sequence from Pan troglodytes (PTR-CAR.875) was closely related (97 to 98%) to three published sequences from Pan troglodytes, two of unknown geographical origin and one from Sierra Leone. Comparison with all the available HTLV-1 strains also indicated some close relationship: the two new mandrill strains were related to HTLV-1 subtype D strains, including the H2-3 strain originating from a Pygmy from South Cameroon. The CAG-DJA.853 strain exhibited only 2·7% of divergence with the Lib2 strain, the sole HTLV-1 representative of subtype F. The new chimpanzee strain (PTR-CAR.875) was also closely related (97 to 98% of similarity) to several HTLV-1 strains of subtype B (H2-4, T49, St DEN...) originating from Cameroon or Gabon respectively.
The LTR (especially the U3 and U5 regions) is a more variable fragment, and is thus more informative for genetic comparisons and phylogenetic analyses. The full LTR sequence was obtained from CAG-DJA.853, MSP-BET.855 and PTR-CAR.875; a partial LTR sequence was also obtained from the second mandrill strain and was nearly identical to the corresponding region in MSP-BET.855. Comparison of the three new complete LTR STLV-1 sequences with the HTLV-1 prototypes indicated that the important regulatory elements of the LTR such as the three tax-responsive elements (TRE), the c-ets-responsive element, the rex-responsive element and the rex-binding region were highly conserved, suggesting that their functions were maintained. The LTR sequence comparative analyses revealed again some close similarities between the two new mandrill strains and the HTLV-1/STLV-1 subtype D strains as well as between the GAG-DJA.853 and the HTLV1/STLV-1 subtype F strains (Mnd9 and Lib2). Lastly, comparison of the new PTR-CAR.875 strain with the few other available subtype B STLV-1 and several HTLV-1 sequences confirm its closest relationship to some human strains (98·8% with T49) rather than to the other Pan troglodytes strains (96·9 to 97·5%).
Phylogenetic analyses were performed on all the available STLV-1 sequences from Africa as well as several representatives of HTLV-1 strains of the different subtypes as previously described (Salemi et al., 1998), using both neighbour-joining (NJ) and DNA maximum parsimony (MP) methods. Similar results were obtained by both methods. Analyses of the trees (Figs 1 and 2
) reinforced the close relationship of the four new STLV-1 strains with some HTLV-1 strains. Indeed, the highly supported HTLV/STLV subtype D and subtype F clades comprised the two new mandrill strains and the new Cercocebus agilis respectively. This was clear for the two genomic regions analysed (LTR and env) (Figs 1
and 2
). Regarding the new chimpanzee isolate, it clustered always in the large subtype B clade, which comprise several HTLV-1 and very few STLV-1, mostly from Central Africa. However, within this clade, the new chimpanzee strain was closely affiliated (NJ and MP bootstrap=96% for LTR) to two HTLV-1 (T49, PH236) originating from South Cameroon and Gabon.
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Acknowledgments |
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References |
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Received 30 May 2001;
accepted 15 August 2001.