Jean-Christophe Plantier

Centre Hospitalier Universitaire Rouen, Rouen, Upper Normandy, France

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Publications (63)359.86 Total impact

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    ABSTRACT: NF-κB is essential for effective transcription of primate lentiviral genomes and also activates antiviral host genes. Here, we show that the early protein Nef of most primate lentiviruses enhances NF-κB activation. In contrast, the late protein Vpu of HIV-1 and its simian precursors inhibits activation of NF-κB, even in the presence of Nef. Although this effect of Vpu did not correlate with its ability to interact with β-TrCP, it involved the stabilization of IκB and reduced nuclear translocation of p65. Interestingly, however, Vpu did not affect casein kinase II-mediated phosphorylation of p65. Lack of Vpu was associated with increased NF-κB activation and induction of interferon and interferon-stimulated genes (ISGs) in HIV-1-infected T cells. Thus, HIV-1 and its simian precursors employ Nef to boost NF-κB activation early during the viral life cycle to initiate proviral transcription, while Vpu is used to downmodulate NF-κB-dependent expression of ISGs at later stages. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.
    Cell Reports 01/2015; 10(4). · 7.21 Impact Factor
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    ABSTRACT: Acute respiratory infections (ARIs) are a major cause of morbidity and mortality in children in Africa. The circulation of viruses classically implicated in ARIs is poorly known in Burkina Faso. The aim of this study was to identify the respiratory viruses present in children admitted to or consulting at the pediatric hospital in Ouagadougou.
    PLoS ONE 10/2014; 9(10):e110435. · 3.53 Impact Factor
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    ABSTRACT: The presence of HIV-1 non-B subtypes in Western Europe is commonly attributed to migration of individuals from non-European countries, but the possible role of domestic infections with non-B subtypes is not well investigated. French mandatory anonymous reporting system for HIV is linked to a virological surveillance using assays for recent infection (<6 months) and serotyping. During the first semester of years 2007 to 2010, any sample corresponding to a non-B recent infection was analyzed by sequencing a 415 bp env region, followed by phylogenetic analysis and search for transmission clusters. Two hundred and thirty three recent HIV-1 infections with non-B variants were identified. They involved 5 subtypes and 7 CRFs. Ninety-two cases (39.5%) were due to heterosexual transmissions, of which 39 occurred in patients born in France. Eighty-five cases (36.5%) were identified in men having sex with men (MSM). Forty-three recent non-B infections (18.5%) segregated into 14 clusters, MSM being involved in 11 of them. Clustered transmissions events included 2 to 7 cases per cluster. The largest cluster involved MSM infected by a CRF02_AG variant. In conclusion, we found that the spread of non-B subtypes in France occurs in individuals of French origin and that MSM are particularly involved in this dynamic.
    Journal of Clinical Microbiology 09/2014; · 4.23 Impact Factor
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    ABSTRACT: We report the case of a multi-experienced patient, infected with an HIV-1 strain, which selected multiple resistance mutations. We designed a novel well-tolerated and effective rescue treatment including dolutegravir, rilpivirine, and foscarnet, allowing a 60 week sustained virological response for the first time in 23 years of HIV infection.
    Journal of Clinical Virology 08/2014; · 3.47 Impact Factor
  • Journal of Clinical Microbiology 07/2014; 52(7):2740-1. · 4.23 Impact Factor
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    ABSTRACT: The French National Agency for HIV/AIDS Research has previously developed a widely used method for HIV-1 RNA quantification (Biocentric). Here we developed a new specific and sensitive method for HIV-2 RNA quantification, based on an adaptation of the existing HIV-1 protocol. The new test is based on Taqman one-step qRT-PCR targeting two conserved consensus regions of HIV-2 (LTR and Gag). Analytic performances were determined in three laboratories. Clinical performances were evaluated on 100 plasma samples from HIV-2-infected patients (group A, B and H), by comparison with the assay currently used for the ANRS HIV-2 cohort. The specificity was 100%. Sensitivity was 50 cp/mL and could be optimized to 10 cp/mL. The within-run coefficients of variation in the three laboratories varied from 0.54% to 1.61% at 4 log10 copies/mL, and from 7.24% to 14.32% at 2 log10 cp/mL. The between-run coefficients of variation varied from 2.28 to 6.43%. Of the 39 clinical samples below 2 log10 in the current assay, the new test improved the detection or quantification of 17 samples, including eight group B. For quantifiable samples, similar loads were obtained with the two assays for group A samples. The median difference between the two assays for group B samples was +0.18, but with greater heterogeneity. The HIV-2 group H sample gave similar results with the two assays. This new assay is highly sensitive and accurately quantifies the most prevalent HIV-2 groups. This test will be useful for monitoring low loads in HIV-2 infected patients.
    Journal of Clinical Microbiology 06/2014; · 4.23 Impact Factor
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    ABSTRACT: To assess the virological response, genotypic resistance profiles, and antiretroviral plasma concentrations in HIV-2 antiretroviral-treated (antiretroviral therapy, ART) patients in Côte d'Ivoire. A cross-sectional survey was conducted among HIV-2 patients receiving ART. Plasma HIV-2 viral load was performed using the ANRS assay. Protease and reverse transcriptase sequencing was performed using in-house methods and antiretroviral plasma concentrations were assessed using ultra performance liquid chromatography combined with tandem mass spectrometry. One hundred forty five HIV-2-treated patients were enrolled with a median CD4 cell count of 360/μl (interquartile range, IQR = 215-528). Median duration of ART was 4 years (IQR = 2-7) and 74% of patients displayed viral load less than 50 copies/ml. Median plasma HIV-2 RNA among patients with viral load more than 50 copies/ml was 3016 copies/ml (IQR = 436-5156). Most patients (84%) received a lopinavir/ritonavir-based regimen. HIV-2 resistance mutations to nucleoside reverse transcriptase inhibitors and protease inhibitors were detected in 21 of 25 (84%) and 20 of 29 (69%) samples, respectively. The most prevalent nucleoside reverse transcriptase inhibitor resistance mutations were M184I/V (90%), Q151M (24%), and S215F/Y (24%). The most prevalent protease inhibitor resistance mutations were V47A (60%) and I54M (30%). Median CD4 cell counts were 434/μl (292-573) and 204/μl (122-281) in patients with viral load less than 50 copies/ml and those exhibiting virological failure (P < 0.0001), respectively. The proportions of patients with adequate antiretroviral plasma concentrations were 81 and 93% in patients displaying virological failure and in those with viral load less than 50 copies/ml, respectively (P = 0.046), suggesting good treatment adherence. We observed adequate drug plasma concentrations and virological suppression in a high proportion of HIV-2-infected patients. However, in cases of virological failure, the limited HIV-2 therapeutic arsenal and cross-resistance dramatically reduced treatment options.
    AIDS (London, England) 02/2014; · 6.56 Impact Factor
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    ABSTRACT: Fourth generation assays for HIV diagnosis are progressively being introduced into routine services, due to their improvement of diagnosis. In spite of this, HIV diagnosis remains a challenge in sub-Saharan Africa, due to false positive reactivity. There is a continuous need for field evaluations and routine validations of fourth generation HIV tests in African populations. Evaluate the performances of the ARCHITECT HIV Ag/Ab kit (Abbott) in a population living in an African setting-Cameroon compared to a population living in a European setting-France. 645 HIV samples from both France and Cameroon were evaluated. The positive panel (378 samples) included a diverse series of HIV-1 variants (groups M, N, O, and P) as well as HIV-2 samples. Results were compared to original diagnosis done with other 4th generation assays (AxSYM HIV Ag/Ab (Abbott) and Vidas HIV DUO QUICK) (bioMérieux). Sensitivity of the ARCHITECT was 100% in both sites. It diagnosed all variants of the panel with different reactivity profiles following strain diversity. A wider range of reactivity was observed for group O. Specificity was slightly lower (97.6%) in Cameroon than in France (98.6%), probably due to a higher rate of false positive reactivity. ARCHITECT HIV Ag/Ab assay had high performances in clinical sensitivity and specificity and is adapted to the wide genetic diversity of viruses circulating in West Central Africa. Our results further highlight the need to evaluate HIV diagnostic tests before introduction into routine diagnostic services both in the North and in the South.
    Journal of clinical virology: the official publication of the Pan American Society for Clinical Virology 12/2013; 58 Suppl 1:e70-5. · 3.12 Impact Factor
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    ABSTRACT: Hepatitis C remains a challenging public health problem worldwide. The identification of viral variants establishing de novo infections and definition of the phenotypic requirements for transmission would facilitate the design of preventive strategies. We explored the transmission of HCV variants in three cases of acute hepatitis following needlestick accidents. We used single-genome amplification of glycoprotein E1E2 gene sequences to map the genetic bottleneck upon transmission accurately. We found that infection was likely established by a single variant in two cases and six variants in the third case. Studies of donor samples showed that the transmitted variant E1E2 amino-acid sequences were identical or closely related to those of variants from the donor virus populations. The transmitted variants harbored a common signature site at position 394, within hyper variable region 1 of E2, together with additional signature amino acids specific to each transmission pair. Surprisingly, these E1E2 variants conferred no greater capacity for entry than the E1E2 derived from non transmitted variants, in lentiviral pseudoparticle assays. Mutants escaping the antibodies of donor sera did not predominate among the transmitted variants either. The fitness parameters affecting the selective outgrowth of HCV variants after transmission in an immunocompetant host may thus be more complex than suggested by mouse models. Human antibodies directed against HCV envelope effectively cross-neutralized the lentiviral particles bearing E1E2 derived from transmitted variants. These findings provide insight into the molecular mechanisms underlying HCV transmission and suggest that viral entry is a potential target for the prevention of HCV infection.
    Journal of Virology 10/2013; · 4.65 Impact Factor
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    ABSTRACT: Several B/CRF02_AG Unique Recombinant Forms (URFs) have previously been identified in France. Here we show that one of them (URF5_B/02/G) is emerging in MSM, a high-risk population where HIV incidence and number of superinfections are increasing. We describe this new Circulating Recombinant Form, CRF56_cpx, estimate the time to its most recent common ancestor, investigate its origins and show that it probably shares common ancestors with strains from the East Mediterranean.
    AIDS (London, England) 09/2013; 27(14):2309-12. · 6.56 Impact Factor
  • Thomas Mourez, François Simon, Jean-Christophe Plantier
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    ABSTRACT: SUMMARY The AIDS pandemic that started in the early 1980s is due to human immunodeficiency virus type 1 (HIV-1) group M (HIV-M), but apart from this major group, many divergent variants have been described (HIV-1 groups N, O, and P and HIV-2). The four HIV-1 groups arose from independent cross-species transmission of the simian immunodeficiency viruses (SIVs) SIVcpz, infecting chimpanzees, and SIVgor, infecting gorillas. This, together with human adaptation, accounts for their genomic, phylogenetic, and virological specificities. Nevertheless, the natural course of non-M HIV infection seems similar to that of HIV-M. The virological monitoring of infected patients is now possible with commercial kits, but their therapeutic management remains complex. All non-M variants were principally described for patients linked to Cameroon, where HIV-O accounts for 1% of all HIV infections; only 15 cases of HIV-N infection and 2 HIV-P infections have been reported. Despite improvements in our knowledge, many fascinating questions remain concerning the origin, genetic evolution, and slow spread of these variants. Other variants may already exist or may arise in the future, calling for close surveillance. This review provides a comprehensive, up-to-date summary of the current knowledge on these pathogens, including the historical background of their discovery; the latest advances in the comprehension of their origin and spread; and clinical, therapeutic, and laboratory aspects that may be useful for the management and the treatment of patients infected with these divergent viruses.
    Clinical microbiology reviews 07/2013; 26(3):448-61. · 16.00 Impact Factor
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    ABSTRACT: To optimize standard treatment of chronic hepatitis C in responder patients who have achieved undetectable viral load, a prospective study was conducted to determine the factors and kinetics of virologic relapse. Responder patients were monitored 2, 4, 8, 12, 16, and 24 weeks after the end of treatment with pegylated interferon and ribavirin. Forty-seven of the 154 patients (30.5%) relapsed. Relapse was significantly associated with absence of rapid virologic response (RVR), retreatment, higher baseline viral load, older age, and lower weight-based dose of pegylated interferon. Relapse was more frequent in patients failing to achieve a RVR after receiving pegylated interferon alpha 2a < 2.5 µg/week or alpha 2b < 1.5 µg/week (P = 0.002). Among patients infected with hepatitis C virus (HCV) genotype 1 with non-CC IL-28B polymorphism (rs12979860), viral decay during treatment was lower in relapsers (P = 0.003 at week 4). Relapse was detected at weeks 2, 4, 8, and 12 after the end of treatment for 5, 8, 10, and 6 patients infected with HCV genotype 1, respectively. Positive predictive values for sustained virologic response were 70.9%, 80.2%, 91.9%, and 98.8% at weeks 2, 4, 8, and 12, respectively. Only one patient relapsed beyond 24 weeks. Closer follow-up and treatment adaptation in patients failing to achieve RVR may decrease the relapse rate in slower responders and heavier patients. Monitoring viral load as early as 1 month after the end of treatment could be useful to assess virologic response. J. Med. Virol. 85:1191-1198, 2013. © 2013 Wiley Periodicals, Inc.
    Journal of Medical Virology 07/2013; 85(7):1191-8. · 2.22 Impact Factor
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    ABSTRACT: We compared the performance of a specific genotypic algorithm for HIV-1 subtype D and the geno2pheno algorithm, with different cut-offs, to predict tropism. The D-specific algorithm and Geno2pheno2.5 had the same concordance with the phenotypic determination. Geno2pheno2.5, more sensitive but slightly less specific, seems to be an appropriate alternative.
    Journal of clinical microbiology 06/2013; · 4.23 Impact Factor
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    ABSTRACT: This study aimed to identify factors associated with virological response (VR) to raltegravir (RAL)-containing regimens in 468 treatment-experienced but integrase inhibitor-naive HIV-1 patients receiving a RAL-containing regimen. VR was defined at Month 6 (M6) as HIV-1 RNA viral load (VL) <50copies/mL. The impacts on VR of baseline integrase mutations, VL, CD4 count, genotypic sensitivity score for nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors and protease inhibitors, and the number of new antiretrovirals used for the first time associated with RAL were investigated. For patients with VL >50copies/mL at M6, integrase mutations selected were characterised. Median baseline VL was 4.2log10copies/mL (IQR 3.3-4.9log10copies/mL) and CD4 count was 219 cells/mm(3) (IQR 96-368 cells/mm(3)). At M6, 71% of patients were responders. In multivariate analysis, baseline VL and CD4 count and ≥2 new antiretrovirals among darunavir, etravirine, maraviroc and enfuvirtide were associated with VR to RAL. Neither HIV-1 subtype nor baseline integrase polymorphisms were associated with VR to RAL. Among 63 failing patients at M6, selection of ≥1 change in the integrase gene was observed in 49 (77.8%), and 27/63 (42.9%) were considered as RAL-associated resistance mutations. Factors independently associated with the occurrence of ≥1 RAL-associated resistance mutation were VL at failure >3log10 and having no new drugs associated with RAL. RAL showed great potency in treatment-experienced patients. The number of new drugs associated with RAL was an important factor associated with VR. HIV-1 subtype and baseline integrase polymorphisms do not influence the RAL VR.
    International journal of antimicrobial agents 04/2013; · 3.03 Impact Factor
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    ABSTRACT: Hepatitis C virus (HCV) protease inhibitor resistance-associated substitutions are selected during triple therapy breakthrough. This multicenter quality control study evaluated the expertise in HCV protease inhibitor resistance genotyping of 23 French laboratories. A panel of 12 well-defined blinded samples comprising two wild-type HCV strains, nine transcripts from synthetic NS3 mutant samples or from clinical strains, and one HCV RNA-negative sample was provided to the participating laboratories. The results showed that any laboratory with expertise in sequencing techniques should be able to provide reliable HCV protease inhibitor resistance genotyping. Only 0.7% erroneous results were reported over the amino acid sites studied. The accuracy of substitution identification ranged from 75% to 100%, depending on the laboratory. Incorrect results were mainly related to the methodology used. The results could be improved by changing the primers and modifying the process in order to avoid cross-contaminations. This study underlines the value of quality control programs for viral resistance genotyping, required prior to launching observational collaborative multicenter studies on HCV resistance to direct-acting antiviral agents.
    Journal of clinical microbiology 02/2013; · 4.23 Impact Factor
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    ABSTRACT: BACKGROUND: Surveillance of HIV-1 drug resistance in treated patients with plasma viral load (VL) >50 copies/mL. METHODS: The protease and reverse transcriptase (RT) genes were systematically sequenced in samples from 756 patients with VL >50 copies/mL in 2009. The genotyping results were interpreted for each antiretroviral drug (ARV) by using the ANRS algorithm v21. Weighted analyses were used to derive representative estimates of percentages of patients. Prevalence rates were compared with those obtained in 2004 among patients with VL >1000 copies/mL. RESULTS: Sequences were obtained for 506 patients. Sequencing was successful in 45%, 80% and 96% of samples with VL of 51-500, 501-1000 and >1000 copies/mL, respectively. Resistance or possible resistance to at least one ARV was observed in 59% of samples. Overall, 0.9% of samples contained viruses resistant to all drugs belonging to at least three drug classes. All resistance prevalence rates were significantly lower in 2009 than in 2004. CONCLUSION: In France, where 86% of patients were receiving combination antiretroviral therapy in 2009, only 15.0% of patients had a VL >50 copies/mL, suggesting that only 8.9% of treated patients could potentially transmit resistant viruses. Only 0.08% of patients harboured viruses fully resistant to at least three antiretroviral drug classes. Further studies are needed to determine whether resistance continues to decline over time.
    Journal of Antimicrobial Chemotherapy 02/2013; · 5.34 Impact Factor
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    ABSTRACT: OBJECTIVE:: HIV-1 has been classified into 4 groups: M, N, O and P. The aim of this study was to revisit the cross-group neutralization using a highly diverse panel of primary isolates (PI). DESIGN:: The panel of viruses included 9 HIV-1 group O PIs, 1 recombinant M/O PI, 1 group N PI, 1 group P PI, 2 group M (subtype B) PIs and the HIV-1 group M adapted strain MN. METHODS:: All the viruses were tested for neutralization in TZM-bl cells, using sera issued from patients infected by viruses of group M (n = 11), O (n = 12) and P (n = 1), and a panel of nine human monoclonal broadly neutralizing antibodies (HuMo bNAbs). RESULTS:: Although the PIs displayed a wide spectrum of sensitivity to neutralization by the human sera, cross-group neutralization was clearly observed. In contrast, the bNAbs did not show any cross-group neutralization, except PG9 and PG16. Interestingly, the group N prototype strain YBF30 was highly sensitive to neutralization by PG9 (IC50: 0.28 μg/mL) and PG16 (IC50: < 0.12 μg/mL). The interaction between PG9 and key residues of YBF30 was confirmed by molecular modeling. CONCLUSIONS:: The conservation of the PG9 and PG16 epitopes within groups M and N provides an argument for their relevance as components of a potentially efficient HIV vaccine immunogen.
    AIDS (London, England) 01/2013; · 6.56 Impact Factor
  • JAIDS Journal of Acquired Immune Deficiency Syndromes 09/2012; 61(1):e1-3. · 4.39 Impact Factor
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    ABSTRACT: OBJECTIVES: This observational study was requested by French health authorities to determine the impact of lopinavir/ritonavir (Kaletra(®)) on antiretroviral resistance in clinical practice. Virological failures of lopinavir/ritonavir and their effects on the resistance to protease inhibitors and reverse transcriptase inhibitors were evaluated in protease inhibitor-experienced patients. PATIENTS AND METHODS: Virological failure was defined as an HIV-1 plasma viral load >50 copies/mL after at least 3 months of lopinavir/ritonavir-containing antiretroviral therapy. For all patients, a resistance genotypic test was available at failure and before lopinavir/ritonavir treatment. Data from 72 patients with inclusion criteria were studied. RESULTS: The mean viral load at baseline was 4 log(10) copies/mL (1.6-6.5). Mutations in the protease gene significantly selected between baseline and failure were L10V, K20R, L33F, M36I, I47V, I54V, A71V and I85V (P < 0.05). Patients who had more than seven protease inhibitor mutations at baseline showed a significantly increased risk of occurrence of protease inhibitor mutations. The proportion of viruses susceptible to atazanavir, fosamprenavir and darunavir decreased significantly between baseline and failure (P < 0.05). Among patients with a virus susceptible to atazanavir at day 0, 26% (n = 14) exhibited a virus resistant or possibly resistant at the time of failure. This proportion was 32% (n = 16) for fosamprenavir and 16% (n = 7) for darunavir. CONCLUSIONS: A darunavir-based regimen appears to be a sequential option in the case of lopinavir/ritonavir failure. To compare and determine the best treatment sequencing, similar studies should be performed for darunavir/ritonavir and atazanavir/ritonavir.
    Journal of Antimicrobial Chemotherapy 06/2012; 67(10):2487-2493. · 5.34 Impact Factor
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    ABSTRACT: A new subgroup of HIV-1, designated Group P, was recently detected in two unrelated patients of Cameroonian origin. HIV-1 Group P phylogenetically clusters with SIVgor suggesting that it is the result of a cross-species transmission from gorillas. Until today, HIV-1 Group P has only been detected in two patients, and its degree of adaptation to the human host is largely unknown. Previous data have shown that pandemic HIV-1 Group M, but not non-pandemic Group O or rare Group N viruses, efficiently antagonize the human orthologue of the restriction factor tetherin (BST-2, HM1.24, CD317) suggesting that primate lentiviruses may have to gain anti-tetherin activity for efficient spread in the human population. Thus far, three SIV/HIV gene products (vpu, nef and env) are known to have the potential to counteract primate tetherin proteins, often in a species-specific manner. Here, we examined how long Group P may have been circulating in humans and determined its capability to antagonize human tetherin as an indicator of adaptation to humans. Our data suggest that HIV-1 Group P entered the human population between 1845 and 1989. Vpu, Env and Nef proteins from both Group P viruses failed to counteract human or gorilla tetherin to promote efficient release of HIV-1 virions, although both Group P Nef proteins moderately downmodulated gorilla tetherin from the cell surface. Notably, Vpu, Env and Nef alleles from the two HIV-1 P strains were all able to reduce CD4 cell surface expression. Our analyses of the two reported HIV-1 Group P viruses suggest that zoonosis occurred in the last 170 years and further support that pandemic HIV-1 Group M strains are better adapted to humans than non-pandemic or rare Group O, N and P viruses. The inability to antagonize human tetherin may potentially explain the limited spread of HIV-1 Group P in the human population.
    Retrovirology 12/2011; 8:103. · 4.77 Impact Factor

Publication Stats

1k Citations
359.86 Total Impact Points


  • 2003–2014
    • Centre Hospitalier Universitaire Rouen
      • Service d'Urologie
      Rouen, Upper Normandy, France
    • Centre Hospitalier Charles PERRENS
      Burdeos, Aquitaine, France
  • 2011
    • Hôpital Charles-Nicolle
      Tunis-Ville, Tūnis, Tunisia
  • 2009–2011
    • Université de Rouen
      Mont-Saint-Aignan, Upper Normandy, France
    • Robert Koch Institut
      Berlín, Berlin, Germany
    • Pasteur Center of Cameroon
      Jaúnde, Centre Region, Cameroon
  • 2010
    • Assistance Publique – Hôpitaux de Paris
      Lutetia Parisorum, Île-de-France, France
    • Université de Montpellier 1
      Montpelhièr, Languedoc-Roussillon, France
    • Paris Diderot University
      Lutetia Parisorum, Île-de-France, France
  • 2005
    • Hôpital Bichat - Claude-Bernard (Hôpitaux Universitaires Paris Nord Val de Seine)
      Lutetia Parisorum, Île-de-France, France
  • 2002
    • Cheikh Anta Diop University, Dakar
      Dakar, Dakar, Senegal