Martine Braibant

Publications of Martine Braibant

• Envelope glycoproteins of Human Immunodeficiency Virus type 1 variants issued from mother-infant pairs display a wide spectrum of biological properties.

  Authors: Suzie Thenin, Tanawan Samleerat, Elsa Tavernier, Nicole Ngo-Giang-Huong, Gonzague Jourdain, Marc Lallemant, Francis Barin, Martine Braibant

  Virology. 04/2012; 426(1):12-21.

  Several studies have shown that the early virus population present in HIV-1 infected infants usually is homogeneous when compared to the highly diversified viral population present at delivery inSeveral studies have shown that the early virus population present in HIV-1 infected infants usually is homogeneous when compared to the highly diversified viral population present at delivery in their mothers. We explored the antigenic and functional properties of pseudotyped viruses expressing gp120 encoded by env clones issued from four mother-infant pairs infected by CRF01_AE viruses. We compared their sensitivity to neutralization and to entry inhibitors, their infectivity levels and the Env processing and incorporation levels. We found that both transmitted viruses present in infants and the variants present in their chronically infected mothers display a wide spectrum of biological properties that could not distinguish between them. In contrast, we found that all the transmitted viruses in the infants were more sensitive to neutralization by PG9 and PG16 than the maternal variants, an observation that may have implications for the development of prophylactic strategies to prevent mother-to-child transmission.

• Naturally occurring substitutions of conserved residues in HIV-1 variants of different clades are involved in PG9 and PG16 resistance to neutralization.

  Authors: Suzie Thenin, Emanuelle Roch, Tanawan Samleerat, Thierry Moreau, Antoine Chaillon, Alain Moreau, Francis Barin, Martine Braibant

  The Journal of general virology. 04/2012;

  The recently described anti-HIV-1 human monoclonal antibodies PG9 and PG16 are cross-clade broadly neutralizing. Therefore, it can be postulated that the targeted epitope(s) are highly conservedThe recently described anti-HIV-1 human monoclonal antibodies PG9 and PG16 are cross-clade broadly neutralizing. Therefore, it can be postulated that the targeted epitope(s) are highly conserved among variants of the entire group M. We analyzed the sensitivity to PG9 and PG16 of pseudotyped viruses carrying envelope glycoproteins from the viral quasispecies of three HIV-1 clade CRF01_AE-infected patients. The broad heterogeneity in sensitivity to PG9 and PG16 despite closely genetically-related envelope glycoproteins issued from single individuals, allowed us to identify two gp120 cross-clade conserved residues, a lysine at position 168 in the V2 loop and an isoleucine at position 215 in the C2 region, whose substitutions were associated with resistance to PG9 and PG16. By site-directed mutagenesis, we confirmed both in clades B and CRF01_AE, that the substitutions K168E and I215M have a major impact on PG9 and PG16 neutralization sensitivity of pseudotyped viruses.

• The V1V2 domain and an N-linked glycosylation site in the V3 loop of the HIV-1 envelope glycoprotein modulate neutralization sensitivity to the human broadly neutralizing antibody 2G12.

  Authors: Antoine Chaillon, Martine Braibant, Thierry Moreau, Suzie Thenin, Alain Moreau, Brigitte Autran, Francis Barin

  Journal of virology. 01/2011; 85(7):3642-8.

  The broadly neutralizing human monoclonal antibody 2G12 binds to a carbohydrate-dependent epitope involving three major potential N-linked glycosylation sites (PNGS) of gp120 (N295, N332, and N392).The broadly neutralizing human monoclonal antibody 2G12 binds to a carbohydrate-dependent epitope involving three major potential N-linked glycosylation sites (PNGS) of gp120 (N295, N332, and N392). Through analysis of the sensitivity to 2G12 of pseudotyped viruses carrying envelope proteins from HIV-1 clade B-infected long-term nonprogressors, we selected two naturally occurring env clones with opposite sensitivities to 2G12, albeit harboring the 3 particular PNGS known to be essential for 2G12 binding (N295, N332, and N392). The resistant clone presented a long and potentially heavily glycosylated V1V2 loop and an additional PNGS (N302) in the V3 loop. The sensitive clone harbored a short V1V2 loop and lacked the PNGS at N302. We created chimeric envelope genes by swapping the V1V2 domains of the two env clones. The influence of N302 on 2G12 sensitivity was assessed by PCR-based site-directed mutagenesis. Both the exchange of the V1V2 domain and the introduction of the PNGS at N302 on the 2G12-sensitive clone induced a significant decrease in sensitivity to 2G12. In contrast, the reverse V1V2 exchange and the removal of the PNGS at N302 on the 2G12-resistant clone increased sensitivity to 2G12, confirming the influence of these regions on 2G12 sensitivity. Our results, supported by a molecular-modeling study, suggest that both the V1V2 loop and an additional PNGS in V3 might limit access to the 2G12 epitope.

• Disease progression due to dual infection in an HLA-B57-positive asymptomatic long-term nonprogressor infected with a nef-defective HIV-1 strain.

  Authors: Martine Braibant, Jing Xie, Assia Samri, Henri Agut, Brigitte Autran, Francis Barin

  Virology. 09/2010; 405(1):81-92.

  We describe the case of an HLA-B57-positive long-term nonprogressor in whom we previously showed that PBMCs accumulated HIV-1 subtype B proviruses defective in the env gene. After more than 10 yearsWe describe the case of an HLA-B57-positive long-term nonprogressor in whom we previously showed that PBMCs accumulated HIV-1 subtype B proviruses defective in the env gene. After more than 10 years of control of infection, plasma viremia increased progressively, with a concomitant loss of CD4(+) T cells. By phylogenetic analyses of env, nef, vif, and gag sequences obtained at different time points, we suggest here that this patient was initially infected by a putatively attenuated nef-defective variant and that loss of control was due to superinfection with a fully competent virus belonging to the same clade B. At the time of superinfection, its plasma was unable to efficiently neutralize the superinfecting virus and moderate Gag-specific CD8(+) T-cell responses were observed. This suggests the limited capacity of even a long-lasting natural infection with a nef-deficient HIV-1 strain to elicit immune responses able to prevent and control superinfection with a virus of the same clade.

• Maternal neutralizing antibodies against a CRF01_AE primary isolate are associated with a low rate of intrapartum HIV-1 transmission.

  Authors: Tanawan Samleerat, Suzie Thenin, Gonzague Jourdain, Nicole Ngo-Giang-Huong, Alain Moreau, Pranee Leechanachai, Jirapan Ithisuknanth, Karin Pagdi, Pornpun Wannarit, Suraphan Sangsawang, Marc Lallemant, Francis Barin, Martine Braibant

  Virology. 04/2009;

  Mother-to-child transmission (MTCT) of HIV-1 provides a model for studying the role of passively acquired antibodies in preventing HIV infection. We determined the titers of neutralizing antibodiesMother-to-child transmission (MTCT) of HIV-1 provides a model for studying the role of passively acquired antibodies in preventing HIV infection. We determined the titers of neutralizing antibodies (NAbs) against six primary isolates of clades B and CRF01_AE in sera from 45 transmitting and 45 nontransmitting mothers matched for the main independent factors associated with MTCT in Thailand. A lower risk of MTCT, particularly for intrapartum transmission, was associated only with higher NAb titers against the CRF01_AE strain, MBA. The envelope glycoprotein of this strain showed an unusually long V2 domain of 63 amino acids, encoding six potential N-linked glycosylation sites. We provided experimental data indicating that the extended V2 domain contributed to the higher level of resistance to neutralization by mothers' sera in this strain. Taken together the data suggest that some primary isolates with specific properties may be useful indicators for identifying protective antibodies.

• Maternal neutralizing antibodies against a CRF01_AE primary isolate are associated with a low rate of intrapartum HIV-1 transmission in Thailand

  Authors: Suzie Thenin, Tanawan Samleerat, Gonzague Jourdain, Nicole Ngo-Giang-Huong, Alain Moreau, Pranee Leechanachai, Marc Lallemand, Françis Barin, Martine Braibant

  Retrovirology. 01/2009;

• Anticardiolipin Antibodies in HIV Infection Are Independently Associated with Antibodies to the Membrane Proximal External Region of gp41 and with Cell-Associated HIV DNA and Immune Activation.

  Authors: Valérie Martinez, Marie-Claude Diemert, Martine Braibant, Valérie Potard, Jean-Luc Charuel, Francis Barin, Dominique Costagliola, Eric Caumes, Jean-Pierre Clauvel, Brigitte Autran, Lucile Musset

  Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 12/2008;

  Background. @nbsp; The demonstration of in vitro cardiolipin reactivity with 2 human immunodeficiency virus (HIV)-specific, broadly neutralizing antibodies (2F5 and 4E10) has prompted reevaluation ofBackground. @nbsp; The demonstration of in vitro cardiolipin reactivity with 2 human immunodeficiency virus (HIV)-specific, broadly neutralizing antibodies (2F5 and 4E10) has prompted reevaluation of autoimmune manifestations in HIV infection. Methods. @nbsp; We evaluated autoantibodies, particularly anticardiolipin (aCL), in 67 untreated, asymptomatic, HIV-infected individuals with slow progression of HIV disease and their correlation with 2F5-, 4E10-, b12-, and 2G12-like antibodies directed against epitopes involved in broad neutralization, as well as their correlation with immune activation and virological and clinical indicators. Fifty individuals with chronic HIV infection and standard disease progression were control patients. Results. @nbsp; The majority of the study patients with slow progression of HIV disease were men (78%); their median age was 37 years, their median CD4(+) cell count was 672 cells/muL, and their median plasma HIV load was 6200 copies/mL. The majority of the control patients were also men (76%), and most (62%) were receiving highly active antiretroviral therapy; their median age was 43 years, their median CD4(+) cell count was 202 cells/muL, and their median plasma HIV load was 2265 copies/mL. aCL immunoglobulin G was detected at similar levels in 49% of patients with slow progression of HIV disease and in 58% of control patients. Viral load was positively associated with aCL in both groups ([Formula: see text]), independent of CD4(+) cell counts. In patients with slow progression of HIV disease, aCL levels were also correlated with plasma HIV load and cell-associated DNA level ([Formula: see text] and [Formula: see text], respectively; [Formula: see text]), with the proportion of activated CD4(+) cells, human leukocyte antigen-DR(+) cells ([Formula: see text]; [Formula: see text]) but not activated CD8(+) T cells, and with the level of B cell activation (quantified by soluble CD23; [Formula: see text]; [Formula: see text]). The level of aCL antibodies was associated with the level of antibodies to the membrane proximal region of gp41 ([Formula: see text]). Conclusion. @nbsp; aCL is frequently detected in HIV-infected patients, regardless of disease stage, and is strongly linked with the level of viral replication, the level of CD4(+) T and B cell activation, and the level of antibodies to the membrane proximal external region of gp41, independent of CD4(+) cell deficiency.

• Characteristics of HIV Type 1 (HIV-1) Glycoprotein 120 env Sequences in Mother-Infant Pairs Infected with HIV-1 Subtype CRF01_AE.

  Authors: Tanawan Samleerat, Martine Braibant, Gonzague Jourdain, Alain Moreau, Nicole Ngo-Giang-Huong, Pranee Leechanachai, Jittapol Hemvuttiphan, Temsiri Hinjiranandana, Tikamporn Changchit, Boonyarat Warachit, Veera Suraseranivong, Marc Lallemant, Francis Barin

  The Journal of infectious diseases. 10/2008; 198(6):868-876.

  We analyzed the characteristics of the envelope genes of human immunodeficiency virus type 1 in 17 mother-infant pairs infected with variants of the CRF01_AE clade. A total of 353 sequences coveringWe analyzed the characteristics of the envelope genes of human immunodeficiency virus type 1 in 17 mother-infant pairs infected with variants of the CRF01_AE clade. A total of 353 sequences covering almost the entire glycoprotein (gp) 120 region were available for analysis. We found that, even if the virus population in the mother was complex, only viruses of a restricted subset were transmitted to her infant, independently of whether transmission occurred in utero or during the intrapartum period. We did not find that shorter gp120 regions or fewer potential N-glycosylation sites (PNGS) were characteristic of viruses transmitted from mother to infant. However, our data suggest that a limited number of PNGS that seem to be conserved in all variants in infants but are not uniformly present in variants in mothers may confer an advantage for transmission of the virus, thereby highlighting the potentially important role of the "glycan shield." This finding was particularly significant for the PNGS at positions N301 and N384.

• Characteristics of the env genes of HIV type 1 quasispecies in long-term nonprogressors with broadly neutralizing antibodies.

  Authors: Martine Braibant, Henri Agut, Christine Rouzioux, Dominique Costagliola, Brigitte Autran, Francis Barin

  Journal of acquired immune deficiency syndromes (1999). 04/2008; 47(3):274-84.

  Primary isolates of different subtypes of HIV-1 can be neutralized in vitro by the broadly neutralizing antibodies (NAbs) found in the sera of a small number of HIV-1-infected patients. This broadPrimary isolates of different subtypes of HIV-1 can be neutralized in vitro by the broadly neutralizing antibodies (NAbs) found in the sera of a small number of HIV-1-infected patients. This broad response is most frequent in long-term nonprogressors (LTNPs). We investigated whether the presence of NAbs in the sera of some LTNPs was associated with particular properties of the envelope glycoproteins of the variants found in these patients. Toward that aim, 147 env gene fragments (encoding almost the entire gp120) amplified from the proviral DNA of 5 LTNPs who developed broadly NAbs (NAb+) and of 4 LTNPs who did not develop such broadly NAbs (NAb-) were cloned, sequenced, and compared. We found that the development of broadly NAbs was associated with high viral loads, greater diversity in the gp120 of the viruses infecting these patients, and longer V1 sequences and additional N-gly sites in V1. In addition, a higher proportion of defective clones was found among the env genes of NAb- patients (25% to 93%)-particularly those with lower viral loads and low levels of env diversity-than among those of NAb+ patients (7% to 19%).

• Characteristics of HIV-1 gp120 env sequences in mother-child pairs infected with HIV-1 subtype CRF01_AE

  Authors: Tanawan Samleerat, Martine Braibant, Gonzague Jourdain, Alain Moreau, Nicole Ngo-Giang-Huong, Pranee Leechanachai, Jittapol Hemvuttiphan, Temsiri Hinjiranandana, Tikamporn Changchit, Boonyarat Warachit, Veera Suraseranivong, Marc Lallemant, Francis Barin

  Retrovirology. 01/2008;

• Antibodies to conserved epitopes of the HIV-1 envelope in sera from long-term non-progressors: prevalence and association with neutralizing activity.

  Authors: Martine Braibant, Sylvie Brunet, Dominique Costagliola, Christine Rouzioux, Henri Agut, Hermann Katinger, Brigitte Autran, Francis Barin

  AIDS (London, England). 11/2006; 20(15):1923-30.

  OBJECTIVE: Previous studies have shown that broadly neutralizing antibodies (NAb) are more frequent in long-term non-progressors (LTNP) than in other HIV-1 infected patients, but nothing is knownOBJECTIVE: Previous studies have shown that broadly neutralizing antibodies (NAb) are more frequent in long-term non-progressors (LTNP) than in other HIV-1 infected patients, but nothing is known about the envelope regions targeted by these broadly NAb. We investigated whether the breadth of neutralizing activity of sera was associated with the presence of specific antibodies (2F5- and/or 4E10-like, b12-like or 2G12-like antibodies) directed against conserved epitopes known to be involved in broad neutralization. METHODS: We assessed the ability of sera from 67 LTNP of the French ANRS cohort (ANRS CO15) to neutralize four heterologous primary isolates of four various clades. Competitive and non-competitive ELISA were developed for the specific comparison of levels of antibodies against these specific epitopes in neutralizing and non-neutralizing sera from LTNP. RESULTS: We found that higher 2G12-like antibody levels were significantly associated with the broadest neutralizing activity in sera from LTNP. Levels of 2G12-like antibodies were higher in the sera that neutralized the four isolates than in the others, with a median of 5.7 microg/ml [interquartile range (IQR), 2.7-9.3 microg/ml] versus 2.3 microg/ml (IQR, 1.1-3.9 microg/ml) (Mann-Whitney test, P = 0.03). Levels of antibodies against the other targeted envelope epitopes did not differ significantly between broadly and non-broadly neutralizing sera. CONCLUSION: These results suggest that the antigenicity of the "silent face" of gp120 that exposes the 2G12 epitope should be analysed in more detail, to find ways to induce broadly neutralizing antibodies.

• Structural and functional study of the phenicol-specific efflux pump FloR belonging to the major facilitator superfamily.

  Authors: Martine Braibant, Jacqueline Chevalier, Elisabeth Chaslus-Dancla, Jean-Marie Pagès, Axel Cloeckaert

  Antimicrobial agents and chemotherapy. 08/2005; 49(7):2965-71.

  The florfenicol-chloramphenicol resistance gene floR from Salmonella enterica was previously identified and postulated to belong to the major facilitator (MF) superfamily of drug exporters. Here, weThe florfenicol-chloramphenicol resistance gene floR from Salmonella enterica was previously identified and postulated to belong to the major facilitator (MF) superfamily of drug exporters. Here, we confirmed a computer-predicted transmembrane topological model of FloR, using the phoA gene fusion method, and classified this protein in the DHA12 family (containing 12 transmembrane domains) of MF efflux transporters. We also showed that FloR is a transporter specific for structurally associated phenicol drugs (chloramphenicol, florfenicol, thiamphenicol) which utilizes the proton motive force to energize an active efflux mechanism. By site-directed mutagenesis of specific charged residues belonging to putative transmembrane segments (TMS), two residues essential for active efflux function, D23 in TMS1 and R109 in TMS4, were identified. Of these, the acidic residue D23 seems to participate directly in the affinity pocket involved in phenicol derivative recognition. A third residue, E283 in TMS9, seems to be necessary for correct membrane folding of the transporter.

• Functional characterization of Brucella melitensis NorMI, an efflux pump belonging to the multidrug and toxic compound extrusion family.

  Authors: Martine Braibant, Laurence Guilloteau, Michel S Zygmunt

  Antimicrobial agents and chemotherapy. 10/2002; 46(9):3050-3.

  Two putative proteins (NorMI and NorMII) similar to the multidrug efflux protein NorM of Vibrio parahaemolyticus are encoded by the Brucella melitensis 16 M genome. We show that aTwo putative proteins (NorMI and NorMII) similar to the multidrug efflux protein NorM of Vibrio parahaemolyticus are encoded by the Brucella melitensis 16 M genome. We show that a drug-hypersusceptible Escherichia coli strain overexpressing NorMI displays increased resistance to norfloxacin, ciprofloxacin, gentamicin, tetraphenylphosphonium ion, acriflavine, and berberine. This elevated resistance was proven to be mediated by an energy-dependent efflux mechanism. NorMI belongs to the multidrug and toxic compound extrusion family and is the first multidrug efflux protein identified in Brucella spp.