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Dr. Elmostafa Bahraoui
University Toulouse III, INSERM, U1043, CNRS U5282 INFINITY, Toulouse, France

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0 Glycosylation
0 inflammatory responses
0 Vaccine development
0 Innate immune response
0 RNA viruses

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Journal article
Published: 18 May 2020 in Scientific Reports
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In the present study we showed that HIV-1 Tat protein stimulated the expression of Indoleamine 2,3 dioxygenase (IDO) -1 in human monocytes derived dendritic cells (MoDC) but not IDO-2 by acting directly at the cell membrane level. This induction of IDO-1 is dependent on the secondary structure of Tat protein, since stimulation with a chemically oxidized Tat protein loses its capacity to induce the production of IDO-1. Among the variety of candidate receptors described for Tat, we demonstrated that Tat protein interacted physically with TLR4/MD2 complex. Strikingly, blockade of Tat-TLR4 interaction by anti-TLR4 antibodies (clone HTA125), LPS-RS, a known TLR4 antagonist, or by soluble recombinant TLR4/MD2 complex inhibited strongly or totally the capacity of Tat to induce IDO-1 in MoDC while such treatments had no effect on IFN-γ-induced IDO-1. Furthermore, we showed that the activation of the transcription factor NF-κB by Tat is essential for the production of IDO-1 by human MoDC. Indeed, Tat activated NF-κB pathway in MoDC as demonstrated by the phosphorylation of p65 in Tat-treated MoDC. Further, we demonstrate that the stimulation of IDO-1 by Tat or by IFN-γ was totally or partially inhibited in the presence of NF-κB inhibitor respectively. These results suggest that Tat and IFN-γ act probably by two distinct mechanisms to induce the production of IDO-1. Our results clearly demonstrated that, although TLR4 pathway is necessary for Tat-induced IDO-1 in MoDC, it seems not to be sufficient since stable transfection of a functional TLR4/MD2 pathway in HEK or HeLa cell lines which are endogenously defectives for TLR4, did not restore the capacity of Tat to induce IDO-1 while IFN-γ treatment induces IDO-1 in HeLa cells independently of TLR4 pathway. These results suggest the involvement of additional stimuli in addition to TLR4 pathway which remain to be identified. Altogether our results demonstrated that, in human MoDC, HIV-1 Tat protein induced IDO-1 expression and activity in a NF-κB dependent-manner by recruiting TLR4 pathway.

ACS Style

Elmostafa Bahraoui; Manutea Serrero; Rémi Planes. HIV-1 Tat – TLR4/MD2 interaction drives the expression of IDO-1 in monocytes derived dendritic cells through NF-κB dependent pathway. Scientific Reports 2020, 10, 8177 .

AMA Style

Elmostafa Bahraoui, Manutea Serrero, Rémi Planes. HIV-1 Tat – TLR4/MD2 interaction drives the expression of IDO-1 in monocytes derived dendritic cells through NF-κB dependent pathway. Scientific Reports. 2020; 10 (1):8177.

Chicago/Turabian Style

Elmostafa Bahraoui; Manutea Serrero; Rémi Planes. 2020. "HIV-1 Tat – TLR4/MD2 interaction drives the expression of IDO-1 in monocytes derived dendritic cells through NF-κB dependent pathway." Scientific Reports 10, no. 1: 8177.

Journal article
Published: 24 September 2019 in Bioscience Reports
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The trimeric heptad repeat domains HR1 and HR2 of the human immunodeficiency virus 1 (HIV-1) gp41 play a key role in HIV-1-entry by membrane fusion. To develop efficient inhibitors against this step, the corresponding trimeric-N36 and C34 peptides were designed and synthesized. Analysis by circular dichroism of monomeric and trimeric N36 and C34 peptides showed their capacities to adopt α-helical structures and to establish physical interactions. At the virological level, while trimeric-C34 conserves the same high anti-fusion activity as monomeric-C34, trimerization of N36-peptide induced a significant increase, reaching 500-times higher in anti-fusion activity, against R5-tropic virus-mediated fusion. This result was associated with increased stability of the N36 trimer peptide with respect to the monomeric form, as demonstrated by the comparative kinetics of their antiviral activities during 6-day incubation in a physiological medium. Collectively, our findings demonstrate that while the trimerization of C34 peptide had no beneficial effect on its stability and antiviral activity, the trimerization of N36 peptide strengthened both stability and antiviral activity. This approach, promotes trimers as new promising HIV-1 inhibitors and point to future development aimed toward innovative peptide fusion inhibitors, microbicides or as immunogens.

ACS Style

Olfa Mzoughi; Meritxell Teixido; Rémi Planès; Manutea Serrero; Ibtissem Hamimed; Esther Zurita; Miguel Moreno; Giovana Granados; Faouzi Lakhdar-Ghazal; Lbachir Benmohamed; Ernest Giralt; Elmostafa Bahraoui. Trimeric heptad repeat synthetic peptides HR1 and HR2 efficiently inhibit HIV-1 entry. Bioscience Reports 2019, 39, 1 .

AMA Style

Olfa Mzoughi, Meritxell Teixido, Rémi Planès, Manutea Serrero, Ibtissem Hamimed, Esther Zurita, Miguel Moreno, Giovana Granados, Faouzi Lakhdar-Ghazal, Lbachir Benmohamed, Ernest Giralt, Elmostafa Bahraoui. Trimeric heptad repeat synthetic peptides HR1 and HR2 efficiently inhibit HIV-1 entry. Bioscience Reports. 2019; 39 (9):1.

Chicago/Turabian Style

Olfa Mzoughi; Meritxell Teixido; Rémi Planès; Manutea Serrero; Ibtissem Hamimed; Esther Zurita; Miguel Moreno; Giovana Granados; Faouzi Lakhdar-Ghazal; Lbachir Benmohamed; Ernest Giralt; Elmostafa Bahraoui. 2019. "Trimeric heptad repeat synthetic peptides HR1 and HR2 efficiently inhibit HIV-1 entry." Bioscience Reports 39, no. 9: 1.

Journal article
Published: 21 November 2018 in Scientific Reports
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Human HIV-1 infection leads inevitably to a chronic hyper-immune-activation. However, the nature of the targeted receptors and the pathways involved remain to be fully elucidated. We demonstrate that X4-tropic gp120 induced the production of TNF-α and IL-10 by monocytes through activation of a cell membrane receptor, distinct from the CD4, CXCR4, and MR receptors. Gp120 failed to stimulate IL-10 and TNF-α production by monocytes in Ca2+ free medium. This failure was total for IL-10 and partial for TNF-α. However, IL-10 and TNF-α production was fully restored following the addition of exogenous calcium. Accordingly, addition of BAPTA-AM and cyclosporine-A, fully and partially inhibited IL-10 and TNF-α respectively. The PKA pathway was crucial for IL-10 production but only partially involved in gp120-induced TNF-α. The PLC pathway was partially and equivalently involved in gp120-induced TNF-α and IL-10. Moreover, the inhibition of PI3K, ERK1/2, p38 MAP-kinases and NF-κB pathways totally abolished the production of both cytokines. In conclusion, this study revealed the crucial calcium signaling pathway triggered by HIV-1 gp120 to control the production of these two cytokines: TNF-α and IL-10. The finding could help in the development of a new therapeutic strategy to alleviate the chronic hyper-immune-activation observed in HIV-1 infected patients.

ACS Style

Rémi Planès; Manutea Serrero; Kaoutar Leghmari; Lbachir Benmohamed; Elmostafa Bahraoui. HIV-1 Envelope Glycoproteins Induce the Production of TNF-α and IL-10 in Human Monocytes by Activating Calcium Pathway. Scientific Reports 2018, 8, 1 -15.

AMA Style

Rémi Planès, Manutea Serrero, Kaoutar Leghmari, Lbachir Benmohamed, Elmostafa Bahraoui. HIV-1 Envelope Glycoproteins Induce the Production of TNF-α and IL-10 in Human Monocytes by Activating Calcium Pathway. Scientific Reports. 2018; 8 (1):1-15.

Chicago/Turabian Style

Rémi Planès; Manutea Serrero; Kaoutar Leghmari; Lbachir Benmohamed; Elmostafa Bahraoui. 2018. "HIV-1 Envelope Glycoproteins Induce the Production of TNF-α and IL-10 in Human Monocytes by Activating Calcium Pathway." Scientific Reports 8, no. 1: 1-15.

Journal article
Published: 15 April 2018 in Journal of Virology
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There is an urgent need for chemical-free and biological-free safe adjuvants to enhance the immunogenicity of vaccines against widespread viral pathogens, such as herpes simplex virus 2 (HSV-2), that infect a large proportion of the world human population. In the present study, we investigated the safety, immunogenicity, and protective efficacy of a laser adjuvant-assisted peptide (LAP) vaccine in the B6 mouse model of genital herpes. This LAP vaccine and its laser-free peptide (LFP) vaccine analog contain the immunodominant HSV-2 glycoprotein B CD8 + T cell epitope (HSV-gB 498–505 ) covalently linked with the promiscuous glycoprotein D CD4 + T helper cell epitope (HSV-gD 49–89 ). Prior to intradermal delivery of the LAP vaccine, the lower-flank shaved skin of B6 or CD11c/eYFP transgenic mice received a topical skin treatment with 5% imiquimod cream and then was exposed for 60 s to a laser, using the FDA-approved nonablative diode. Compared to the LFP vaccine, the LAP vaccine (i) triggered mobilization of dendritic cells (DCs) in the skin, which formed small spots along the laser-treated areas, (ii) induced phenotypic and functional maturation of DCs, (iii) stimulated long-lasting HSV-specific effector memory CD8 + T cells (T EM cells) and tissue-resident CD8 + T cells (T RM cells) locally in the vaginal mucocutaneous tissues (VM), and (iv) induced protective immunity against genital herpes infection and disease. As an alternative to currently used conventional adjuvants, the chemical- and biological-free laser adjuvant offers a well-tolerated, simple-to-produce method to enhance mass vaccination for widespread viral infections. IMPORTANCE Herpes simplex viruses 1 and 2 (HSV-1 and HSV-2) infect a large proportion of the world population. There is an urgent need for chemical-free and biological-free safe adjuvants that would advance mass vaccination against the widespread herpes infections. The present study demonstrates that immunization with a laser-assisted herpes peptide vaccine triggered skin mobilization of dendritic cells (DCs) that stimulated strong and long-lasting HSV-specific effector memory CD8 + T cells (T EM cells) and tissue-resident CD8 + T cells (T RM cells) locally in the vaginal mucocutaneous tissues. The induced local CD8 + T cell response was associated with protection against genital herpes infection and disease. These results draw attention to chemical- and biological-free laser adjuvants as alternatives to currently used conventional adjuvants to enhance mass vaccination for widespread viral infections, such as those caused by HSV-1 and HSV-2.

ACS Style

Patricia P. Lopes; George Todorov; Thanh T. Pham; Anthony B. Nesburn; Elmostafa Bahraoui; Lbachir BenMohamed. Laser Adjuvant-Assisted Peptide Vaccine Promotes Skin Mobilization of Dendritic Cells and Enhances Protective CD8 + T EM and T RM Cell Responses against Herpesvirus Infection and Disease. Journal of Virology 2018, 92, 1 .

AMA Style

Patricia P. Lopes, George Todorov, Thanh T. Pham, Anthony B. Nesburn, Elmostafa Bahraoui, Lbachir BenMohamed. Laser Adjuvant-Assisted Peptide Vaccine Promotes Skin Mobilization of Dendritic Cells and Enhances Protective CD8 + T EM and T RM Cell Responses against Herpesvirus Infection and Disease. Journal of Virology. 2018; 92 (8):1.

Chicago/Turabian Style

Patricia P. Lopes; George Todorov; Thanh T. Pham; Anthony B. Nesburn; Elmostafa Bahraoui; Lbachir BenMohamed. 2018. "Laser Adjuvant-Assisted Peptide Vaccine Promotes Skin Mobilization of Dendritic Cells and Enhances Protective CD8 + T EM and T RM Cell Responses against Herpesvirus Infection and Disease." Journal of Virology 92, no. 8: 1.

Journal article
Published: 16 March 2018 in The Journal of Immunology
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Circulating conventional memory CD8+ T cells (i.e., the CD8+ effector memory T [TEM] cell and CD8+ central memory T [TCM] cell subsets) and the noncirculating CD8+ tissue-resident memory T (TRM) cell subset play a critical role in mucosal immunity. Mucosal chemokines, including the recently discovered CXCL17, are also important in mucosal immunity because they are homeostatically expressed in mucosal tissues. However, whether the CXCL17 chemokine contributes to the mobilization of memory CD8+ T cell subsets to access infected mucosal tissues remains to be elucidated. In this study, we report that after intravaginal HSV type 1 infection of B6 mice, we detected high expression levels of CXCL17 and increased numbers of CD44highCD62LlowCD8+ TEM and CD103highCD8+ TRM cells expressing CXCR8, the cognate receptor of CXCL17, in the vaginal mucosa (VM) of mice with reduced genital herpes infection and disease. In contrast to wild-type B6 mice, the CXCL17−/− mice developed 1) fewer CXCR8+CD8+ TEM and TRM cells associated with more virus replication in the VM and more latency established in dorsal root ganglia, and 2) reduced numbers and frequencies of functional CD8+ T cells in the VM. These findings suggest that the CXCL17/CXCR8 chemokine pathway plays a crucial role in mucosal vaginal immunity by promoting the mobilization of functional protective CD8+ TEM and CD8+ TRM cells, within this site of acute and recurrent herpes infection.

ACS Style

Ruchi Srivastava; Marcela Hernández; Arif A. Khan; Mona A. Fouladi; Grace J. Kim; Vincent T. Ly; Taikun Yamada; Cynthia Lam; Sheilouise A. B. Sarain; Undariya Boldbaatar; Albert Zlotnik; Elmostafa Bahraoui; Lbachir Benmohamed. CXCL17 Chemokine–Dependent Mobilization of CXCR8+CD8+Effector Memory and Tissue-Resident Memory T Cells in the Vaginal Mucosa Is Associated with Protection against Genital Herpes. The Journal of Immunology 2018, 200, 2915 -2926.

AMA Style

Ruchi Srivastava, Marcela Hernández, Arif A. Khan, Mona A. Fouladi, Grace J. Kim, Vincent T. Ly, Taikun Yamada, Cynthia Lam, Sheilouise A. B. Sarain, Undariya Boldbaatar, Albert Zlotnik, Elmostafa Bahraoui, Lbachir Benmohamed. CXCL17 Chemokine–Dependent Mobilization of CXCR8+CD8+Effector Memory and Tissue-Resident Memory T Cells in the Vaginal Mucosa Is Associated with Protection against Genital Herpes. The Journal of Immunology. 2018; 200 (8):2915-2926.

Chicago/Turabian Style

Ruchi Srivastava; Marcela Hernández; Arif A. Khan; Mona A. Fouladi; Grace J. Kim; Vincent T. Ly; Taikun Yamada; Cynthia Lam; Sheilouise A. B. Sarain; Undariya Boldbaatar; Albert Zlotnik; Elmostafa Bahraoui; Lbachir Benmohamed. 2018. "CXCL17 Chemokine–Dependent Mobilization of CXCR8+CD8+Effector Memory and Tissue-Resident Memory T Cells in the Vaginal Mucosa Is Associated with Protection against Genital Herpes." The Journal of Immunology 200, no. 8: 2915-2926.

Journal article
Published: 15 July 2017 in Journal of Virology
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Herpes simplex virus 1 (HSV-1) establishes latency within the sensory neurons of the trigeminal ganglia (TG). HSV-specific memory CD8 + T cells play a critical role in preventing HSV-1 reactivation from TG and subsequent virus shedding in tears that trigger recurrent corneal herpetic disease. The CXC chemokine ligand 10 (CXCL10)/CXC chemokine receptor 3 (CXCR3) chemokine pathway promotes T cell immunity to many viral pathogens, but its importance in CD8 + T cell immunity to recurrent herpes has been poorly elucidated. In this study, we determined how the CXCL10/CXCR3 pathway affects TG- and cornea-resident CD8 + T cell responses to recurrent ocular herpesvirus infection and disease using a well-established murine model in which HSV-1 reactivation was induced from latently infected TG by UV-B light. Following UV-B-induced HSV-1 reactivation, a significant increase in both the number and function of HSV-specific CXCR3 + CD8 + T cells was detected in TG and corneas of protected C57BL/6 (B6) mice, but not in TG and corneas of nonprotected CXCL10 −/− or CXCR3 −/− deficient mice. This increase was associated with a significant reduction in both virus shedding and recurrent corneal herpetic disease. Furthermore, delivery of exogenous CXCL10 chemokine in TG of CXCL10 −/− mice, using the neurotropic adeno-associated virus type 8 (AAV8) vector, boosted the number and function of effector memory CD8 + T cells (T EM ) and tissue-resident memory CD8 + T cells (T RM ), but not of central memory CD8 + T cells (T CM ), locally within TG, and improved protection against recurrent herpesvirus infection and disease in CXCL10 −/− deficient mice. These findings demonstrate that the CXCL10/CXCR3 chemokine pathway is critical in shaping CD8 + T cell immunity, locally within latently infected tissues, which protects against recurrent herpesvirus infection and disease. IMPORTANCE We determined how the CXCL10/CXCR3 pathway affects CD8 + T cell responses to recurrent ocular herpesvirus infection and disease. Using a well-established murine model, in which HSV-1 reactivation in latently infected trigeminal ganglia was induced by UV-B light, we demonstrated that lack of either CXCL10 chemokine or its CXCR3 receptor compromised the mobilization of functional CD8 + T EM and CD8 + T RM cells within latently infected trigeminal ganglia following virus reactivation. This lack of T cell mobilization was associated with an increase in recurrent ocular herpesvirus infection and disease. Inversely, augmenting the amount of CXCL10 in trigeminal ganglia of latently infected CXCL10-deficient mice significantly restored the number of local antiviral CD8 + T EM and CD8 + T RM cells associated with protection against recurrent ocular herpes. Based on these findings, a novel “prime/pull” therapeutic ocular herpes vaccine strategy is proposed and discussed.

ACS Style

Ruchi Srivastava; Arif A. Khan; Sravya Chilukuri; Sabrina A. Syed; Tien T. Tran; Julie Furness; Elmostafa Bahraoui; Lbachir BenMohamed. CXCL10/CXCR3-Dependent Mobilization of Herpes Simplex Virus-Specific CD8 + T EM and CD8 + T RM Cells within Infected Tissues Allows Efficient Protection against Recurrent Herpesvirus Infection and Disease. Journal of Virology 2017, 91, e00278-17 .

AMA Style

Ruchi Srivastava, Arif A. Khan, Sravya Chilukuri, Sabrina A. Syed, Tien T. Tran, Julie Furness, Elmostafa Bahraoui, Lbachir BenMohamed. CXCL10/CXCR3-Dependent Mobilization of Herpes Simplex Virus-Specific CD8 + T EM and CD8 + T RM Cells within Infected Tissues Allows Efficient Protection against Recurrent Herpesvirus Infection and Disease. Journal of Virology. 2017; 91 (14):e00278-17.

Chicago/Turabian Style

Ruchi Srivastava; Arif A. Khan; Sravya Chilukuri; Sabrina A. Syed; Tien T. Tran; Julie Furness; Elmostafa Bahraoui; Lbachir BenMohamed. 2017. "CXCL10/CXCR3-Dependent Mobilization of Herpes Simplex Virus-Specific CD8 + T EM and CD8 + T RM Cells within Infected Tissues Allows Efficient Protection against Recurrent Herpesvirus Infection and Disease." Journal of Virology 91, no. 14: e00278-17.

Journal article
Published: 24 May 2017 in Scientific Reports
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HIV-1 Tat protein induces the production of CXCL8 chemokine in a TLR4/MD2 and PKC dependent manner. The objective of this study was to understand whether these two pathways were distinct or constituted a single common pathway, and to determine the nature of the PKC isoforms involved and their interrelation with the activation of NF-κB and CXCL8 gene product expression. Here, we show that Tat-induced CXCL8 production is essentially dependent on the activation of PKC delta isoform, as shown a) by the capacity of PKC delta dominant negative (DN), and Rottlerin, a selective PKC delta pharmacological inhibitor, to inhibit Tat-induced CXCL8 production and b) by the ability of the constitutively active (CAT) isoform of PKC delta to induce CXCL8 production in a HEK cell line in the absence of Tat stimulation. The finding that comparable amounts of CXCL8 were produced following stimulation with either Tat protein, PKC-delta CAT transfection, or both, argue for the implication of one common pathway where PKC delta is activated downstream of TLR4 recruitment and leads to the activation of NF-κB. Altogether, our results underline the crucial role of PKC delta isoform in activating gene expression of CXCL8, a cytokine largely implicated in the physiopathology of HIV-1 infection.

ACS Style

Manutea Serrero; Rémi Planès; Elmostafa Bahraoui. PKC-δ isoform plays a crucial role in Tat-TLR4 signalling pathway to activate NF-κB and CXCL8 production. Scientific Reports 2017, 7, 1 -12.

AMA Style

Manutea Serrero, Rémi Planès, Elmostafa Bahraoui. PKC-δ isoform plays a crucial role in Tat-TLR4 signalling pathway to activate NF-κB and CXCL8 production. Scientific Reports. 2017; 7 (1):1-12.

Chicago/Turabian Style

Manutea Serrero; Rémi Planès; Elmostafa Bahraoui. 2017. "PKC-δ isoform plays a crucial role in Tat-TLR4 signalling pathway to activate NF-κB and CXCL8 production." Scientific Reports 7, no. 1: 1-12.

Journal article
Published: 01 July 2016 in Journal of Virology
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In this study, we show that the HIV-1 Tat protein interacts with rapid kinetics to engage the Toll-like receptor 4 (TLR4) pathway, leading to the production of proinflammatory and anti-inflammatory cytokines. The pretreatment of human monocytes with Tat protein for 10 to 30 min suffices to irreversibly engage the activation of the TLR4 pathway, leading to the production of tumor necrosis factor alpha (TNF-α) and interleukin-10 (IL-10), two cytokines strongly implicated in the chronic activation and dysregulation of the immune system during HIV-1 infection. Therefore, this study analyzed whether the HIV-1 Tat protein is able to activate these two pathways separately or simultaneously. Using three complementary approaches, including mice deficient in the MyD88, TIRAP/MAL, or TRIF adaptor, biochemical analysis, and the use of specific small interfering RNAs (siRNAs), we demonstrated (i) that Tat was able to activate both the MyD88 and TRIF pathways, (ii) the capacity of Tat to induce TIRAP/MAL degradation, (iii) the crucial role of the MyD88 pathway in the production of Tat-induced TNF-α and IL-10, (iv) a reduction but not abrogation of IL-10 and TNF-α by Tat-stimulated macrophages from mice deficient in TIRAP/MAL, and (v) the crucial role of the TRIF pathway in Tat-induced IL-10 production. Further, we showed that downstream of the MyD88 and TRIF pathways, the Tat protein activated the protein kinase C (PKC) βII isoform, the mitogen-activated protein (MAP) kinases p38 and extracellular signal-regulated kinase 1/2 (ERK1/2), and NF-κB in a TLR4-dependent manner. Collectively, our data show that by recruiting the TLR4 pathway with rapid kinetics, the HIV-1 Tat protein leads to the engagement of both the MyD88 and TRIF pathways and to the activation of PKC, MAP kinase, and NF-κB signaling to induce the production of TNF-α and IL-10. IMPORTANCE In this study, we demonstrate that by recruiting the TLR4 pathway with rapid kinetics, the HIV-1 Tat protein leads to the engagement of both the MyD88 and TRIF pathways and to the activation of PKC-βII, MAP kinase, and NF-κB signaling to induce the production of TNF-α and IL-10, two cytokines strongly implicated in the chronic activation and dysregulation of the immune system during HIV-1 infection. Thus, it may be interesting to target Tat as a pathogenic factor early after HIV-1 infection. This could be achieved either by vaccination approaches including Tat as an immunogen in potential candidate vaccines or by developing molecules capable of neutralizing the effect of the Tat protein.

ACS Style

Rémi Planès; Nawal Ben Haij; Kaoutar Leghmari; Manutea Serrero; Lbachir BenMohamed; Elmostafa Bahraoui. HIV-1 Tat Protein Activates both the MyD88 and TRIF Pathways To Induce Tumor Necrosis Factor Alpha and Interleukin-10 in Human Monocytes. Journal of Virology 2016, 90, 5886 -5898.

AMA Style

Rémi Planès, Nawal Ben Haij, Kaoutar Leghmari, Manutea Serrero, Lbachir BenMohamed, Elmostafa Bahraoui. HIV-1 Tat Protein Activates both the MyD88 and TRIF Pathways To Induce Tumor Necrosis Factor Alpha and Interleukin-10 in Human Monocytes. Journal of Virology. 2016; 90 (13):5886-5898.

Chicago/Turabian Style

Rémi Planès; Nawal Ben Haij; Kaoutar Leghmari; Manutea Serrero; Lbachir BenMohamed; Elmostafa Bahraoui. 2016. "HIV-1 Tat Protein Activates both the MyD88 and TRIF Pathways To Induce Tumor Necrosis Factor Alpha and Interleukin-10 in Human Monocytes." Journal of Virology 90, no. 13: 5886-5898.

Research article
Published: 02 September 2015 in PLOS ONE
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Fibroblast growth factor 1 (FGF1) is induced during myoblast differentiation at both transcriptional and translational levels. Here, we identify hnRNPM and p54nrb/NONO present in protein complexes bound to the FGF1 promoter and to the mRNA internal ribosome entry site (IRES). Knockdown or overexpression of these proteins indicate that they cooperate in activating IRES-dependent translation during myoblast differentiation, in a promoter-dependent manner. Importantly, mRNA transfection and promoter deletion experiments clearly demonstrate the impact of the FGF1 promoter on the activation of IRES-dependent translation via p54nrb and hnRNPM. Accordingly, knockdown of either p54 or hnRNPM also blocks endogenous FGF1 induction and myotube formation, demonstrating the physiological relevance of this mechanism and the role of these two proteins in myogenesis. Our study demonstrates the cooperative function of hnRNPM and p54nrb as regulators of IRES-dependent translation and indicates the involvement of a promoter-dependent mechanism.

ACS Style

Nadera Ainaoui; Fransky Hantelys; Edith Renaud-Gabardos; Morgane Bunel; Frédéric Lopez; Françoise Pujol; Remi Planes; Elmostafa Bahraoui; Carole Pichereaux; Odile Schiltz; Angelo Parini; Barbara Garmy-Susini; Anne-Catherine Prats. Promoter-Dependent Translation Controlled by p54nrb and hnRNPM during Myoblast Differentiation. PLOS ONE 2015, 10, e0136466 .

AMA Style

Nadera Ainaoui, Fransky Hantelys, Edith Renaud-Gabardos, Morgane Bunel, Frédéric Lopez, Françoise Pujol, Remi Planes, Elmostafa Bahraoui, Carole Pichereaux, Odile Schiltz, Angelo Parini, Barbara Garmy-Susini, Anne-Catherine Prats. Promoter-Dependent Translation Controlled by p54nrb and hnRNPM during Myoblast Differentiation. PLOS ONE. 2015; 10 (9):e0136466.

Chicago/Turabian Style

Nadera Ainaoui; Fransky Hantelys; Edith Renaud-Gabardos; Morgane Bunel; Frédéric Lopez; Françoise Pujol; Remi Planes; Elmostafa Bahraoui; Carole Pichereaux; Odile Schiltz; Angelo Parini; Barbara Garmy-Susini; Anne-Catherine Prats. 2015. "Promoter-Dependent Translation Controlled by p54nrb and hnRNPM during Myoblast Differentiation." PLOS ONE 10, no. 9: e0136466.

Research article
Published: 19 June 2015 in PLOS ONE
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We recently reported that the human immunodeficiency virus type-1 (HIV-1) Tat protein induced the expression of programmed death ligand-1 (PD-L1) on dendritic cells (DCs) through a TLR4 pathway. However, the underlying mechanisms by which HIV-1 Tat protein induces the abnormal hyper-activation of the immune system seen in HIV-1 infected patients remain to be fully elucidated. In the present study, we report that HIV-1 Tat protein induced the production of significant amounts of the pro-inflammatory IL-6 and IL-8 cytokines by DCs and monocytes from both healthy and HIV-1 infected patients. Such production was abrogated in the presence of anti-TLR4 blocking antibodies or soluble recombinant TLR4-MD2 as a decoy receptor, suggesting TLR4 was recruited by Tat protein. Tat-induced murine IL-6 and CXCL1/KC a functional homologue of human IL-8 was abolished in peritoneal macrophages derived from TLR4 KO but not from Wt mice, confirming the involvement of the TLR4 pathway. Furthermore, the recruitment of TLR4-MD2-CD14 complex by Tat protein was demonstrated by the activation of TLR4 downstream pathways including NF-κB and SOCS-1 and by down-modulation of cell surface TLR4 by endocytosis in dynamin and lipid-raft-dependent manners. Collectively, these findings demonstrate, for the first time, that HIV-1 Tat interacts with TLR4-MD2-CD14 complex and activates the NF-κB pathway, leading to overproduction of IL-6 and IL-8 pro-inflammatory cytokines by myeloid cells from both healthy and HIV-1 infected patients. This study reveals a novel mechanism by which HIV-1, via its early expressed Tat protein, hijacks the TLR4 pathway, hence establishing abnormal hyper-activation of the immune system.

ACS Style

Nawal Ben Haij; Rémi Planès; Kaoutar Leghmari; Manutea Serrero; Pierre Delobel; Jacques Izopet; Lbachir Benmohamed; Elmostafa Bahraoui. HIV-1 Tat Protein Induces Production of Proinflammatory Cytokines by Human Dendritic Cells and Monocytes/Macrophages through Engagement of TLR4-MD2-CD14 Complex and Activation of NF-κB Pathway. PLOS ONE 2015, 10, e0129425 .

AMA Style

Nawal Ben Haij, Rémi Planès, Kaoutar Leghmari, Manutea Serrero, Pierre Delobel, Jacques Izopet, Lbachir Benmohamed, Elmostafa Bahraoui. HIV-1 Tat Protein Induces Production of Proinflammatory Cytokines by Human Dendritic Cells and Monocytes/Macrophages through Engagement of TLR4-MD2-CD14 Complex and Activation of NF-κB Pathway. PLOS ONE. 2015; 10 (6):e0129425.

Chicago/Turabian Style

Nawal Ben Haij; Rémi Planès; Kaoutar Leghmari; Manutea Serrero; Pierre Delobel; Jacques Izopet; Lbachir Benmohamed; Elmostafa Bahraoui. 2015. "HIV-1 Tat Protein Induces Production of Proinflammatory Cytokines by Human Dendritic Cells and Monocytes/Macrophages through Engagement of TLR4-MD2-CD14 Complex and Activation of NF-κB Pathway." PLOS ONE 10, no. 6: e0129425.

Short report
Published: 04 December 2014 in Virology Journal
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In HIV-1 infected patients, production of interleukin-10 (IL-10), a highly immunosuppressive cytokine, is associated with progression of infection toward AIDS. HIV-1 Tat protein, by interacting with TLR4-MD2 at the membrane level, induces IL-10 production by primary human monocytes and macrophages. In the present study we evaluated the effect of the TLR4 antagonist Eritoran tetrasodium (E5564) on HIV-1 Tat-induced IL-10 production. Here, we confirm that the recombinant HIV-1 Tat protein and the GST-Tat 1-45 fusion protein efficiently stimulate IL-10 production by primary monocytes and macrophages and that this stimulation is inhibited by blocking anti-TLR4 mAbs. We show that a similar inhibition is observed by preincubating the cells with the TLR4 antagonist E5564. This study provides compelling data showing for the first time that the TLR4 antagonist E5564 inhibits the immunosuppressive cytokine IL-10 production by primary human monocytes and macrophages incubated in the presence of HIV-1 Tat protein.

ACS Style

Elmostafa Bahraoui; Laurence Briant; Nathalie Chazal. E5564 inhibits immunosuppressive cytokine IL-10 induction promoted by HIV-1 Tat protein. Virology Journal 2014, 11, 214 .

AMA Style

Elmostafa Bahraoui, Laurence Briant, Nathalie Chazal. E5564 inhibits immunosuppressive cytokine IL-10 induction promoted by HIV-1 Tat protein. Virology Journal. 2014; 11 (1):214.

Chicago/Turabian Style

Elmostafa Bahraoui; Laurence Briant; Nathalie Chazal. 2014. "E5564 inhibits immunosuppressive cytokine IL-10 induction promoted by HIV-1 Tat protein." Virology Journal 11, no. 1: 214.

Journal article
Published: 15 June 2014 in Journal of Virology
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Chronic human immunodeficiency virus type 1 (HIV-1) infection is associated with induction of T-cell coinhibitory pathways. However, the mechanisms by which HIV-1 induces upregulation of coinhibitory molecules remain to be fully elucidated. The aim of the present study was to determine whether and how HIV-1 Tat protein, an immunosuppressive viral factor, induces the PD-1/PD-L1 coinhibitory pathway on human dendritic cells (DCs). We found that treatment of DCs with whole HIV-1 Tat protein significantly upregulated the level of expression of PD-L1. This PD-L1 upregulation was observed in monocyte-derived dendritic cells (MoDCs) obtained from either uninfected or HIV-1-infected patients as well as in primary myeloid DCs from HIV-negative donors. In contrast, no effect on the expression of PD-L2 or PD-1 molecules was detected. The induction of PD-L1 on MoDCs by HIV-1 Tat (i) occurred in dose- and time-dependent manners, (ii) was mediated by the N-terminal 1–45 fragment of Tat, (iii) did not require direct cell-cell contact but appeared rather to be mediated by soluble factor(s), (iv) was abrogated following neutralization of tumor necrosis factor alpha (TNF-α) or blocking of Toll-like receptor 4 (TLR4), (v) was absent in TLR4-knockoout (KO) mice but could be restored following incubation with Tat-conditioned medium from wild-type DCs, (vi) impaired the capacity of MoDCs to functionally stimulate T cells, and (vii) was not reversed functionally following PD-1/PD-L1 pathway blockade, suggesting the implication of other Tat-mediated coinhibitory pathways. Our results demonstrate that HIV-1 Tat protein upregulates PD-L1 expression on MoDCs through TNF-α- and TLR4-mediated mechanisms, functionally compromising the ability of DCs to stimulate T cells. The findings offer a novel potential molecular target for the development of an anti-HIV-1 treatment. IMPORTANCE The objective of this study was to investigate the effect of human immunodeficiency virus type 1 (HIV-1) Tat on the PD-1/PD-L1 coinhibitory pathway on human monocyte-derived dendritic cells (MoDCs). We found that treatment of MoDCs from either healthy or HIV-1-infected patients with HIV-1 Tat protein stimulated the expression of PD-L1. We demonstrate that this stimulation was mediated through an indirect mechanism, involving tumor necrosis factor alpha (TNF-α) and Toll-like receptor 4 (TLR4) pathways, and resulted in compromised ability of Tat-treated MoDCs to functionally stimulate T-cell proliferation.

ACS Style

Rémi Planès; Lbachir BenMohamed; Kaoutar Leghmari; Pierre Delobel; Jacques Izopet; Elmostafa Bahraoui. HIV-1 Tat Protein Induces PD-L1 (B7-H1) Expression on Dendritic Cells through Tumor Necrosis Factor Alpha- and Toll-Like Receptor 4-Mediated Mechanisms. Journal of Virology 2014, 88, 6672 -6689.

AMA Style

Rémi Planès, Lbachir BenMohamed, Kaoutar Leghmari, Pierre Delobel, Jacques Izopet, Elmostafa Bahraoui. HIV-1 Tat Protein Induces PD-L1 (B7-H1) Expression on Dendritic Cells through Tumor Necrosis Factor Alpha- and Toll-Like Receptor 4-Mediated Mechanisms. Journal of Virology. 2014; 88 (12):6672-6689.

Chicago/Turabian Style

Rémi Planès; Lbachir BenMohamed; Kaoutar Leghmari; Pierre Delobel; Jacques Izopet; Elmostafa Bahraoui. 2014. "HIV-1 Tat Protein Induces PD-L1 (B7-H1) Expression on Dendritic Cells through Tumor Necrosis Factor Alpha- and Toll-Like Receptor 4-Mediated Mechanisms." Journal of Virology 88, no. 12: 6672-6689.

Journal article
Published: 01 September 2013 in Retrovirology
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Rémi Planes; Elmostafa Bahraoui. HIV-1 Tat protein induces the production of IDO in human monocyte derived-dendritic cells through a direct mechanism: effect on T cells proliferation. Retrovirology 2013, 8, P113 -P113.

AMA Style

Rémi Planes, Elmostafa Bahraoui. HIV-1 Tat protein induces the production of IDO in human monocyte derived-dendritic cells through a direct mechanism: effect on T cells proliferation. Retrovirology. 2013; 8 (9):P113-P113.

Chicago/Turabian Style

Rémi Planes; Elmostafa Bahraoui. 2013. "HIV-1 Tat protein induces the production of IDO in human monocyte derived-dendritic cells through a direct mechanism: effect on T cells proliferation." Retrovirology 8, no. 9: P113-P113.

Journal article
Published: 01 January 2013 in Retrovirology
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HIV-1 infection results in hyper-immune activation and immunological disorders as early as the asymptomatic stage. Here, we hypothesized that during early HIV-1 infection, HIV-1 Tat protein acts on monocytes/macrophages to induce anti-inflammatory and proinflammatory cytokines and participates in immune dysregulation.

ACS Style

Nawal Ben Haij; Kaoutar Leghmari; Rémi Planès; Nathalie Thieblemont; Elmostafa Bahraoui. HIV-1 Tat protein binds to TLR4-MD2 and signals to induce TNF-α and IL-10. Retrovirology 2013, 10, 123 -123.

AMA Style

Nawal Ben Haij, Kaoutar Leghmari, Rémi Planès, Nathalie Thieblemont, Elmostafa Bahraoui. HIV-1 Tat protein binds to TLR4-MD2 and signals to induce TNF-α and IL-10. Retrovirology. 2013; 10 (1):123-123.

Chicago/Turabian Style

Nawal Ben Haij; Kaoutar Leghmari; Rémi Planès; Nathalie Thieblemont; Elmostafa Bahraoui. 2013. "HIV-1 Tat protein binds to TLR4-MD2 and signals to induce TNF-α and IL-10." Retrovirology 10, no. 1: 123-123.

Journal article
Published: 03 May 2012 in Retrovirology
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Macrophages, which are CD4 and CCR5 positive, can sustain HIV-1 replication for long periods of time. Thus, these cells play critical roles in the transmission, dissemination and persistence of viral infection. Of note, current antiviral therapies do not target macrophages efficiently. Previously, it was demonstrated that interactions between CCR5 and gp120 stimulate PKC. However, the PKC isozymes involved were not identified.

ACS Style

Xavier Contreras; Olfa Mzoughi; Fabrice Gaston; Matija B Peterlin; Elmostafa Bahraoui. Protein kinase C-delta regulates HIV-1 replication at an early post-entry step in macrophages. Retrovirology 2012, 9, 37 -37.

AMA Style

Xavier Contreras, Olfa Mzoughi, Fabrice Gaston, Matija B Peterlin, Elmostafa Bahraoui. Protein kinase C-delta regulates HIV-1 replication at an early post-entry step in macrophages. Retrovirology. 2012; 9 (1):37-37.

Chicago/Turabian Style

Xavier Contreras; Olfa Mzoughi; Fabrice Gaston; Matija B Peterlin; Elmostafa Bahraoui. 2012. "Protein kinase C-delta regulates HIV-1 replication at an early post-entry step in macrophages." Retrovirology 9, no. 1: 37-37.

Journal article
Published: 06 July 2011 in International Journal of Pharmaceutics
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The objective of this study was to test the immunogenicity of SIV Nef protein formulated in cationic nanoglycolipidic particles of 100nm of diameter. In parallel, the adjuvant effect of these nanoglycolipidic particles was compared in similar experiments using GST-Nef in association with the commonly strongest used complete Freund's adjuvant (CFA) or incomplete Freund's adjuvant in association with MDP or MDP alone. Our results showed that these particles do not alter the integrity of our immunogen GST-Nef, which remains stable for more than three months at 4°C. We demonstrated that in the presence of nanoglycolipidic particles antibodies against Nef were produced since the first injection and remained stable after the third injection with high titers for long lasting periods as observed with CFA and IFA/MDP adjuvant. The analysis of immunoglobulin isotype profiles of antibodies generated by the different protocols of immunization showed the preponderance of IgG1 isotypes suggesting the predominance of Th2-type immune response.

ACS Style

Nawal Ben Haij; Olfa Mzoughi; Rémi Planès; Elmostafa Bahraoui. Cationic nanoglycolipidic particles as vector and adjuvant for the study of the immunogenicity of SIV Nef protein. International Journal of Pharmaceutics 2011, 423, 116 -123.

AMA Style

Nawal Ben Haij, Olfa Mzoughi, Rémi Planès, Elmostafa Bahraoui. Cationic nanoglycolipidic particles as vector and adjuvant for the study of the immunogenicity of SIV Nef protein. International Journal of Pharmaceutics. 2011; 423 (1):116-123.

Chicago/Turabian Style

Nawal Ben Haij; Olfa Mzoughi; Rémi Planès; Elmostafa Bahraoui. 2011. "Cationic nanoglycolipidic particles as vector and adjuvant for the study of the immunogenicity of SIV Nef protein." International Journal of Pharmaceutics 423, no. 1: 116-123.

Journal article
Published: 04 October 2010 in ChemMedChem
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The objective of this project was to study the interaction between HR1 and HR2, the stability of the complex formed, and to characterize the antibodies produced against monomeric HR1 and HR2 peptides as well as the HR1–HR2 complex. In this work, HR1 was mimicked by peptide N36, and HR2 was mimicked by peptide C34L and its analogues C34M2, C34M3, and C34D. Whereas C34M2 and C34M3 are partially composed of D‐amino acids, C34D has same sequence as C34L, but is assembled entirely of D‐amino acids. Using CD analysis, SPR assays, and gel filtration chromatography, we demonstrate the physical interaction between N36 and C34L and its analogues C34M2 and C34M3, but not C34D. We show that the HR1–HR2 complex is formed rapidly (<1 min) and remains stable, as demonstrated by its inability, in contrast to each free peptide, to inhibit the formation of syncytia. To generate antibodies with predetermined specificity against the transiently exposed intermediate that corresponds to the six‐helix bundle structure, purified preformed HR1–HR2 complex was used, in parallel with monomeric HR1 and HR2 peptides, as immunogens in mice. Although the produced antibodies recognize total HIV‐1 envelope glycoproteins in ELISA, they are unable to neutralize HIV‐1‐mediated fusion at 37 °C. However, if the incubation with these antibodies is carried out at 27 °C, a temperature that allows stabilization of the transient intermediate complex, anti‐peptide antibodies are able to bind their corresponding domains in HeLa cells expressing HIV‐1 gp41 in co‐culture with HeLa CD4‐CCR5/CXCR4 during the dynamic mechanism of membrane fusion. In agreement with the latter results, these antibodies, if previously incubated for 2 h at 27 °C, are able to strongly neutralize HIV‐1 entry by membrane fusion, as shown by their ability to block the formation of syncytia.

ACS Style

Olfa Mzoughi; Fabrice Gaston; Giovana C. Granados; Faouzi Lakhdar-Ghazal; Ernest Giralt; Elmostafa Bahraoui. Fusion Intermediates of HIV-1 gp41 as Targets for Antibody Production: Design, Synthesis, and HR1-HR2 Complex Purification and Characterization of Generated Antibodies. ChemMedChem 2010, 5, 1907 -1918.

AMA Style

Olfa Mzoughi, Fabrice Gaston, Giovana C. Granados, Faouzi Lakhdar-Ghazal, Ernest Giralt, Elmostafa Bahraoui. Fusion Intermediates of HIV-1 gp41 as Targets for Antibody Production: Design, Synthesis, and HR1-HR2 Complex Purification and Characterization of Generated Antibodies. ChemMedChem. 2010; 5 (11):1907-1918.

Chicago/Turabian Style

Olfa Mzoughi; Fabrice Gaston; Giovana C. Granados; Faouzi Lakhdar-Ghazal; Ernest Giralt; Elmostafa Bahraoui. 2010. "Fusion Intermediates of HIV-1 gp41 as Targets for Antibody Production: Design, Synthesis, and HR1-HR2 Complex Purification and Characterization of Generated Antibodies." ChemMedChem 5, no. 11: 1907-1918.

Journal article
Published: 11 November 2009 in Journal of Peptide Science
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The objective of this study was to analyze the immunogenicity and antigenicity of the V3 domain (Cys313–Cys346) of the external envelope glycoprotein gp125 of SIVmac251. The corresponding peptide was synthesized and characterized as linear and cyclic peptides. Our results showed that this region, as for HIV‐1, contained an immunodominant epitope. The antigenicity was similar for the linear and cyclic peptides when tested against a panel of 15 sera from SIV infected macaques. Similarly, both peptide structures presented similar immunogenicity as shown by the characterization of the anti‐peptide antibodies produced in rabbits against the cyclic and linear forms. But, unexpectedly, the antibodies produced against linear peptides recognized with a relatively higher intensity the native envelope gp140 than those produced against the cyclic structure. Furthermore, we showed that these antibodies recognized better the deglycosylated form of the glycoprotein. But, in contrast to the neutralizing activity obtained with anti‐V3 peptides from HIV‐1, no antiviral activity was obtained with antibodies generated against linear or cyclic SIVmac V3 peptides. Copyright © 2009 European Peptide Society and John Wiley & Sons, Ltd.

ACS Style

Fabrice Gaston; Tahar Babas; Faouzi Lakhdar-Ghazal; Elmostafa Bahraoui. Structure-antigenicity of the V3 region of SIVmac envelope glycoprotein. Journal of Peptide Science 2009, 16, 48 -57.

AMA Style

Fabrice Gaston, Tahar Babas, Faouzi Lakhdar-Ghazal, Elmostafa Bahraoui. Structure-antigenicity of the V3 region of SIVmac envelope glycoprotein. Journal of Peptide Science. 2009; 16 (1):48-57.

Chicago/Turabian Style

Fabrice Gaston; Tahar Babas; Faouzi Lakhdar-Ghazal; Elmostafa Bahraoui. 2009. "Structure-antigenicity of the V3 region of SIVmac envelope glycoprotein." Journal of Peptide Science 16, no. 1: 48-57.

Journal article
Published: 17 April 2009 in ChemMedChem
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The aim of this study was to design synthetic peptides with D-amino acid substitutions that mimic the human immunodeficiency virus (HIV) gp41 HR2 region. The objective was to develop new and active C34 analogue peptides by introducing D-amino acid point substitutions at nonessential sites for HR1-HR2 interaction without disrupting the structure of the peptide. Herein we report a study with C34L peptide analogues, including the enantiomer peptide C34D, the retro-inverso analogue (RI), and two peptides with D-amino acid point substitutions (C34M2 and C34M3). Our results show that, with the exception of RI, these peptides adopt an alpha-helical structure and are, like C34L, able to interact with HR1, mimicked by the N36 peptide. Furthermore, we show that modifications introduced in C34M2, but not in C34M3, enhance its resistance to trypsin-mediated hydrolysis and increase the stability of C34M2 in physiological medium. Interestingly, our results show that C34 peptide analogues C34M2 and C34M3, but not C34D and its RI analogue, retain their ability to inhibit HIV-1 replication with an efficiency similar to that of the C34L peptide. These data underscore the interest in using D-amino acids at specific sites in the C34 peptide sequence and may lead to a new strategy for the development of more stable and active anti-HIV-1 peptidic drugs.

ACS Style

Fabrice Gaston; Giovana C. Granados; Sergio Madurga; Francesc Rabanal; Faouzi Lakhdar-Ghazal; Ernest Giralt; Elmostafa Bahraoui. Development and Characterization of Peptidic Fusion Inhibitors Derived from HIV-1 gp41 with Partial D-Amino Acid Substitutions. ChemMedChem 2009, 4, 570 -581.

AMA Style

Fabrice Gaston, Giovana C. Granados, Sergio Madurga, Francesc Rabanal, Faouzi Lakhdar-Ghazal, Ernest Giralt, Elmostafa Bahraoui. Development and Characterization of Peptidic Fusion Inhibitors Derived from HIV-1 gp41 with Partial D-Amino Acid Substitutions. ChemMedChem. 2009; 4 (4):570-581.

Chicago/Turabian Style

Fabrice Gaston; Giovana C. Granados; Sergio Madurga; Francesc Rabanal; Faouzi Lakhdar-Ghazal; Ernest Giralt; Elmostafa Bahraoui. 2009. "Development and Characterization of Peptidic Fusion Inhibitors Derived from HIV-1 gp41 with Partial D-Amino Acid Substitutions." ChemMedChem 4, no. 4: 570-581.

Journal article
Published: 12 January 2009 in International Journal of Peptide and Protein Research
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A region of the toxin II of the scorpion Androctonus australis Hector, possessing a loop structure, is shown to be antigenic. Some clear hints for the probable antigenic character of this region were obtained by the protruding properties of the loop region, as assessed by accessibility computations using atomic coordinates of the toxin and Lee-Richards algorithm. A synthetic replica of the loop region was obtained in a linear and cyclised form. Within the total anti-toxin antibody population, we have found and isolated those that recognize the model peptides. A high affinity binding of these specific antibodies to the parent toxin was demonstrated, affording experimental evidence for the antigenic properties of the loop region.

ACS Style

P. Fourquet; Elmostafa Bahraoui; J. Rietschoten; H. Rochat; C. Granier; J.C. Fontecilla-Camps. Immunochemistry of scorpion toxins Synthesis and antigenic properties of a model of a loop region specific to α-toxins. International Journal of Peptide and Protein Research 2009, 32, 81 -88.

AMA Style

P. Fourquet, Elmostafa Bahraoui, J. Rietschoten, H. Rochat, C. Granier, J.C. Fontecilla-Camps. Immunochemistry of scorpion toxins Synthesis and antigenic properties of a model of a loop region specific to α-toxins. International Journal of Peptide and Protein Research. 2009; 32 (2):81-88.

Chicago/Turabian Style

P. Fourquet; Elmostafa Bahraoui; J. Rietschoten; H. Rochat; C. Granier; J.C. Fontecilla-Camps. 2009. "Immunochemistry of scorpion toxins Synthesis and antigenic properties of a model of a loop region specific to α-toxins." International Journal of Peptide and Protein Research 32, no. 2: 81-88.