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A glycomimetic compound inhibits DC-SIGN mediated HIV infection in cellular and cervical explant models


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dc.creator Berzi, Angela es
dc.creator Reina, José J. es
dc.creator Ottria, Roberta es
dc.creator Sutkeviciute, Ieva es
dc.creator Antonazzo, Patrizio es
dc.creator Sánchez Navarro, Macarena es
dc.creator Chabrol, Eric es
dc.creator Biasini, M. es
dc.creator Trabattoni, Daria es
dc.creator Cetin, Irene es
dc.creator Rojo Marcos, Francisco Javier es
dc.creator Fieschi, Franck es
dc.creator Bernardi, Anna es
dc.creator Clerici, Mario es 2018-10-18T15:57:02Z 2018-10-18T15:57:02Z 2012
dc.identifier.citation Berzi, A., Reina, J.J., Ottria, R., Sutkeviciute, I., Antonazzo, P., Sánchez Navarro, M.,...,Clerici, M. (2012). A glycomimetic compound inhibits DC-SIGN mediated HIV infection in cellular and cervical explant models. AIDS, 26 (2), 127-137.
dc.identifier.issn 0269-9370 (impreso) es
dc.identifier.issn 1473-5571(electrónico) es
dc.description.abstract Objective: Dendritic cell-specific intercellular adhesion molecule (ICAM)-3 grabbing nonintegrin (DC-SIGN) participates in the initial stages of sexually transmitted HIV-1 infection by recognizing highly mannosylated structures presented in multiple copies on HIV-1 gp120 and promoting virus dissemination. Inhibition of HIV interaction with DC-SIGN thus represents a potential therapeutic approach for viral entry inhibition at the mucosal level. Design: Herein we evaluate the efficacy in inhibiting HIV-1 infection and the potential toxicity of a multimeric glycomimetic DC-SIGN ligand (Dendron 12). Methods: The ability of Dendron 12 to block HIV-1 infection was assessed in cellular and human cervical explant models. Selectivity of Dendron 12 towards DC-SIGN and langerin was evaluated by surface plasmon resonance studies. β chemokine production following stimulation with Dendron 12 was also analyzed. Toxicity of the compound was evaluated in cellular and tissue models. Results: Dendron 12 averted HIV-1 trans infection of CD4+ T lymphocytes in presence of elevated viral loads and prevented HIV-1 infection of human cervical tissues, under conditions mimicking compromised epithelial integrity, by multiple clades of R5 and X4 tropic viruses. Treatment with Dendron 12 did not interfere with the activity of langerin and also significantly elicited the production of the β chemokines MIP-1α, MIP-1β and RANTES. Conclusion: Dendron 12 thus inhibits HIV-1 infection by competition with binding of HIV to DC-SIGN and stimulation of β-chemokine production. Dendron 12 represents a promising lead compound for the development of anti-HIV topical microbicides. es
dc.description.sponsorship EU programme EVA B-THP-1, B-THP-1/DC-SIGN cells, HIV-1 BaL,DU174 es
dc.description.sponsorship FIRB CHEM-PROFARMANET (RBPR05NWWC) es
dc.description.sponsorship Istituto Superiore di Sanità ‘Programma Nazionale di Ricerca sull’AIDS’, EMPRO, AVIP EC WP6, the nGIN EC WP7 es
dc.description.sponsorship Ministeria de Ciencia e Innovación CTQ2008-01694/BQU, European FP7 project: EU ITN CARMUSYS (PITN-GA-2008-213592) es
dc.format application/pdf es
dc.language.iso eng es
dc.publisher Lippincott, Williams & Wilkins es
dc.relation.ispartof AIDS, 26 (2), 127-137.
dc.rights Attribution-NonCommercial-NoDerivatives 4.0 Internacional *
dc.rights.uri *
dc.title A glycomimetic compound inhibits DC-SIGN mediated HIV infection in cellular and cervical explant models es
dc.type info:eu-repo/semantics/article es
dc.type.version info:eu-repo/semantics/acceptedVersion es
dc.rights.accessrights info:eu-repo/semantics/openAccess es
dc.relation.projectID B-THP-1 es
dc.relation.projectID B-THP-1/DC-SIGN cells es
dc.relation.projectID HIV-1 BaL es
dc.relation.projectID DU174 es
dc.relation.projectID RBPR05NWWC es
dc.relation.projectID AVIP EC WP6 es
dc.relation.projectID nGIN EC WP7 es
dc.relation.projectID CTQ2008-01694/BQU es
dc.relation.projectID PITN-GA-2008-213592 es
dc.relation.publisherversion es
dc.identifier.doi 10.1097/QAD.0b013e32834e1567 es
idus.format.extent 20 es
dc.journaltitle AIDS es
dc.publication.volumen 26 es
dc.publication.issue 2 es
dc.publication.initialPage 127 es
dc.publication.endPage 137 es
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