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Pornapat  SURASOMBATPATTANA (unité MIVEGEC-UMR 224) soutiendra sa thèse le jeudi 12 décembre 2013, à 14h, dans l’amphithéâtre des plantes (centre IRD / Montpellier), devant le jury composé de :


Directeur de Recherches                                     INSERM, Montpellier          Dr. Jean-Luc BATTINI         Président

Directeur de Recherches                                     INSERM, Paris                    Dr. Hans YSSEL                 Rapporteur

Directeur de Recherches                                     Institut Pasteur, Paris          Dr. Philippe DESPRES       Rapporteur

Maître de conférences                                         UM1                                    Dr. Nathalie CHAZAL          Examinateur

Chargé de recherche                                           INSERM, Paris                    Dr. Ali AMARA                     Examinateur

Praticien Hospitalier                                            CHU, Nice                           Dr. Pascal DELAUNAY        Examinateur

Chargé de recherche                                           IRD, Montpellier                  Dr. Dorothée MISSE           Directrice de thèse

 

Transmission du virus de la dengue: rôle de la salive d’Aedes aegypti

 

 

ABSTRACT

Dengue virus (DENV) transmission is initiated when a blood-feeding Aedes (Ae) aegypti mosquito injects saliva, together with the virus, into the epidermis of its mammalian host. Studies of DENV should, therefore, take into account the triad virus-vector-vertebrate host. We have used functional genomic and proteomic analyses, of the salivary glands of female Ae. Aegypti, to demonstrate that this compartment harbors a potent immune response against DENV, represented by the production of an antimicrobial peptide (AMP). This AMP was found to exert, in addition to its anti-bacterial activity, an anti-viral activity against DENV and Chikungunya. Our data demonstrate, for the first time, the permissiveness of human epidermal keratinocytes to DENV infection. Remarkably, DENV replication in keratinocytes contributes to the establishment of anti-viral innate immunity that might occur shortly after the mosquito bite. To investigate the role of Ae. aegypti saliva in DENV transmission to man, primary human keratinocytes were infected with DENV in the presence of Ae. aegypti salivary gland extract. We show that Ae. aegypti saliva enhances dengue virus infection of human keratinocytes by suppressing innate immune responses. Furthermore, we have found a 34-kDa protein, in the saliva of Ae.aegypti, that strongly enhances DENV replication by suppressing type-I IFN production. This study provides new insights into the role of Ae. aegypti salivary glands and saliva in DENV transmission. The data presented here provide novel targets for the control of DENV replication in mammalian hosts.

 

Key words: Aedes aegypti, dengue, saliva proteins, keratinocytes, innate immune, 34kDa, antimicrobial peptides.