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Identification and Characterization of RNA/protein complexes involving untranslated region of the genome of Dengue and Zika viruses

Contacts: Eric Ennifar, Isabelle Lebars

Collaborators: Joao Marques (Federal University of Minas Gerais, Brazil & CNRS UPR 9022 IBMC), Karim Majzoub (IGMM Montpellier, CNRS UMR 5535)

Zika (ZIKV) and Dengue (DENV) are mosquito-borne viruses belonging to the Flaviviridae family. With an estimated 390 million new infections every year, DENV is considered by the World Health Organization to be the most critical mosquito-borne viral disease worldwide. Regarding ZIKV, it was a relatively obscure pathogen until 2007, when it started causing outbreaks in Pacific islands and later in the Americas, with a massive outbreak in Brazil in 2015-2016. Currently, no efficient treatments or vaccines are available against these viruses. Considering that DENV and ZIKV circulate in both vertebrate and invertebrate hosts, targeting specific steps of viral replication would be an efficient strategy to block viral transmission and disease spread. The development of new specific antiviral strategies against ZIKV and DENV requires a precise understanding of key steps of the viral lifecycle. RNA viruses often harbor, within their genomes, multifunctional non-coding structured regions. The 5’ and 3’ untranslated regions (UTR) in the genomes of DENV and ZIKV are very conserved and have important functions during viral replication.

Viral genome organization

RNA-protein interactions play a crucial role in the viral replication cycle and for hijacking host cell machinery. In order to develop new antiviral strategies, our aims are to : (i) decipher RNA-protein interactions involved in DENV and ZIKV replication cycle and (ii) identify and characterize mosquito factors interacting with the RNA genome of these viruses. For that purpose, we use an integrated biophysical approach including Isothermal microcalorimetry (ITC), electro switchable DNA nanolevers on biochips using the switchSENSE biosensor technology, UV-visible spectrometry, Mass Spectrometry (MS), Electron Paramagnetic Resonance (EPR, in collaboration), CryoElectron Microscopy (CryoEM), Nuclear Magnetic Resonance (NMR) and X-ray Crystallography.