Deciphering the RBPome in mosquitoes during virus infection

Projektbeschreibung

Entschlüsselung der Rolle der Ribonukleinsäure-bindenden Proteine bei Stechmücken

Winzige sechsbeinige Kreaturen, die Stechmücken, sind eine Gefahr für die Gesundheit des Menschen, da sie die wirkungsvollsten Krankheitsüberträger des gesamten Tierreichs sind. Unter diesen sind die Mücken der Gattung Aedes am tödlichsten, da sie Viren wie Zika, Denguefieber, Chikungunya und Gelbfieber übertragen. Jahrzehntelang wurden Insektizide zur Bekämpfung von Stechmückenpopopulationen eingesetzt, aber die Stechmücken haben ihr Talent zur Entwicklung von Resistenzen unter Beweis gestellt. Das EU-finanzierte Projekt DRmov wird die Ribonukleinsäure-bindenden Proteine (RBP) der Stechmücken untersuchen. Die Ribonukleinsäure-bindenden Proteine, die am zellulären und viralen Stoffwechsel der Ribonukleinsäure (RNA) beteiligt sind, gelten als ideale Ziele für antivirale Therapien. Das Projekt schlägt vor, das Kompendium der RNA-bindenden Proteine von Stechmücken (RBPome) mittels RNA-Interactome Capture (RNA-IC) zu profilieren.

Ziel

The impact of mosquito-borne diseases has expanded dramatically in the last few decades to become an emerging global health problem, with around 1 billion new infections and 1 million deaths each year. In Europe there are more than 20 countries with established populations of invasive Aedes mosquitoes. Aedes mosquitoes are the principle vectors responsible for transmitting high-risk pathogens such as ZIKA virus (ZIKV), dengue (DENV), yellow fever virus (YFV), chikungunya virus (CHKV) and Venezuelan equine encephalitic virus (VEEV). Despite our vulnerabilities to mosquito-borne diseases, virus replication dynamics is still poorly understood especially in the invertebrate vectors. No treatment against these viruses targeting essential viral proteins are currently available. Thus, the World Health Organisation (WHO) and its Vector Control Advisory Group has urged for insect vector control. Vector control is usually performed through insecticides; however, resistance can emerge in mosquitoes leading to persistence of the disease. Therefore, virologists are turning their interests toward host factors that play essential roles in infection as novel antiviral targets, since they can potentially exhibit broad-spectrum efficacy. In particular, scientists envision that genetically modified mosquitoes with disrupted genes required for infection can be re-inserted into natural habitats or through targeting these genes by RNAi in order to control viral spread. As all mosquito-borne viruses have RNA genome, cellular RNA-binding proteins (RBPs) emerge as ideal targets for antiviral therapies, as they are key players in cellular and viral RNA metabolism . Thus, we propose here to profile comprehensively the compendium of mosquito RBPs (RBPome) using RNA-interactome capture (RNA-IC). Furthermore, we will apply different cutting-edge methods to identify the role of mosquito RBPs during virus infection.