Identification and characterization of NS5-interacting factors involved in anti-flaviviral response in Aedes mosquito

• Applicant: Professorin Dr. Esther Schnettler
• Subject Area: Virology ; Cell Biology
• Term: since 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 500072465

Mosquito-borne flaviviruses include many of the most prevalent viral scourges known to humanity, such as dengue virus (DENV). DENV exists as four closely related but antigenically distinct serotypes (DENV-1, -2, -3, and -4), all of which have Aedes aegypti mosquitoes as their primary vector. Like DENV, ZIKV is also mainly transmitted by Ae. aegypti and is often endemic in the same area than DENV. Field studies and laboratory infections clearly showed that Ae. aegypti mosquito is highly permissive to coinfection with DENV and ZIKV. While DENV and ZIKV infections are often asymptomatic or elicit mild flu-like symptoms; some infected people develop strong pathogenicity, like severe bleeding, organ impairment and/or plasma leakage in case of DENV or birth defects, known as congenital Zika syndrome, and even death of infected fetus in case of ZIKV. Despite this great burden, vaccines and specific antivirals remain elusive. Very little is known at the moment about the interaction and importance of mosquito proteins during DENV or ZIKV infection (either single or co-infection). The overall aim of the collaborative project is to identify mosquito proteins interacting with DENV-2 NS5 protein, for the first time, during natural virus infection, their importance for DENV-2 in single or coinfection with ZIKV and the extrapolation to other DENV serotypes. Therefore, we use a recently created DENV expressing a tagged version of NS5, which is essential due to the lack of antibodies. Understanding the interaction of DENV NS5 and mosquito proteins and its importance for successful infection of the vector could identify valuable targets for novel intervention strategies. Besides it could give information about factors affecting vector competence (ability of a mosquito to successfully transmit a certain virus) in single and coinfection and thereby helps to predict future outbreaks.Each of the institutions and collaborators provide an inherent expertise in a specific field important for the proposed project. Thereby, combining these expertise will yield a unique functional connection and thereby result in findings that would be not possible for each of the applicant by themselves.

• DFG Programme: Research Grants
• International Connection: Thailand
• Partner Organisation: National Science and Technology Development Agency (NSTDA); National Innovation Agency; Program Management Unit for Human Resources ; and Institutional Development
• Cooperation Partner: Dr. Sarin Chimnaronk