Project Details
Projekt
Induction and Suppression of antiviral RNAi pathways by mosquito-specific and mosquito-borne viruses
Applicants
Professorin Dr. Sandra Junglen; Dr. Ronald van Rij
Subject Area
Virology
Term
from 2013 to 2020
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 226337221
Background. Nearly one-fourth of emerging infectious diseases in humans is vector-borne and causes some of the most debilitating human diseases. Arthropod-borne viruses (arboviruses) are naturally maintained in an enzootic (sylvatic) cycle in which virus is transmitted during blood-feeding between arthropod vectors and amplifying vertebrate hosts. Human infections can be caused by spill-over infections or due to viral adaptation to new mosquito species and to human hosts. Especially flaviviruses are prone to escape their natural transmission cycles and to adapt to urban cycles where direct human-to-human transmission via mosquitoes occurs. For example, Dengue virus and Yellow fever virus emerged from enzootic cycles that involved non-human primates and forest-dwelling mosquitoes to epidemic cycles using the anthropophilic mosquitoes Aedes albopictus and Aedes aegypti as vectors and humans as amplifying hosts. With the increasing global spread of arboviruses, it is important to understand the factors that affect virus transmission by mosquitoes and to predict the potential of arboviruses to emerge into epidemic cycles. Previous research and preliminary observations. We and others have previously shown that RNA interference (RNAi) is an important antiviral defense mechanism in insects, including the major vector mosquito Aedes aegypti, and that RNAi plays a critical role in vector competence. More recently, we demonstrated that a related small RNA-based mechanism, the Piwi-associated RNA pathway, is also able to recognize and process arbovirus RNA in mosquitoes. Furthermore, we demonstrated that insect RNA viruses, including viruses with a tropism for mosquitoes, frequently suppress RNAi. Aim, approach and objectives. The overall aim of this project is to understand the role of antiviral RNAi and piRNA responses and viral counter-defense in establishing vector competence in mosquitoes. We will compare the induction and suppression of RNAi among representatives of the genus Flavivirus (Flaviviridae family) that differ in their mode of transmission, vector tropism, and sylvatic or epidemic origin. Specifically, we will i) profile viral small RNAs in different mosquito vectors; ii) compare RNAi suppressive activity among flaviviruses that differ in their vector competence; iii) elucidate the mechanism of the identified viral suppressors of RNAi. Importance. Arboviruses are an important group of human and animal pathogens and their emergence and re-emergence requires thorough understanding of vector transmission. This proposal will have a major impact on our understanding of vector competence. Furthermore, our results will contribute to our ability to predict the ability of arboviruses to cross the species barrier and the potential of known and novel sylvatic arboviruses to transfer into epidemic amplification cycles.
DFG Programme
Priority Programmes
International Connection
Netherlands
