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Dynamics of the RNAi-mediated antiviral immunity

Final Report Summary - RNAIMMUNITY (Dynamics of the RNAi-mediated antiviral immunity)

The immunology of insects receives much research interest due to their ability to act as vectors to viral pathogens that impact human, animal and plant health. The insect immune response comprises both resistance and tolerance mechanisms. More than simply limiting pathogen replication, insects also cope with infection by reducing disease severity. Within the last decade, our work has parsed the complex dynamics of insect antiviral immune response with its multitude of defence mechanisms and variation across populations and species. We demonstrated that RNA interference (RNAi) is a nucleic acid-based immune system in insects and that insect tolerance of viruses relies on the establishment and maintenance of persistent infections through a mechanism involving RNAi and transposons. From there, we undertook an ambitious project to develop novel vector control strategies by modulating mosquito tolerance to viral infections. Through this work we were the first to show that it is possible to selectively eliminate only virus-infected mosquitoes by blocking the establishment of tolerance. We have not only deciphered the genetic and molecular basis of the RNAi immune mechanism but went further to understand its amplification and systemic spread throughout the insect, and the unexpected manifestation of "memory" within a fundamentally innate process. We have brought together a unique team who can make major contributions towards redefining host-pathogen biology and bring new perspectives on the transmission of (re)emergent viral diseases by insect vectors.