Project Details
Description
Mosquitoes are potent transmitters of disease-causing viruses. Mosquito-borne viruses (MBVs) switch replication between mosquitoes and vertebrate hosts, two evolutionary distant organisms that both try to identify and eliminate viral infections. The genomes of MBVs resemble the genetic code of vertebrate hosts, which provides camouflage and helps evade detection by vertebrate immune responses. In contrast to the situation in vertebrates, MBV genomes markedly deviate from the genetic code of mosquitoes. I recently provided the first experimental evidence that mosquito-borne Zika virus (ZIKV) consequently replicates suboptimally in mosquitoes. Viral replication was strongly enhanced when the genome of ZIKV was artificially modified to resemble the genetic code of mosquitoes (mosquito-optimized). This indicates that in mosquitoes, the replication of natural (poorly camouflaged) MBVs is restricted via as yet undefined mechanisms. By studying the underlying molecular mechanisms in mosquitoes I aim to unravel how MBVs balance their replication between vertebrate hosts and mosquitoes.
Modified viruses (mosquito-optimized/deoptimized) of phylogenetically distinct MBVs will be generated to reveal generic mechanisms applicable to a wide variety of important viral pathogens and mosquito vector species. First, I will determine the evolutionary pressures encountered by MBVs in vertebrate host and mosquito cells. Next, I will analyse whether mosquito populations retain and transmit (modified) viruses and whether infections with those viruses affect mosquito fitness and protect against secondary infections with pathogenic virus isolates. Crucially, I will investigate how mosquito cells detect viral genomes by identifying cellular components that specifically interact with viral RNA. The expected findings will yield fundamental and mechanistic insights into the arms race between virus and mosquito, extending our knowledge on virus evolution and invertebrate immunity against viruses. This information will strengthen the design of viruses with a host/mosquito-specific replicative phenotype and spark novel ways of intervening in MBV transmission cycles to improve human and animal health.
Modified viruses (mosquito-optimized/deoptimized) of phylogenetically distinct MBVs will be generated to reveal generic mechanisms applicable to a wide variety of important viral pathogens and mosquito vector species. First, I will determine the evolutionary pressures encountered by MBVs in vertebrate host and mosquito cells. Next, I will analyse whether mosquito populations retain and transmit (modified) viruses and whether infections with those viruses affect mosquito fitness and protect against secondary infections with pathogenic virus isolates. Crucially, I will investigate how mosquito cells detect viral genomes by identifying cellular components that specifically interact with viral RNA. The expected findings will yield fundamental and mechanistic insights into the arms race between virus and mosquito, extending our knowledge on virus evolution and invertebrate immunity against viruses. This information will strengthen the design of viruses with a host/mosquito-specific replicative phenotype and spark novel ways of intervening in MBV transmission cycles to improve human and animal health.
Status | Active |
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Effective start/end date | 1/01/23 → … |
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