Monique van Oers
Gorben Pijlman; Jelke Fros
+31 (0) 6 81212433
The recent rather impetuous developments of this modern world the past decades invites more viruses to (re-)emerge in the future; and mosquito-borne viruses (MBVs) are no exception to that. The still intensifying intercontinental travel and trade together with climate change expand the mosquito habitat and affect virus-mosquito interactions; hence fueling the endemic potential of many (yet unknown) MBVs. The main aim of this project is to understand molecular determinants required for a virus to infect vertebrates and to use this knowledge to protect humans and animals from pathogenic MBV infections.
MBVs have adapted to replicate in two evolutionary very distant hosts: the vertebrate and invertebrate host. In vertebrates an underrepresentation of CpG and UpA dinucleotides is observed, whereas invertebrates only suppress UpA. Interestingly viruses seem to mimic the dinucleotide content of their host: vertebrate infecting MBVs suppress both CpG and UpA, and insect-specific viruses UpA dinucleotides. Synonymously increasing the CpG content in vertebrate infecting MBVs attenuates the virus in vertebrate cells; viral fitness was restored again when interfering with the expression of the host’s antiviral proteins. Thus lowering the CpG content is an attempt of viruses to escape its vertebrate host’s antiviral pathways. Opposing to what was found in vertebrates, CpG-high mutants reached higher viral titers compared to wild type virus in invertebrate cells. A high CpG content seems a genomic feature restricting insect-specific viruses from replicating in vertebrates.
In this project we aim to understand the molecular features and mechanisms that restrict insect-specific viruses from being transmitted to the vertebrate host and eventually incorporate these features into the genome of vertebrate infecting MBVs. We hypothesize that this approach will reduce the MBV’s replication rate in humans and vertebrate animals, resulting in a strategy to create next-generation vaccines that is applicable to a much wider range of viruses.
Research questions / objectives