Potential of Ilhéus virus to emerge

Ilhéus virus (ILHV)(Flaviviridae:Orthoflavivirus) is an arthropod-borne virus (arbovirus) endemic to Central and South America and the Caribbean. First isolated in 1944, most of our knowledge derives from surveillance and seroprevalence studies. These efforts have detected ILHV in a broad range of mosquito and vertebrate species, including humans, but laboratory investigations of pathogenesis and vector competence have been lacking. Here, we develop an immune intact murine model with several ages and routes of administration. Our model closely recapitulates human neuroinvasive disease with ILHV strain- and mouse age-specific virulence, as well as a uniformly lethal Ifnar−/− A129 immunocompromised model. Replication kinetics in several vertebrate and invertebrate cell lines demonstrate that ILHV is capable of replicating to high titers in a wide variety of potential host and vector species. Lastly, vector competence studies provide strong evidence for efficient infection of and potential transmission by Aedes species mosquitoes, despite ILHV's phylogenetically clustering with Culex vectored flaviviruses, suggesting ILHV is poised for emergence in the neotropics. •In vitro and in vivo characterization of Ilhéus virus (ILHV).•Cell lines from a wide range of species are permissive to infection.•Uniform lethality with high viremia in Ifnar−/− A129 mice.•Strain-, route-, and age-dependent lethality and neuroinvasion in CD-1 mice.•Aedes spp. mosquitoes more susceptible than Culex spp. mosquitoes to ILHV infection.