The dinucleotide composition of the Zika virus genome is shaped by conflicting evolutionary pressures in mammalian hosts and mosquito vectors

• DOI: 10.1371/journal.pbio.3001201
• Publication Date: 2021-04-19T21:36:15Z
• Authors: Jelke J. Fros; Imke Visser; Bing Tang; Kexin Yan; Eri Nakayama; Tessa M. Visser; Constantianus J. ...; Monique M. van Oers; Gorben P. Pijlman; Andreas Suhrbier; Peter Simmonds
• Keywords: CpG site; Antiviral protein; Zika Virus

Most vertebrate RNA viruses show pervasive suppression of CpG and UpA dinucleotides, closely resembling the dinucleotide composition host cell transcriptomes. In contrast, is absent in both invertebrate mRNA that exclusively infect arthropods. Arthropod-borne (arbo) are transmitted between hosts by vectors thus encounter potentially conflicting evolutionary pressures different cytoplasmic environments. Using a newly developed Zika virus (ZIKV) model, we have investigated how demands for cells can be reconciled with quite compositional requirements invertebrates this affects ZIKV replication transmission. Mutant synonymously elevated or frequencies showed attenuated lines, which was rescued knockout zinc-finger antiviral protein (ZAP). Conversely, mosquito cells, mutants substantially enhanced compared to wild type. Host-driven effects on attenuation enhancement were even more apparent mouse models. Infections CpG- UpA-high mice did not cause typical ZIKV-induced tissue damage completely protected during subsequent challenge wild-type virus, demonstrates their potential as live-attenuated vaccines. CpG-high displayed Aedes aegypti mosquitoes larger proportion carried infectious saliva. These findings also capable discriminating based composition. However, pressure dinucleotides viral genomes arthropod directly opposes present provides evidence an adaptive compromise required arbovirus This suggests genome arbo flaviviruses crucial maintain balance high-level persistent vector.