An adaptive compromise - Conflicting evolutionary pressures on arthropod borne Zika virus dinucleotide composition in mammalian hosts and mosquito vectors

摘要: 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 wildtype. 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 wildtype 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 arthropod-borne flaviviruses crucial maintain balance high-level persistent vector.