RNA Structure Duplications and Flavivirus Host Adaptation

Flaviviruses include a highly diverse group of arboviruses with a global distribution and a high human disease burden. Most flaviviruses cycle between insects and vertebrate hosts; thus, they are obligated to use different cellular machinery for their replication and mount different mechanisms to evade specific antiviral responses. In addition to coding for viral proteins, the viral genome contains signals in RNA structures that govern the amplification of viral components and participate in triggering or evading antiviral responses. In this review, we focused on new information about host-specific functions of RNA structures present in the 3′ untranslated region (3′ UTR) of flavivirus genomes. Models and conservation patterns of RNA elements of distinct flavivirus ecological groups are revised. An intriguing feature of the 3′ UTR of insect-borne flavivirus genomes is the conservation of complex RNA structure duplications. Here, we discuss new hypotheses of how these RNA elements specialize for replication in vertebrate and invertebrate hosts, and present new ideas associating the significance of RNA structure duplication, small subgenomic flavivirus RNA formation, and host adaptation.

TrendsRecent advances in molecular virology provide new hypotheses of how RNA structures in mosquito-borne flavivirus genomes mediate host adaptation, viral replication, and evasion of antiviral responses.Dengue virus RNA structures play different functions during infection in vertebrate and invertebrate hosts.Conflicting requirements of viral RNA elements shape the composition of viral populations obtained in human or mosquito cells.Viral RNA structures can modulate the type and extent of host antiviral responses.Complex RNA structures present at the viral 3′ untranslated region (3′ UTR) that stall the host exoribonuclease XRN1 and generate small virus-derived RNAs are duplicated in mosquito-borne flaviviruses.Conservation of RNA structure duplication in the 3′ UTR of insect-borne viruses is associated with mechanisms of host adaptation.