Current research classifies Zika virus (ZIKV) strains into the ancestral African and contemporary Asian lineages, with the latter found to be responsible for the recent epidemics associated with neurological conditions. The authors were interested in how these Asian strains lead to exacerbated disease in order to identify genomic variations that affect infectivity and pathogenicity. They used two sequencing approaches to assess RNA secondary structures and intramolecular RNA-RNA interactions in vivo for the RNA genomes of Asian and African ZIKV lineages. The authors were able to identify functional RNA structural elements and a functional long-range intramolecular interaction specific for the Asian epidemic strains. Mutations that disrupt this extended RNA interaction between the 5′ UTR and the E protein coding region were found to reduce virus infectivity and this could be partially rescued with compensatory mutants, restoring the RNA-RNA interaction. Therefore this appears to be the structural basis of ZIKV regulation, providing a resource for the discovery of RNA structural elements important for ZIKV infection.
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