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Explaining Flavivirus Congenital Neurotropism with Thermodynamics



Flaviviruses represent a global health threat and are responsible for millions of infections in humans every year. During the 2015-2017 outbreak of Zika virus (ZIKV) in the Americas accumulation of congenital microcephaly cases was observed, which has been associated with ZIKV infection. However, the underlying biological mechanisms remain elusive. Recently, experimental studies showed that the host protein Musashi-1 (Msi1) mediates ZIKV replication. Msi1, which is expressed in neuronal progenitor cells and tumors, typically binds single-standed UAG motifs in the 3'UTR of RNA. Here we employ a biophysical model of RNA structure formation to show that UAGs within ZIKV 3'UTRs are highly accessible and therefore represent optimal Msi1 binding targets. More generally, the theoretical approach presented here allows to predict the Msi-mediated teratogenic potential of related arboviruses.
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