Interactions of the Zika virus 3’ UTR with Host Cellular Proteins

Flaviviruses are causative agents of mosquito-borne diseases in humans. Among these, Zika virus (ZIKV) possesses the unique ability to cross the placenta and cause neurological damage in the developing brain of the fetus. This infection results in a condition called microcephaly, the shrinking of an unborn child’s head due to improper brain development spurred by the infection of undifferentiated brain cells. The untranslated regions (UTRs) of the ZIKV ssRNA genome play an important regulatory role in productive infections. The UTRs adopt complex RNA structures that protect the viral genome from host nucleases and interfere with antiviral cellular responses. The precise mechanisms by which the virus halts cellular antiviral responses is unclear. To understand these virus-host interactions, we are developing a biochemical approach to identify interactions between ZIKV 3’ UTR and host proteins. To this end, we express recombinant ZIKV 3’ UTR RNAs, which we biotinylate and use as “baits” in an RNA-pulldown assay aimed at identifying interacting proteins by mass spectrometry. This approach has the potential to identify proteins important for ZIKV infection. Ultimately, our observations will allow the identification of proteins with the potential to be drug targets to curb ZIKV infection.