The translational landscape of Zika virus during infection of mammalian and insect cells

Nerea Irigoyen; Adam M. Dinan; Luke W. Meredith; Ian Goodfellow; Ian Brierley; Andrew E. Firth

The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. It . https://doi.org/10.1101/112904 doi: bioRxiv preprint 3 Like other flaviviruses, ZIKV possesses a positive-sense, single-stranded RNA genome (gRNA) of 51 ~11 kb, which contains a long open reading frame (ORF) flanked by 5′ and 3′ "untranslated" 52 regions (UTRs) of approximately 100 and 400 nucleotides, respectively (Fig. 1A) . The ORF 53 encodes a polyprotein which is cleaved by host and viral proteases to yield three structural proteins 54 located in the N-terminal region (capsid -C, precursor/membrane -Pr/M, and envelope -E) and 55 seven non-structural proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B, NS5) (6). Consequently, 56 these proteins are expected to be produced in equimolar amounts during infection, although the 57 former set are presumed to be required in higher quantities for the production of progeny virus 58 particles (7). Indeed, in the flavivirus lineage that includes West Nile virus, efficient ribosomal 59 frameshifting in the NS2A region diverts up to 50% of translating ribosomes into an overlapping 60 ORF, resulting in a substantial reduction in synthesis of the 3′-encoded replicative proteins relative 61 to the 5′-encoded structural proteins (8). A similar phenomenon is also seen in a group of insect-62 specific flaviviruses (9). 63 64