Distinct roles for the IIId2 sub-domain in pestivirus and picornavirus Internal Ribosome Entry Sites
2017
Viral internal ribosomes entry site (IRES) elements coordinate the recruitment of the host translation
machinery to direct the initiation of viral protein synthesis. Within hepatitis C virus (HCV)-like IRES
elements, the sub-domain IIId(1) is crucial for recruiting the 40S ribosomal subunit. However, some
HCV-like IRES elements possess an additional sub-domain, termed IIId2, whose function remains
unclear. Herein we show that IIId2 sub-domains from divergent viruses have different functions. The
IIId2 sub-domain present in Seneca valley virus (SVV), a picornavirus, is dispensable for IRES activity,
while the IIId2 sub-domains of two pestiviruses, classical swine fever virus (CSFV) and border
disease virus (BDV), are required for 80S ribosomes assembly and IRES activity. Unlike in SVV, the
deletion of IIId2 from the CSFV and BDV IRES elements impairs initiation of translation by inhibiting
the assembly of 80S ribosomes. Consequently, this negatively affects the replication of CSFV and
BDV. Finally, we show that the SVV IIId2 sub-domain is required for efficient viral RNA synthesis and
growth of SVV, but not for IRES function. This study sheds light on the molecular evolution of viruses
by clearly demonstrating that conserved RNA structures, within distantly related RNA viruses, have
acquired different roles in the virus life cycles.
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