Distinct roles for the IIId2 sub-domain in pestivirus and picornavirus internal ribosome entry sites

Margaret M. Willcocks, Salmah Zaini, Nathalie Chamond, Nathalie Ulryck, Delphine Allouche, Noemie Rajagopalan, Nana A Davids, Ulrik Fahn E, Johanne Hadsbjerg, Thomas Bruun Rasmussen, Lisa O. Roberts, Bruno Sargueil, Graham J Belsham, Nicolas Locker

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    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.
    Original languageEnglish
    Article numbergkx991
    JournalNucleic acids research
    Number of pages13
    Publication statusPublished - 2017

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    This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

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    Willcocks, M. M., Zaini, S., Chamond, N., Ulryck, N., Allouche, D., Rajagopalan, N., Davids, N. A., Fahn E, U., Hadsbjerg, J., Rasmussen, T. B., Roberts, L. O., Sargueil, B., Belsham, G. J., & Locker, N. (2017). Distinct roles for the IIId2 sub-domain in pestivirus and picornavirus internal ribosome entry sites. Nucleic acids research, 2017, [gkx991]. https://doi.org/10.1093/nar/gkx991