Comparative structural studies of bovine viral diarrhea virus IRES RNA

The internal ribosomal entry site (IRES) RNA of bovine viral diarrhea virus (BVDV) has been implicated in virus propagation. To gain insight into the structure and potential function of the BVDV IRES RNA, we collected and aligned 663 of its sequences. Compensatory Watson-Crick and wobble G·U pairs were investigated to establish phylogenetically supported secondary structures for each of the BVDV IRES RNA sequences. The extensively folded BVDV IRES RNAs were composed of helices 2, 3 and 4. Helix 2 consisted of five helical sections. Helix 3 contained sections 3a to 3j as well as six helical insertions 3.1-3.6. Sections 3a and 3b together with helices 3.6 and 4 formed an RNA pseudoknot. Two highly variable regions corresponded to hairpins 3j and 3.4. Three-dimensional modeling of the BVDV-1b strain Osloss IRES RNA predicted an elongated structure with approximate dimensions of 170 Å by 65 Å by 90 Å. The model of the IRES RNA-ribosome complex suggested proximity between helix 2 of the BVDV IRES and ribosomal proteins S5 and S25.

► We studied BVDV IRES RNA structure using sequence analysis and molecular modeling. ► 663 sequences were used to determine phylogenetically supported 2D and 3D models. ► Alternative pseudoknot base pairing was established. ► 3D model displays feasible orientations of helices 3.3 and 3.4 on the ribosome. ► The models will help in developing strategies for disrupting viral RNA translation.