A Distinct Class of Internal Ribosomal Entry Site in Members of the Kobuvirus and Proposed Salivirus and Paraturdivirus Genera of the Picornaviridae

Abstract

The 5=-untranslated regions (5= UTRs) of picornavirus genomes contain an internal ribosomal entry site (IRES) that promotes the end-independent initiation of translation. Picornavirus IRESs are classified into four structurally distinct groups, each with different initiation factor requirements. Here, we identify a fifth IRES class in members of Kobuvirus, Salivirus, and Paraturdivirus genera of Picornaviridae: Aichi virus (AV), bovine kobuvirus (BKV), canine kobuvirus (CKoV), mouse kobuvirus (MKoV), sheep kobuvirus (SKV), salivirus A (SV-A), turdivirus 2 (TV2), and TV3. The 410-nucleotide (nt)-long AV IRES comprises four domains (I to L), including a hairpin (L) that overlaps a Yn-Xm-AUG (pyrimidine tract/spacer/initiation codon) motif. SV-A, CKoV, and MKoV also contain these four domains, whereas BKV, SKV, and TV2/TV3 5= UTRs contain domains that are related to domain I and equivalent to domains J and K but lack an AV-like domain L. These IRESs are located at different relative positions between a conserved 5=-terminal origin of replication and divergent coding sequences. Elements in these IRESs also occur elsewhere: domain J's apical subdomain, which contains a GNRA tetraloop, matches an element in type 1 IRESs, and eIF4G-binding motifs in domain K and in type 2 IRESs are identical. Other elements are unique, and their presence leads to unique initiation factor requirements. In vitro reconstitution experiments showed that like AV, but in contrast to other currently characterized IRESs, SV-A requires the DExH-box protein DHX29 during initiation, which likely ensures that the initiation codon sequestered in domain L is properly accommodated in the ribosomal mRNA-binding cleft.

Modification of the internal ribosome entry site element impairs the growth of foot-and-mouth disease virus in porcine-derived cells

“…These IRES elements are classified into five types based on sequence and structural homology: type I IRES of the enterovirus group with poliovirus as prototype, type II IRES of the cardiovirus/aphthovirus group with encephalomyocarditis virus (EMCV) and FMDV as prototypes type III IRES of hepatitis A virus (HAV), and type IV IRES of porcine teschovirus (PTV) (Borman et al, 1997;Brown et al, 1991;Jackson et al, 1994;Pisarev et al, 2004). Sweeney et al (2012) and colleagues recently identified a fifth IRES class among members of the Kobuvirus, Salivirus and Oscivirus genera. The nucleotide sequence identity among IRES elements of the same type is only moderate, but their predicted secondary structure is highly conserved.…”

Picornavirus IRES elements: RNA structure and host protein interactions

“…These elements are cis-acting RNA regulatory sequences endowed with the capacity to govern cap-independent translation initiation in mRNAs that are translated when cap-dependent translation is compromised. Subsequent studies demonstrated that IRES elements drive internal initiation of translation in the RNA of all members of the Picornaviridae family (Bakhshesh et al, 2008;Borman and Jackson, 1992;Brown et al, 1991;Hinton and Crabb, 2001;Hinton et al, 2000;Kaku et al, 2002;Kuhn et al, 1990;Nateri et al, 2000;Sweeney et al, 2012;Willcocks et al, 2011;Yu et al, 2011b). The genome of other RNA viruses also contains IRES elements, as illustrated by hepacivirus, pestivirus, dicistrovirus, retrovirus Tsukiyama-Kohara et al, 1992;Vallejos et al, 2010;Wilson et al, 2000), as well as some RNA viruses infecting plants and protozoa (reviewed in Martinez-Salas et al, 2012).…”

RNA–protein interaction methods to study viral IRES elements

“…These elements are diverse in primary sequence and secondary RNA structure, being classified into five different types [16]. Functionally related picornavirus IRESs harbor a common RNA structure core and sequence motifs maintained by evolutionary conserved covariant substitutions [17].…”