Dissemination of Internal Ribosomal Entry Sites (IRES) Between Viruses by Horizontal Gene Transfer

Abstract

Members of Picornaviridae and of the Hepacivirus, Pegivirus and Pestivirus genera of Flaviviridae all contain an internal ribosomal entry site (IRES) in the 5′-untranslated region (5′UTR) of their genomes. Each class of IRES has a conserved structure and promotes 5′-end-independent initiation of translation by a different mechanism. Picornavirus 5′UTRs, including the IRES, evolve independently of other parts of the genome and can move between genomes, most commonly by intratypic recombination. We review accumulating evidence that IRESs are genetic entities that can also move between members of different genera and even between families. Type IV IRESs, first identified in the Hepacivirus genus, have subsequently been identified in over 25 genera of Picornaviridae, juxtaposed against diverse coding sequences. In several genera, members have either type IV IRES or an IRES of type I, II or III. Similarly, in the genus Pegivirus, members contain either a type IV IRES or an unrelated type; both classes of IRES also occur in members of the genus Hepacivirus. IRESs utilize different mechanisms, have different factor requirements and contain determinants of viral growth, pathogenesis and cell type specificity. Their dissemination between viruses by horizontal gene transfer has unexpectedly emerged as an important facet of viral evolution.

Non-Canonical Translation Initiation Mechanisms Employed by Eukaryotic Viral mRNAs

“…In addition to Flaviviridae, HCV-like IRESs have been also found in some groups of Picornaviridae (see review by Arhab et al [ 59 ] for details), which confirms the existence of horizontal transfer of not only genes but also of individual regulatory elements of viral RNA.…”

“…At the base of domain VI is an oligopyrimidine tract (Y n ) containing the conserved UUUCC sequence. Other representatives of this type of IRESs – such as those present in the gRNA of enterovirus A71 (enterovirus EV-A71), Coxsackievirus type B (Coxsackievirus B3, CVB3), and human rhinovirus A (human rhinovirus A2, HRV A2) – have a similar structure (for details, see reviews [ 56 , 59 , 80 ]).…”

“…Another group of IRESs that do not fall into the above classification are “chimeric” IRESs found in some picornaviruses. In terms of domain organization, they are similar to types I and II; however, some domains in their composition are more similar to the corresponding regions of the type I IRESs, while others to domains of the type II elements [ 59 ]. Among the representatives of Flaviviridae, there are also viruses carrying IRESs of the picornavirus type with poorly characterized structure [ 59 ].…”

Resurrection of a viral internal ribosome entry site from a 700 year old ancient Northwest Territories cripavirus

“…IGR IRESs likely evolved through recombination of independent functional domains; the PKI domains can be functionally swapped between Type I and II IRESs (21,22). Furthermore, IRES elements in unrelated viruses appear to have disseminated between these viruses via horizontal gene transfer (38), further supporting the idea that dicistrovirus IGR IRESs may have originated via recombination events.…”

Resurrection of a Viral Internal Ribosome Entry Site from a 700 Year Old Ancient Northwest Territories Cripavirus

“…IGR IRESs are likely to have evolved through recombination of independent functional domains; the PKI domains can be functionally swapped between Type I and II IRESs [20,21]. Furthermore, IRES elements in unrelated viruses appear to have disseminated between these viruses via horizontal gene transfer [43], further supporting the idea that dicistrovirus IGR IRESs may have originated via recombination events.…”