Horizontal gene transfer as a mechanism for the promiscuous acquisition of distinct classes of IRES by avian caliciviruses

Abstract

In contrast to members of Picornaviridae which have long 5′-untranslated regions (5′UTRs) containing internal ribosomal entry sites (IRESs) that form five distinct classes, members of Caliciviridae typically have short 5′UTRs and initiation of translation on them is mediated by interaction of the viral 5′-terminal genome-linked protein (VPg) with subunits of eIF4F rather than by an IRES. The recent description of calicivirus genomes with 500–900nt long 5′UTRs was therefore unexpected and prompted us to examine them in detail. Sequence analysis and structural modelling of the atypically long 5′UTRs of Caliciviridae sp. isolate yc-13 and six other caliciviruses suggested that they contain picornavirus-like type 2 IRESs, whereas ruddy turnstone calicivirus (RTCV) and Caliciviridae sp. isolate hwf182cal1 calicivirus contain type 4 and type 5 IRESs, respectively. The suggestion that initiation on RTCV mRNA occurs by the type 4 IRES mechanism was confirmed experimentally using in vitro reconstitution. The high sequence identity between identified calicivirus IRESs and specific picornavirus IRESs suggests a common evolutionary origin. These calicivirus IRESs occur in a single phylogenetic branch of Caliciviridae and were likely acquired by horizontal gene transfer.

A novel calicivirus discovered in trumpeter swans (Cygnus buccinator) expands the richness of known avian caliciviruses

“…A 5′ UTR that is hundreds of nucleotides long can be found in caliciviruses of birds ( Arhab et al., 2022 ) while the 5′ UTRs of non-avian viruses are typically much shorter ( Alhatlani et al., 2015 ). Interestingly, as also observed for several other avian caliciviruses ( Arhab et al., 2022 ), the 5′UTR of the identified virus could be folded into a type 2 IRES ( Fig. 1 ), although the apical part of domain J was slightly different from what was predicted for other viruses.…”

“…The putative AUG start codon is included in a box and nucleotides are numbered according to the sequence deposited in GenBank under accession number OP271827. The model was built in mFold using annotations from ( Arhab et al., 2022 ). …”

“…Motif search and genome annotations were performed with Geneious R11 (Biomatters). The internal ribosomal entry site (IRES) prediction was performed by aligning the 5′UTR sequence of the identified virus to those of other caliciviruses and mFold ( Zuker, 2003 ) was used to build the model using what was predicted by Arhab et al. (2022 ) as template.…”

Ribosomal control in RNA virus-infected cells

“…Notably, viral IRES elements are expressed in heterologous viral genomes in hosts with mixed infectious viruses (Arhab et al, 2020). In the case of avian calicivirus and picornavirus co-infection, the 5'-UTR of avian calicivirus was found to contain a conformation consistent with the 5'-UTR secondary structure of picornavirus (IRES type V) (Arhab et al, 2022). These discoveries of IRES structure may be due to genetic recombination with other viruses and reflects the importance of analyzing the interaction of the ribosome with the viral RNA genome to resolve the mechanism of viral protein synthesis.…”

“…Each ORF encoded by the virus has unique IRES structure ( Roberts and Groppelli, 2009 ; Kerr et al, 2015 ; Gross et al, 2017 ). However, many other IRES structures are challenging to categorize because of their diversity, such as IRES structures in SARS-CoV-2, alphavirus, infectious pancreatic necrosis virus (IPNV), drosophila C virus (DCV), dengue fever virus (DENV), and calicivirus ( Kamrud et al, 2007 ; Landry et al, 2009 ; Rivas-Aravena et al, 2017 ; Fernandez-Garcia et al, 2020 ; Arhab et al, 2022 ; Slobodin et al, 2022 ). Notably, viral IRES elements are expressed in heterologous viral genomes in hosts with mixed infectious viruses ( Arhab et al, 2020 ).…”