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

Abstract

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.