APPLICATION OF GENOME SEQUENCE INFORMATION TO THE CLASSIFICATION OF BOVINE ENTEROVIRUSES - THE IMPORTANCE OF 5'-NONTRANSLATED AND 3'-NONTRANSLATED REGIONS

Comparative genomics of viruses in evolutionary and phylogenetic studi es is well established. Previous nucleic acid sequence analyses have d emonstrated that enteroviruses and rhinoviruses of the family Picornav iridae exhibit a similar structure of the 5'-nontranslated region (NTR ) differing significantly from the 5'-NTR of cardiovirus, aphthovirus, hepatovirus, and echovirus 22 (provisionally parechovirus 1). Availab le nucleotide sequence information of the 5'-and 3'-nontranslated regi ons of more than 70 serotypes of enteroviruses, bovine enteroviruses a nd rhinoviruses has been compared and correlated with previous finding s obtained after analysis of the coding and noncoding genome regions. As a result, the 5'-and 3'-NTRs of all three virus groups are characte rized by group-specific nucleotide sequences. Focusing on bovine enter ovirus (BEV) serotypes, unique characteristics in all secondary struct ures of the NTRs were observed. These features clearly separate the BE Vs from the human enteroviruses and rhinoviruses. Concerning the 5'-NT R, the most remarkable property is an insertion of about 110 nucleotid es between the putative cloverleaf structure at the very 5'-end of the viral genome and the IRES element. This insertion was demonstrated fo r BEV 1 and 2 and has a predicted folding pattern which is very simila r to the 5'-cloverleaf structure. One stem-loop of this second cloverl eaf is almost identical to the 3CD(pro)-binding domain of rhinoviral 5 '-cloverleafs. It was also demonstrated that the IRES elements and the 3'-NTRs of both, enteroviruses and rhinoviruses, have group-specific features which differ significantly from the corresponding genome regi ons of BEV. These results suggest that bovine enteroviruses hold an ex ceptional taxonomic position besides the established genera Enteroviru s and Rhinovirus. Within the Enterovirus and Rhinovirus genera, the ex istence of virus clusters representing subgenera was previously propos ed. Whereas the 5'-NTRs of the four human enterovirus clusters fall in to two groups, all four clusters have characteristic secondary structu res at the 3'-NTR supporting the concept of enterovirus clusters. For rhinoviruses, the existence of two virus clusters was confirmed. (C) 1 997 Elsevier Science B.V.