Biochemistry and function of nidovirus replicase proteins

Abstract

The order Nidovirales comprises a monophyletic group of viruses with positive-stranded RNA genomes that are classified in the families Arteriviridae, Coronaviridae, Mesoniviridae, and Roniviridae. They share a conserved genome organization and a characteristic set of key replicative proteins. Although, in principle, this suggests a conserved replication mechanism, it is currently unclear how far exactly the resemblance extends on a more detailed level. This is foremost due to our poor understanding of the role of most viral proteins in the replication cycle. In addition, most of the knowledge that was obtained predominantly derives from studies of only few coronaviruses, the nidovirus subgroup with the largest known genome and therefore presumably employing the most complex replication strategy. In contrast, thus far only limited attention was given to the RNA rep_licating and processing enzymes of arteriviruses, and none at all to those of mesoni- and roniviruses, whose genome sizes are (much) smaller than those of coronaviruses. The work described in this thesis addresses some poorly or uncharacterized (domains of ) nonstructural proteins (nsps) that are likely involved in one or multiple steps of RNA replication and/or transcription of the prototypic arterivirus equine arteritis virus (EAV).