Viruses depend on their host cell for the production of their progeny. The genetic information that is required to regulate this process is contained in the viral genome. In the case of plus-stranded RNA viruses, like nidoviruses, the RNA genome is directly involved in translation (resulting in the synthesis of viral enzymes), replication, transcription and encapsidation into progeny virions. The multifunctional nature of these viral RNA genomes requires the tight control of all these processes for which they are equipped with RNA sequence motifs and higher order RNA structures. At 25-32 kilobases, nidoviruses possess the largest known RNA genomes. One characteristic of nidoviruses is that in infected cells they produce a nested set of subgenomic (sg) mRNAs. The sg mRNAs of two nidovirus families, arteri- and coronaviruses, consist of two RNA stretches that are noncontiguous in the genome. It was demonstrated that primary and higher order RNA structures play a crucial role during the synthesis of these special sg mRNAs. The obtained knowledge of arterivirus RNA synthesis, formed the basis for an virus inhibitor study in which regulatory RNA sequences were targeted in an attempt to block virus replication in cell culture using phosphorodiamidate morpholino oligomers (P-PMOs).Leiden University Medical HospitalNWO-CW 99-010Moleculaire basis van virus pathogenese en antivirale strategiee
