Saccharomyces cerevisiae: a useful model host to study fundamental biology of viral replication

Abstract

Understanding the fundamental steps of virus life cycles including virus-host interactions is essential for the design of effective antiviral strategies. Such understanding has been deferred by the complexity of higher eukaryotic host organisms. To circumvent experimental difficulties associated with this, systems were developed to replicate viruses in the yeast Saccharomyces cerevisiae. The systems include viruses with RNA and DNA genomes that infect plants, animals and humans. By using the powerful methodologies available for yeast genetic analysis, fundamental processes occurring during virus replication have been brought to light. Here, we review the different viruses able to direct replication and gene expression in yeast and discuss their main contributions in the understanding of virus biology.

Fig. 1

(A) Schematic illustration of common features of positive-strand RNA virus replication in yeast. The viral RNA-dependent RNA polymerase (RdRp) and the auxiliary protein (if required) are expressed from mRNA transcripts derived from two yeast plasmids by using inducible GAL1 or constitutive ADH1 yeast promoters. The expression of the two mRNA transcripts will generate the viral replicase. The replicative RNA is normally transcribed from a plasmid by using the inducible GAL1 promoter and contains a ribozyme sequence to generate authentic 3′ ends. In some of the systems, the replicative RNA can also include a reporter gene, which expression is dependent on viral RNA replication. All yeast plasmids carry a selectable marker to allow stable expression. (B) Schematic illustration of common features of DNA virus replication in yeast. The full length circular DNA genomes are linked in cis to a selectable yeast marker gene. Alternatively, for BPV-1, the incubation of yeast protoplast with virions is enough to obtain viral replication and production of infectious BPV-1 particles. P, yeasts promoter; A_n, poly(A) signal; Rz, self-cleaving ribozyme; YSM, yeast selectable marker.