How yeast can be used as a genetic platform to explore virus–host interactions: from ‘omics’ to functional studies

• Several RNA viruses of plants and animals can replicate in yeast cells.
• Systematic genome-wide screens of yeast genes are powerful tools for identifying host factors.
• Global proteomics screens in yeast strengthen the datasets from genomics screens.
• Functional studies in yeast can lead to novel insights into virus–host interactions.

The yeast Saccharomyces cerevisiae is an advanced model organism that has emerged as an effective host to gain insights into the intricate interactions of viruses with host cells. RNA viruses have limited coding potential and need to coopt numerous host cellular factors to facilitate their replication. To identify the host factors subverted by viruses, high-throughput genomics and global proteomics approaches have been performed with plant viruses such as brome mosaic virus (BMV) and tomato bushy stunt virus (TBSV). Accordingly, several hundred susceptibility and restriction factors for BMV and TBSV have been identified using yeast as a model host. Amazingly, host factors affecting viral genetic recombination and evolution have also been identified in genome-wide screens in yeast. The roles of many yeast host factors involved in various steps of the viral replication process have been validated by exploiting the orthologous genes in plant hosts. This Opinion summarizes the advantages of using simple viruses and yeast model host to advance our general understanding of virus–host interactions. The knowledge gained on host factors could lead to novel specific or broad-range resistance and antiviral tools against viruses.