Exploration of plant virus replication inside a surrogate host, Saccharomyces cerevisiae, elucidates complex and conserved mechanisms

Plant RNA viruses are intracellular infectious agents with limited coding capacity. Therefore, these viruses have developed sophisticated ways to co-opt numerous cellular factors to facilitate the viral infectious cycle. To understand virus-host interactions, it is necessary to identify all the host components that are co-opted for viral infections. Development of yeast (Saccharomyces cerevisiae) as a host greatly facilitated the progress in our understanding of plant virus, such as brome mosaic virus (BMV) and tomato bushy stunt virus (TBSV), interactions with the host cells. Systematic genome-wide screens using yeast genomic libraries have led to the identification of a large number of host factors affecting (+)RNA virus replication. In combination with proteomic approaches, both susceptibility and restriction factors for BMV and TBSV have been identified using yeast. More detailed biochemical and cellular studies then led to the dissection of molecular functions of many host factors that promote each step of the viral replication process. The development of in vitro systems with TBSV, such as yeast cell-free extract and purified active replicase assays, together with proteomics, lipidomics and artificial vesicle-based assays helped to comprehend the complex nature of virus replication. Subsequently, comparable pro- or antiviral functions of several of the characterized yeast host factors have been validated in plant hosts. Overall, yeast is an advanced model organism that has emerged as an attractive host to gain insights into the intricate interactions of plant viruses with host cells. This chapter describes our current understanding of virus-host interactions, based mostly on TBSV-yeast system. Many of the pioneering findings with TBSV are likely applicable to other plant and animal viruses and their interactions with their hosts. The gained knowledge on host factors could lead to novel specific or broad-range antiviral tools against viruses.