Diverse innate immune factors protect yeast from lethal viral pathogenesis

In recent years, newly characterized antiviral systems have been found to be remarkably conserved from bacteria to mammals, revealing the potential to gain unique insight into these systems through the study of microbial organisms[1][1]. Despite the enthusiasm generated by these findings, the key microbial model organism Saccharomyces cerevisiae (budding yeast) has been minimally exploited for studies of viral defense, primarily because it is not infected with exogenously transmitted viruses. However, most yeast strains are infected with an endogenous double stranded RNA (dsRNA) virus called L-A, and previous studies have identified conserved antiviral systems that attenuate L-A replication[2][2]. Although these systems do not lead to eradication of L-A, we show here that they collaboratively prevent massive over-proliferation of L-A that leads to proteostatic stress and lethality. Exploiting this new insight, we asked if the powerful genetic screening methods available in yeast could be used to identify additional conserved antiviral systems. Validating this approach, we discovered antiviral functions for the yeast homologs of polyA-binding protein (PABPC1) and the La-domain containing protein Larp1, which are both involved in viral innate immunity in humans[3][3],[4][4]. We also identify new antiviral functions for the RNA exonucleases REX2 and MYG1 , both of which have distinct but poorly characterized human and bacterial homologs[5][5]–[8][6]. These findings highlight the potential of yeast as a powerful model system for studies of the ubiquitous host-virus arms race. ### Competing Interest Statement The authors have declared no competing interest. [1]: #ref-1 [2]: #ref-2 [3]: #ref-3 [4]: #ref-4 [5]: #ref-5 [6]: #ref-8