Genome-wide screen uncovers novel host factors for L-A virus maintenance and a mutualistic-symbiosis relationship in yeast

Background: Viruses are traditionally viewed as intracellular parasites that exploit host resources to propagate, often at the host’s expense. However, emerging evidence suggests more nuanced interactions, including potential mutualism. The L-A double-stranded RNA (dsRNA) virus, a non-lytic, cytoplasmic virus commonly found in Saccharomyces cerevisiae , presents an intriguing case, as it lacks clear pathogenic effects in the absence of its M1 satellite. Results: To address how and why L-A persistently resides in its yeast host, we conducted a genome-wide screen using yeast deletion and temperature-sensitive mutant collections, covering approximately 93% of annotated genes, to identify host factors essential for L-A maintenance. This screen revealed 96 genes spanning diverse biological processes. Transcriptomic profiling indicated that L-A presence alters the host stress-response gene expression. Furthermore, competitive fitness assays under stress conditions demonstrated that L-A can enhance host resilience, suggesting a mutualistic relationship. Conclusion: Our findings uncover a previously unrecognized virus-host mutualism, wherein L-A benefits its host under environmental stress. These results not only expand our understanding of persistent viral infections in eukaryotes but also challenge the canonical view of viruses as purely parasitic, offering new insights into virus-host co-evolution and endogenous viral persistence.