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

Abstract

Viruses are often regarded as obligate intracellular parasites that exploit host resources for their own propagation. However, emerging evidence suggests that virus-host interactions can be more complex than simple antagonism. Here, we performed a genome-wide screen in Saccharomyces cerevisiae to identify host factors required for the maintenance of the L-A double-stranded RNA virus, a persistent and non-lytic resident of most laboratory yeast strains. Using two complementary mutant collections encompassing [~]6,000 yeast genes ([~]93% genome coverage), we identified 96 host genes essential for L-A maintenance, spanning diverse biological functions. Transcriptome profiling revealed that the presence of L-A virus alters the host stress-response gene expression program. Strikingly, competitive fitness assays under environmental stress conditions showed that L-A enhances host stress tolerance, revealing a previously unrecognized mutualistic relationship. Together, our findings redefine the L-A-yeast interaction as a form of stable mutualism and highlight the utility of functional genomics and systems-level approaches in uncovering hidden dimensions of virus-host coevolution. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=71 SRC="FIGDIR/small/655038v1_ufig1.gif" ALT="Figure 1"> View larger version (27K): org.highwire.dtl.DTLVardef@4bfa69org.highwire.dtl.DTLVardef@25205forg.highwire.dtl.DTLVardef@1703f19org.highwire.dtl.DTLVardef@3e9375_HPS_FORMAT_FIGEXP M_FIG C_FIG