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.研究背景：传统观点将病毒视为利用宿主资源进行增殖、且常以牺牲宿主利益为代价的胞内寄生物。然而，新兴研究证据表明二者间存在更为复杂的相互作用，包括潜在的互利共生关系。L-A双链RNA（double-stranded RNA, dsRNA）病毒是一类非裂解性细胞质病毒，常见于酿酒酵母（Saccharomyces cerevisiae）中；在缺乏其M1卫星病毒的情况下，该病毒未表现出明确的致病效应，这是一个极具研究价值的案例。 研究结果：为探究L-A病毒如何以及为何能在酿酒酵母宿主中长期存续，我们利用酵母基因敲除与温度敏感突变体库开展了全基因组筛选，覆盖约93%的已注释基因，以鉴定维持L-A病毒存活所必需的宿主因子。本次筛选共发现96个涉及多种生物学过程的基因。转录组分析显示，L-A病毒的存在会改变宿主应激反应相关基因的表达模式。此外，在应激条件下开展的竞争适应性实验表明，L-A病毒可增强宿主的抗逆能力，这提示二者间存在互利共生关系。 研究结论：本研究揭示了此前未被认知的病毒-宿主互利共生关系：L-A病毒可在环境胁迫条件下为宿主提供生存益处。该研究不仅拓展了学界对真核生物持续性病毒感染的认知，同时挑战了“病毒仅为纯粹寄生物”的经典观点，为病毒-宿主共进化以及内源性病毒持续存续的机制提供了全新的研究视角。