Alphaviruses are globally distributed, vector-borne RNA viruses with high outbreak potential and no clinical interventions, posing a significant global health threat. Previously, the production and packaging of both viral capped and noncapped genomic RNAs (cgRNA and ncgRNA) during infection was reported. Studies have linked ncgRNA production to viral infectivity and pathogenesis, but its precise role remains unclear. To define the benefits of ncgRNAs, pure populations of capped and noncapped Sindbis virus (SINV) gRNAs were synthesized and transfected into host cells. The data showed that mixtures of cgRNAs and ncgRNAs had higher infectivity compared to pure cgRNAs, with mixtures containing low cgRNA proportions exceeding linear infectivity expectations. This enhancement depended on co-delivery of cgRNAs and ncgRNAs to the same cell and required the noncapped RNAs to be viral in origin. Contrary to the initial hypothesis that the ncgRNAs serve as replication templates, the cgRNAs were preferentially replicated. Further analysis revealed that viral gene expression, viral RNA (vRNA) synthesis and particle production were enhanced in the presence of ncgRNAs, which function to promote cgRNA translation early in infection. Our findings highlight the importance of ncgRNAs in alphaviral infection, showing they enhance cgRNA functions and significantly contribute to viral infectivity.

中文翻译：

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Sindbis 病毒感染的机制见解：非加帽基因组 RNA 增强加帽基因组 RNA 的翻译以促进病毒感染性


甲病毒是分布于全球的载体传播 RNA 病毒，具有很高的爆发可能性，且无需临床干预，对全球健康构成重大威胁。以前，据报道，在感染过程中病毒加帽和非加帽基因组 RNA（cgRNA 和 ncgRNA）的生产和包装。研究将 ncgRNA 的产生与病毒感染性和发病机制联系起来，但其确切作用尚不清楚。为了确定 ncgRNA 的优势，合成加帽和非加帽 Sindbis 病毒 （SINV） gRNA 的纯种群并将其转染到宿主细胞中。数据显示，与纯 cgRNA 相比，cgRNA 和 ncgRNA 的混合物具有更高的传染性，含有低 cgRNA 比例的混合物超过了线性传染性预期。这种增强依赖于 cgRNA 和 ncgRNA 共同递送到同一细胞，并且要求未加帽的 RNA 起源于病毒。与 ncgRNA 作为复制模板的最初假设相反，cgRNA 被优先复制。进一步分析表明，在 ncgRNA 存在下，病毒基因表达、病毒 RNA （vRNA） 合成和颗粒产生增强，其功能是在感染早期促进 cgRNA 翻译。我们的研究结果强调了 ncgRNA 在 α 病毒感染中的重要性，表明它们增强了 cgRNA 功能并显着促进了病毒感染。