Sethi Meher, VanInsberghe David, Mainou Bernardo A, Lowen Anice C
Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA, USA.
Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA.
bioRxiv. 2025 Jul 3:2025.07.03.662980. doi: 10.1101/2025.07.03.662980.
Viral spread is classically thought to be mediated by single viral particles. However, viruses often disseminate in groups - as aggregates, inside membranous vesicles, or as clusters associated with bacterial components or other complex surfaces. The implications of collective dispersal for viral infectivity and evolution remain incompletely defined. Here, we used mammalian orthoreovirus to evaluate the impact of aggregation on the propagation of infection and the generation of viral diversity through reassortment. Aggregation of free virions was induced by manipulating pH and ionic conditions. This treatment promoted coordinated delivery of viruses to cells, increasing the number of virions per infected cell and number of virions per occupied endosome at early times of infection. Likely due to a consolidation of infectious units, aggregation concomitantly reduced the overall infectivity of the viral population and progeny virus yields. When viral populations comprised two genetically distinct viruses, aggregation increased the frequency of mixed infection and of genetic exchange through reassortment. Thus, the formation of collective infectious units lowers the replicative potential of mammalian orthoreovirus populations but increases viral evolutionary potential by promoting genetic diversification.
传统观点认为病毒传播是由单个病毒粒子介导的。然而，病毒通常以群体形式传播——如聚集体、在膜泡内、或作为与细菌成分或其他复杂表面相关的簇。集体传播对病毒感染性和进化的影响仍未完全明确。在这里，我们使用哺乳动物正呼肠孤病毒来评估聚集对感染传播以及通过重配产生病毒多样性的影响。通过调节pH值和离子条件诱导游离病毒粒子聚集。这种处理促进了病毒向细胞的协同递送，在感染早期增加了每个感染细胞的病毒粒子数量以及每个被占据的内体中的病毒粒子数量。可能由于感染单位的聚集，聚集同时降低了病毒群体的总体感染性和子代病毒产量。当病毒群体包含两种基因不同的病毒时，聚集增加了混合感染的频率以及通过重配进行基因交换的频率。因此，集体感染单位的形成降低了哺乳动物正呼肠孤病毒群体的复制潜力，但通过促进基因多样化增加了病毒的进化潜力。
