Institute for Integrative Systems Biology (I2SysBio), Consejo Superior de Investigaciones Científicas-Universitat de València, C/ Catedrático Agustín Escardino 9, 46980, Paterna, València, Spain.
Institute for Integrative Systems Biology (I2SysBio), Consejo Superior de Investigaciones Científicas-Universitat de València, C/ Catedrático Agustín Escardino 9, 46980, Paterna, València, Spain.
Virus Res. 2019 Jul 2;267:41-48. doi: 10.1016/j.virusres.2019.05.005. Epub 2019 May 8.
Viruses can spread collectively using different types of structures such as extracellular vesicles, virion aggregates, polyploid capsids, occlusion bodies, and even cells that accumulate virions at their surface, such as bacteria and dendritic cells. Despite the mounting evidence for collective spread, its implications for viral fitness and diversity remain poorly understood. It has been postulated that, by increasing the cellular multiplicity of infection, collective spread could enable mutually beneficial interactions among different viral genetic variants. One such interaction is genetic complementation, whereby deleterious mutations carried by different genomes are compensated. Here, we used simulations to evaluate whether complementation is likely to increase the fitness of viruses spreading collectively. We show that complementation among co-spreading viruses initially buffers the deleterious effects of mutations, but has no positive effect on mean population fitness over the long term, and even promotes error catastrophe at high mutation rates. Additionally, we found that collective spread increases the risk of invasion by social cheaters such as defective interfering particles. We also show that mutation accumulation depends on the type of collective infectious units considered. Co-spreading viral genomes produced in the same cell (e.g. extracellular vesicles, polyploid capsids, occlusion bodies) should exhibit higher genetic relatedness than groups formed extracellularly by viruses released from different cells (aggregates, binding to bacterial or dendritic cell surfaces), and we found that increased relatedness limits the adverse effects of complementation as well cheater invasion risk. Finally, we found that the costs of complementation can be offset by recombination. Based on our results, we suggest that alternative factors promoting collective spread should be considered.
病毒可以通过不同类型的结构集体传播，如细胞外囊泡、病毒聚集体、多倍体衣壳、包裹体，甚至是在其表面积累病毒的细胞，如细菌和树突状细胞。尽管有越来越多的证据表明存在集体传播，但它对病毒适应性和多样性的影响仍知之甚少。有人假设，通过增加细胞感染的多重性，集体传播可以使不同病毒遗传变体之间产生互利的相互作用。这种相互作用之一是遗传互补，即不同基因组携带的有害突变可以得到补偿。在这里，我们使用模拟来评估遗传互补是否可能增加集体传播病毒的适应性。我们表明，共同传播病毒之间的互补最初缓冲了突变的有害影响，但对长期的种群平均适应性没有积极影响，甚至在高突变率下促进了错误灾难。此外，我们发现集体传播增加了社交骗子（如缺陷干扰颗粒）入侵的风险。我们还表明，突变积累取决于所考虑的集体感染单位的类型。在同一细胞中产生的共同传播病毒基因组（例如细胞外囊泡、多倍体衣壳、包裹体）的遗传相关性应该高于由不同细胞释放的病毒在细胞外形成的群体（聚集体、与细菌或树突状细胞表面结合），我们发现，遗传相关性的增加限制了互补的不利影响以及骗子入侵的风险。最后，我们发现互补的代价可以通过重组来抵消。基于我们的结果，我们建议应考虑促进集体传播的其他因素。
