Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA.
Center for Immunity and Immunotherapies, Seattle Children's Research Institute, Seattle, WA, USA.
Nucleic Acids Res. 2022 Apr 22;50(7):e41. doi: 10.1093/nar/gkab1259.
Adaptation of viruses to their environments occurs through the acquisition of both novel single-nucleotide variants (SNV) and recombination events including insertions, deletions, and duplications. The co-occurrence of SNVs in individual viral genomes during their evolution has been well-described. However, unlike covariation of SNVs, studying the correlation between recombination events with each other or with SNVs has been hampered by their inherent genetic complexity and a lack of bioinformatic tools. Here, we expanded our previously reported CoVaMa pipeline (v0.1) to measure linkage disequilibrium between recombination events and SNVs within both short-read and long-read sequencing datasets. We demonstrate this approach using long-read nanopore sequencing data acquired from Flock House virus (FHV) serially passaged in vitro. We found SNVs that were either correlated or anti-correlated with large genomic deletions generated by nonhomologous recombination that give rise to Defective-RNAs. We also analyzed NGS data from longitudinal HIV samples derived from a patient undergoing antiretroviral therapy who proceeded to virological failure. We found correlations between insertions in the p6Gag and mutations in Gag cleavage sites. This report confirms previous findings and provides insights on novel associations between SNVs and specific recombination events within the viral genome and their role in viral evolution.
病毒对其环境的适应是通过获得新的单核苷酸变异 (SNV) 和重组事件来实现的，包括插入、缺失和重复。在病毒基因组的进化过程中，单个病毒基因组中 SNV 的共现已经得到了很好的描述。然而，与 SNV 的共变不同，研究重组事件之间以及与 SNV 之间的相关性受到其内在遗传复杂性和缺乏生物信息学工具的阻碍。在这里，我们扩展了我们之前报道的 CoVaMa 管道 (v0.1)，以测量短读和长读测序数据集中重组事件和 SNV 之间的连锁不平衡。我们使用从体外连续传代的 Flock House 病毒 (FHV) 的长读纳米孔测序数据来演示这种方法。我们发现了与非同源重组产生的大基因组缺失相关或不相关的 SNV，这些缺失会产生缺陷 RNA。我们还分析了来自接受抗逆转录病毒治疗的患者的纵向 HIV 样本的 NGS 数据，该患者进展为病毒学失败。我们发现了 p6Gag 中的插入与 Gag 切割位点突变之间的相关性。本报告证实了之前的发现，并提供了关于病毒基因组中 SNV 与特定重组事件之间及其在病毒进化中的作用的新关联的见解。
