<br>SARS-CoV-2缺陷病毒基因组的生物信息分析及其对人群感染特征的影响,Frontiers in Immunology

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SARS-CoV-2缺陷病毒基因组的生物信息分析及其对人群感染特征的影响
Frontiers in Immunology ( IF 5.7 ) Pub Date : 2024-01-29 , DOI: 10.3389/fimmu.2024.1341906
Zhaobin Xu ₁ , Qingzhi Peng ₁ , Jian Song ₁ , Hongmei Zhang ₁ , Dongqing Wei _{2,

3,

4,

5} , Jacques Demongeot ₆ , Qiangcheng Zeng ₁

Affiliation

DVG（缺陷病毒基因组）在 RNA 病毒感染中普遍存在。在这项调查中，我们对高通量测序数据进行了分析，并观察到 DVG 在 SARS-CoV-2 中广泛存在。 SARS-CoV-2 与多种 DNA 病毒之间的比较分析表明，SARS-CoV-2 基因组内对损伤的敏感性更高，测序样本异质性也有所增加。全基因组测序深度变异性分析显示 SARS-CoV-2 具有较高的变异系数，而 DVG 分析表明存在很大比例的重组位点，表明基因组异质性显着，并表明大部分组装的病毒颗粒含有不完整的 RNA 序列。此外，我们的调查还探讨了不同菌株之间的测序深度和 DVG 含量差异。我们的研究结果表明，随着病毒的进化，病毒颗粒内完整基因组的比例显着增加，第三代测序数据证明了这一点。具体来说，Omicron 菌株中完整基因组的比例超过了 Delta 和 Alpha 菌株。这一观察结果有效地阐明了与 Delta 和 Alpha 毒株相比，Omicron 毒株的传染性更高。我们还假设这种完整性的提高源于病毒组装能力的增强，因为 Omicron 菌株可以迅速促进 RNA 和衣壳蛋白的结合，从而减少易受攻击的病毒 RNA 在宿主环境中的暴露时间，并显着减轻其降解。最后，我们利用数学模型模拟了不同环境因素下DVG效应对感染特征和种群进化的影响。我们的研究结果解释了症状严重程度与病毒入侵程度之间的密切关系，以及同一毒株在不同环境条件下引起的人群感染特征的巨大差异。这项研究为未来病毒研究和疫苗开发提供了一种新方法。

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Bioinformatic analysis of defective viral genomes in SARS-CoV-2 and its impact on population infection characteristics

DVGs (Defective Viral Genomes) are prevalent in RNA virus infections. In this investigation, we conducted an analysis of high-throughput sequencing data and observed widespread presence of DVGs in SARS-CoV-2. Comparative analysis between SARS-CoV-2 and diverse DNA viruses revealed heightened susceptibility to damage and increased sequencing sample heterogeneity within the SARS-CoV-2 genome. Whole-genome sequencing depth variability analysis exhibited a higher coefficient of variation for SARS-CoV-2, while DVG analysis indicated a significant proportion of recombination sites, signifying notable genome heterogeneity and suggesting that a large proportion of assembled virus particles contain incomplete RNA sequences. Moreover, our investigation explored the sequencing depth and DVG content differences among various strains. Our findings revealed that as the virus evolves, there is a notable increase in the proportion of intact genomes within virus particles, as evidenced by third-generation sequencing data. Specifically, the proportion of intact genome in the Omicron strain surpassed that of the Delta and Alpha strains. This observation effectively elucidates the heightened infectiousness of the Omicron strain compared to the Delta and Alpha strains. We also postulate that this improvement in completeness stems from enhanced virus assembly capacity, as the Omicron strain can promptly facilitate the binding of RNA and capsid protein, thereby reducing the exposure time of vulnerable virus RNA in the host environment and significantly mitigating its degradation. Finally, employing mathematical modeling, we simulated the impact of DVG effects under varying environmental factors on infection characteristics and population evolution. Our findings provide an explanation for the close association between symptom severity and the extent of virus invasion, as well as the substantial disparity in population infection characteristics caused by the same strain under distinct environmental conditions. This study presents a novel approach for future virus research and vaccine development.

更新日期：2024-01-29

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