The Shmunis School of Biomedicine and Cancer Research, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel.
Clinical Virology Unit, Hadassah Hebrew University Medical Center, Jerusalem, Israel.
PLoS Pathog. 2020 Nov 4;16(11):e1009029. doi: 10.1371/journal.ppat.1009029. eCollection 2020 Nov.
Genetic diversity is the fuel of evolution and facilitates adaptation to novel environments. However, our understanding of what drives differences in the genetic diversity during the early stages of viral infection is somewhat limited. Here, we use ultra-deep sequencing to interrogate 43 clinical samples taken from early infections of the human-infecting viruses HIV, RSV and CMV. Hundreds to thousands of virus templates were sequenced per sample, allowing us to reveal dramatic differences in within-host genetic diversity among virus populations. We found that increased diversity was mostly driven by presence of multiple divergent genotypes in HIV and CMV samples, which we suggest reflect multiple transmitted/founder viruses. Conversely, we detected an abundance of low frequency hyper-edited genomes in RSV samples, presumably reflecting defective virus genomes (DVGs). We suggest that RSV is characterized by higher levels of cellular co-infection, which allow for complementation and hence elevated levels of DVGs.
遗传多样性是进化的燃料，有助于适应新环境。然而，我们对于在病毒感染的早期阶段驱动遗传多样性差异的因素的理解还比较有限。在这里，我们使用超深度测序技术检测了来自人类感染病毒 HIV、RSV 和 CMV 的 43 个早期感染样本。每个样本中都有数百到数千个病毒模板进行测序，使我们能够揭示病毒种群在宿主内遗传多样性方面的显著差异。我们发现，多样性的增加主要是由 HIV 和 CMV 样本中存在多种不同的基因型驱动的，我们认为这反映了多个传播/原始病毒。相反，我们在 RSV 样本中检测到大量低频率的超编辑基因组，可能反映了缺陷病毒基因组（DVGs）。我们认为，RSV 的特点是细胞合并感染水平较高，这允许互补，从而提高了 DVG 的水平。
