Laboratory of Biology, Department of Medicine, Democritus University of Thrace, Alexandroupolis, Greece.
Molecular Carcinogenesis Group, Department of Histology and Embryology, Medical School, National and Kapodistrian University of Athens, Greece.
FEBS J. 2023 Mar;290(5):1384-1392. doi: 10.1111/febs.16230. Epub 2021 Nov 8.
In-depth analysis of SARS-CoV-2 biology and pathogenesis is rapidly unraveling the mechanisms through which the virus induces all aspects of COVID-19 pathology. Emergence of hundreds of variants and several important variants of concern has focused research on the mechanistic elucidation of virus mutagenesis. RNA viruses evolve quickly either through the error-prone polymerase or the RNA-editing machinery of the cell. In this review, we are discussing the links between cellular senescence, a natural aging process that has been recently linked to SARS-CoV-2 infection, and virus mutagenesis through the RNA-editing enzymes APOBEC. The action of APOBEC, enhanced by cellular senescence, is hypothesized to assist the emergence of novel variants, called quasispecies, within a cell or organism. These variants when introduced to the community may lead to the generation of a variant of concern, depending on fitness and transmissibility of the new genome. Such a mechanism of virus evolution may highlight the importance of inhibitors of cellular senescence during SARS-CoV-2 clinical treatment.
深入分析 SARS-CoV-2 的生物学和发病机制正在迅速揭示病毒诱导 COVID-19 病理学各个方面的机制。数百种变体的出现和几种重要的关注变体使研究集中在病毒突变机制的阐明上。RNA 病毒要么通过易错聚合酶，要么通过细胞的 RNA 编辑机制快速进化。在这篇综述中，我们讨论了细胞衰老（一种最近与 SARS-CoV-2 感染相关的自然衰老过程）与通过 RNA 编辑酶 APOBEC 进行病毒突变之间的联系。细胞衰老增强了 APOBEC 的作用，据推测，它有助于在细胞或生物体内部出现新的变体，称为准种。当这些变体被引入社区时，可能会导致关注变体的产生，这取决于新基因组的适应性和传染性。这种病毒进化的机制可能强调了在 SARS-CoV-2 临床治疗期间抑制细胞衰老的抑制剂的重要性。
