Core Research Laboratory, ISPRO, 50139, Firenze, Italy.
German Cancer Research Center (DKFZ), Division of Immune Diversity, Foundation Under Public Law, Im Neuenheimer Feld 280, 69120, Heidelberg, Germany.
J Appl Genet. 2022 May;63(2):423-428. doi: 10.1007/s13353-022-00688-x. Epub 2022 Mar 12.
Analysis of the SARS-CoV-2 transcriptome has revealed a background of low-frequency intra-host genetic changes with a strong bias towards transitions. A similar pattern is also observed when inter-host variability is considered. We and others have shown that the cellular RNA editing machinery based on ADAR and APOBEC host-deaminases could be involved in the onset of SARS-CoV-2 genetic variability. Our hypothesis is based both on similarities with other known forms of viral genome editing and on the excess of transition changes, which is difficult to explain with errors during viral replication. Zong et al. criticize our analysis on both conceptual and technical grounds. While ultimate proof of an involvement of host deaminases in viral RNA editing will depend on experimental validation, here, we address the criticism to suggest that viral RNA editing is the most reasonable explanation for the observed intra- and inter-host variability.
对 SARS-CoV-2 转录组的分析显示,在宿主内遗传变化的背景下存在低频变化,且具有强烈的转换偏向。当考虑宿主间变异性时,也观察到类似的模式。我们和其他人已经表明,基于 ADAR 和 APOBEC 宿主脱氨酶的细胞 RNA 编辑机制可能参与了 SARS-CoV-2 遗传变异性的发生。我们的假设既基于与其他已知形式的病毒基因组编辑的相似性,也基于转换变化的过剩,这很难用病毒复制过程中的错误来解释。Zong 等人从概念和技术方面批评了我们的分析。虽然宿主脱氨酶参与病毒 RNA 编辑的最终证据将取决于实验验证,但在这里,我们提出了批评意见,以表明病毒 RNA 编辑是观察到的宿主内和宿主间变异性的最合理解释。