Lee Sung-Gwon, Furth Priscilla A, Hennighausen Lothar, Lee Hye Kyung
Section of Genetics and Physiology, Laboratory of Molecular and Cellular Biology, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health (NIH), Bethesda, MD, USA.
iScience. 2024 Feb 8;27(3):109177. doi: 10.1016/j.isci.2024.109177. eCollection 2024 Mar 15.
The COVID-19 pandemic, driven by the SARS-CoV-2 virus and its variants, highlights the important role of understanding host-viral molecular interactions influencing infection outcomes. Alternative splicing post-infection can impact both host responses and viral replication. We analyzed RNA splicing patterns in immune cells across various SARS-CoV-2 variants, considering immunization status. Using a dataset of 190 RNA-seq samples from our prior studies, we observed a substantial deactivation of alternative splicing and RNA splicing-related genes in COVID-19 patients. The alterations varied significantly depending on the infecting variant and immunization history. Notably, Alpha or Beta-infected patients differed from controls, while Omicron-infected patients displayed a splicing profile closer to controls. Particularly, vaccinated Omicron-infected individuals showed a distinct dynamic in alternative splicing patterns not widely shared among other groups. Our findings underscore the intricate interplay between SARS-CoV-2 variants, vaccination-induced immunity, and alternative splicing, emphasizing the need for further investigations to deepen understanding and guide therapeutic development.
由严重急性呼吸综合征冠状病毒2（SARS-CoV-2）病毒及其变体引发的新冠疫情，凸显了理解影响感染结果的宿主-病毒分子相互作用的重要作用。感染后的可变剪接可影响宿主反应和病毒复制。我们考虑了免疫状态，分析了不同SARS-CoV-2变体感染的免疫细胞中的RNA剪接模式。利用我们先前研究中的190个RNA测序样本数据集，我们观察到新冠患者中可变剪接和RNA剪接相关基因大量失活。这些改变因感染变体和免疫史的不同而有显著差异。值得注意的是，感染阿尔法或贝塔变体的患者与对照组不同，而感染奥密克戎变体的患者的剪接谱更接近对照组。特别是，接种疫苗的奥密克戎感染个体在可变剪接模式上表现出独特的动态变化，这在其他组中并不常见。我们的研究结果强调了SARS-CoV-2变体、疫苗诱导的免疫力和可变剪接之间的复杂相互作用，强调需要进一步研究以加深理解并指导治疗开发。
