Department of Genetic Engineering & Biotechnology, University of Dhaka, Dhaka, 1000, Bangladesh.
Department of Mathematics and Natural Sciences, BRAC University, Dhaka, Bangladesh.
J Transl Med. 2021 Jan 7;19(1):32. doi: 10.1186/s12967-020-02695-0.
Although it is becoming evident that individual's immune system has a decisive influence on SARS-CoV-2 disease progression, pathogenesis is largely unknown. In this study, we aimed to profile the host transcriptome of COVID-19 patients from nasopharyngeal samples along with virus genomic features isolated from respective host, and a comparative analyses of differential host responses in various SARS-CoV-2 infection systems.
Unique and rare missense mutations in 3C-like protease observed in all of our reported isolates. Functional enrichment analyses exhibited that the host induced responses are mediated by innate immunity, interferon, and cytokine stimulation. Surprisingly, induction of apoptosis, phagosome, antigen presentation, hypoxia response was lacking within these patients. Upregulation of immune and cytokine signaling genes such as CCL4, TNFA, IL6, IL1A, CCL2, CXCL2, IFN, and CCR1 were observed in lungs. Lungs lacked the overexpression of ACE2 as suspected, however, high ACE2 but low DPP4 expression was observed in nasopharyngeal cells. Interestingly, directly or indirectly, viral proteins specially non-structural protein mediated overexpression of integrins such as ITGAV, ITGA6, ITGB7, ITGB3, ITGA2B, ITGA5, ITGA6, ITGA9, ITGA4, ITGAE, and ITGA8 in lungs compared to nasopharyngeal samples suggesting the possible way of enhanced invasion. Furthermore, we found comparatively highly expressed transcription factors such as CBP, CEBP, NFAT, ATF3, GATA6, HDAC2, TCF12 which have pivotal roles in lung injury.
Even though this study incorporates a limited number of cases, our data will provide valuable insights in developing potential studies to elucidate the differential host responses on the viral pathogenesis in COVID-19, and incorporation of further data will enrich the search of an effective therapeutics.
尽管越来越明显的是，个体的免疫系统对 SARS-CoV-2 疾病的进展有决定性的影响，但发病机制在很大程度上仍是未知的。在这项研究中，我们旨在对来自鼻咽样本的 COVID-19 患者的宿主转录组进行分析，以及从各自宿主中分离的病毒基因组特征，并对各种 SARS-CoV-2 感染系统中的差异宿主反应进行比较分析。
在我们报告的所有分离株中，3C 样蛋白酶都观察到独特和罕见的错义突变。功能富集分析表明，宿主诱导的反应是由先天免疫、干扰素和细胞因子刺激介导的。令人惊讶的是，在这些患者中缺乏细胞凋亡、吞噬体、抗原呈递、缺氧反应的诱导。在肺部观察到免疫和细胞因子信号基因如 CCL4、TNFA、IL6、IL1A、CCL2、CXCL2、IFN 和 CCR1 的上调。肺部缺乏像预期的那样过度表达 ACE2，但在鼻咽细胞中观察到高 ACE2 但低 DPP4 表达。有趣的是，病毒蛋白，特别是非结构蛋白，直接或间接地介导了整合素如 ITGAV、ITGA6、ITGB7、ITGB3、ITGA2B、ITGA5、ITGA6、ITGA9、ITGA4、ITGAE 和 ITGA8 的过度表达，与鼻咽样本相比，这表明了增强入侵的可能途径。此外，我们发现了一些转录因子如 CBP、CEBP、NFAT、ATF3、GATA6、HDAC2、TCF12 的表达水平相对较高，这些转录因子在肺损伤中具有关键作用。
尽管这项研究纳入的病例数量有限，但我们的数据将为开发潜在的研究提供有价值的见解，以阐明 COVID-19 中病毒发病机制的差异宿主反应，并纳入更多的数据将丰富寻找有效的治疗方法的探索。
