竞争性病毒RNA在新型冠状病毒感染引发免疫风暴中的调控机制研究

新型冠状病毒（后文简称新冠病毒）作为基因组最大的RNA病毒感染宿主细胞后大量表达病毒RNA/mRNAs和蛋白，其中病毒RNA/mRNAs会竞争性结合细胞中多种miRNA，从而解除miRNA对靶基因的抑制、引发宿主细胞基因表达紊乱。本项目将全面研究竞争性病毒RNA调控肺上皮细胞与区域免疫细胞之间相互作用的关键细胞因子和相关通路，建立调控网络模型，揭示冠状病毒基因组多样性演化过程、进化规律。深入剖析病毒mRNA直接影响肺炎免疫病理的分子机制，发现新冠肺炎重症化和免疫风暴的预警标志物及治疗靶点。

SARS-CoV-2 having the largest identified RNA genome produces large amounts of viral RNA/mRNA and proteins under infection of host cells. Viral RNA/mRNAs competitively bind multiple cellular miRNAs, and thereby derepress their target genes and result in aberrant gene expression. In this project the key cytokines and pathways mediated by competitive viral RNAs will be explored involving in cross-regulation between alveolar epithelial cells and tissue-specific immune cells. The regulatory network model will be established, which may reveal the evolution process of genomic diversity of coronavirus. Mechanisms of lung immunopathology by viral mRNAs will be studied. Early warning biomarkers and therapeutic targets for severe pneumonia and cytokine storm will be identified in this study.