Crooke Philip S, Tossberg John T, Porter Krislyn P, Aune Thomas M
Department of Mathematics, Vanderbilt University, Nashville, TN, 37212, USA.
Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, 37212, USA.
Curr Res Immunol. 2021;2:52-59. doi: 10.1016/j.crimmu.2021.04.001. Epub 2021 Apr 30.
Due to potential severity of disease caused by SARS-CoV-2 infection, it is critical to understand both mechanisms of viral pathogenesis as well as diversity of host responses to infection. Reduced A-to-I editing of endogenous double-stranded RNAs (dsRNAs), as a result of inactivating mutations in , produces one form of Aicardi-Goutières Syndrome, with an immune response similar to an anti-viral response. By analyzing whole genome RNA sequencing data, we find reduced levels of A-to-I editing of endogenous Alu RNAs in normal human lung cells after infection by SARS-CoV-2 as well as in lung biopsies from patients with SARS-CoV-2 infections. Unedited Alu RNAs, as seen after infection, induce IRF and NF-kB transcriptional responses and downstream target genes, while edited Alu RNAs as seen in the absence of infection, fail to activate these transcriptional responses. Thus, decreased A-to-I editing may represent an important host response to SARS-CoV-2 infection.
由于严重急性呼吸综合征冠状病毒2（SARS-CoV-2）感染所导致疾病的潜在严重性，了解病毒发病机制以及宿主对感染反应的多样性至关重要。由于ADAR1基因的失活突变，内源性双链RNA（dsRNA）的A到I编辑减少，会产生一种Aicardi-Goutières综合征，其免疫反应类似于抗病毒反应。通过分析全基因组RNA测序数据，我们发现在SARS-CoV-2感染后的正常人肺细胞以及SARS-CoV-2感染患者的肺活检组织中，内源性Alu RNA的A到I编辑水平降低。感染后出现的未编辑Alu RNA会诱导干扰素调节因子（IRF）和核因子κB（NF-κB）转录反应以及下游靶基因，而在未感染时出现的编辑后Alu RNA则无法激活这些转录反应。因此，A到I编辑减少可能代表宿主对SARS-CoV-2感染的一种重要反应。
