Through DNA sensors and hidden mitochondrial effects of SARS-CoV-2

Abstract The COVID-19 pandemic brought attention to studies about viral infections and their impact on the cell machinery. SARS-CoV-2, for example, invades the host cells by ACE2 interaction and possibly hijacks the mitochondria. To better understand the disease and to propose novel treatments, crucial aspects of SARS-CoV-2 enrolment with host mitochondria must be studied. The replicative process of the virus leads to consequences in mitochondrial function, and cell metabolism. The hijacking of mitochondria, on the other hand, can drive the extrusion of mitochondrial DNA (mtDNA) to the cytosol. Extracellular mtDNA evoke robust proinflammatory responses once detected, that may act in different pathways, eliciting important immune responses. However, few receptors are validated and are able to detect and respond to mtDNA. In this review, we propose that the mtDNA and its detection might be important in the immune process generated by SARS-CoV-2 and that this mechanism might be important in the lung pathogenesis seen in clinical symptoms. Therefore, investigating the mtDNA receptors and their signaling pathways might provide important clues for therapeutic interventions.

摘要 新型冠状病毒肺炎（COVID-19）大流行使得病毒感染及其对细胞机制的影响相关研究受到广泛关注。例如，严重急性呼吸综合征冠状病毒2型（SARS-CoV-2）通过血管紧张素转换酶2（ACE2）侵入宿主细胞，并可能劫持线粒体。为深入理解该疾病并提出全新治疗策略，亟需对SARS-CoV-2与宿主线粒体结合的关键环节开展研究。病毒的复制过程会对线粒体功能及细胞代谢造成影响。而线粒体被劫持后，可介导线粒体DNA（mtDNA）释放至细胞质中。细胞外mtDNA一旦被检测到，即可引发强烈的促炎反应，该反应可通过多种通路发挥作用，诱发关键免疫应答。然而，目前经验证且可识别并响应mtDNA的受体寥寥无几。在本综述中，我们提出mtDNA及其识别过程或许在SARS-CoV-2诱导的免疫进程中发挥重要作用，且该机制可能与临床症状中观察到的肺部发病机制密切相关。因此，对mtDNA受体及其信号通路展开研究，可为治疗干预提供重要线索。