The renin-angiotensin system (RAS) is the most important regulatory system of electrolyte homeostasis and blood pressure and acts through angiotensin-converting enzyme (ACE)/angiotensin II (Ang II)/Ang II type 1 (AT1) receptor axis and angiotensin-converting enzyme 2 (ACE2)/angiotensin (1-7)/MAS receptor axis. RAS dysfunction is related to the occurrence and development of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) and causes a serious prognosis and even death. ALI/ARDS can be induced by various ways, one of which is viral infections, such as SARS-CoV, SARS-CoV-2, H5N1, H7N9, and EV71. This article reviews the specific mechanism on how RAS dysfunction affects ALI/ARDs caused by viral infections. SARS-CoV and SARS-CoV-2 enter the host cells by binding with ACE2. H5N1 and H7N9 avian influenza viruses reduce the ACE2 level in the body, and EV71 increases Ang II concentration. Treatment with angiotensin-converting enzyme inhibitor and angiotensin AT1 receptor blocker can alleviate ALI/ARDS symptoms. This review provides suggestions for the treatment of lung injury caused by viral infections.

The outbreaks of enterovirus 71 (EV71)-associated hand, foot, and mouth disease (HFMD) have emerged as an emergency of global health due to its association with fatal encephalitis and subsequent neurogenic pulmonary edema; however, the molecular characteristics and pathological features underlying EV71-associated encephalitis and pulmonary edema remain largely unknown. In this study, we performed a proteomic analysis of fresh brain and lung tissues from EV71-infected mice at 7 days post infection. We detected a perturbed expression of 148 proteins in the brain and 78 proteins in the lung after EV71 expression. Further analysis showed that the dysregulated proteins in the brain are involved in a variety of fundamental biological pathways, including complement and coagulation cascades, innate and adaptive immune responses, platelet activation, and nitrogen metabolism, and those proteins in the lung participate in innate and adaptive immune responses, phagosome, arginine biosynthesis, and hypoxia-inducible factor 1 signaling pathway. Our results suggested that immune activation, complement and coagulation dysfunction, platelet activation, imbalance of nitrogen metabolism, and hypoxia could be involved in the pathogenesis of EV71, which explains the major clinical manifestation of hyperinflammatory status of severe HFMD cases. Our study provides further understanding of the molecular basis of EV71 pathogenesis.

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