ABSTRACT
Coronavirus (SARS-CoV-2) enters the cell by binding to a transmembrane glycoprotein, angiotensin-converting en-zyme-2 (ACE2), which is expressed on the surface of the bronchial and alveolar epithelium. In this regard, the aim of this study was to determine changes in the content and characteristics of tissue localization of ACE2 in the model of acute bronchopulmonary inflammation. The latter was modeled by endotracheal injection of a foreign body (Capron thread) and a solution of lipopolysaccharide (LPS;50 μl at a dose of 12.5 mg/kg) against the background of systemic administration of LPS for two days before surgery (250 mg/ kg). ACE2 localization and quantity were evaluated by im-munohistochemical and western blot assays with the use of a specific monoclonal antibody. The experiment reproduced acute exudative-hemorrhagic bronchopneumonia with the development of diffuse progressive pulmonary fibrosis with lethality in 36% of animals. Acute exudative inflammation was accompanied by complete inhibition of ACE2 expression in bronchial epitheliocytes and its significant decrease in alveolocytes type II. With the development of the proliferative stage of bronchopneumonia, the level of ACE2 was restored, subsequently remaining without significant changes. The obtained experimental data suggest the existence of a relationship between the features of quantitative changes in the ACE2 level in the bronchopulmonary epithelium and the undulating course of the inflammatory process during SARS-CoV-2 infection. © 2022, Bogomoletz Institute of Physiology, National Academy of Sciences of Ukraine. All rights reserved.
ABSTRACT
Understanding the pathogenesis of the SARS-CoV-2 infection is key to developing preventive and therapeutic strategies against COVID-19, in the case of severe illness but also when the disease is mild. The use of appropriate experimental animal models remains central in the in vivo exploration of the physiopathology of infection and antiviral strategies. This study describes SARS-CoV-2 intranasal infection in ferrets and hamsters with low doses of low-passage SARS-CoV-2 clinical French isolate UCN19, describing infection levels, excretion, immune responses and pathological patterns in both animal species. Individual infection with 103 p.f.u. SARS-CoV-2 induced a more severe disease in hamsters than in ferrets. Viral RNA was detected in the lungs of hamsters but not of ferrets and in the brain (olfactory bulb and/or medulla oblongata) of both species. Overall, the clinical disease remained mild, with serological responses detected from 7 days and 10 days post-inoculation in hamsters and ferrets respectively. The virus became undetectable and pathology resolved within 14 days. The kinetics and levels of infection can be used in ferrets and hamsters as experimental models for understanding the pathogenicity of SARS-CoV-2, and testing the protective effect of drugs.