Vascular Inflammation Is Associated with Loss of Aquaporin 1 Expression on Endothelial Cells and Increased Fluid Leakage in SARS-CoV-2 Infected Golden Syrian Hamsters

Viruses

Gülsah Gabriel¹  Berfin Schaumburg¹  Sebastian Beck¹  Nancy Mounogou Kouassi¹  Martin Zickler¹  Stephanie Stanelle-Bertram¹  Eva Leitzen²  Franz-Josef Kaup²  Wolfgang Baumgärtner²  Lisa Allnoch²  Vanessa Herder²  Kathrin Becker²  Georg Beythien² 

[1] Department for Viral Zoonoses-One Health, Heinrich Pette Institute, Leibniz Institute for Experimental Virology, 20251 Hamburg, Germany;Department of Pathology, University of Veterinary Medicine Hannover, 30559 Hannover, Germany;

关键词: vasculitis;    vasculopathy;    SARS-CoV-2;    COVID-19;    aquaporin 1;    hamster;   

DOI  :  10.3390/v13040639

来源: DOAJ

【 摘 要 】

Vascular changes represent a characteristic feature of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection leading to a breakdown of the vascular barrier and subsequent edema formation. The aim of this study was to provide a detailed characterization of the vascular alterations during SARS-CoV-2 infection and to evaluate the impaired vascular integrity. Groups of ten golden Syrian hamsters were infected intranasally with SARS-CoV-2 or phosphate-buffered saline (mock infection). Necropsies were performed at 1, 3, 6, and 14 days post-infection (dpi). Lung samples were investigated using hematoxylin and eosin, alcian blue, immunohistochemistry targeting aquaporin 1, CD3, CD204, CD31, laminin, myeloperoxidase, SARS-CoV-2 nucleoprotein, and transmission electron microscopy. SARS-CoV-2 infected animals showed endothelial hypertrophy, endothelialitis, and vasculitis. Inflammation mainly consisted of macrophages and lower numbers of T-lymphocytes and neutrophils/heterophils infiltrating the vascular walls as well as the perivascular region at 3 and 6 dpi. Affected vessels showed edema formation in association with loss of aquaporin 1 on endothelial cells. In addition, an ultrastructural investigation revealed disruption of the endothelium. Summarized, the presented findings indicate that loss of aquaporin 1 entails the loss of intercellular junctions resulting in paracellular leakage of edema as a key pathogenic mechanism in SARS-CoV-2 triggered pulmonary lesions.

【 授权许可】

Unknown