ヒトコロナウイルス229Eはヒト肺血管内皮細胞に感染し、遅延性の炎症および抗ウイルス応答を誘発する可能性がある
Robert Szewczyk1, Mateusz Gawrysiak1, Jolanta Kalinowska1
1Department of Immunology and Allergy, Chair of Rheumatology, Clinical Immunology and Transplantology, Medical University of Lodz, Lodz, Poland.
Abstract:
The effect of human coronaviruses (HCoVs) on airway epithelial cells is known and very well described. However, their influence on the human lung endothelium remains poorly understood. In this study, we assess the effect of low pathogenic HCoV-229E on the inflammatory and antiviral response of Human Lung Microvascular Endothelial Cells (HMVEC-L). Human Lung Microvascular Endothelial Cells were infected with HCoV-229E and then mRNA expression, protein release, cell viability, apoptosis rate, and presence of AP-N in flow cytometry were assessed. The infection of HMVEC-L with HCoV-229E led to the massive replication picked at 96 h post infection (hpi); however, the virus efficiently replicated at 48 hpi. Despite the inflammatory (IL-8, IL-6) and antiviral (IFN-β, OAS-1, PKR, MX-1) response, as well as the pattern recognition receptors activation (TLR3, TLR7/8, RIG-I, MDA5) occurred only at hour 72. Additionally, the cytopathic effect and the increase in apoptosis were observed. AP-N blockade inhibited inflammatory and antiviral induction, as well as decreased HCoV-229E genome copy numbers in HMVEC-L. We proved that the lung microvascular endothelium may be infected by human coronavirus 229E and that this infection may lead to a robust, but delayed inflammatory and antiviral response. Secondly, HMVEC-L may play an important role during Coronaviridae upper and lower airway infections.
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