Kallikrein 13 serves as a priming protease during infection by the human coronavirus HKU1
| Autor: | Paweł Mak, Magdalena Kulczycka, Aleksandra Milewska, Elftherios Diamandis, Antonina Naskalska, Adam Lesner, Krzysztof Pyrc, Ewa Bielecka, Marek Ochman, Maciej Urlik, Ioannis Prassas, Katherine Falkowski, Tomasz Kantyka, Jan Potempa |
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| Rok vydání: | 2020 |
| Předmět: |
viruses
medicine.medical_treatment Priming (immunology) Respiratory Mucosa Biology Biochemistry Virus Betacoronavirus 03 medical and health sciences 0302 clinical medicine stomatognathic system Viral entry Cell Line Tumor Virology medicine Humans Molecular Biology Research Articles 030304 developmental biology 0303 health sciences Protease urogenital system virus diseases Epithelial Cells STKE Research Articles Cell Biology biology.organism_classification Coronavirus Viral replication Kallikrein 13 Cell culture 030220 oncology & carcinogenesis Spike Glycoprotein Coronavirus Kallikreins Human coronavirus HKU1 Coronavirus Infections circulatory and respiratory physiology Research Article |
| Zdroj: | Science Signaling |
| ISSN: | 1937-9145 1945-0877 |
| Popis: | The protease kallikrein 13 cleaves the spike protein of the human coronavirus HKU1 to facilitate viral entry. Priming viral entry Unlike SARS-CoV-2, the human coronavirus HKU1 normally causes relatively mild respiratory tract infections; however, it shares with SARS-CoV-2 the mechanism of using its surface spike (S) protein to enter target cells. Because the host receptor for HCoV-HKU1 is unknown, efforts to study the virus in cell culture systems have proved difficult. Milewska et al. found that knockout of the protease kallikrein 13 (KLK13) in human airway epithelial cells blocked their infection by HCoV-HKU1, that overexpression of KLK13 in nonpermissive cells enabled their infection by the virus, and that KLK13 cleaved the viral S protein. Together, these findings suggest that KLK13 is a priming enzyme for viral entry and may help to establish cell lines that can facilitate further investigation of the mechanism of viral pathogenesis. Human coronavirus HKU1 (HCoV-HKU1) is associated with respiratory disease and is prevalent worldwide, but an in vitro model for viral replication is lacking. An interaction between the coronaviral spike (S) protein and its receptor is the primary determinant of tissue and host specificity; however, viral entry is a complex process requiring the concerted action of multiple cellular elements. Here, we found that the protease kallikrein 13 (KLK13) was required for the infection of human respiratory epithelial cells and was sufficient to mediate the entry of HCoV-HKU1 into nonpermissive RD cells. We also demonstrated the cleavage of the HCoV-HKU1 S protein by KLK13 in the S1/S2 region, suggesting that KLK13 is the priming enzyme for this virus. Together, these data suggest that protease distribution and specificity determine the tissue and cell specificity of the virus and may also regulate interspecies transmission. |
| Databáze: | OpenAIRE |
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