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Kallikrein 13 serves as a priming protease during infection by the human coronavirus HKU1

Authors
  • Milewska, Aleksandra1, 2
  • Falkowski, Katherine2
  • Kulczycka, Magdalena3
  • Bielecka, Ewa3
  • Naskalska, Antonina1
  • Mak, Pawel4
  • Lesner, Adam5
  • Ochman, Marek6
  • Urlik, Maciej6
  • Diamandis, Elftherios7, 8, 9, 10
  • Prassas, Ioannis8, 10
  • Potempa, Jan2, 11
  • Kantyka, Tomasz3, 12
  • Pyrc, Krzysztof1
  • 1 Virogenetics Laboratory of Virology, Malopolska Centre of Biotechnology, Jagiellonian University, Gronostajowa 7a, 30-387 Krakow, Poland.
  • 2 Microbiology Department, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Gronostajowa 7, 30-387 Krakow, Poland.
  • 3 Laboratory of Proteolysis and Post-translational Modification of Proteins, Malopolska Centre of Biotechnology, Jagiellonian University, Gronostajowa 7, 30-387 Krakow, Poland.
  • 4 Department of Analytical Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Gronostajowa 7 St., 30-387 Krakow, Poland.
  • 5 Faculty of Chemistry, University of Gdansk, Wita Stwosza 63, 80-308 Gdansk, Poland.
  • 6 Department of Cardiac, Vascular and Endovascular Surgery and Transplantology, Medical University of Silesia in Katowice, Silesian Centre for Heart Diseases, Zabrze, Poland.
  • 7 Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada.
  • 8 Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Canada.
  • 9 Department of Clinical Biochemistry, University Health Network, Toronto, Canada.
  • 10 Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Canada.
  • 11 Centre for Oral Health and Systemic Diseases, University of Louisville School of Dentistry, Louisville, KY 40202, USA.
  • 12 Broegelmann Research Laboratory, Department of Clinical Science, University of Bergen, 5020 Bergen, Norway.
Type
Published Article
Journal
Science Signaling
Publisher
American Association for the Advancement of Science (AAAS)
Publication Date
Nov 24, 2020
Volume
13
Issue
659
Identifiers
DOI: 10.1126/scisignal.aba9902
PMID: 33234691
PMCID: PMC7857416
Source
PubMed Central
Disciplines
  • Coronavirus
License
Unknown

Abstract

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.

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