RT Journal Article
SR Electronic
T1 Kallikrein 13: a new player in coronaviral infections
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.03.01.971499
DO 10.1101/2020.03.01.971499
A1 Aleksandra Milewska
A1 Katherine Falkowski
A1 Magdalena Kalinska
A1 Ewa Bielecka
A1 Antonina Naskalska
A1 Pawel Mak
A1 Adam Lesner
A1 Marek Ochman
A1 Maciej Urlik
A1 Jan Potempa
A1 Tomasz Kantyka
A1 Krzysztof Pyrc
YR 2020
UL http://biorxiv.org/content/early/2020/03/02/2020.03.01.971499.abstract
AB Human coronavirus HKU1 (HCoV-HKU1) is associated with respiratory disease and is prevalent worldwide, but in vitro model for virus replication is lacking. Interaction between the coronaviral spike (S) protein and its receptor is the major determinant of virus tissue and host specificity, but virus entry is a complex process requiring a concerted action of multiple cellular elements. Here, we show that KLK13 is required for the infection of the human respiratory epithelium and is sufficient to mediate the entry of HCoV-HKU1 to non-permissive RD cells. We also demonstrated HCoV-HKU1 S protein cleavage by KLK13 in the S1/S2 region, proving that KLK13 is the priming enzyme for this virus. Summarizing, we show for the first time that protease distribution and specificity predetermines the tissue and cell specificity of the virus and may also regulate interspecies transmission. It is also of importance that presented data may be relevant for the emerging coronaviruses, including SARS-CoV-2 and may help to understand the differences in their zoonotic potential.