Elsevier

Virology

Volume 517, April 2018, Pages 9-15
Virology

Brief Communication
Wild-type human coronaviruses prefer cell-surface TMPRSS2 to endosomal cathepsins for cell entry

https://doi.org/10.1016/j.virol.2017.11.012Get rights and content
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Highlights

  • Clinical isolates of HCoV-OC43 and -HKU1 were isolated from ALI-cultured HBTE cells.

  • Clinical isolates of HCoVs preferred the TMRRSS2 to cathepsins for cell entry.

  • Cell culture adapted HCoV-OC43 lost the ability to replicate in HBTE-ALI culture.

Abstract

Human coronaviruses (HCoVs) enter cells via two distinct pathways: the endosomal pathway using cathepsins to activate spike protein and the cell-surface or early endosome pathway using extracellular proteases such as transmembrane protease serine 2 (TMPRSS2). We previously reported that clinical isolates of HCoV-229E preferred cell-surface TMPRSS2 to endosomal cathepsin for cell entry, and that they acquired the ability to use cathepsin L by repeated passage in cultured cells and were then able to enter cells via the endosomal pathway. Here, we show that clinical isolates of HCoV-OC43 and -HKU1 preferred the cell-surface TMRRSS2 to endosomal cathepsins for cell entry, similar to HCoV-229E. In addition, the cell-culture-adapted HCoV-OC43 lost the ability to infect and replicate in air-liquid interface cultures of human bronchial tracheal epithelial cells. These results suggest that circulating HCoVs in the field generally use cell-surface TMPRSS2 for cell entry, not endosomal cathepsins, in human airway epithelial cells.

Abbreviations

ATCC
American Tissue Culture Collection
Cam
Camostat
CatL
Cathepsin L
DMEM
Dulbecco's modified Eagle's medium
HCoV
human coronavirus
S
spike
VHCR
very highly conserved region

Keywords

Human coronavirus
Entry
Human bronchial tracheal epithelial cells
Air-liquid interface culture

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