Functional assessment of cell entry and receptor usage for lineage B β-coronaviruses, including 2019-nCoV
Open Access
- 22 January 2020
- preprint content
- Published by Cold Spring Harbor Laboratory in bioRxiv : the preprint server for biology
Abstract
Over the past 20 years, several coronaviruses have crossed the species barrier into humans, causing outbreaks of severe, and often fatal, respiratory illness. Since SARS-CoV was first identified in animal markets, global viromics projects have discovered thousands of coronavirus sequences in diverse animals and geographic regions. Unfortunately, there are few tools available to functionally test these novel viruses for their ability to infect humans, which has severely hampered efforts to predict the next zoonotic viral outbreak. Here we developed an approach to rapidly screen lineage B betacoronaviruses, such as SARS-CoV and the recent 2019-nCoV, for receptor usage and their ability to infect cell types from different species. We show that host protease processing during viral entry is a significant barrier for several lineage B viruses and that bypassing this barrier allows several lineage B viruses to enter human cells through an unknown receptor. We also demonstrate how different lineage B viruses can recombine to gain entry into human cells and confirm that human ACE2 is the receptor for the recently emerging 2019-nCoV.Keywords
This publication has 36 references indexed in Scilit:
- Differential Sensitivity of Bat Cells to Infection by Enveloped RNA Viruses: Coronaviruses, Paramyxoviruses, Filoviruses, and Influenza VirusesPLOS ONE, 2013
- Cleavage and Activation of the Severe Acute Respiratory Syndrome Coronavirus Spike Protein by Human Airway Trypsin-Like ProteaseJournal of Virology, 2011
- A Transmembrane Serine Protease Is Linked to the Severe Acute Respiratory Syndrome Coronavirus Receptor and Activates Virus EntryJournal of Virology, 2011
- Efficient Activation of the Severe Acute Respiratory Syndrome Coronavirus Spike Protein by the Transmembrane Protease TMPRSS2Journal of Virology, 2010
- Recombination, Reservoirs, and the Modular Spike: Mechanisms of Coronavirus Cross-Species TransmissionJournal of Virology, 2010
- Cleavage of the SARS Coronavirus Spike Glycoprotein by Airway Proteases Enhances Virus Entry into Human Bronchial Epithelial Cells In VitroPLOS ONE, 2009
- Activation of the SARS coronavirus spike protein via sequential proteolytic cleavage at two distinct sitesProceedings of the National Academy of Sciences of the United States of America, 2009
- Synthetic recombinant bat SARS-like coronavirus is infectious in cultured cells and in miceProceedings of the National Academy of Sciences of the United States of America, 2008
- Conformational Reorganization of the SARS Coronavirus Spike Following Receptor Binding: Implications for Membrane FusionPLOS ONE, 2007
- Bats Are Natural Reservoirs of SARS-Like CoronavirusesScience, 2005