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Spike independent replication of human coronavirus in bat cells

View ORCID ProfileMartin Linster, View ORCID ProfileMarcus G Mah, View ORCID ProfileDolyce HW Low, Zhuang Yan, Jayanthi Jayakumar, Firdaus Samsudin, Foong Ying Wong, View ORCID ProfilePeter J Bond, View ORCID ProfileIan H Mendenhall, View ORCID ProfileYvonne CF Su, View ORCID ProfileGavin JD Smith
doi: https://doi.org/10.1101/2021.09.18.460924
Martin Linster
1Programme in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore
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  • For correspondence: gavin.smith@duke-nus.edu.sg
Marcus G Mah
1Programme in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore
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Dolyce HW Low
1Programme in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore
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Zhuang Yan
1Programme in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore
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Jayanthi Jayakumar
1Programme in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore
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Firdaus Samsudin
2Bioinformatics Institute, Agency for Science, Technology, and Research, Singapore
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Foong Ying Wong
1Programme in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore
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Peter J Bond
2Bioinformatics Institute, Agency for Science, Technology, and Research, Singapore
3Department of Biological Sciences, National University of Singapore, Singapore
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Ian H Mendenhall
1Programme in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore
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Yvonne CF Su
1Programme in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore
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Gavin JD Smith
1Programme in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore
4SingHealth Duke-NUS Global Health Institute, SingHealth Duke-NUS Academic Medical Centre, Singapore
5Duke Global Health Institute, Duke University, United States
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  • For correspondence: gavin.smith@duke-nus.edu.sg
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Abstract

Bats are a likely zoonotic reservoir for a range of human pathogens including endemic human coronaviruses and SARS-CoV-2. Despite the high burden caused by these viruses, the factors required for the establishment and ongoing transmission in humans are not well understood, hampering efforts for pandemic preparedness. To help understand those adaptations required to cross the species barrier, we serially passaged endemic human coronavirus 229E isolates in a newly established Rhinolophus (horseshoe bat) kidney cell line. Here we report extensive mutations, including deletions, in the virus genome that result in the loss of spike protein expression, while maintaining the capability to infect bat cells. While we observed a loss of infectivity of human cells for all viruses with spike deletions, one isolate (2613) with an insertion that results in an early stop codon, was recovered from human cells. Deep sequencing of isolate 2613 showed that the majority population had acquired additional nucleotide insertions in the spike resulting in an additional codon that restores spike function. Spike-independent replication of coronaviruses provides an alternative route for infection of host species that don’t share common cell-entry receptors.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted September 27, 2021.
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Spike independent replication of human coronavirus in bat cells
Martin Linster, Marcus G Mah, Dolyce HW Low, Zhuang Yan, Jayanthi Jayakumar, Firdaus Samsudin, Foong Ying Wong, Peter J Bond, Ian H Mendenhall, Yvonne CF Su, Gavin JD Smith
bioRxiv 2021.09.18.460924; doi: https://doi.org/10.1101/2021.09.18.460924
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Spike independent replication of human coronavirus in bat cells
Martin Linster, Marcus G Mah, Dolyce HW Low, Zhuang Yan, Jayanthi Jayakumar, Firdaus Samsudin, Foong Ying Wong, Peter J Bond, Ian H Mendenhall, Yvonne CF Su, Gavin JD Smith
bioRxiv 2021.09.18.460924; doi: https://doi.org/10.1101/2021.09.18.460924

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