Zoonotic transmission of animal sarbecoviruses threatens public health, as evidenced by the SARS epidemic and the COVID-19 pandemic. The attenuated Omicron variant dominates the COVID-19 pandemic since winter 2021 and attenuation is believed to be at least partially due to inefficient infection of lung cells. Here, we investigated whether reduced capacity to spread in the lung has been preserved during evolution of Omicron subvariants. We report that the spike proteins of Omicron subvariants BA.4 and BA.5, which are identical at the amino acid level, show increased cleavage by host cell proteases and augmented capacity to drive cell-cell fusion. Furthermore, BA.4/BA.5 spike facilitated increased entry into Calu-3 lung cells and augmented entry was due to deletion of H69 and V70 but was not associated with altered TMPRSS2 usage. Furthermore, increased Calu-3 cell entry of pseudotypes bearing BA.5 spike translated into augmented Calu-3 cells infection by authentic BA.5 virus. Finally, BA.5 spread in the nasal epithelium of ferrets and in the lungs of mice with much higher efficiency than previously circulating Omicron subvariants. These results indicate that attenuation of the Omicron variant can at least by partially lost during evolution of subvariants.
Keywords
SARS-CoV-2, spike, BA.5, lung
| Registration-ID code |
480
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| Professional Status of the Speaker |
Professor
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| Junior Scientist Status |
No, I am not a Junior Scientist.
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Dr
Markus Hoffmann
(Infection Biology Unit, German Primate Center – Leibniz Institute for Primate Research, Göttingen, Germany)
Stefan Pöhlmann
Dr
Lok-Yin Roy Wong
(Departments of Microbiology and Immunology, University of Iowa, Iowa City, USA)
Dr
Prerna Arora
(Infection Biology Unit, German Primate Center – Leibniz Institute for Primate Research, Göttingen, Germany)
Ms
Lu Zhang
(Infection Biology Unit, German Primate Center – Leibniz Institute for Primate Research, Göttingen, Germany)
Dr
Cheila Rocha
(Infection Biology Unit, German Primate Center – Leibniz Institute for Primate Research, Göttingen, Germany)
Ms
Abby Odle
(Departments of Microbiology and Immunology, University of Iowa, Iowa City, USA)
Ms
Inga Nehlmeier
(Infection Biology Unit, German Primate Center – Leibniz Institute for Primate Research, Göttingen, Germany)
Ms
Amy Kempf
(Infection Biology Unit, German Primate Center – Leibniz Institute for Primate Research, Göttingen, Germany)
Ms
Anja Richter
(4Institute of Virology, Charité - Universitätsmedizin Berlin, Campus Charité Mitte, Berlin, Germany)
Dr
Nico Joel Halwe
(Institut für Virusdiagnostik (IVD), Friedrich-Loeffler-Institut, Greifswald - Insel Riems, Germany)
Dr
Jacob Schön
(Institut für Virusdiagnostik (IVD), Friedrich-Loeffler-Institut, Greifswald - Insel Riems, Germany)
Dr
Lorenz Ulrich
(Institut für Virusdiagnostik (IVD), Friedrich-Loeffler-Institut, Greifswald - Insel Riems, Germany)
Dr
Donata Hoffmann
(Institut für Virusdiagnostik (IVD), Friedrich-Loeffler-Institut, Greifswald - Insel Riems, Germany)
Prof.
Martin Beer
(Institut für Virusdiagnostik (IVD), Friedrich-Loeffler-Institut, Greifswald - Insel Riems, Germany)
Prof.
Christian Drosten
(Institute of Virology, Charité - Universitätsmedizin Berlin, Campus Charité Mitte, Berlin, Germany)
Prof.
Stanley Perlman
(Departments of Microbiology and Immunology, University of Iowa, Iowa City, USA)
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