Omicron subvariant BA.5 efficiently infects lung cells

Markus Hoffmann (), Lok-Yin Roy Wong, Prerna Arora, Lu Zhang, Cheila Rocha, Abby Odle, Inga Nehlmeier, Amy Kempf, Anja Richter, Nico Joel Halwe, Jacob Schön, Lorenz Ulrich, Donata Hoffmann, Martin Beer, Christian Drosten, Stanley Perlman and Stefan Pöhlmann ()
Additional contact information
Markus Hoffmann: Infection Biology Unit, German Primate Center – Leibniz Institute for Primate Research
Lok-Yin Roy Wong: University of Iowa
Prerna Arora: Infection Biology Unit, German Primate Center – Leibniz Institute for Primate Research
Lu Zhang: Infection Biology Unit, German Primate Center – Leibniz Institute for Primate Research
Cheila Rocha: Infection Biology Unit, German Primate Center – Leibniz Institute for Primate Research
Abby Odle: University of Iowa
Inga Nehlmeier: Infection Biology Unit, German Primate Center – Leibniz Institute for Primate Research
Amy Kempf: Infection Biology Unit, German Primate Center – Leibniz Institute for Primate Research
Anja Richter: Institute of Virology, Charité - Universitätsmedizin Berlin, Campus Charité Mitte
Nico Joel Halwe: Institut für Virusdiagnostik (IVD), Friedrich-Loeffler-Institut
Jacob Schön: Institut für Virusdiagnostik (IVD), Friedrich-Loeffler-Institut
Lorenz Ulrich: Institut für Virusdiagnostik (IVD), Friedrich-Loeffler-Institut
Donata Hoffmann: Institut für Virusdiagnostik (IVD), Friedrich-Loeffler-Institut
Martin Beer: Institut für Virusdiagnostik (IVD), Friedrich-Loeffler-Institut
Christian Drosten: Institute of Virology, Charité - Universitätsmedizin Berlin, Campus Charité Mitte
Stanley Perlman: University of Iowa
Stefan Pöhlmann: Infection Biology Unit, German Primate Center – Leibniz Institute for Primate Research

Nature Communications, 2023, vol. 14, issue 1, 1-11

Abstract: Abstract The SARS-CoV-2 Omicron subvariants BA.1 and BA.2 exhibit reduced lung cell infection relative to previously circulating SARS-CoV-2 variants, which may account for their reduced pathogenicity. However, it is unclear whether lung cell infection by BA.5, which displaced these variants, remains attenuated. Here, we show that the spike (S) protein of BA.5 exhibits increased cleavage at the S1/S2 site and drives cell-cell fusion and lung cell entry with higher efficiency than its counterparts from BA.1 and BA.2. Increased lung cell entry depends on mutation H69Δ/V70Δ and is associated with efficient replication of BA.5 in cultured lung cells. Further, BA.5 replicates in the lungs of female Balb/c mice and the nasal cavity of female ferrets with much higher efficiency than BA.1. These results suggest that BA.5 has acquired the ability to efficiently infect lung cells, a prerequisite for causing severe disease, suggesting that evolution of Omicron subvariants can result in partial loss of attenuation.

Date: 2023
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DOI: 10.1038/s41467-023-39147-4

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