Journal article
Omicron subvariant BA.5 efficiently infects lung cells
Nature communications, Vol.14(1), 3500
06/13/2023
DOI: 10.1038/s41467-023-39147-4
PMCID: PMC10262933
PMID: 37311762
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.
The Omicron variant is partially attenuated, likely because it fails to efficiently infect lung cells. Here, Hoffmann et. al. show that this defect can be lost during Omicron evolution as demonstrated for the subvariant BA.5 that robustly infects lung cells in vitro and in vivo.
Details
- Title: Subtitle
- Omicron subvariant BA.5 efficiently infects lung cells
- Creators
- Markus Hoffmann - Göttingen, Germany Göttingen, GermanyLok-Yin Roy Wong - Iowa City, IA USAPrerna Arora - Göttingen, Germany Göttingen, GermanyLu Zhang - Göttingen, Germany Göttingen, GermanyCheila Rocha - Göttingen, Germany Göttingen, GermanyAbby Odle - Iowa City, IA USAInga Nehlmeier - Göttingen, GermanyAmy Kempf - Göttingen, Germany Göttingen, GermanyAnja Richter - Berlin, GermanyNico Joel Halwe - Greifswald - Insel Riems, GermanyJacob Schön - Greifswald - Insel Riems, GermanyLorenz Ulrich - Greifswald - Insel Riems, GermanyDonata Hoffmann - Greifswald - Insel Riems, GermanyMartin Beer - Greifswald - Insel Riems, GermanyChristian Drosten - Berlin, GermanyStanley Perlman - Iowa City, IA USAStefan Pöhlmann - Göttingen, Germany Göttingen, Germany
- Resource Type
- Journal article
- Publication Details
- Nature communications, Vol.14(1), 3500
- DOI
- 10.1038/s41467-023-39147-4
- PMID
- 37311762
- PMCID
- PMC10262933
- NLM abbreviation
- Nat Commun
- eISSN
- 2041-1723
- Publisher
- Nature Publishing Group UK
- Grant note
- UNDINE / ; 14-76103-184, COFONI Network, including projects 7FF22, 6FF22, 10FF22 / ; 01KI2006D, 01KI20328A, 01KX2021 / ; MB 453012513; PO 716/11-1, PO 716/14-1 / ;
- Language
- English
- Date published
- 06/13/2023
- Academic Unit
- Microbiology and Immunology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Infectious Disease (Pediatrics)
- Record Identifier
- 9984430332702771
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