Divergent trajectory of replication and intrinsic pathogenicity of SARS-CoV-2 Omicron post-BA.2/5 subvariants in the upper and lower respiratory tract
Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved..
BACKGROUND: Earlier Omicron subvariants including BA.1, BA.2, and BA.5 emerged in waves, with a subvariant replacing the previous one every few months. More recently, the post-BA.2/5 subvariants have acquired convergent substitutions in spike that facilitated their escape from humoral immunity and gained ACE2 binding capacity. However, the intrinsic pathogenicity and replication fitness of the evaluated post-BA.2/5 subvariants are not fully understood.
METHODS: We systemically investigated the replication fitness and intrinsic pathogenicity of representative post-BA.2/5 subvariants (BL.1, BQ.1, BQ.1.1, XBB.1, CH.1.1, and XBB.1.5) in weanling (3-4 weeks), adult (8-10 weeks), and aged (10-12 months) mice. In addition, to better model Omicron replication in the human nasal epithelium, we further investigated the replication capacity of the post-BA.2/5 subvariants in human primary nasal epithelial cells.
FINDINGS: We found that the evaluated post-BA.2/5 subvariants are consistently attenuated in mouse lungs but not in nasal turbinates when compared with their ancestral subvariants BA.2/5. Further investigations in primary human nasal epithelial cells revealed a gained replication fitness of XBB.1 and XBB.1.5 when compared to BA.2 and BA.5.2.
INTERPRETATION: Our study revealed that the post-BA.2/5 subvariants are attenuated in lungs while increased in replication fitness in the nasal epithelium, indicating rapid adaptation of the circulating Omicron subvariants in the human populations.
FUNDING: The full list of funding can be found at the Acknowledgements section.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:99 |
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| Enthalten in: |
EBioMedicine - 99(2024) vom: 19. Jan., Seite 104916 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Hu, Bingjie [VerfasserIn] |
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| Links: |
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| Themen: |
Aged mice |
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| Anmerkungen: |
Date Completed 22.01.2024 Date Revised 22.01.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.ebiom.2023.104916 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 245 | 1 | 0 | |a Divergent trajectory of replication and intrinsic pathogenicity of SARS-CoV-2 Omicron post-BA.2/5 subvariants in the upper and lower respiratory tract |
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| 520 | |a Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved. | ||
| 520 | |a BACKGROUND: Earlier Omicron subvariants including BA.1, BA.2, and BA.5 emerged in waves, with a subvariant replacing the previous one every few months. More recently, the post-BA.2/5 subvariants have acquired convergent substitutions in spike that facilitated their escape from humoral immunity and gained ACE2 binding capacity. However, the intrinsic pathogenicity and replication fitness of the evaluated post-BA.2/5 subvariants are not fully understood | ||
| 520 | |a METHODS: We systemically investigated the replication fitness and intrinsic pathogenicity of representative post-BA.2/5 subvariants (BL.1, BQ.1, BQ.1.1, XBB.1, CH.1.1, and XBB.1.5) in weanling (3-4 weeks), adult (8-10 weeks), and aged (10-12 months) mice. In addition, to better model Omicron replication in the human nasal epithelium, we further investigated the replication capacity of the post-BA.2/5 subvariants in human primary nasal epithelial cells | ||
| 520 | |a FINDINGS: We found that the evaluated post-BA.2/5 subvariants are consistently attenuated in mouse lungs but not in nasal turbinates when compared with their ancestral subvariants BA.2/5. Further investigations in primary human nasal epithelial cells revealed a gained replication fitness of XBB.1 and XBB.1.5 when compared to BA.2 and BA.5.2 | ||
| 520 | |a INTERPRETATION: Our study revealed that the post-BA.2/5 subvariants are attenuated in lungs while increased in replication fitness in the nasal epithelium, indicating rapid adaptation of the circulating Omicron subvariants in the human populations | ||
| 520 | |a FUNDING: The full list of funding can be found at the Acknowledgements section | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Aged mice | |
| 650 | 4 | |a Human primary nasal epithelial cells | |
| 650 | 4 | |a Omicron | |
| 650 | 4 | |a Post-BA.2/5 subvariants | |
| 650 | 4 | |a SARS-CoV-2 | |
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| 700 | 1 | |a Liu, Yuanchen |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Huan |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Yan-Xia |e verfasserin |4 aut | |
| 700 | 1 | |a Shuai, Huiping |e verfasserin |4 aut | |
| 700 | 1 | |a Hu, Ye-Fan |e verfasserin |4 aut | |
| 700 | 1 | |a Hartnoll, Madeline |e verfasserin |4 aut | |
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| 700 | 1 | |a Hou, Yuxin |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Xiner |e verfasserin |4 aut | |
| 700 | 1 | |a Chai, Yue |e verfasserin |4 aut | |
| 700 | 1 | |a Zhu, Tianrenzheng |e verfasserin |4 aut | |
| 700 | 1 | |a Shi, Jialu |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Yang |e verfasserin |4 aut | |
| 700 | 1 | |a He, Yixin |e verfasserin |4 aut | |
| 700 | 1 | |a Cai, Jian-Piao |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Jie |e verfasserin |4 aut | |
| 700 | 1 | |a Yuan, Shuofeng |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Jinxia |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Jian-Dong |e verfasserin |4 aut | |
| 700 | 1 | |a Yuen, Kwok-Yung |e verfasserin |4 aut | |
| 700 | 1 | |a To, Kelvin Kai-Wang |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Bao-Zhong |e verfasserin |4 aut | |
| 700 | 1 | |a Chu, Hin |e verfasserin |4 aut | |
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