Abstract

In late 2022, various Omicron subvariants emerged and cocirculated worldwide. These variants convergently acquired amino acid substitutions at critical residues in the spike protein, including residues R346, K444, L452, N460, and F486. Here, we characterize the convergent evolution of Omicron subvariants and the properties of one recent lineage of concern, BQ.1.1. Our phylogenetic analysis suggests that these five substitutions are recurrently acquired, particularly in younger Omicron lineages. Epidemic dynamics modelling suggests that the five substitutions increase viral fitness, and a large proportion of the fitness variation within Omicron lineages can be explained by these substitutions. Compared to BA.5, BQ.1.1 evades breakthrough BA.2 and BA.5 infection sera more efficiently, as demonstrated by neutralization assays. The pathogenicity of BQ.1.1 in hamsters is lower than that of BA.5. Our multiscale investigations illuminate the evolutionary rules governing the convergent evolution for known Omicron lineages as of 2022.

Recent Omicron SARS-CoV-2 subvariants independently acquire 5 key Spike mutations. Here, the authors evaluate the evolutionary importance of the 5 mutations and characterize the virological properties of variant BQ.1.1 harboring all 5 mutations.

Details

Title
Convergent evolution of SARS-CoV-2 Omicron subvariants leading to the emergence of BQ.1.1 variant
Author
Ito, Jumpei 1   VIAFID ORCID Logo  ; Suzuki, Rigel 2 ; Uriu, Keiya 3 ; Itakura, Yukari 4   VIAFID ORCID Logo  ; Zahradnik, Jiri 5   VIAFID ORCID Logo  ; Kimura, Kanako Terakado 6 ; Deguchi, Sayaka 7 ; Wang, Lei 8   VIAFID ORCID Logo  ; Lytras, Spyros 9   VIAFID ORCID Logo  ; Tamura, Tomokazu 2 ; Kida, Izumi 10   VIAFID ORCID Logo  ; Nasser, Hesham 11   VIAFID ORCID Logo  ; Shofa, Maya 12 ; Begum, Mst Monira 13 ; Tsuda, Masumi 8   VIAFID ORCID Logo  ; Oda, Yoshitaka 14 ; Suzuki, Tateki 6   VIAFID ORCID Logo  ; Sasaki, Jiei 6 ; Sasaki-Tabata, Kaori 15 ; Fujita, Shigeru 3   VIAFID ORCID Logo  ; Yoshimatsu, Kumiko 16   VIAFID ORCID Logo  ; Ito, Hayato 2 ; Nao, Naganori 17 ; Asakura, Hiroyuki 18 ; Nagashima, Mami 18 ; Sadamasu, Kenji 18 ; Yoshimura, Kazuhisa 18 ; Yamamoto, Yuki 19 ; Nagamoto, Tetsuharu 19 ; Kuramochi, Jin 20   VIAFID ORCID Logo  ; Schreiber, Gideon 21   VIAFID ORCID Logo  ; Suzuki, Saori 2 ; Kato, Marie 14 ; Ferdous, Zannatul 14 ; Mouri, Hiromi 14 ; Shishido, Kenji 14 ; Misawa, Naoko 1 ; Kimura, Izumi 1 ; Kosugi, Yusuke 1 ; Lin, Pan 1 ; Suganami, Mai 1 ; Chiba, Mika 1 ; Yoshimura, Ryo 1 ; Yasuda, Kyoko 1 ; Iida, Keiko 1 ; Ohsumi, Naomi 1 ; Strange, Adam P. 1 ; Sauter, Daniel 22 ; Nakagawa, So 23 ; Wu, Jiaqi 23 ; Watanabe, Yukio 7 ; Sakamoto, Ayaka 7 ; Yasuhara, Naoko 7 ; Nakajima, Yukari 24 ; Yajima, Hisano 24 ; Shirakawa, Kotaro 24 ; Takaori-Kondo, Akifumi 24 ; Nagata, Kayoko 24 ; Kazuma, Yasuhiro 24 ; Nomura, Ryosuke 24 ; Horisawa, Yoshihito 24 ; Tashiro, Yusuke 24 ; Kawa, Yugo 24 ; Irie, Takashi 25 ; Kawabata, Ryoko 25 ; Shimizu, Ryo 13 ; Takahashi, Otowa 13 ; Ichihara, Kimiko 13 ; Motozono, Chihiro 26 ; Toyoda, Mako 26 ; Ueno, Takamasa 26 ; Shibatani, Yuki 27 ; Nishiuchi, Tomoko 27 ; Saito, Akatsuki 28   VIAFID ORCID Logo  ; Matsuno, Keita 29   VIAFID ORCID Logo  ; Takayama, Kazuo 30 ; Hashiguchi, Takao 6   VIAFID ORCID Logo  ; Tanaka, Shinya 8   VIAFID ORCID Logo  ; Fukuhara, Takasuke 31   VIAFID ORCID Logo  ; Ikeda, Terumasa 13   VIAFID ORCID Logo  ; Sato, Kei 32   VIAFID ORCID Logo 

1  The University of Tokyo, Division of Systems Virology, Department of Microbiology and Immunology, The Institute of Medical Science, Tokyo, Japan (GRID:grid.26999.3d) (ISNI:0000 0001 2151 536X) 
2  Hokkaido University, Department of Microbiology and Immunology, Faculty of Medicine, Sapporo, Japan (GRID:grid.39158.36) (ISNI:0000 0001 2173 7691) 
3  The University of Tokyo, Division of Systems Virology, Department of Microbiology and Immunology, The Institute of Medical Science, Tokyo, Japan (GRID:grid.26999.3d) (ISNI:0000 0001 2151 536X); The University of Tokyo, Graduate School of Medicine, Tokyo, Japan (GRID:grid.26999.3d) (ISNI:0000 0001 2151 536X) 
4  Hokkaido University, Division of Molecular Pathobiology, International Institute for Zoonosis Control, Sapporo, Japan (GRID:grid.39158.36) (ISNI:0000 0001 2173 7691) 
5  Weizmann Institute of Science, Department of Biomolecular Sciences, Rehovot, Israel (GRID:grid.13992.30) (ISNI:0000 0004 0604 7563); Charles University, First Medical Faculty at Biocev, Vestec-Prague, Czechia (GRID:grid.4491.8) (ISNI:0000 0004 1937 116X) 
6  Kyoto University, Laboratory of Medical Virology, Institute for Life and Medical Sciences, Kyoto, Japan (GRID:grid.258799.8) (ISNI:0000 0004 0372 2033) 
7  Kyoto University, Center for iPS Cell Research and Application (CiRA), Kyoto, Japan (GRID:grid.258799.8) (ISNI:0000 0004 0372 2033) 
8  Hokkaido University, Department of Cancer Pathology, Faculty of Medicine, Sapporo, Japan (GRID:grid.39158.36) (ISNI:0000 0001 2173 7691); Hokkaido University, Institute for Chemical Reaction Design and Discovery (WPI-ICReDD), Sapporo, Japan (GRID:grid.39158.36) (ISNI:0000 0001 2173 7691) 
9  Medical Research Council-University of Glasgow Centre for Virus Research, Glasgow, UK (GRID:grid.8756.c) (ISNI:0000 0001 2193 314X) 
10  Hokkaido University, Division of Risk Analysis and Management, International Institute for Zoonosis Control, Sapporo, Japan (GRID:grid.39158.36) (ISNI:0000 0001 2173 7691) 
11  Kumamoto University, Division of Molecular Virology and Genetics, Joint Research Center for Human Retrovirus infection, Kumamoto, Japan (GRID:grid.274841.c) (ISNI:0000 0001 0660 6749); Suez Canal University, Department of Clinical Pathology, Faculty of Medicine, Ismailia, Egypt (GRID:grid.33003.33) (ISNI:0000 0000 9889 5690) 
12  University of Miyazaki, Department of Veterinary Science, Faculty of Agriculture, Miyazaki, Japan (GRID:grid.410849.0) (ISNI:0000 0001 0657 3887); University of Miyazaki, Graduate School of Medicine and Veterinary Medicine, Miyazaki, Japan (GRID:grid.410849.0) (ISNI:0000 0001 0657 3887) 
13  Kumamoto University, Division of Molecular Virology and Genetics, Joint Research Center for Human Retrovirus infection, Kumamoto, Japan (GRID:grid.274841.c) (ISNI:0000 0001 0660 6749) 
14  Hokkaido University, Department of Cancer Pathology, Faculty of Medicine, Sapporo, Japan (GRID:grid.39158.36) (ISNI:0000 0001 2173 7691) 
15  Kyushu University, Department of Medicinal Sciences, Graduate School of Pharmaceutical Sciences, Fukuoka, Japan (GRID:grid.177174.3) (ISNI:0000 0001 2242 4849) 
16  Hokkaido University, Institute for Genetic Medicine, Sapporo, Japan (GRID:grid.39158.36) (ISNI:0000 0001 2173 7691) 
17  Hokkaido University, Division of International Research Promotion, International Institute for Zoonosis Control, Sapporo, Japan (GRID:grid.39158.36) (ISNI:0000 0001 2173 7691); Hokkaido University, One Health Research Center, Sapporo, Japan (GRID:grid.39158.36) (ISNI:0000 0001 2173 7691); Hokkaido University, Institute for Vaccine Research and Development: HU-IVReD, Sapporo, Japan (GRID:grid.39158.36) (ISNI:0000 0001 2173 7691) 
18  Tokyo Metropolitan Institute of Public Health, Tokyo, Japan (GRID:grid.417096.d) 
19  HiLung, Inc, Kyoto, Japan (GRID:grid.417096.d) 
20  Interpark Kuramochi Clinic, Utsunomiya, Japan (GRID:grid.417096.d); Tokyo Medical and Dental University, Department of Global Health Promotion, Tokyo, Japan (GRID:grid.265073.5) (ISNI:0000 0001 1014 9130) 
21  Weizmann Institute of Science, Department of Biomolecular Sciences, Rehovot, Israel (GRID:grid.13992.30) (ISNI:0000 0004 0604 7563) 
22  The University of Tokyo, Division of Systems Virology, Department of Microbiology and Immunology, The Institute of Medical Science, Tokyo, Japan (GRID:grid.26999.3d) (ISNI:0000 0001 2151 536X); University Hospital Tübingen, Tübingen, Germany (GRID:grid.411544.1) (ISNI:0000 0001 0196 8249) 
23  Tokai University School of Medicine, Isehara, Japan (GRID:grid.265061.6) (ISNI:0000 0001 1516 6626) 
24  Kyoto University, Kyoto, Japan (GRID:grid.258799.8) (ISNI:0000 0004 0372 2033) 
25  Hiroshima University, Hiroshima, Japan (GRID:grid.257022.0) (ISNI:0000 0000 8711 3200) 
26  Kumamoto University, Kumamoto, Japan (GRID:grid.274841.c) (ISNI:0000 0001 0660 6749) 
27  University of Miyazaki, Department of Veterinary Science, Faculty of Agriculture, Miyazaki, Japan (GRID:grid.410849.0) (ISNI:0000 0001 0657 3887) 
28  University of Miyazaki, Department of Veterinary Science, Faculty of Agriculture, Miyazaki, Japan (GRID:grid.410849.0) (ISNI:0000 0001 0657 3887); University of Miyazaki, Graduate School of Medicine and Veterinary Medicine, Miyazaki, Japan (GRID:grid.410849.0) (ISNI:0000 0001 0657 3887); University of Miyazaki, Center for Animal Disease Control, Miyazaki, Japan (GRID:grid.410849.0) (ISNI:0000 0001 0657 3887) 
29  Hokkaido University, Division of Risk Analysis and Management, International Institute for Zoonosis Control, Sapporo, Japan (GRID:grid.39158.36) (ISNI:0000 0001 2173 7691); Hokkaido University, Institute for Vaccine Research and Development: HU-IVReD, Sapporo, Japan (GRID:grid.39158.36) (ISNI:0000 0001 2173 7691); Hokkaido University, International Collaboration Unit, International Institute for Zoonosis Control, Sapporo, Japan (GRID:grid.39158.36) (ISNI:0000 0001 2173 7691) 
30  Kyoto University, Center for iPS Cell Research and Application (CiRA), Kyoto, Japan (GRID:grid.258799.8) (ISNI:0000 0004 0372 2033); AMED-CREST, Japan Agency for Medical Research and Development (AMED), Tokyo, Japan (GRID:grid.480536.c) (ISNI:0000 0004 5373 4593) 
31  Hokkaido University, Department of Microbiology and Immunology, Faculty of Medicine, Sapporo, Japan (GRID:grid.39158.36) (ISNI:0000 0001 2173 7691); AMED-CREST, Japan Agency for Medical Research and Development (AMED), Tokyo, Japan (GRID:grid.480536.c) (ISNI:0000 0004 5373 4593); Osaka University, Laboratory of Virus Control, Research Institute for Microbial Diseases, Suita, Japan (GRID:grid.136593.b) (ISNI:0000 0004 0373 3971) 
32  The University of Tokyo, Division of Systems Virology, Department of Microbiology and Immunology, The Institute of Medical Science, Tokyo, Japan (GRID:grid.26999.3d) (ISNI:0000 0001 2151 536X); The University of Tokyo, Graduate School of Medicine, Tokyo, Japan (GRID:grid.26999.3d) (ISNI:0000 0001 2151 536X); The University of Tokyo, International Research Center for Infectious Diseases, The Institute of Medical Science, Tokyo, Japan (GRID:grid.26999.3d) (ISNI:0000 0001 2151 536X); The University of Tokyo, International Vaccine Design Center, The Institute of Medical Science, Tokyo, Japan (GRID:grid.26999.3d) (ISNI:0000 0001 2151 536X); The University of Tokyo, Graduate School of Frontier Sciences, Kashiwa, Japan (GRID:grid.26999.3d) (ISNI:0000 0001 2151 536X); Kumamoto University, Collaboration Unit for Infection, Joint Research Center for Human Retrovirus infection, Kumamoto, Japan (GRID:grid.274841.c) (ISNI:0000 0001 0660 6749); CREST, Japan Science and Technology Agency, Kawaguchi, Japan (GRID:grid.419082.6) (ISNI:0000 0004 1754 9200) 
Pages
2671
Publication year
2023
Publication date
2023
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41467-023-38188-z
ProQuest document ID
2812330308
Copyright
© The Author(s) 2023. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.