Abstract

In late 2022, SARS-CoV-2 Omicron subvariants have become highly diversified, and XBB is spreading rapidly around the world. Our phylogenetic analyses suggested that XBB emerged through the recombination of two cocirculating BA.2 lineages, BJ.1 and BM.1.1.1 (a progeny of BA.2.75), during the summer of 2022. XBB.1 is the variant most profoundly resistant to BA.2/5 breakthrough infection sera to date and is more fusogenic than BA.2.75. The recombination breakpoint is located in the receptor-binding domain of spike, and each region of the recombinant spike confers immune evasion and increases fusogenicity. We further provide the structural basis for the interaction between XBB.1 spike and human ACE2. Finally, the intrinsic pathogenicity of XBB.1 in male hamsters is comparable to or even lower than that of BA.2.75. Our multiscale investigation provides evidence suggesting that XBB is the first observed SARS-CoV-2 variant to increase its fitness through recombination rather than substitutions.

XBB is the first recombinant, globally dominant variant of SARS-CoV-2. Here, the authors examine the variant’s origins and virological properties, showing it is the first example of SARS-CoV-2 improving its fitness through recombination.

Details

Title
Virological characteristics of the SARS-CoV-2 XBB variant derived from recombination of two Omicron subvariants
Author
Tamura, Tomokazu 1   VIAFID ORCID Logo  ; Ito, Jumpei 2   VIAFID ORCID Logo  ; Uriu, Keiya 3 ; Zahradnik, Jiri 4   VIAFID ORCID Logo  ; Kida, Izumi 5   VIAFID ORCID Logo  ; Anraku, Yuki 6   VIAFID ORCID Logo  ; Nasser, Hesham 7   VIAFID ORCID Logo  ; Shofa, Maya 8 ; Oda, Yoshitaka 9 ; Lytras, Spyros 10   VIAFID ORCID Logo  ; Nao, Naganori 11 ; Itakura, Yukari 12   VIAFID ORCID Logo  ; Deguchi, Sayaka 13 ; Suzuki, Rigel 1 ; Wang, Lei 14   VIAFID ORCID Logo  ; Begum, MST Monira 15 ; Kita, Shunsuke 6   VIAFID ORCID Logo  ; Yajima, Hisano 16 ; Sasaki, Jiei 16 ; Sasaki-Tabata, Kaori 17 ; Shimizu, Ryo 15 ; Tsuda, Masumi 14   VIAFID ORCID Logo  ; Kosugi, Yusuke 3 ; Fujita, Shigeru 3   VIAFID ORCID Logo  ; Pan, Lin 18 ; Sauter, Daniel 19   VIAFID ORCID Logo  ; Yoshimatsu, Kumiko 20   VIAFID ORCID Logo  ; Suzuki, Saori 1   VIAFID ORCID Logo  ; Asakura, Hiroyuki 21 ; Nagashima, Mami 21 ; Sadamasu, Kenji 21 ; Yoshimura, Kazuhisa 21 ; Yamamoto, Yuki 22 ; Nagamoto, Tetsuharu 22 ; Schreiber, Gideon 23   VIAFID ORCID Logo  ; Maenaka, Katsumi 24   VIAFID ORCID Logo  ; Ito, Hayato 25 ; Misawa, Naoko 2 ; Kimura, Izumi 2 ; Suganami, Mai 2 ; Chiba, Mika 2 ; Yoshimura, Ryo 2 ; Yasuda, Kyoko 2 ; Iida, Keiko 2 ; Ohsumi, Naomi 2 ; Strange, Adam P. 2 ; Takahashi, Otowa 15 ; Ichihara, Kimiko 15 ; Shibatani, Yuki 26 ; Nishiuchi, Tomoko 26 ; Kato, Marie 9 ; Ferdous, Zannatul 9 ; Mouri, Hiromi 9 ; Shishido, Kenji 9 ; Sawa, Hirofumi 27 ; Hashimoto, Rina 13 ; Watanabe, Yukio 13 ; Sakamoto, Ayaka 13 ; Yasuhara, Naoko 13 ; Suzuki, Tateki 16 ; Kimura, Kanako 16 ; Nakajima, Yukari 16 ; Nakagawa, So 28 ; Wu, Jiaqi 28 ; Shirakawa, Kotaro 29 ; Takaori-Kondo, Akifumi 29 ; Nagata, Kayoko 29 ; Kazuma, Yasuhiro 29 ; Nomura, Ryosuke 29 ; Horisawa, Yoshihito 29 ; Tashiro, Yusuke 29 ; Kawai, Yugo 29 ; Irie, Takashi 30 ; Kawabata, Ryoko 30 ; Motozono, Chihiro 31 ; Toyoda, Mako 31 ; Ueno, Takamasa 31 ; Hashiguchi, Takao 32   VIAFID ORCID Logo  ; Ikeda, Terumasa 15   VIAFID ORCID Logo  ; Fukuhara, Takasuke 33   VIAFID ORCID Logo  ; Saito, Akatsuki 34   VIAFID ORCID Logo  ; Tanaka, Shinya 14   VIAFID ORCID Logo  ; Matsuno, Keita 35   VIAFID ORCID Logo  ; Takayama, Kazuo 36 ; Sato, Kei 37   VIAFID ORCID Logo 

1  Hokkaido University, Department of Microbiology and Immunology, Faculty of Medicine, 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) 
2  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) 
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  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) 
5  Hokkaido University, Division of Risk Analysis and Management, International Institute for Zoonosis Control, Sapporo, Japan (GRID:grid.39158.36) (ISNI:0000 0001 2173 7691) 
6  Hokkaido University, Laboratory of Biomolecular Science and Center for Research and Education on Drug Discovery, Faculty of Pharmaceutical Sciences, Sapporo, Japan (GRID:grid.39158.36) (ISNI:0000 0001 2173 7691) 
7  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) 
8  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) 
9  Hokkaido University, Department of Cancer Pathology, Faculty of Medicine, Sapporo, Japan (GRID:grid.39158.36) (ISNI:0000 0001 2173 7691) 
10  Medical Research Council-University of Glasgow Centre for Virus Research, Glasgow, UK (GRID:grid.8756.c) (ISNI:0000 0001 2193 314X) 
11  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) 
12  Hokkaido University, Institute for Vaccine Research and Development, HU-IVReD, Sapporo, Japan (GRID:grid.39158.36) (ISNI:0000 0001 2173 7691); Hokkaido University, Division of Molecular Pathobiology, International Institute for Zoonosis Control, Sapporo, Japan (GRID:grid.39158.36) (ISNI:0000 0001 2173 7691) 
13  Kyoto University, Center for iPS Cell Research and Application (CiRA), Kyoto, Japan (GRID:grid.258799.8) (ISNI:0000 0004 0372 2033) 
14  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) 
15  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) 
16  Kyoto University, Laboratory of Medical Virology, Institute for Life and Medical Sciences, Kyoto, Japan (GRID:grid.258799.8) (ISNI:0000 0004 0372 2033) 
17  Kyushu University, Department of Medicinal Sciences, Graduate School of Pharmaceutical Sciences, Fukuoka, Japan (GRID:grid.177174.3) (ISNI:0000 0001 2242 4849) 
18  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 Frontier Sciences, Kashiwa, Japan (GRID:grid.26999.3d) (ISNI:0000 0001 2151 536X) 
19  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, Institute for Medical Virology and Epidemiology of Viral Diseases, Tübingen, Germany (GRID:grid.411544.1) (ISNI:0000 0001 0196 8249) 
20  Hokkaido University, Institute for Genetic Medicine, Sapporo, Japan (GRID:grid.39158.36) (ISNI:0000 0001 2173 7691) 
21  Tokyo Metropolitan Institute of Public Health, Tokyo, Japan (GRID:grid.417096.d) 
22  HiLung, Inc., Kyoto, Japan (GRID:grid.417096.d) 
23  Weizmann Institute of Science, Department of Biomolecular Sciences, Rehovot, Israel (GRID:grid.13992.30) (ISNI:0000 0004 0604 7563) 
24  Hokkaido University, Institute for Vaccine Research and Development, HU-IVReD, Sapporo, Japan (GRID:grid.39158.36) (ISNI:0000 0001 2173 7691); Hokkaido University, Laboratory of Biomolecular Science and Center for Research and Education on Drug Discovery, Faculty of Pharmaceutical Sciences, Sapporo, Japan (GRID:grid.39158.36) (ISNI:0000 0001 2173 7691); Hokkaido University, Global Station for Biosurfaces and Drug Discovery, Sapporo, Japan (GRID:grid.39158.36) (ISNI:0000 0001 2173 7691); Hokkaido University, Division of Pathogen Structure, International Institute for Zoonosis Control, Sapporo, Japan (GRID:grid.39158.36) (ISNI:0000 0001 2173 7691) 
25  Hokkaido University, Department of Microbiology and Immunology, Faculty of Medicine, Sapporo, Japan (GRID:grid.39158.36) (ISNI:0000 0001 2173 7691) 
26  University of Miyazaki, Department of Veterinary Science, Faculty of Agriculture, Miyazaki, Japan (GRID:grid.410849.0) (ISNI:0000 0001 0657 3887) 
27  Hokkaido University, Institute for Vaccine Research and Development, HU-IVReD, Sapporo, Japan (GRID:grid.39158.36) (ISNI:0000 0001 2173 7691); 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, Division of Molecular Pathobiology, International Institute for Zoonosis Control, Sapporo, Japan (GRID:grid.39158.36) (ISNI:0000 0001 2173 7691) 
28  Tokai University School of Medicine, Isehara, Japan (GRID:grid.265061.6) (ISNI:0000 0001 1516 6626) 
29  Kyoto University, Kyoto, Japan (GRID:grid.258799.8) (ISNI:0000 0004 0372 2033) 
30  Hiroshima University, Hiroshima, Japan (GRID:grid.257022.0) (ISNI:0000 0000 8711 3200) 
31  Kumamoto University, Kumamoto, Japan (GRID:grid.274841.c) (ISNI:0000 0001 0660 6749) 
32  Kyoto University, Laboratory of Medical Virology, Institute for Life and Medical Sciences, Kyoto, Japan (GRID:grid.258799.8) (ISNI:0000 0004 0372 2033); CREST, Japan Science and Technology Agency, Kawaguchi, Japan (GRID:grid.419082.6) (ISNI:0000 0004 1754 9200) 
33  Hokkaido University, Department of Microbiology and Immunology, Faculty of Medicine, 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); 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) 
34  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) 
35  Hokkaido University, Institute for Vaccine Research and Development, HU-IVReD, Sapporo, Japan (GRID:grid.39158.36) (ISNI:0000 0001 2173 7691); 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, One Health Research Center, 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) 
36  Kyoto University, Center for iPS Cell Research and Application (CiRA), Kyoto, Japan (GRID:grid.258799.8) (ISNI:0000 0004 0372 2033); CREST, Japan Science and Technology Agency, Kawaguchi, Japan (GRID:grid.419082.6) (ISNI:0000 0004 1754 9200) 
37  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, Graduate School of Frontier Sciences, Kashiwa, Japan (GRID:grid.26999.3d) (ISNI:0000 0001 2151 536X); CREST, Japan Science and Technology Agency, Kawaguchi, Japan (GRID:grid.419082.6) (ISNI:0000 0004 1754 9200); 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); Kumamoto University, Collaboration Unit for Infection, Joint Research Center for Human Retrovirus infection, Kumamoto, Japan (GRID:grid.274841.c) (ISNI:0000 0001 0660 6749) 
Pages
2800
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/s41467-023-38435-3
ProQuest document ID
2814206715
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.