Multiple mutations of SARS-CoV-2 Omicron BA.2 variant orchestrate its virological characteristics

Izumi Kimura; Daichi Yamasoba; Hesham Nasser; Hayato Ito; Jiri Zahradnik; Jiaqi Wu; Shigeru Fujita; Keiya Uriu; Jiei Sasaki; Tomokazu Tamura; Rigel Suzuki; Sayaka Deguchi; Arnon Plianchaisuk; Kumiko Yoshimatsu; Yasuhiro Kazuma; Shuya Mitoma; Gideon Schreiber; Hiroyuki Asakura; Mami Nagashima; Kenji Sadamasu; Kazuhisa Yoshimura; Akifumi Takaori-Kondo; Genotype to Phenotype Japan (G2P-Japan) Consortium; Jumpei Ito; Kotaro Shirakawa; Kazuo Takayama; Takashi Irie; Takao Hashiguchi; So Nakagawa; Takasuke Fukuhara; Akatsuki Saito; Terumasa Ikeda; Kei Sato

doi:10.1128/jvi.01011-23

Multiple mutations of SARS-CoV-2 Omicron BA.2 variant orchestrate its virological characteristics

J Virol. 2023 Oct 31;97(10):e0101123. doi: 10.1128/jvi.01011-23. Epub 2023 Oct 5.

Authors

Izumi Kimura^#¹, Daichi Yamasoba^#^{1

2}, Hesham Nasser^#^{3

4}, Hayato Ito^#⁵, Jiri Zahradnik^#^{6

7}, Jiaqi Wu^#⁸, Shigeru Fujita^#^{1

9}, Keiya Uriu^#^{1

9}, Jiei Sasaki¹⁰, Tomokazu Tamura^{5

11}, Rigel Suzuki^{5

11}, Sayaka Deguchi¹², Arnon Plianchaisuk¹, Kumiko Yoshimatsu¹³, Yasuhiro Kazuma¹⁴, Shuya Mitoma^{15

16}, Gideon Schreiber⁶, Hiroyuki Asakura¹⁷, Mami Nagashima¹⁷, Kenji Sadamasu¹⁷, Kazuhisa Yoshimura¹⁷, Akifumi Takaori-Kondo¹⁴; Genotype to Phenotype Japan (G2P-Japan) Consortium; Jumpei Ito^{1

18}, Kotaro Shirakawa¹⁴, Kazuo Takayama^{12

19}, Takashi Irie²⁰, Takao Hashiguchi¹⁰, So Nakagawa^{8

21

22}, Takasuke Fukuhara^{5

11

19

23}, Akatsuki Saito^{15

16

24}, Terumasa Ikeda³, Kei Sato^{1

9

18

21

25

26

27}

Collaborators

Genotype to Phenotype Japan (G2P-Japan) Consortium:
Naoko Misawa, Yusuke Kosugi, Lin Pan, Mai Suganami, Mika Chiba, Ryo Yoshimura, Kyoko Yasuda, Keiko Iida, Naomi Ohsumi, Adam P Strange, Yu Kaku, Arnon Plianchaisuk, Ziyi Guo, Alfredo Jr Amolong Hinay, Jarel Elgin Mendoza Tolentino, Luo Chen, Ryo Shimizu, M S T Monira Begum, Otowa Takahashi, Kimiko Ichihara, Michael Jonathan, Yuka Mugita, Saori Suzuki, Tateki Suzuki, Kanako Kimura, Yukari Nakajima, Hisano Yajima, Rina Hashimoto, Yukio Watanabe, Ayaka Sakamoto, Naoko Yasuhara, Kayoko Nagata, Ryosuke Nomura, Yoshihito Horisawa, Yusuke Tashiro, Yugo Kawai, Yuki Shibatani, Tomoko Nishiuchi, Isao Yoshida, Ryoko Kawabata, Keita Matsuno, Naganori Nao, Hirofumi Sawa, Shinya Tanaka, Masumi Tsuda, Lei Wang, Yoshikata Oda, Zannatul Ferdous, Kenji Shishido, Chihiro Motozono, Mako Toyoda, Takamasa Ueno, Kaori Tabata

Affiliations

¹ Division of Systems Virology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo , Tokyo, Japan.
² Faculty of Medicine, Kobe University , Kobe, Japan.
³ Division of Molecular Virology and Genetics, Joint Research Center for Human Retrovirus infection, Kumamoto University , Kumamoto, Japan.
⁴ Department of Clinical Pathology, Faculty of Medicine, Suez Canal University , Ismailia, Egypt.
⁵ Department of Microbiology and Immunology, Faculty of Medicine, Hokkaido University , Sapporo, Japan.
⁶ Department of Biomolecular Sciences, Weizmann Institute of Science , Rehovot, Israel.
⁷ First Medical Faculty at Biocev, Charles University , Vestec-Prague, Czechia.
⁸ Department of Molecular Life Science, Tokai University School of Medicine , Isehara, Japan.
⁹ Graduate School of Medicine, The University of Tokyo , Tokyo, Japan.
¹⁰ Laboratory of Medical Virology, Institute for Life and Medical Sciences, Kyoto University , Kyoto, Japan.
¹¹ Institute for Vaccine Research and Development (HU-IVReD), Hokkaido University , Sapporo, Japan.
¹² Center for iPS Cell Research and Application (CiRA), Kyoto University , Kyoto, Japan.
¹³ Institute for Genetic Medicine, Hokkaido University , Sapporo, Japan.
¹⁴ Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University , Kyoto, Japan.
¹⁵ Department of Veterinary Science, Faculty of Agriculture, University of Miyazaki , Miyazaki, Japan.
¹⁶ Graduate School of Medicine and Veterinary Medicine, University of Miyazaki , Miyazaki, Japan.
¹⁷ Tokyo Metropolitan Institute of Public Health , Tokyo, Japan.
¹⁸ International Research Center for Infectious Diseases, The Institute of Medical Science, The University of Tokyo , Tokyo, Japan.
¹⁹ AMED-CREST, Japan Agency for Medical Research and Development (AMED) , Tokyo, Japan.
²⁰ Graduate School of Biomedical and Health Sciences, Hiroshima University , Hiroshima, Japan.
²¹ CREST, Japan Science and Technology Agency , Saitama, Japan.
²² Bioinformation and DDBJ Center, National Institute of Genetics , Mishima, Japan.
²³ Laboratory of Virus Control, Research Institute for Microbial Diseases, Osaka University , Suita, Japan.
²⁴ Center for Animal Disease Control, University of Miyazaki , Miyazaki, Japan.
²⁵ International Vaccine Design Center, The Institute of Medical Science, The University of Tokyo , Tokyo, Japan.
²⁶ Graduate School of Frontier Sciences, The University of Tokyo , Kashiwa, Japan.
²⁷ Collaboration Unit for Infection, Joint Research Center for Human Retrovirus infection, Kumamoto University , Kumamoto, Japan.

^# Contributed equally.

Abstract

Most studies investigating the characteristics of emerging SARS-CoV-2 variants have been focusing on mutations in the spike proteins that affect viral infectivity, fusogenicity, and pathogenicity. However, few studies have addressed how naturally occurring mutations in the non-spike regions of the SARS-CoV-2 genome impact virological properties. In this study, we proved that multiple SARS-CoV-2 Omicron BA.2 mutations, one in the spike protein and another downstream of the spike gene, orchestrally characterize this variant, shedding light on the importance of Omicron BA.2 mutations out of the spike protein.

Keywords: BA.1; BA.2; COVID-19; Omicron; SARS-CoV-2; fusogenicity; growth capacity; immune resistance; pathogenicity.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

COVID-19 / virology
Genome, Viral* / genetics
Humans
Mutation*
SARS-CoV-2* / genetics
SARS-CoV-2* / pathogenicity
SARS-CoV-2* / physiology
Spike Glycoprotein, Coronavirus* / genetics

Multiple mutations of SARS-CoV-2 Omicron BA.2 variant orchestrate its virological characteristics

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