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Virological characteristics of the SARS-CoV-2 XBB variant derived from recombination of two Omicron subvariants

2023; Nature Portfolio; Volume: 14; Issue: 1 Linguagem: Inglês

10.1038/s41467-023-38435-3

2041-1723

Tomokazu Tamura, Jumpei Ito, Keiya Uriu, Jiří Zahradník, Izumi Kida, Yuki Anraku, Hesham Nasser, Maya Shofa, Yoshitaka Oda, Spyros Lytras, Naganori Nao, Yukari Itakura, Sayaka Deguchi, Rigel Suzuki, Lei Wang, MST Monira Begum, Shunsuke Kita, Hisano Yajima, Jiei Sasaki, Kaori Sasaki‐Tabata, Ryo Shimizu, Masumi Tsuda, Yusuke Kosugi, Shigeru Fujita, Lin Pan, Daniel Sauter, Kumiko Yoshimatsu, Saori Suzuki, Hiroyuki Asakura, Mami Nagashima, Kenji Sadamasu, Kazuhisa Yoshimura, Yuki Yamamoto, Tetsuharu Nagamoto, Gideon Schreiber, Katsumi Maenaka, Hayato Ito, Naoko Misawa, Izumi Kimura, Mai Suganami, Mika Chiba, Ryo Yoshimura, Kyoko Yasuda, Keiko Iida, Naomi Ohsumi, Adam Strange, Otowa Takahashi, Kimiko Ichihara, Yuki Shibatani, Tomoko Nishiuchi, Marie Kato, Zannatul Ferdous, Hiromi Mouri, Kenji Shishido, Hirofumi Sawa, Rina Hashimoto, Yukio Watanabe, Ayaka Sakamoto, Naoko Yasuhara, Tateki Suzuki, Kanako Kimura, Yukari Nakajima, So Nakagawa, Jiaqi Wu, Kotaro Shirakawa, Akifumi Takaori‐Kondo, Kayoko Nagata, Yasuhiro Kazuma, Ryosuke Nomura, Yoshihito Horisawa, Yusuke Tashiro, Yugo Kawai, Takashi Irie, Ryoko Kawabata, Chihiro Motozono, Mako Toyoda, Takamasa Ueno, Takao Hashiguchi, Terumasa Ikeda, Takasuke Fukuhara, Akatsuki Saito, Shinya Tanaka, Keita Matsuno, Kazuo Takayama, Kei Sato,

Animal Virus Infections Studies

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.