Virological characteristics of the SARS-CoV-2 Omicron XBB.1.5 variant

Tomokazu Tamura, Takashi Irie, Sayaka Deguchi, Hisano Yajima, Masumi Tsuda, Hesham Nasser, Keita Mizuma, Arnon Plianchaisuk, Saori Suzuki, Keiya Uriu, Mst Monira Begum, Ryo Shimizu, Michael Jonathan, Rigel Suzuki, Takashi Kondo, Hayato Ito, Akifumi Kamiyama, Kumiko Yoshimatsu, Maya Shofa, Rina Hashimoto, Yuki Anraku, Kanako Terakado Kimura, Shunsuke Kita, Jiei Sasaki, Kaori Sasaki-Tabata, Katsumi Maenaka, Naganori Nao, Lei Wang, Yoshitaka Oda, Terumasa Ikeda, Akatsuki Saito, Keita Matsuno, Jumpei Ito, Shinya Tanaka (), Kei Sato (), Takao Hashiguchi (), Kazuo Takayama () and Takasuke Fukuhara ()
Additional contact information
Tomokazu Tamura: Hokkaido University
Takashi Irie: Hiroshima University
Sayaka Deguchi: Kyoto University
Hisano Yajima: Kyoto University
Masumi Tsuda: Hokkaido University
Hesham Nasser: Kumamoto University
Keita Mizuma: Hokkaido University
Arnon Plianchaisuk: The University of Tokyo
Saori Suzuki: Hokkaido University
Keiya Uriu: The University of Tokyo
Mst Monira Begum: Kumamoto University
Ryo Shimizu: Kumamoto University
Michael Jonathan: Kumamoto University
Rigel Suzuki: Hokkaido University
Takashi Kondo: Hokkaido University
Hayato Ito: Hokkaido University
Akifumi Kamiyama: Hokkaido University
Kumiko Yoshimatsu: Hokkaido University
Maya Shofa: University of Miyazaki
Rina Hashimoto: Kyoto University
Yuki Anraku: Hokkaido University
Kanako Terakado Kimura: Kyoto University
Shunsuke Kita: Hokkaido University
Jiei Sasaki: Kyoto University
Kaori Sasaki-Tabata: Kyushu University
Katsumi Maenaka: Hokkaido University
Naganori Nao: Hokkaido University
Lei Wang: Hokkaido University
Yoshitaka Oda: Hokkaido University
Terumasa Ikeda: Kumamoto University
Akatsuki Saito: University of Miyazaki
Keita Matsuno: Hokkaido University
Jumpei Ito: The University of Tokyo
Shinya Tanaka: Hokkaido University
Kei Sato: The University of Tokyo
Takao Hashiguchi: Kyoto University
Kazuo Takayama: Kyoto University
Takasuke Fukuhara: Hokkaido University

Nature Communications, 2024, vol. 15, issue 1, 1-17

Abstract: Abstract Circulation of SARS-CoV-2 Omicron XBB has resulted in the emergence of XBB.1.5, a new Variant of Interest. Our phylogenetic analysis suggests that XBB.1.5 evolved from XBB.1 by acquiring the S486P spike (S) mutation, subsequent to the acquisition of a nonsense mutation in ORF8. Neutralization assays showed similar abilities of immune escape between XBB.1.5 and XBB.1. We determine the structural basis for the interaction between human ACE2 and the S protein of XBB.1.5, showing similar overall structures between the S proteins of XBB.1 and XBB.1.5. We provide the intrinsic pathogenicity of XBB.1 and XBB.1.5 in hamsters. Importantly, we find that the ORF8 nonsense mutation of XBB.1.5 resulted in impairment of MHC suppression. In vivo experiments using recombinant viruses reveal that the XBB.1.5 mutations are involved with reduced virulence of XBB.1.5. Together, our study identifies the two viral functions defined the difference between XBB.1 and XBB.1.5.

Date: 2024
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DOI: 10.1038/s41467-024-45274-3

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