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

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作者
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
Takasuke Fukuhara
机构
[1] Hokkaido University,Department of Microbiology and Immunology, Faculty of Medicine
[2] Hokkaido University,Graduate School of Medicine
[3] Hokkaido University,School of Medicine
[4] Hokkaido University,Institute for the Advancement of Higher Education
[5] Hokkaido University,Institute for Vaccine Research and Development (IVReD)
[6] Hokkaido University,One Health Research Center
[7] Hiroshima University,Graduate School of Biomedical and Health Sciences
[8] Kyoto University,Center for iPS Cell Research and Application (CiRA)
[9] Kyoto University,Laboratory of Medical Virology, Institute for Life and Medical Sciences
[10] Hokkaido University,Department of Cancer Pathology, Faculty of Medicine
[11] Hokkaido University,Institute for Chemical Reaction Design and Discovery (WPI
[12] Kumamoto University,ICReDD)
[13] Suez Canal University,Division of Molecular Virology and Genetics, Joint Research Center for Human Retrovirus Infection
[14] Hokkaido University,Department of Clinical Pathology, Faculty of Medicine
[15] The University of Tokyo,Division of Risk Analysis and Management, International Institute for Zoonosis Control
[16] The University of Tokyo,Division of Systems Virology, Department of Microbiology and Immunology, The Institute of Medical Science
[17] Hokkaido University,Graduate School of Medicine
[18] University of Miyazaki,Institute for Genetic Medicine
[19] University of Miyazaki,Department of Veterinary Science, Faculty of Agriculture
[20] Hokkaido University,Graduate School of Medicine and Veterinary Medicine
[21] Kyushu University,Laboratory of Biomolecular Science and Center for Research and Education on Drug Discovery, Faculty of Pharmaceutical Sciences
[22] Hokkaido University,Department of Medicinal Sciences, Graduate School of Pharmaceutical Sciences
[23] Hokkaido University,Division of Pathogen Structure, International Institute for Zoonosis Control
[24] Hokkaido University,Global Station for Biosurfaces and Drug Discovery
[25] University of Miyazaki,Division of International Research Promotion, International Institute for Zoonosis Control
[26] Hokkaido University,Center for Animal Disease Control
[27] The University of Tokyo,International Collaboration Unit, International Institute for Zoonosis Control
[28] The University of Tokyo,International Research Center for Infectious Diseases, The Institute of Medical Science
[29] CREST,Graduate School of Frontier Sciences
[30] Japan Science and Technology Agency,International Vaccine Design Center, The Institute of Medical Science
[31] The University of Tokyo,Collaboration Unit for Infection, Joint Research Center for Human Retrovirus Infection
[32] Kumamoto University,Kyoto University Immunomonitoring Center
[33] Kyoto University,Laboratory of Virus Control, Research Institute for Microbial Diseases
[34] AMED-CREST,Division of Molecular Pathobiology, International Institute for Zoonosis Control
[35] Japan Agency for Medical Research and Development (AMED),School of Medicine
[36] Osaka University,Division of Infection and Immunity, Joint Research Center for Human Retrovirus Infection
[37] Hokkaido University,undefined
[38] Kobe University,undefined
[39] Tokyo Metropolitan Institute of Public Health,undefined
[40] Tokai University School of Medicine,undefined
[41] Kyoto University,undefined
[42] Kumamoto University,undefined
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摘要
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.
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