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Enhanced fusogenicity and pathogenicity of SARS-CoV-2 Delta P681R mutation

Author

Listed:
  • Akatsuki Saito

    (University of Miyazaki
    University of Miyazaki
    University of Miyazaki)

  • Takashi Irie

    (Hiroshima University)

  • Rigel Suzuki

    (Hokkaido University)

  • Tadashi Maemura

    (University of Tokyo
    University of Wisconsin-Madison)

  • Hesham Nasser

    (Kumamoto University
    Suez Canal University)

  • Keiya Uriu

    (The University of Tokyo)

  • Yusuke Kosugi

    (The University of Tokyo)

  • Kotaro Shirakawa

    (Kyoto University)

  • Kenji Sadamasu

    (Tokyo Metropolitan Institute of Public Health)

  • Izumi Kimura

    (The University of Tokyo)

  • Jumpei Ito

    (The University of Tokyo)

  • Jiaqi Wu

    (Tokai University School of Medicine
    CREST, Japan Science and Technology Agency)

  • Kiyoko Iwatsuki-Horimoto

    (University of Tokyo)

  • Mutsumi Ito

    (University of Tokyo)

  • Seiya Yamayoshi

    (University of Tokyo
    National Center for Global Health and Medicine Research Institute)

  • Samantha Loeber

    (University of Wisconsin)

  • Masumi Tsuda

    (Hokkaido University
    Hokkaido University)

  • Lei Wang

    (Hokkaido University
    Hokkaido University)

  • Seiya Ozono

    (National Institute of Infectious Diseases)

  • Erika P. Butlertanaka

    (University of Miyazaki)

  • Yuri L. Tanaka

    (University of Miyazaki)

  • Ryo Shimizu

    (Kumamoto University
    Kumamoto University)

  • Kenta Shimizu

    (Hokkaido University)

  • Kumiko Yoshimatsu

    (Hokkaido University)

  • Ryoko Kawabata

    (Hiroshima University)

  • Takemasa Sakaguchi

    (Hiroshima University)

  • Kenzo Tokunaga

    (National Institute of Infectious Diseases)

  • Isao Yoshida

    (Tokyo Metropolitan Institute of Public Health)

  • Hiroyuki Asakura

    (Tokyo Metropolitan Institute of Public Health)

  • Mami Nagashima

    (Tokyo Metropolitan Institute of Public Health)

  • Yasuhiro Kazuma

    (Kyoto University)

  • Ryosuke Nomura

    (Kyoto University)

  • Yoshihito Horisawa

    (Kyoto University)

  • Kazuhisa Yoshimura

    (Tokyo Metropolitan Institute of Public Health)

  • Akifumi Takaori-Kondo

    (Kyoto University)

  • Masaki Imai

    (University of Tokyo
    National Center for Global Health and Medicine Research Institute)

  • Shinya Tanaka

    (Hokkaido University
    Hokkaido University)

  • So Nakagawa

    (Tokai University School of Medicine
    CREST, Japan Science and Technology Agency)

  • Terumasa Ikeda

    (Kumamoto University)

  • Takasuke Fukuhara

    (Hokkaido University)

  • Yoshihiro Kawaoka

    (University of Tokyo
    University of Wisconsin-Madison
    National Center for Global Health and Medicine Research Institute)

  • Kei Sato

    (The University of Tokyo
    CREST, Japan Science and Technology Agency)

Abstract

During the current coronavirus disease 2019 (COVID-19) pandemic, a variety of mutations have accumulated in the viral genome of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and, at the time of writing, four variants of concern are considered to be potentially hazardous to human society1. The recently emerged B.1.617.2/Delta variant of concern is closely associated with the COVID-19 surge that occurred in India in the spring of 2021 (ref. 2). However, the virological properties of B.1.617.2/Delta remain unclear. Here we show that the B.1.617.2/Delta variant is highly fusogenic and notably more pathogenic than prototypic SARS-CoV-2 in infected hamsters. The P681R mutation in the spike protein, which is highly conserved in this lineage, facilitates cleavage of the spike protein and enhances viral fusogenicity. Moreover, we demonstrate that the P681R-bearing virus exhibits higher pathogenicity compared with its parental virus. Our data suggest that the P681R mutation is a hallmark of the virological phenotype of the B.1.617.2/Delta variant and is associated with enhanced pathogenicity.

Suggested Citation

  • Akatsuki Saito & Takashi Irie & Rigel Suzuki & Tadashi Maemura & Hesham Nasser & Keiya Uriu & Yusuke Kosugi & Kotaro Shirakawa & Kenji Sadamasu & Izumi Kimura & Jumpei Ito & Jiaqi Wu & Kiyoko Iwatsuki, 2022. "Enhanced fusogenicity and pathogenicity of SARS-CoV-2 Delta P681R mutation," Nature, Nature, vol. 602(7896), pages 300-306, February.
    • Handle: RePEc:nat:nature:v:602:y:2022:i:7896:d:10.1038_s41586-021-04266-9
    DOI: 10.1038/s41586-021-04266-9
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    Cited by:

    1. 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 & Michae, 2024. "Virological characteristics of the SARS-CoV-2 Omicron XBB.1.5 variant," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    2. Tomokazu Tamura & Jumpei Ito & Keiya Uriu & Jiri Zahradnik & Izumi Kida & Yuki Anraku & Hesham Nasser & Maya Shofa & Yoshitaka Oda & Spyros Lytras & Naganori Nao & Yukari Itakura & Sayaka Deguchi & Ri, 2023. "Virological characteristics of the SARS-CoV-2 XBB variant derived from recombination of two Omicron subvariants," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    3. Srikanth Sadhu & Rajdeep Dalal & Jyotsna Dandotiya & Akshay Binayke & Virendra Singh & Manas Ranjan Tripathy & Vinayaka Das & Sandeep Goswami & Shakti Kumar & Zaigham Abbas Rizvi & Amit Awasthi, 2023. "IL-9 aggravates SARS-CoV-2 infection and exacerbates associated airway inflammation," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    4. Naoko Iwata-Yoshikawa & Masatoshi Kakizaki & Nozomi Shiwa-Sudo & Takashi Okura & Maino Tahara & Shuetsu Fukushi & Ken Maeda & Miyuki Kawase & Hideki Asanuma & Yuriko Tomita & Ikuyo Takayama & Shutoku , 2022. "Essential role of TMPRSS2 in SARS-CoV-2 infection in murine airways," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    5. Rajeshwer S. Sankhala & Kerri G. Lal & Jaime L. Jensen & Vincent Dussupt & Letzibeth Mendez-Rivera & Hongjun Bai & Lindsay Wieczorek & Sandra V. Mayer & Michelle Zemil & Danielle A. Wagner & Samantha , 2024. "Diverse array of neutralizing antibodies elicited upon Spike Ferritin Nanoparticle vaccination in rhesus macaques," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    6. Cassia Wagner & Kathryn E. Kistler & Garrett A. Perchetti & Noah Baker & Lauren A. Frisbie & Laura Marcela Torres & Frank Aragona & Cory Yun & Marlin Figgins & Alexander L. Greninger & Alex Cox & Hann, 2024. "Positive selection underlies repeated knockout of ORF8 in SARS-CoV-2 evolution," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    7. Ana S. Gonzalez-Reiche & Hala Alshammary & Sarah Schaefer & Gopi Patel & Jose Polanco & Juan Manuel Carreño & Angela A. Amoako & Aria Rooker & Christian Cognigni & Daniel Floda & Adriana Guchte & Zain, 2023. "Sequential intrahost evolution and onward transmission of SARS-CoV-2 variants," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    8. Jumpei Ito & Rigel Suzuki & Keiya Uriu & Yukari Itakura & Jiri Zahradnik & Kanako Terakado Kimura & Sayaka Deguchi & Lei Wang & Spyros Lytras & Tomokazu Tamura & Izumi Kida & Hesham Nasser & Maya Shof, 2023. "Convergent evolution of SARS-CoV-2 Omicron subvariants leading to the emergence of BQ.1.1 variant," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    9. Zhenzhen Wang & Shiqi Hu & Kristen D. Popowski & Shuo Liu & Dashuai Zhu & Xuan Mei & Junlang Li & Yilan Hu & Phuong-Uyen C. Dinh & Xiaojie Wang & Ke Cheng, 2024. "Inhalation of ACE2-expressing lung exosomes provides prophylactic protection against SARS-CoV-2," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    10. Nicolas Prost & Etienne Audureau & Nicholas Heming & Elyanne Gault & Tài Pham & Amal Chaghouri & Nina Montmollin & Guillaume Voiriot & Laurence Morand-Joubert & Adrien Joseph & Marie-Laure Chaix & Séb, 2022. "Clinical phenotypes and outcomes associated with SARS-CoV-2 variant Omicron in critically ill French patients with COVID-19," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    11. Hidetoshi Igari & Seiichiro Sakao & Takayuki Ishige & Kengo Saito & Shota Murata & Misuzu Yahaba & Toshibumi Taniguchi & Akiko Suganami & Kazuyuki Matsushita & Yutaka Tamura & Takuji Suzuki & Eiji Ido, 2024. "Dynamic diversity of SARS-CoV-2 genetic mutations in a lung transplantation patient with persistent COVID-19," Nature Communications, Nature, vol. 15(1), pages 1-11, December.

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