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Characterization of SARS-CoV-2 Omicron BA.4 and BA.5 isolates in rodents

Author

Listed:
  • Ryuta Uraki

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

  • Peter J. Halfmann

    (University of Wisconsin-Madison)

  • Shun Iida

    (National Institute of Infectious Diseases)

  • Seiya Yamayoshi

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

  • Yuri Furusawa

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

  • Maki Kiso

    (University of Tokyo)

  • Mutsumi Ito

    (University of Tokyo)

  • Kiyoko Iwatsuki-Horimoto

    (University of Tokyo)

  • Sohtaro Mine

    (National Institute of Infectious Diseases)

  • Makoto Kuroda

    (University of Wisconsin-Madison)

  • Tadashi Maemura

    (University of Wisconsin-Madison)

  • Yuko Sakai-Tagawa

    (University of Tokyo)

  • Hiroshi Ueki

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

  • Rong Li

    (Utah State University)

  • Yanan Liu

    (Utah State University)

  • Deanna Larson

    (Utah State University)

  • Shuetsu Fukushi

    (National Institute of Infectious Diseases)

  • Shinji Watanabe

    (National Institute of Infectious Diseases)

  • Ken Maeda

    (National Institute of Infectious Diseases)

  • Andrew Pekosz

    (The Johns Hopkins Bloomberg School of Public Health)

  • Ahmed Kandeil

    (St Jude Children’s Research Hospital
    National Research Centre)

  • Richard J. Webby

    (St Jude Children’s Research Hospital)

  • Zhongde Wang

    (Utah State University)

  • Masaki Imai

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

  • Tadaki Suzuki

    (National Institute of Infectious Diseases)

  • Yoshihiro Kawaoka

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

Abstract

The BA.2 sublineage of the SARS-CoV-2 Omicron variant has become dominant in most countries around the world; however, the prevalence of BA.4 and BA.5 is increasing rapidly in several regions. BA.2 is less pathogenic in animal models than previously circulating variants of concern1–4. Compared with BA.2, however, BA.4 and BA.5 possess additional substitutions in the spike protein, which play a key role in viral entry, raising concerns that the replication capacity and pathogenicity of BA.4 and BA.5 are higher than those of BA.2. Here we have evaluated the replicative ability and pathogenicity of BA.4 and BA.5 isolates in wild-type Syrian hamsters, human ACE2 (hACE2) transgenic hamsters and hACE2 transgenic mice. We have observed no obvious differences among BA.2, BA.4 and BA.5 isolates in growth ability or pathogenicity in rodent models, and less pathogenicity compared to a previously circulating Delta (B.1.617.2 lineage) isolate. In addition, in vivo competition experiments revealed that BA.5 outcompeted BA.2 in hamsters, whereas BA.4 and BA.2 exhibited similar fitness. These findings suggest that BA.4 and BA.5 clinical isolates have similar pathogenicity to BA.2 in rodents and that BA.5 possesses viral fitness superior to that of BA.2.

Suggested Citation

  • Ryuta Uraki & Peter J. Halfmann & Shun Iida & Seiya Yamayoshi & Yuri Furusawa & Maki Kiso & Mutsumi Ito & Kiyoko Iwatsuki-Horimoto & Sohtaro Mine & Makoto Kuroda & Tadashi Maemura & Yuko Sakai-Tagawa , 2022. "Characterization of SARS-CoV-2 Omicron BA.4 and BA.5 isolates in rodents," Nature, Nature, vol. 612(7940), pages 540-545, December.
    • Handle: RePEc:nat:nature:v:612:y:2022:i:7940:d:10.1038_s41586-022-05482-7
    DOI: 10.1038/s41586-022-05482-7
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    Citations

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    Cited by:

    1. Markus Hoffmann & Lok-Yin Roy Wong & Prerna Arora & Lu Zhang & Cheila Rocha & Abby Odle & Inga Nehlmeier & Amy Kempf & Anja Richter & Nico Joel Halwe & Jacob Schön & Lorenz Ulrich & Donata Hoffmann & , 2023. "Omicron subvariant BA.5 efficiently infects lung cells," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    2. Maki Kiso & Yuri Furusawa & Ryuta Uraki & Masaki Imai & Seiya Yamayoshi & Yoshihiro Kawaoka, 2023. "In vitro and in vivo characterization of SARS-CoV-2 strains resistant to nirmatrelvir," Nature Communications, Nature, vol. 14(1), pages 1-8, December.
    3. Maki Kiso & Seiya Yamayoshi & Shun Iida & Yuri Furusawa & Yuichiro Hirata & Ryuta Uraki & Masaki Imai & Tadaki Suzuki & Yoshihiro Kawaoka, 2023. "In vitro and in vivo characterization of SARS-CoV-2 resistance to ensitrelvir," Nature Communications, Nature, vol. 14(1), pages 1-8, December.
    4. Rafael R. G. Machado & Jordyn L. Walker & Dionna Scharton & Grace H. Rafael & Brooke M. Mitchell & Rachel A. Reyna & William M. Souza & Jianying Liu & David H. Walker & Jessica A. Plante & Kenneth S. , 2023. "Immunogenicity and efficacy of vaccine boosters against SARS-CoV-2 Omicron subvariant BA.5 in male Syrian hamsters," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    5. Julia M. Adler & Ricardo Martin Vidal & Christine Langner & Daria Vladimirova & Azza Abdelgawad & Daniela Kunecova & Xiaoyuan Lin & Geraldine Nouailles & Anne Voss & Sandra Kunder & Achim D. Gruber & , 2024. "An intranasal live-attenuated SARS-CoV-2 vaccine limits virus transmission," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    6. Ryuta Uraki & Shun Iida & Peter J. Halfmann & Seiya Yamayoshi & Yuichiro Hirata & Kiyoko Iwatsuki-Horimoto & Maki Kiso & Mutsumi Ito & Yuri Furusawa & Hiroshi Ueki & Yuko Sakai-Tagawa & Makoto Kuroda , 2023. "Characterization of SARS-CoV-2 Omicron BA.2.75 clinical isolates," Nature Communications, Nature, vol. 14(1), pages 1-11, December.

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