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

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, Hiroshi Ueki, Rong Li, Yanan Liu, Deanna Larson, Shuetsu Fukushi, Shinji Watanabe, Ken Maeda, Andrew Pekosz, Ahmed Kandeil, Richard J. Webby, Zhongde Wang, Masaki Imai (), Tadaki Suzuki () and Yoshihiro Kawaoka ()
Additional contact information
Ryuta Uraki: University of Tokyo
Peter J. Halfmann: University of Wisconsin-Madison
Shun Iida: National Institute of Infectious Diseases
Seiya Yamayoshi: University of Tokyo
Yuri Furusawa: University of Tokyo
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
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
Richard J. Webby: St Jude Children’s Research Hospital
Zhongde Wang: Utah State University
Masaki Imai: University of Tokyo
Tadaki Suzuki: National Institute of Infectious Diseases
Yoshihiro Kawaoka: University of Tokyo

Nature, 2022, vol. 612, issue 7940, 540-545

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41586-022-05482-7

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