Department of Veterinary Science, Faculty of Agriculture, University of Miyazaki, Miyazaki, Japan.
Center for Animal Disease Control, University of Miyazaki, Miyazaki, Japan.
Graduate School of Medicine and Veterinary Medicine, University of Miyazaki, Miyazaki, Japan.
Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
Department of Microbiology and Immunology, Graduate School of Medicine, Hokkaido University, Hokkaido, Japan.
Division of Virology, Institute of Medical Science, University of Tokyo, Tokyo, Japan.
Influenza Research Institute, Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI, USA.
Division of Molecular Virology and Genetics, Joint Research Center for Human Retrovirus infection, Kumamoto University, Kumamoto, Japan.
Department of Clinical Pathology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt.
Division of Systems Virology, Department of Infectious Disease Control, International Research Center for Infectious Diseases, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Tokyo Metropolitan Institute of Public Health, Tokyo, Japan.
Department of Molecular Life Science, Tokai University School of Medicine, Kanagawa, Japan.
CREST, Japan Science and Technology Agency, Saitama, Japan.
The Research Center for Global Viral Diseases, National Center for Global Health and Medicine Research Institute, Tokyo, Japan.
Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI, USA.
Department of Cancer Pathology, Faculty of Medicine, Hokkaido University, Hokkaido, Japan.
Institute for Chemical Reaction Design and Discovery (WPI-ICReDD), Hokkaido University, Hokkaido, Japan.
Department of Pathology, National Institute of Infectious Diseases, Tokyo, Japan.
Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
Institute for Genetic Medicine, Hokkaido University, Hokkaido, Japan.
Department of Cancer Pathology, Faculty of Medicine, Hokkaido University, Hokkaido, Japan. tanaka@med.hokudai.ac.jp.
Institute for Chemical Reaction Design and Discovery (WPI-ICReDD), Hokkaido University, Hokkaido, Japan. tanaka@med.hokudai.ac.jp.
Department of Molecular Life Science, Tokai University School of Medicine, Kanagawa, Japan. so@tokai.ac.jp.
CREST, Japan Science and Technology Agency, Saitama, Japan. so@tokai.ac.jp.
Division of Molecular Virology and Genetics, Joint Research Center for Human Retrovirus infection, Kumamoto University, Kumamoto, Japan. ikedat@kumamoto-u.ac.jp.
Department of Microbiology and Immunology, Graduate School of Medicine, Hokkaido University, Hokkaido, Japan. fukut@pop.med.hokudai.ac.jp.
Division of Virology, Institute of Medical Science, University of Tokyo, Tokyo, Japan. yoshihiro.kawaoka@wisc.edu.
Influenza Research Institute, Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI, USA. yoshihiro.kawaoka@wisc.edu.
The Research Center for Global Viral Diseases, National Center for Global Health and Medicine Research Institute, Tokyo, Japan. yoshihiro.kawaoka@wisc.edu.
Division of Systems Virology, Department of Infectious Disease Control, International Research Center for Infectious Diseases, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan. KeiSato@g.ecc.u-tokyo.ac.jp.
CREST, Japan Science and Technology Agency, Saitama, Japan. KeiSato@g.ecc.u-tokyo.ac.jp.
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.
