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Literature detail

Virological characteristics of a SARS-CoV-2-related bat coronavirus, BANAL-20-236.

Shigeru Fujita1,2 Arnon Plianchaisuk3 Sayaka Deguchi4 Hayato Ito5 Naganori Nao6,7,8 Lei Wang9,10 Hesham Nasser11,12 Tomokazu Tamura13,6,14 Izumi Kimura3 Yukie Kashima15 Rigel Suzuki13,14 Saori Suzuki13,14 Izumi Kida16 Masumi Tsuda9,10 Yoshitaka Oda17 Rina Hashimoto4 Yukio Watanabe4 Keiya Uriu1,2 Daichi Yamasoba1,18 Ziyi Guo3 Alfredo A Hinay3 Yusuke Kosugi1,2 Luo Chen1,15 Lin Pan1,15 Yu Kaku3 Hin Chu19 Flora Donati20,21 Sarah Temmam22,23 Marc Eloit22,23 Yuki Yamamoto24 Tetsuharu Nagamoto24 Hiroyuki Asakura25 Mami Nagashima25 Kenji Sadamasu25 Kazuhisa Yoshimura25 Yutaka Suzuki15 Genotype to Phenotype Japan (G2P-Japan) Consortium Jumpei Ito1,26 Terumasa Ikeda27 Shinya Tanaka9,28 Keita Matsuno6,7,29,30 Takasuke Fukuhara13,6,7,31,32 Kazuo Takayama33,34 Kei Sato1,35,36,37,38,39,40,41
Affiliations 41 institutions
  1. Division of Systems Virology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
  2. Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
  3. Division of Systems Virology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
  4. Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan.
  5. Department of Microbiology and Immunology, Faculty of Medicine, Hokkaido University, Sapporo, Japan.
  6. One Health Research Center, Hokkaido University, Sapporo, Japan
  7. Institute for Vaccine Research and Development (IVReD), Hokkaido University, Sapporo, Japan
  8. Division of International Research Promotion, International Institute for Zoonosis Control, Hokkaido University, Sapporo, Japan.
  9. Department of Cancer Pathology, Faculty of Medicine, Hokkaido University, Sapporo, Japan
  10. Institute for Chemical Reaction Design and Discovery (WPI-ICReDD), Hokkaido University, Sapporo, Japan.
  11. Division of Molecular Virology and Genetics, Joint Research Center for Human Retrovirus infection, Kumamoto University, Kumamoto, Japan
  12. Department of Clinical Pathology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt.
  13. Department of Microbiology and Immunology, Faculty of Medicine, Hokkaido University, Sapporo, Japan
  14. Institute for Vaccine Research and Development (IVReD), Hokkaido University, Sapporo, Japan.
  15. Graduate School of Frontier Sciences, The University of Tokyo, Chiba, Japan.
  16. Division of Risk Analysis and Management, International Institute for Zoonosis Control, Hokkaido University, Sapporo, Japan.
  17. Department of Cancer Pathology, Faculty of Medicine, Hokkaido University, Sapporo, Japan.
  18. Faculty of Medicine, Kobe University, Kobe, Japan.
  19. State Key Laboratory of Emerging Infectious Diseases, Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China.
  20. Institut Pasteur, Université Paris Cité, CNRS UMR 3569, Molecular Genetics of RNA Viruses Unit, Paris, France
  21. Institut Pasteur, Université Paris Cité, National Reference Center for Respiratory Viruses, Paris, France.
  22. Institut Pasteur, Université Paris Cité, Pathogen Discovery Laboratory, Paris, France
  23. Institut Pasteur, Université Paris Cité, The WOAH(OIE) Collaborating Center for the Detection and Identification in Humans of Emerging Animal Pathogens, Paris, France.
  24. HiLung Inc., Kyoto, Japan.
  25. Tokyo Metropolitan Institute of Public Health, Tokyo, Japan.
  26. International Research Center for Infectious Diseases, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
  27. Division of Molecular Virology and Genetics, Joint Research Center for Human Retrovirus infection, Kumamoto University, Kumamoto, Japan.
  28. Institute for Chemical Reaction Design and Discovery (WPI-ICReDD), Hokkaido University, Sapporo, Japan. Electronic address: [email protected].
  29. Division of Risk Analysis and Management, International Institute for Zoonosis Control, Hokkaido University, Sapporo, Japan
  30. International Collaboration Unit, International Institute for Zoonosis Control, Hokkaido University, Sapporo, Japan. Electronic address: [email protected].
  31. AMED-CREST, Japan Agency for Medical Research and Development (AMED), Tokyo, Japan
  32. Laboratory of Virus Control, Research Institute for Microbial Diseases, Osaka University, Suita, Japan. Electronic address: [email protected].
  33. Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan
  34. AMED-CREST, Japan Agency for Medical Research and Development (AMED), Tokyo, Japan. Electronic address: [email protected].
  35. Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
  36. Graduate School of Frontier Sciences, The University of Tokyo, Chiba, Japan
  37. International Research Center for Infectious Diseases, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
  38. CREST, Japan Science and Technology Agency, Saitama, Japan
  39. International Vaccine Design Center, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
  40. Collaboration Unit for Infection, Joint Research Center for Human Retrovirus infection, Kumamoto University, Kumamoto, Japan
  41. MRC-University of Glasgow Centre for Virus Research, Glasgow, UK. Electronic address: [email protected].
PMID 38838469 2024 EBioMedicine eng ppublish
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Article

Publication summary

Although several SARS-CoV-2-related coronaviruses (SC2r-CoVs) were discovered in bats and pangolins, the differences in virological characteristics between SARS-CoV-2 and SC2r-CoVs remain poorly understood. Recently, BANAL-20-236 (B236) was isolated from a rectal swab of Malayan horseshoe bat and was found to lack a furin cleavage site (FCS) in the spike (S) protein. The comparison of its virological characteristics with FCS-deleted SARS-CoV-2 (SC2ΔFCS) has not been conducted yet. We prepared human induced pluripotent stem cell (iPSC)-derived airway and lung epithelial cells and colon organoids as human organ-relevant models. B236, SARS-CoV-2, and artificially generated SC2ΔFCS were used for viral experiments. To investigate the pathogenicity of B236 in vivo, we conducted intranasal infection experiments in hamsters. In human iPSC-derived airway epithelial cells, the growth of B236 was significantly lower than that of the SC2ΔFCS. A fusion assay showed that the B236 and SC2ΔFCS S proteins were less fusogenic than the SARS-CoV-2 S protein. The infection experiment in hamsters showed that B236 was less pathogenic than SARS-CoV-2 and even SC2ΔFCS. Interestingly, in human colon organoids, the growth of B236 was significantly greater than that of SARS-CoV-2. Compared to SARS-CoV-2, we demonstrated that B236 exhibited a tropism toward intestinal cells rather than respiratory cells. Our results are consistent with a previous report showing that B236 is enterotropic in macaques. Altogether, our report strengthens the assumption that SC2r-CoVs in horseshoe bats replicate primarily in the intestinal tissues rather than respiratory tissues. This study was supported in part by AMED ASPIRE (JP23jf0126002, to Keita Matsuno, Kazuo Takayama, and Kei Sato); AMED SCARDA Japan Initiative for World-leading Vaccine Research and Development Centers "UTOPIA" (JP223fa627001, to Kei Sato), AMED SCARDA Program on R&D of new generation vaccine including new modality application (JP223fa727002, to Kei Sato); AMED SCARDA Hokkaido University Institute for Vaccine Research and Development (HU-IVReD) (JP223fa627005h0001, to Takasuke Fukuhara, and Keita Matsuno); AMED Research Program on Emerging and Re-emerging Infectious Diseases (JP21fk0108574, to Hesham Nasser; JP21fk0108493, to Takasuke Fukuhara; JP22fk0108617 to Takasuke Fukuhara; JP22fk0108146, to Kei Sato; JP21fk0108494 to G2P-Japan Consortium, Keita Matsuno, Shinya Tanaka, Terumasa Ikeda, Takasuke Fukuhara, and Kei Sato; JP21fk0108425, to Kazuo Takayama and Kei Sato; JP21fk0108432, to Kazuo Takayama, Takasuke Fukuhara and Kei Sato; JP22fk0108534, Terumasa Ikeda, and Kei Sato; JP22fk0108511, to Yuki Yamamoto, Terumasa Ikeda, Keita Matsuno, Shinya Tanaka, Kazuo Takayama, Takasuke Fukuhara, and Kei Sato; JP22fk0108506, to Kazuo Takayama and Kei Sato); AMED Research Program on HIV/AIDS (JP22fk0410055, to Terumasa Ikeda; and JP22fk0410039, to Kei Sato); AMED Japan Program for Infectious Diseases Research and Infrastructure (JP22wm0125008 to Keita Matsuno); AMED CREST (JP21gm1610005, to Kazuo Takayama; JP22gm1610008, to Takasuke Fukuhara; JST PRESTO (JPMJPR22R1, to Jumpei Ito); JST CREST (JPMJCR20H4, to Kei Sato); JSPS KAKENHI Fund for the Promotion of Joint International Research (International Leading Research) (JP23K20041, to G2P-Japan Consortium, Keita Matsuno, Takasuke Fukuhara and Kei Sato); JST SPRING (JPMJSP2108 to Shigeru Fujita); JSPS KAKENHI Grant-in-Aid for Scientific Research C (22K07103, to Terumasa Ikeda); JSPS KAKENHI Grant-in-Aid for Scientific Research B (21H02736, to Takasuke Fukuhara); JSPS KAKENHI Grant-in-Aid for Early-Career Scientists (22K16375, to Hesham Nasser; 20K15767, to Jumpei Ito); JSPS Core-to-Core Program (A. Advanced Research Networks) (JPJSCCA20190008, to Kei Sato); JSPS Research Fellow DC2 (22J11578, to Keiya Uriu); JSPS Research Fellow DC1 (23KJ0710, to Yusuke Kosugi); JSPS Leading Initiative for Excellent Young Researchers (LEADER) (to Terumasa Ikeda); World-leading Innovative and Smart Education (WISE) Program 1801 from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) (to Naganori Nao); Ministry of Health, Labour and Welfare (MHLW) under grant 23HA2010 (to Naganori Nao and Keita Matsuno); The Cooperative Research Program (Joint Usage/Research Center program) of Institute for Life and Medical Sciences, Kyoto University (to Kei Sato); International Joint Research Project of the Institute of Medical Science, the University of Tokyo (to Terumasa Ikeda and Takasuke Fukuhara); The Tokyo Biochemical Research Foundation (to Kei Sato); Takeda Science Foundation (to Terumasa Ikeda and Takasuke Fukuhara); Mochida Memorial Foundation for Medical and Pharmaceutical Research (to Terumasa Ikeda); The Naito Foundation (to Terumasa Ikeda); Hokuto Foundation for Bioscience (to Tomokazu Tamura); Hirose Foundation (to Tomokazu Tamura); and Mitsubishi Foundation (to Kei Sato).

BANAL-20-236 Bat coronavirus SARS-CoV-2 Spillover Chiroptera COVID-19 SARS-CoV-2 Animals Chlorocebus aethiops Cricetinae Epithelial Cells Furin Humans Induced Pluripotent Stem Cells Organoids Spike Glycoprotein, Coronavirus Vero Cells spike protein, SARS-CoV-2

Structured evidence records

Evidence records

2 total
Host Range Experiment 1 records
Host Range Experiment Extraction confidence 0.95
Key finding

BANAL‑20‑236 replicated poorly in human airway epithelial cells but efficiently in human colon organoids and produced mild infection in hamsters, indicating intestinal tropism and reduced respiratory replication compared with SARS‑CoV‑2.

Virus
SARSr-CoV
Location
Not specified
Supporting text

To investigate the pathogenicity of B236 in vivo, we conducted intranasal infection experiments in hamsters. In human iPSC‑derived airway epithelial cells, the growth of B236 was significantly lower than that of the SC2ΔFCS. Interestingly, in human colon organoids, the growth of B236 was significantly greater than that of SARS‑CoV‑2. Compared to SARS‑CoV‑2, we demonstrated that B236 exhibited a tropism toward intestinal cells rather than respiratory cells.

Method
intranasal infection; viral growth assay; fusion assay
Sample type
airway epithelial cells; lung epithelial cells; colon organoids
Experimental system
in vivo animal experiment and in vitro cell culture
Molecular Adaptation 1 records
Molecular Adaptation Extraction confidence 0.90
Key finding

The absence of the furin cleavage site in the B236 spike protein leads to reduced fusogenicity and airway replication, but increased intestinal tropism, reflecting molecular adaptation affecting tissue tropism and pathogenicity relative to SARS-CoV-2.

Virus
SARSr-CoV
Host
Not specified
Location
Not specified
Supporting text

BANAL-20-236 (B236) was found to lack a furin cleavage site (FCS) in the spike (S) protein. A fusion assay showed that the B236 and SC2ΔFCS S proteins were less fusogenic than the SARS-CoV-2 S protein. The growth of B236 was significantly lower than SC2ΔFCS in human airway epithelial cells but higher in human colon organoids, demonstrating an intestinal tropism.

Genes or proteins
spike; furin cleavage site
Mechanism types
pathogenicity; tissue_tropism; fusion_activity