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SARS-CoV-2-related bat virus behavior in human-relevant models sheds light on the origin of COVID-19.
Temmam, Sarah; Montagutelli, Xavier; Herate, Cécile; Donati, Flora; Regnault, Béatrice; Attia, Mikael; Baquero Salazar, Eduard; Chretien, Delphine; Conquet, Laurine; Jouvion, Grégory; Pipoli Da Fonseca, Juliana; Cokelaer, Thomas; Amara, Faustine; Relouzat, Francis; Naninck, Thibaut; Lemaitre, Julien; Derreudre-Bosquet, Nathalie; Pascal, Quentin; Bonomi, Massimiliano; Bigot, Thomas; Munier, Sandie; Rey, Felix A; Le Grand, Roger; van der Werf, Sylvie; Eloit, Marc.
  • Temmam S; Institut Pasteur, Université Paris Cité, Pathogen Discovery Laboratory, Paris, France.
  • Montagutelli X; Institut Pasteur, Université Paris Cité, The OIE Collaborating Center for the Detection and Identification in Humans of Emerging Animal Pathogens, Paris, France.
  • Herate C; Institut Pasteur, Université Paris Cité, Mouse Genetics Laboratory, Paris, France.
  • Donati F; Center for Immunology of Viral, Auto-immune, Hematological and Bacterial Diseases (IMVA-HB/IDMIT), Université Paris-Saclay, Inserm, CEA, Fontenay-aux-Roses, France.
  • Regnault B; Institut Pasteur, Université Paris Cité, CNRS UMR 3569, Molecular Genetics of RNA Viruses Unit, Paris, France.
  • Attia M; Institut Pasteur, Université Paris Cité, National Reference Center for Respiratory Viruses, Paris, France.
  • Baquero Salazar E; Institut Pasteur, Université Paris Cité, Pathogen Discovery Laboratory, Paris, France.
  • Chretien D; Institut Pasteur, Université Paris Cité, The OIE Collaborating Center for the Detection and Identification in Humans of Emerging Animal Pathogens, Paris, France.
  • Conquet L; Institut Pasteur, Université Paris Cité, CNRS UMR 3569, Molecular Genetics of RNA Viruses Unit, Paris, France.
  • Jouvion G; Institut Pasteur, Université Paris Cité, CNRS UMR 3569, Structural Virology Unit, Paris, France.
  • Pipoli Da Fonseca J; Institut Pasteur, Université Paris Cité, Pathogen Discovery Laboratory, Paris, France.
  • Cokelaer T; Institut Pasteur, Université Paris Cité, The OIE Collaborating Center for the Detection and Identification in Humans of Emerging Animal Pathogens, Paris, France.
  • Amara F; Institut Pasteur, Université Paris Cité, Mouse Genetics Laboratory, Paris, France.
  • Relouzat F; Ecole Nationale Vétérinaire d'Alfort, Unité d'Histologie et d'Anatomie Pathologique, Maisons-Alfort, France.
  • Naninck T; Université Paris Est Créteil, EnvA, ANSES, Unité DYNAMYC, Créteil, France.
  • Lemaitre J; Biomics Platform, C2RT, Institut Pasteur, Université Paris Cité, Paris, France.
  • Derreudre-Bosquet N; Biomics Platform, C2RT, Institut Pasteur, Université Paris Cité, Paris, France.
  • Pascal Q; Institut Pasteur, Université Paris Cité, CNRS UMR 3569, Molecular Genetics of RNA Viruses Unit, Paris, France.
  • Bonomi M; Center for Immunology of Viral, Auto-immune, Hematological and Bacterial Diseases (IMVA-HB/IDMIT), Université Paris-Saclay, Inserm, CEA, Fontenay-aux-Roses, France.
  • Bigot T; Center for Immunology of Viral, Auto-immune, Hematological and Bacterial Diseases (IMVA-HB/IDMIT), Université Paris-Saclay, Inserm, CEA, Fontenay-aux-Roses, France.
  • Munier S; Center for Immunology of Viral, Auto-immune, Hematological and Bacterial Diseases (IMVA-HB/IDMIT), Université Paris-Saclay, Inserm, CEA, Fontenay-aux-Roses, France.
  • Rey FA; Center for Immunology of Viral, Auto-immune, Hematological and Bacterial Diseases (IMVA-HB/IDMIT), Université Paris-Saclay, Inserm, CEA, Fontenay-aux-Roses, France.
  • Le Grand R; Center for Immunology of Viral, Auto-immune, Hematological and Bacterial Diseases (IMVA-HB/IDMIT), Université Paris-Saclay, Inserm, CEA, Fontenay-aux-Roses, France.
  • van der Werf S; Institut Pasteur, Université Paris Cité, CNRS UMR 3528, Structural Bioinformatics Unit, Paris, France.
  • Eloit M; Institut Pasteur, Université Paris Cité, Pathogen Discovery Laboratory, Paris, France.
EMBO Rep ; 24(4): e56055, 2023 04 05.
Article in English | MEDLINE | ID: covidwho-2283776
ABSTRACT
Bat sarbecovirus BANAL-236 is highly related to SARS-CoV-2 and infects human cells, albeit lacking the furin cleavage site in its spike protein. BANAL-236 replicates efficiently and pauci-symptomatically in humanized mice and in macaques, where its tropism is enteric, strongly differing from that of SARS-CoV-2. BANAL-236 infection leads to protection against superinfection by a virulent strain. We find no evidence of antibodies recognizing bat sarbecoviruses in populations in close contact with bats in which the virus was identified, indicating that such spillover infections, if they occur, are rare. Six passages in humanized mice or in human intestinal cells, mimicking putative early spillover events, select adaptive mutations without appearance of a furin cleavage site and no change in virulence. Therefore, acquisition of a furin site in the spike protein is likely a pre-spillover event that did not occur upon replication of a SARS-CoV-2-like bat virus in humans or other animals. Other hypotheses regarding the origin of the SARS-CoV-2 should therefore be evaluated, including the presence of sarbecoviruses carrying a spike with a furin cleavage site in bats.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: COVID-19 Type of study: Experimental Studies Limits: Animals / Humans Language: English Journal: EMBO Rep Journal subject: Molecular Biology Year: 2023 Document Type: Article Affiliation country: Embr.202256055

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Full text: Available Collection: International databases Database: MEDLINE Main subject: COVID-19 Type of study: Experimental Studies Limits: Animals / Humans Language: English Journal: EMBO Rep Journal subject: Molecular Biology Year: 2023 Document Type: Article Affiliation country: Embr.202256055