tetano
Editor, Senior Moderator
EMBO Rep
. 2023 Mar 6;e56055.
doi: 10.15252/embr.202256055. Online ahead of print.
SARS-CoV-2-related bat virus behavior in human-relevant models sheds light on the origin of COVID-19
Sarah Temmam[SUP] #[/SUP][SUP] 1 2 [/SUP], Xavier Montagutelli[SUP] #[/SUP][SUP] 3 [/SUP], Cécile Herate[SUP] #[/SUP][SUP] 4 [/SUP], Flora Donati[SUP] #[/SUP][SUP] 5 6 [/SUP], Béatrice Regnault[SUP] 1 2 [/SUP], Mikael Attia[SUP] 5 [/SUP], Eduard Baquero Salazar[SUP] 7 [/SUP], Delphine Chretien[SUP] 1 2 [/SUP], Laurine Conquet[SUP] 3 [/SUP], Grégory Jouvion[SUP] 8 9 [/SUP], Juliana Pipoli Da Fonseca[SUP] 10 [/SUP], Thomas Cokelaer[SUP] 10 [/SUP], Faustine Amara[SUP] 5 [/SUP], Francis Relouzat[SUP] 4 [/SUP], Thibaut Naninck[SUP] 4 [/SUP], Julien Lemaitre[SUP] 4 [/SUP], Nathalie Derreudre-Bosquet[SUP] 4 [/SUP], Quentin Pascal[SUP] 4 [/SUP], Massimiliano Bonomi[SUP] 11 [/SUP], Thomas Bigot[SUP] 1 12 [/SUP], Sandie Munier[SUP] 5 [/SUP], Felix A Rey[SUP] 7 [/SUP], Roger Le Grand[SUP] 4 [/SUP], Sylvie van der Werf[SUP] 5 6 [/SUP], Marc Eloit[SUP] 1 2 13 [/SUP]
Affiliations
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.
Keywords: adaptive mutations; animal model; bat coronavirus; pathogenesis; serology.
. 2023 Mar 6;e56055.
doi: 10.15252/embr.202256055. Online ahead of print.
SARS-CoV-2-related bat virus behavior in human-relevant models sheds light on the origin of COVID-19
Sarah Temmam[SUP] #[/SUP][SUP] 1 2 [/SUP], Xavier Montagutelli[SUP] #[/SUP][SUP] 3 [/SUP], Cécile Herate[SUP] #[/SUP][SUP] 4 [/SUP], Flora Donati[SUP] #[/SUP][SUP] 5 6 [/SUP], Béatrice Regnault[SUP] 1 2 [/SUP], Mikael Attia[SUP] 5 [/SUP], Eduard Baquero Salazar[SUP] 7 [/SUP], Delphine Chretien[SUP] 1 2 [/SUP], Laurine Conquet[SUP] 3 [/SUP], Grégory Jouvion[SUP] 8 9 [/SUP], Juliana Pipoli Da Fonseca[SUP] 10 [/SUP], Thomas Cokelaer[SUP] 10 [/SUP], Faustine Amara[SUP] 5 [/SUP], Francis Relouzat[SUP] 4 [/SUP], Thibaut Naninck[SUP] 4 [/SUP], Julien Lemaitre[SUP] 4 [/SUP], Nathalie Derreudre-Bosquet[SUP] 4 [/SUP], Quentin Pascal[SUP] 4 [/SUP], Massimiliano Bonomi[SUP] 11 [/SUP], Thomas Bigot[SUP] 1 12 [/SUP], Sandie Munier[SUP] 5 [/SUP], Felix A Rey[SUP] 7 [/SUP], Roger Le Grand[SUP] 4 [/SUP], Sylvie van der Werf[SUP] 5 6 [/SUP], Marc Eloit[SUP] 1 2 13 [/SUP]
Affiliations
- PMID: 36876574
- DOI: 10.15252/embr.202256055
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.
Keywords: adaptive mutations; animal model; bat coronavirus; pathogenesis; serology.