Mutations that adapt SARS-CoV-2 to mink or ferret do not increase fitness in the human airway.
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ABSTRACT:
SUBMITTER: Zhou J
PROVIDER: S-EPMC8768428 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from humans to farmed mink has been observed in Europe and the US. In the infected animals, viral variants arose that harbored mutations in the spike (S) protein, the target of neutralizing antibodies, and these variants were transmitted back to humans. This raised concerns that mink might become a constant source of human infection with SARS-CoV-2 variants associated with an increased threat to human health and resulted in mass culling of mink. Here, we report that mutations frequently found in the S proteins of SARS-CoV-2 from mink are mostly compatible with efficient entry into human cells and its inhibition by soluble angiotensin-converting enzyme 2 (ACE2). In contrast, mutation Y453F reduces neutralization by an antibody with emergency use authorization for coronavirus disease 2019 (COVID-19) therapy and sera/plasma from COVID-19 patients. These results suggest that antibody responses induced upon infection or certain antibodies used for treatment might offer insufficient protection against SARS-CoV-2 variants from mink.
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Project description:SARS-CoV-2 has RNA as the genome, which makes the virus more prone to mutations. Occasionally, mutations help a virus to cross the species barrier. SARS-CoV-2 infections in humans and minks (Neovison vison) are examples of zoonotic spillover. Many studies on the mutational analysis of human-derived SARS-CoV-2 have been published, but insight into the mink-derived SARS-CoV-2 genome of mutations is still required. Here, we performed a mutation analysis of the mink-derived SARS-CoV-2 genome sequences. We analyzed all available full-length mink-derived SARS-CoV-2 genome sequences on GISAID (214 genome sequences from the Netherlands and 133 genome sequences from Denmark). We found a striking resemblance between human-derived and mink-derived SARS-CoV-2. Our study showed that mutation patterns in the SARS-CoV-2 genome samples from the Netherlands and Denmark were different. Out of the 201 mutations we found, only 13 mutations were shared by the Netherlands' and Denmark's mink-derived samples. We found that six mutations were prevalent in the mink-derived SARS-CoV-2 genomes, and these six mutations are also known to be prevalent in human-derived SARS-CoV-2 variants. Our study reveals that the G27948T mutation in SARS-CoV-2 leads to truncation of ORF8, which was also reported in human-derived SARS-CoV-2, thus indicating that the virus can replicate without the full-length ORF8. These resemblances between mink-derived and human-derived SARS-CoV-2 enable the virus to cross the species barrier and suggest mink a potential reservoir for the virus.
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