Mutations that adapt SARS-CoV-2 to mink or ferret do not increase fitness in the human airway

Zhou, Jie; Peacock, Thomas P.; Brown, Jonathan C.; Goldhill, Daniel H.; Elrefaey, Ahmed M.E.; Penrice-Randal, Rebekah; Cowton, Vanessa M.; Lorenzo, Giuditta De; Furnon, Wilhelm; Harvey, William T.; Kugathasan, Ruthiran; Frise, Rebecca; Baillon, Laury; Lassaunière, Ria; Thakur, Nazia; Gallo, Giulia; Goldswain, Hannah; Donovan-Banfield, I’ah; Dong, Xiaofeng; Randle, Nadine; Sweeney, Fiachra; Glynn, Martha C.; Quantrill, Jessica L.; McKay, Paul F.; Patel, Arvind H.; Palmarini, Massimo; Hiscox, Julian A.; Bailey, Dalan; Barclay, William

doi:10.1016/j.celrep.2022.110344

Cited by 53 publications

(61 citation statements)

References 57 publications

(62 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Meanwhile, our functional prediction analyses using bioinformatic approaches suggest a minimal impact of all strong candidate Spike mutations, including Spike_F486L, on Spike: mink-ACE2 interactions. This is despite in vitro evidence that these three mutations allow more efficient cellular entry into cells expressing mustelid ACE2 54 . Further, while the strong candidate spike mutations Y453F and N501T were found to improve Spike:human-ACE2 interactions 56 , we find that they confer minimal or no evolutionary advantage for transmission in humans, concordant with in vitro evidence that Y453F attenuates SARS-CoV-2 in human bronchial cells 54 .…”

Section: Discussionmentioning

confidence: 92%

“…Our analyses, focusing on a set of criteria applied to recurrent mutations, identify putative signatures of host adaptation following onward transmission of SARS-CoV-2 in mink and deer. The spike mutations N501T, F486L and Y453F have been shown to improve entry into cells expressing ferret ACE2 and are therefore animal adaptive 54 . Further, phylodynamic analyses of Dutch mink farm outbreaks have previously shown that viruses in minks that carry the Spike_F486L mutation may evolve and transmit at a faster rate 55 .…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Transmission of SARS-CoV-2 from humans to animals and potential host adaptation

et al. 2022

View full text Add to dashboard Cite

SARS-CoV-2, the causative agent of the COVID-19 pandemic, can infect a wide range of mammals. Since its spread in humans, secondary host jumps of SARS-CoV-2 from humans to multiple domestic and wild populations of mammals have been documented. Understanding the extent of adaptation to these animal hosts is critical for assessing the threat that the spillback of animal-adapted SARS-CoV-2 into humans poses. We compare the genomic landscapes of SARS-CoV-2 isolated from animal species to that in humans, profiling the mutational biases indicative of potentially different selective pressures in animals. We focus on viral genomes isolated from mink (Neovison vison) and white-tailed deer (Odocoileus virginianus) for which multiple independent outbreaks driven by onward animal-to-animal transmission have been reported. We identify five candidate mutations for animal-specific adaptation in mink (NSP9_G37E, Spike_F486L, Spike_N501T, Spike_Y453F, ORF3a_L219V), and one in deer (NSP3a_L1035F), though they appear to confer a minimal advantage for human-to-human transmission. No considerable changes to the mutation rate or evolutionary trajectory of SARS-CoV-2 has resulted from circulation in mink and deer thus far. Our findings suggest that minimal adaptation was required for onward transmission in mink and deer following human-to-animal spillover, highlighting the ‘generalist’ nature of SARS-CoV-2 as a mammalian pathogen.

show abstract

Section: Discussionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Transmission of SARS-CoV-2 from humans to animals and potential host adaptation

et al. 2022

View full text Add to dashboard Cite

show abstract

“…Two mutations in the S protein, F486L and N501T have been associated with mustelid (mink or ferret) host adaptations, and N501T has been associated with enhanced ACE2 binding and entry into human (Huh7) cells (Han et al, 2021; Lu et al, 2021; Oude Munnink et al, 2021; Starr et al, 2020). Notably, the Ontario WTD SARS-CoV-2 genomes did not harbour the relatively well-described S:Y453F mutation associated with mink and increased replication and morbidity in ferrets, but reduced replication in primary human airway epithelial cells (Zhou et al, 2022). These WTD genomes provide new insights into viral evolution and inferred virus mobility in animal species outside of the human population.…”

Section: Discussionmentioning

confidence: 99%

Highly divergent white-tailed deer SARS-CoV-2 with potential deer-to-human transmission

Pickering

Lung

Maguire

et al. 2022

Preprint

View full text Add to dashboard Cite

Wildlife reservoirs of SARS-CoV-2 can lead to viral adaptation and spillback from wildlife to humans (Oude Munnink et al., 2021). In North America, there is evidence of spillover of SARS-CoV-2 from humans to white-tailed deer (Odocoileus virginianus), but no evidence of transmission from deer to humans (Hale et al., 2021; Kotwa et al., 2022; Kuchipudi et al., 2021). Through a multidisciplinary research collaboration for SARS-CoV-2 surveillance in Canadian wildlife, we identified a new and highly divergent lineage of SARS-CoV-2. This lineage has 76 consensus mutations including 37 previously associated with non-human animal hosts, 23 of which were not previously reported in deer. There were also mutational signatures of host adaptation under neutral selection. Phylogenetic analysis revealed an epidemiologically linked human case from the same geographic region and sampling period. Together, our findings represent the first evidence of a highly divergent lineage of SARS-CoV-2 in white-tailed deer and of deer-to-human transmission.

show abstract

“…Reverse genetics derived viruses were generated as previously described 12,52,53 . Briefly, recombinant SARS-CoV-2 Wuhan cDNA genomes bearing the D614G, or Delta spike- or Omicron spike-encoding sequence were generated from a set of relevant overlapping genomic cDNA fragments and assembled using the Transformation-Associated Recombination (TAR) in yeast method as described 12 .…”

Section: Methodsmentioning

confidence: 99%

The altered entry pathway and antigenic distance of the SARS-CoV-2 Omicron variant map to separate domains of spike protein

Peacock

Brown

Zhou

et al. 2022

Preprint

Self Cite

306

344

View full text Add to dashboard Cite

At the end of 2021 a new SARS-CoV-2 variant, Omicron, emerged and quickly spread across the world. It has been demonstrated that Omicrons high number of Spike mutations lead to partial immune evasion from even polyclonal antibody responses, allowing frequent re-infection and vaccine breakthroughs. However, it seems unlikely these antigenic differences alone explain its rapid growth; here we show Omicron replicates rapidly in human primary airway cultures, more so even than the previously dominant variant of concern, Delta. Omicron Spike continues to use human ACE2 as its primary receptor, to which it binds more strongly than other variants. Omicron Spike mediates enhanced entry into cells expressing several different animal ACE2s, including various domestic avian species, horseshoe bats and mice suggesting it has an increased propensity for reverse zoonosis and is more likely than previous variants to establish an animal reservoir of SARS-CoV-2. Unlike other SARS-CoV-2 variants, however, Omicron Spike has a diminished ability to induce syncytia formation. Furthermore, Omicron is capable of efficiently entering cells in a TMPRSS2-independent manner, via the endosomal route. We posit this enables Omicron to infect a greater number of cells in the respiratory epithelium, allowing it to be more infectious at lower exposure doses, and resulting in enhanced intrinsic transmissibility.

show abstract

Mutations that adapt SARS-CoV-2 to mink or ferret do not increase fitness in the human airway

Cited by 53 publications

References 57 publications

Transmission of SARS-CoV-2 from humans to animals and potential host adaptation

Transmission of SARS-CoV-2 from humans to animals and potential host adaptation

Highly divergent white-tailed deer SARS-CoV-2 with potential deer-to-human transmission

The altered entry pathway and antigenic distance of the SARS-CoV-2 Omicron variant map to separate domains of spike protein

Contact Info

Product

Resources

About