In vitro Characterization of Fitness and Convalescent Antibody Neutralization of SARS-CoV-2 Cluster 5 Variant Emerging in Mink at Danish Farms

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In addition to humans, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can transmit to animals that include hamsters, cats, dogs, mink, ferrets, tigers, lions, cynomolgus macaques, rhesus macaques, and treeshrew. Among these, mink are particularly susceptible. Indeed, 10 countries in Europe and North America reported SARS-CoV-2 infection among mink on fur farms. In Denmark, SARS-CoV-2 spread rapidly among mink farms and spilled-over back into humans, acquiring mutations/deletions with unknown consequences for virulence and antigenicity. Here we describe a mink-associated SARS-CoV-2 variant (Cluster 5) characterized by 11 amino acid substitutions and four amino acid deletions relative to Wuhan-Hu-1. Temporal virus titration, together with genomic and subgenomic viral RNA quantitation, demonstrated a modest in vitro fitness attenuation of the Cluster 5 virus in the Vero-E6 cell line. Potential alterations in antigenicity conferred by amino acid changes in the spike protein that include three substitutions (Y453F, I692V, and M1229I) and a loss of two amino acid residues 69 and 70 (ΔH69/V70), were evaluated in a virus microneutralization assay. Compared to a reference strain, the Cluster 5 variant showed reduced neutralization in a proportion of convalescent human COVID-19 samples. The findings underscore the need for active surveillance SARS-CoV-2 infection and virus evolution in susceptible animal hosts.

TidsskriftFrontiers in Microbiology
Antal sider9
StatusUdgivet - 2021

Bibliografisk note

Funding Information:
We would like to thank the following valued contributors: Birgit Knudsen, Dennis Jelsbak Schmidt, Randi Th?gersen, Louise Borup, and Anne Louise S?rensen for technical support, Signe Lysemose Villadsen for handling of patient blood samples, the Danish COVID19 Genome Consortium for the continued sequence surveillance of SARS-CoV-2 in Denmark. Funding. No particular funding was obtained for this work, which was a part of the Danish national health response to the COVID-19 pandemic.

Publisher Copyright:
© Copyright © 2021 Lassaunière, Fonager, Rasmussen, Frische, Polacek, Rasmussen, Lohse, Belsham, Underwood, Winckelmann, Bollerup, Bukh, Weis, Sækmose, Aagaard, Alfaro-Núñez, Mølbak, Bøtner and Fomsgaard.

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