TY - JOUR

T1 - In vitro Characterization of Fitness and Convalescent Antibody Neutralization of SARS-CoV-2 Cluster 5 Variant Emerging in Mink at Danish Farms

AU - Lassaunière, Ria

AU - Fonager, Jannik

AU - Rasmussen, Morten

AU - Frische, Anders

AU - Polacek, Charlotta

AU - Rasmussen, Thomas Bruun

AU - Lohse, Louise

AU - Belsham, Graham J.

AU - Underwood, Alexander

AU - Winckelmann, Anni Assing

AU - Bollerup, Signe

AU - Bukh, Jens

AU - Weis, Nina

AU - Sækmose, Susanne Gjørup

AU - Aagaard, Bitten

AU - Alfaro-Núñez, Alonzo

AU - Mølbak, Kåre

AU - Bøtner, Anette

AU - Fomsgaard, Anders

N1 - 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.

PY - 2021

Y1 - 2021

N2 - 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.

AB - 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.

KW - coronavirus

KW - COVID-19

KW - mink

KW - SARS-CoV-2

KW - virus neutralization

U2 - 10.3389/fmicb.2021.698944

DO - 10.3389/fmicb.2021.698944

M3 - Journal article

C2 - 34248922

AN - SCOPUS:85109606136

VL - 12

JO - Frontiers in Microbiology

JF - Frontiers in Microbiology

SN - 1664-302X

M1 - 698944

ER -