SARS-CoV-2 evolution in animals suggests mechanisms for rapid variant selection

Abstract

SARS-CoV-2 spillback from humans into domestic and wild animals has been well documented, and an accumulating number of studies illustrate that human-to-animal transmission is widespread in cats, mink, deer, and other species. Experimental inoculations of cats, mink, and ferrets have perpetuated transmission cycles. We sequenced full genomes of Vero cell–expanded SARS-CoV-2 inoculum and viruses recovered from cats (n = 6), dogs (n = 3), hamsters (n = 3), and a ferret (n = 1) following experimental exposure. Five nonsynonymous changes relative to the USA-WA1/2020 prototype strain were near fixation in the stock used for inoculation but had reverted to wild-type sequences at these sites in dogs, cats, and hamsters within 1- to 3-d postexposure. A total of 14 emergent variants (six in nonstructural genes, six in spike, and one each in orf8 and nucleocapsid) were detected in viruses recovered from animals. This included substitutions in spike residues H69, N501, and D614, which also vary in human lineages of concern. Even though a live virus was not cultured from dogs, substitutions in replicase genes were detected in amplified sequences. The rapid selection of SARS-CoV-2 variants in vitro and in vivo reveals residues with functional significance during host switching. These observations also illustrate the potential for spillback from animal hosts to accelerate the evolution of new viral lineages, findings of particular concern for dogs and cats living in households with COVID-19 patients. More generally, this glimpse into viral host switching reveals the unrealized rapidity and plasticity of viral evolution in experimental animal model systems.

From Deer-to-Deer: SARS-CoV-2 is efficiently transmitted and presents broad tissue tropism and replication sites in white-tailed deer

“…This contrasts with what has been described in other animal species (e.g. tigers, lions, mink, cats, dogs, hamsters and ferrets) naturally and/or experimentally infected with the virus, in which characteristic mutations mainly in the S protein have been observed shortly after infection [ 22 – 25 ]. The findings in WTD can be partially explained by the high degree of homology of the human and deer ACE2 proteins [ 9 ]–the entry receptor for the virus–which may favor interaction of the S protein with the cellular receptor and result in lower selective pressure for virus entry and spread to target cells in secondary sites of replication.…”

Ecological super‐spreaders drive host–range oscillations: Omicron and risk space for emerging infectious disease

“…This explains why traditional approaches for coping with EID have failed. Responding only after the fact for any emergence, no matter how rapidly, is ultimately ineffective and unsustainably costly (Brooks et al., 2021 , 2019 ; Trivellone et al., 2022 ). Even adequately managed EIDs may recycle in the risk space and re‐emerge as distinct lineages with unique epidemiological features.…”

Multiple Introductions of SARS-CoV-2 Alpha and Delta Variants into White-Tailed Deer in Pennsylvania

“…The SARS-CoV-2 pandemic likely began by viral spillover from animals to humans [1][2][3] ; today multiple animal species are known to be susceptible to infection [4][5][6][7][8] . White-tailed deer, Odocoileus virginianus are infected in North America at substantial levels [9][10][11] , and genomic data suggests that a variant in deer may have spilled back to humans 12,13 . Here we characterize SARS-CoV-2 in deer from Pennsylvania (PA) sampled during fall and winter 2021.…”