Peridomestic Mammal Susceptibility to Severe Acute Respiratory Syndrome Coronavirus 2 Infection

Angela M. Bosco-Lauth; J. Jeffrey Root; Stephanie M. Porter; Audrey E. Walker; Lauren Guilbert; Daphne Hawvermale; Aimee Pepper; Rachel M. Maison; Airn E. Hartwig; Paul Gordy; Helle Bielefeldt-Ohmann; Richard A. Bowen

Disclosures

Emerging Infectious Diseases. 2021;27(8):2073-2080. 

In This Article

Abstract and Introduction

Abstract

Wild animals have been implicated as the origin of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but it is largely unknown how the virus affects most wildlife species and if wildlife could ultimately serve as a reservoir for maintaining the virus outside the human population. We show that several common peridomestic species, including deer mice, bushy-tailed woodrats, and striped skunks, are susceptible to infection and can shed the virus in respiratory secretions. In contrast, we demonstrate that cottontail rabbits, fox squirrels, Wyoming ground squirrels, black-tailed prairie dogs, house mice, and racoons are not susceptible to SARS-CoV-2 infection. Our results expand the knowledge base of susceptible species and provide evidence that human–wildlife interactions could result in continued transmission of SARS-CoV-2.

Introduction

The rapid global expansion of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease (COVID-19), has been unprecedented in modern history. Although the original human infection(s) were potentially linked to wild animals in a wet market,[1] human-to-human transmission is currently the dominant mechanism of viral spread. Peridomestic animals, which are represented by wild and feral animals living near humans, represent key species to evaluate for SARS-CoV-2 epidemiology for multiple reasons. First, given their common associations with humans and anthropogenically modified habitats, they represent the wildlife species with the greatest chance of exposure to the virus from humans (i.e., reverse zoonosis) or pets, such as cats. Second, should select peridomestic wildlife prove to be susceptible to the virus and have the capacity to replicate it to high viral titers, those species would have the potential to maintain the virus among conspecifics. Third, should some species possess the maintenance host criteria mentioned, they would represent wildlife species that would have the greatest chance (e.g., shedding ability and proximity to humans) to spread the virus back to humans. Wild rodents, cottontail rabbits (Sylvilagus sp.), raccoons (Procyon lotor), and striped skunks (Mephitis mephitis) can exhibit peridomestic tendencies in urban and suburban environments. Members of all these species/taxonomic groups have been shown to shed influenza A viruses after experimental inoculations,[2–4] suggesting they might harbor productive infections when exposed to other human-pathogenic respiratory viruses.

Based upon protein analyses of amino acid residues of angiotensin-converting enzyme 2 (ACE2), transmembrane protease serine type 2, and spike protein, species susceptibility analyses suggested that, among other taxonomic groups, both carnivores and wild rodents are potentially high-risk groups.[5–7] However, predicting susceptibility of specific species is more challenging. Looking at protein sequence analysis of ACE2 binding with the spike protein of SARS-CoV-2, one study indicated that raccoons could be ruled out as potential hosts for SARS-CoV-2,[6] and a different study based upon sequence analysis suggested that the western spotted skunks (Spilogale gracilis) had a low prediction of SARS-CoV-2 S binding propensity.[7] Similarly, the same study also suggested that American mink (Neovison vison) have a similar prediction as western spotted skunks.[7] However, over the past several months, outbreaks of SAR-CoV-2 in commercial mink farms have been reported in Europe and more recently in the United States.[8,9] Respiratory problems, rapid transmission, or unusually high mortality rates have been reported for this species in various regions,[8,10] which suggests that those analyses have limitations.

Because rodents are the largest and most diverse order of mammals, it is not surprising that the susceptibility of rodents to SARS-CoV-2 varies by species. To date, only a handful of rodent species have been evaluated as potential reservoir hosts or animal models for SARS-CoV-2, and the results largely indicate that outbred species, including laboratory animals, are at most only moderately affected. Most nontransgenic laboratory mice (Mus musculus) are resistant to infection, but transgenic humanized mice and hamsters, including Syrian hamsters (Mesocricetus auratus) and dwarf hamsters (Phodopus sp.), are highly susceptible;[11,12] 1 report described Roborovki dwarf hamsters becoming diseased and dying within 3 days of exposure.[13] Other species, including deer mice (Peromyscus maniculatus), become infected and shed low titers of virus, but the infection is subclinical (A. Fagre, Colorado State University, pers. comm., 2020 Aug 7). Considering that there are >1,700 species of rodents worldwide, many of which exist closely at the human–wildlife interface, there remain many unanswered questions about SARS-CoV-2 and wild rodents.

Various lagomorphs exist as pets, livestock, and peridomestic wildlife, and as such are in a prime position to come into contact with SARS-CoV-2–infected humans. In 1 study, New Zealand white rabbits were experimentally infected and shed infectious virus for ≤7 days without signs of clinical disease.[14] Wild rabbits, particularly cottontails in the United States, are prolific and commonly found around human dwellings, farms, and commercial buildings. Furthermore, as with rodents, wild rabbits are likely to be predated upon by domestic and wild felids and canids. Thus, the susceptibility of these animals must be determined to interpret the risk posed to them and by them from infection with SARS-CoV-2.

Among carnivores, felids and mustelids have been frequently linked to SARS-CoV-2 infections since the early stages of the pandemic. Domestic cats are highly susceptible to SARS-CoV-2 and are capable of transmitting the virus to other cats, suggesting that they could also potentially transmit virus to other animals.[15,16] Although striped skunks are currently considered to be mephitids, they are highly related to mammals within the family Mustelidae and were formerly classified as mustelids. Thus, on the basis of findings for SARS-CoV-2 susceptibility in various mustelids, we determined that the closely related mephitids are a logical candidate to evaluate for replication of this virus. Raccoons are notoriously associated with human environments and frequently interact with human trash and sewage; these interactions have which has been proposed as a potential indirect means for infected humans to transmit SARS-CoV-2 to mammalian wildlife (e.g., raccoons and select mustelids).[17–19] Thus, it is essential to determine the relative susceptibility of these common peridomestic carnivores and assess the likelihood that they could propagate infection.

In this study, we assessed 6 common peridomestic rodent species for susceptibility to SARS-CoV-2: deer mice, wild-caught house mice (Mus musculus), bushy-tailed woodrats (aka pack rats; Neotoma cinerea), fox squirrels (Sciurus niger), Wyoming ground squirrels (Urocitellus elegans), and black-tailed prairie dogs (Cynomys ludovicianus). These rodents are common in many parts of the United States, several of them frequently come into close contact with humans and human dwellings, and some are highly social animals, thus increasing the likelihood of pathogen transmission among conspecifics. In addition, we evaluated 3 other common peridomestic mammals: cottontail rabbits, raccoons, and striped skunks.

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