In 2012, a previously unknown human coronavirus (CoV), now named Middle East respiratory syndrome CoV (MERS-CoV), was isolated from the sputum of a 60-year-old man in Saudi Arabia who presented with acute pneumonia with a fatal outcome (1, 2). To date, several infection clusters have been reported over a 1-year period, with around 50% of the reported human cases being fatal (3). MERS-CoV represents a novel betacoronavirus species, with the closest known relatives being clade 2c bat CoVs detected in bats (4, 5). Although MERS-CoV replicates in cells of bats, pigs, and (non-)human primates (6), its ability to infect some animal species may be restricted given the fact that hamsters were shown to resist MERS-CoV infection (7). However, these host factors have not been well characterized.We recently identified dipeptidyl peptidase 4 (DPP4) as a functional MERS-CoV receptor in human and bat cells (8). To further analyze DPP4 usage by MERS-CoV in vivo, ferrets (Mustela putorius furo; n ϭ 4), known to be susceptible to several respiratory viruses, including severe acute respiratory syndrome CoV (SARS- staining or S1-Fc binding on ferret kidney cells incubated with either goat anti-DPP4 polyclonal serum or S1-Fc (5 g/ml) followed by incubation with fluorescein isothiocyanate (FITC)-labeled rabbit anti-goat IgG antibody or FITC-labeled goat anti-human IgG, respectively (red lines). Normal goat serum, feline CoV S1-Fc protein (blue lines), and mock-incubated cells (gray shading) were used as controls. (E) MERS-CoV infection of primary ferret kidney cells transfected with a control plasmid or with a plasmid encoding hDPP4, stained for DPP4, S1 binding, and MERS-CoV as described previously (13).

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bThe ability of Middle East respiratory syndrome coronavirus (MERS-CoV) to infect small animal species may be restricted given the fact that mice, ferrets, and hamsters were shown to resist MERS-CoV infection. We inoculated rabbits with MERS-CoV. Although virus was detected in the lungs, neither significant histopathological changes nor clinical symptoms were observed. Infectious virus, however, was excreted from the upper respiratory tract, indicating a potential route of MERS-CoV transmission in some animal species.

Ferrets are widely used as a small animal model for a number of viral infections, including influenza A virus and SARS coronavirus. To further analyze the microbiological status of ferrets, their fecal viral flora was studied using a metagenomics approach. Novel viruses from the families Picorna-, Papilloma-, and Anelloviridae as well as known viruses from the families Astro-, Corona-, Parvo-, and Hepeviridae were identified in different ferret cohorts. Ferret kobu- and hepatitis E virus were mainly present in human household ferrets, whereas coronaviruses were found both in household as well as farm ferrets. Our studies illuminate the viral diversity found in ferrets and provide tools to prescreen for newly identified viruses that potentially could influence disease outcome of experimental virus infections in ferrets.