Animal models of Middle East respiratory syndrome coronavirus infection

The emergence of the Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012 marked the second time that a new, highly pathogenic coronavirus has emerged in the human population in the 21st century. In this review, we discuss the current state of knowledge of animal models of MERS-CoV infection. Commonly used laboratory animal species such as Syrian hamsters, mice and ferrets are not susceptible to MERS-CoV, due to differences in the MERS-CoV receptor dipeptidyl peptidase 4 (DPP4). The initially developed animal models comprise two nonhuman primate species, the rhesus macaque and the common marmoset. Rhesus macaques develop a mild to moderate respiratory disease upon inoculation, reminiscent of milder MERS cases, whereas marmosets develop a moderate to severe respiratory disease, recapitulating the severe disease observed in some patients. Dromedary camels, considered to be the reservoir for MERS-CoV, develop a mild upper respiratory tract infection with abundant viral shedding. Although normal mice are not susceptible to MERS-CoV, expression of the human DPP4 (hDPP4) overcomes the lack of susceptibility. Transgenic hDPP4 mice develop severe and lethal respiratory disease upon inoculation with MERS-CoV. These hDPP4 transgenic mice are potentially the ideal first line animal model for efficacy testing of therapeutic and prophylactic countermeasures. Further characterization of identified countermeasures would ideally be performed in the common marmoset model, due to the more severe disease outcome. This article forms part of a symposium in Antiviral Research on "From SARS to MERS: research on highly pathogenic human coronaviruses."