The characteristics of hDPP4 transgenic mice subjected to aerosol MERS coronavirus infection via an animal nose-only exposure device

Hao, Xin-yan; Lv, Qi; Li, Feng-di; Xu, Yan-feng; Gao, Hong

Additionally, immunohistochemical staining revealed that a MERS-CoV antigen was expressed in alveolar pneumocytes and endothelial cells, the brain, and the kidneys in challenged transgenic mice. Studies of a fatal case of MERS-CoV infection evidenced that the expression of a MERS-CoV antigen was predominantly localized in pneumocytes and endothelial cells, resulting in cell necrosis and pneumocyte damage; however, no viral antigens were detected in other tissues in the fatal case. 47 As demonstrated in previous studies, we also discovered high viral loads, pathological changes and the expression of a MERS-CoV antigen in the brain of challenged mice; and no brain lesions, but multiorgan damage, were observed in MERS patients. 35, 48, 49 Zhou et al demonstrated that human dendritic cells and macrophages were permissive to MERS-CoV replication, indicating that the multiorgan injury induced by MERS-CoV may be associated with the distribution of the hDPP4 receptor in many cell types that are spread throughout multiple organs. 38 Some studies have indicated that MERS-CoV has cell and tissue tropisms, especially tropisms for pneumocytes and neurons, and synapses may be one of the structures by which viruses diffuse through the brain after MERS-CoV infection. 31, 35 The mechanisms underlying the brain lesions and death induced by MERS-CoV infection in hDPP4 transgenic mice remain complex and complicated and need to be further investigated.