Abstract
Middle East respiratory syndrome (MERS), which is caused by a newly discovered coronavirus (CoV), has recently emerged. It causes severe viral pneumonia and is associated with a high fatality rate. However, the pathogenesis, comparative pathology and inflammatory cell response of rhesus macaques and common marmosets experimentally infected with MERS-CoV are unknown. We describe the histopathological, immunohistochemical, and ultrastructural findings from rhesus macaque and common marmoset animal models of MERS-CoV infection. The main histopathological findings in the lungs of rhesus macaques and common marmosets were varying degrees of pulmonary lesions, including pneumonia, pulmonary oedema, haemorrhage, degeneration and necrosis of the pneumocytes and bronchial epithelial cells, and inflammatory cell infiltration. The characteristic inflammatory cells in the lungs of rhesus macaques and common marmosets were eosinophils and neutrophils, respectively. Based on these observations, the lungs of rhesus macaques and common marmosets appeared to develop chronic and acute pneumonia, respectively. MERS-CoV antigens and viral RNA were identified in type I and II pneumocytes, alveolar macrophages and bronchial epithelial cells, and ultrastructural observations showed that viral protein was found in type II pneumocytes and inflammatory cells in both species. Correspondingly, the entry receptor DDP4 was found in type I and II pneumocytes, bronchial epithelial cells, and alveolar macrophages. The rhesus macaque and common marmoset animal models of MERS-CoV can be used as a tool to mimic the oncome of MERS-CoV infections in humans. These models can help to provide a better understanding of the pathogenic process of this virus and to develop effective medications and prophylactic treatments.
Highlights
The Middle East respiratory syndrome coronavirus (MERS-CoV) was identified in 2012 in a cell culture taken from a patient who died of pneumonia in Saudi Arabia [1]
HE stained tissues from rhesus macaques experimentally infected with MERS-CoV demonstrate that MERS-CoV induces lesions that are primarily observed in the lungs, with varying degrees of inflammation, interstitial pneumonia (Fig 1A), pulmonary oedema (Fig 1B), haemorrhaging, degeneration and necrosis of pneumocytes and bronchial epithelial cells (Fig 1C), and the infiltration of inflammatory cells
We found that the lungs of both species exhibited varying degrees of lesions, including pneumonia, pulmonary oedema, haemorrhaging, degeneration and necrosis of the pneumocytes and bronchial epithelial cells, and inflammatory cell infiltration
Summary
The Middle East respiratory syndrome coronavirus (MERS-CoV) was identified in 2012 in a cell culture taken from a patient who died of pneumonia in Saudi Arabia [1]. The respiratory symptoms of this infection are primarily related to severe lower respiratory tract complications (e.g., dyspnoea and coughing associated with a fever) that may become fatal, while there is generally little involvement of the upper respiratory tract. MERS-CoV seems to be widely present in dromedary camels in the Middle East and in some parts of Africa [7,8]. Most MERS patients acquire the infection in the Middle East, which subsequently leads to limited human-to-human transmission in local groups and healthcare workers and eventually to travel-related cases outside the region, all of which can result in a mild to severe or even fatal respiratory disease [2]
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