Comparative pathology of rhesus macaque and common marmoset animal models with Middle East respiratory syndrome coronavirus

PLoS One. 2017 Feb 24;12(2):e0172093. doi: 10.1371/journal.pone.0172093. eCollection 2017.

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.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Callithrix / physiology*
  • Callithrix / virology
  • Coronavirus Infections / diagnosis
  • Coronavirus Infections / pathology*
  • Disease Models, Animal*
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization
  • Inflammation
  • Lung / virology
  • Macaca mulatta / physiology*
  • Macaca mulatta / virology
  • Macrophages, Alveolar / metabolism
  • Middle East Respiratory Syndrome Coronavirus*
  • RNA, Viral
  • Species Specificity
  • Virus Replication

Substances

  • RNA, Viral

Grants and funding

This work was supported by the Sector Funds of National Health and Family Planning Commission of the People's Republic of China [201302006].