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

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

Pin Yu  1   2 , Yanfeng Xu  1   2 , Wei Deng  1   2 , Linlin Bao  1   2 , Lan Huang  1   2 , Yuhuan Xu  1   2 , Yanfeng Yao  1   2 , Chuan Qin  1   2
Affiliations
Comparative Study

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

Pin Yu et al. PLoS One. .

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.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Pathological findings in the lungs of rhesus macaques and common marmosets infected with MERS-CoV.
(A) Interstitial pneumonia and eosinophil (black arrowhead) infiltration in the expanded alveolar septum. (B) Pulmonary oedema (arrow) and eosinophil (black arrowhead) infiltration. (C) Necrosis of bronchial epithelial cells and eosinophil (arrow) infiltration. (D) Fibrinous exudation (arrow) and neutrophil (yellow arrowhead) infiltration in the alveoli. (E) Pulmonary oedema (arrow) and neutrophil (yellow arrowhead) infiltration. (F) Necrosis of bronchial epithelial cells and neutrophil (arrow) infiltration. Haematoxylin-eosin staining. Bars represent 20 μm.
Fig 2
Fig 2. Infiltration of inflammatory cells in the lungs of rhesus macaques and common marmosets infected with MERS-CoV.
(A) Numerous eosinophils (black arrowhead) infiltrated the alveolar septum. (B) Diffuse infiltration of macrophages (black arrowhead) in the expanded alveolar septum. (C) Numerous neutrophils (black arrowhead) infiltrated the oedematous alveolar cavities. (D) Diffuse infiltration of macrophages (black arrowhead). For both haematoxylin-eosin staining (A) and immunohistochemistry (B, C and D), bars represent 20 μm.
Fig 3
Fig 3. Distribution of MERS-CoV antigen and viral RNA in the lungs of rhesus macaques and common marmosets infected with MERS-CoV.
(A) Viral antigen in pneumocytes (black arrowhead) and macrophages (arrow). (B) Viral antigen in pneumocytes, eosinophils (arrow) and bronchial epithelial cells (black arrowhead). (C) Viral RNA in pneumocytes (black arrowhead) and inflammatory cells. (D) Viral antigen in pneumocytes (black arrowhead) and inflammatory cells (arrow). (E) Viral antigen in the inflammatory cells (black arrowhead) around the bronchus. (F) Viral RNA in pneumocytes (black arrowhead) and inflammatory cells. For both immunohistochemistry (A, B, D and E) and in situ hybridization (C and F), bars represent 20 μm.
Fig 4
Fig 4. Ultrastructural pathological findings in the lungs of common marmosets infected with MERS-CoV.
Virus particles (arrows, B and C) were visible in type II pneumocytes (blue arrowhead, A). Virus particles (arrow; D, E and F) were also found in the inflammatory cells in the lung (D and E). Transmission electron microscopy.
Fig 5
Fig 5. Distribution of DDP4 in the lungs of rhesus macaques and common marmosets infected with MERS-CoV.
(A) DDP4 expressed in type I and II pneumocytes, inflammatory cells (arrow) and bronchial epithelial cells, primarily in ciliated cells (black arrowhead, a) and basal cells. (B) DDP4 expressed in the type I and II pneumocytes, inflammatory cells, especially macrophages (arrow), and bronchial epithelial cells, primarily ciliated cells and basal cells (black arrowhead, b). Immunohistochemistry. Bars represent 20 μm.
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References

    1. Zaki AM, van Boheemen S, Bestebroer TM, Osterhaus AD, Fouchier RA Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia. N Engl J Med 367: 1814–1820. 10.1056/NEJMoa1211721 - DOI - PubMed
    1. Assiri A, Al-Tawfiq JA, Al-Rabeeah AA, Al-Rabiah FA, Al-Hajjar S, et al. (2013) Epidemiological, demographic, and clinical characteristics of 47 cases of Middle East respiratory syndrome coronavirus disease from Saudi Arabia: a descriptive study. Lancet Infect Dis 13: 752–761. 10.1016/S1473-3099(13)70204-4 - DOI - PMC - PubMed
    1. Al-Tawfiq JA, Hinedi K, Ghandour J, Khairalla H, Musleh S, et al. (2014) Middle East respiratory syndrome coronavirus: a case-control study of hospitalized patients. Clin Infect Dis 59: 160–165. 10.1093/cid/ciu226 - DOI - PMC - PubMed
    1. Arabi YM, Arifi AA, Balkhy HH, Najm H, Aldawood AS, et al. (2014) Clinical course and outcomes of critically ill patients with Middle East respiratory syndrome coronavirus infection. Ann Intern Med 160: 389–397. 10.7326/M13-2486 - DOI - PubMed
    1. Who Mers-Cov Research Group (2013) State of knowledge and data gaps of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) in humans. PLoS Curr 5. - PMC - PubMed

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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].