Middle East respiratory syndrome coronavirus (MERS-CoV) causes transient lower respiratory tract infection in rhesus macaques

Wit, Emmie de; Rasmussen, Angela L.; Falzarano, Darryl; Bushmaker, Trenton; Feldmann, Friederike; Brining, Douglas; Fischer, Elizabeth R.; Martellaro, Cynthia; Okumura, Atsushi; Chang, Jean; Scott, Dana; Benecke, Arndt; Katze, Michael G.; Feldmann, Heinz; Munster, Vincent J.

doi:10.1073/pnas.1310744110

Cited by 285 publications

(311 citation statements)

References 29 publications

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“…77 Infectious virus was isolated from the lungs, 50,77 and MERS-CoV RNA was detected in several upper and lower respiratory tract tissues (Table 2). 22 MERS-CoV RNA was also identified in nasal swabs, bronchoalveolar lavage samples, and a few oropharyngeal swabs. 22 Despite the presence of viral RNA and evidence for viral shedding from the upper respiratory tract, lesions and virus replication were observed only in lower respiratory tract tissues, with virus replication occurring in type I and type II pneumocytes.…”

Section: Rhesus Macaquesmentioning

confidence: 95%

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A Comparative Review of Animal Models of Middle East Respiratory Syndrome Coronavirus Infection

2016

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Middle East respiratory syndrome coronavirus (MERS-CoV) was initially isolated from a Saudi Arabian man with fatal pneumonia. Since the original case in 2012, MERS-CoV infections have been reported in >1500 humans, and the case fatality rate is currently 35%. This lineage C betacoronavirus has been reported to cause a wide range of disease severity in humans, ranging from asymptomatic to progressive fatal pneumonia that may be accompanied by renal or multiorgan failure. Although the clinical presentation of human MERS-CoV infection has been documented, many facets of this emerging disease are still unknown and could be studied with animal models. Several animal models of MERS-CoV have been developed, including New Zealand white rabbits, transduced or transgenic mice that express human dipeptidyl peptidase 4, rhesus macaques, and common marmosets. This review provides an overview of the current state of knowledge on human MERS-CoV infections, the probable origin of MERS-CoV, and the available animal models of MERS-CoV infection. Evaluation of the benefits and limitations of these models will aid in appropriate model selection for studying viral pathogenesis and transmission, as well as for testing vaccines and antivirals against MERS-CoV.Keywords animal models, common marmosets, dipeptidyl peptidase 4, mice, Middle East respiratory syndrome coronavirus, pathogenicity, rabbits, respiratory system, review, rhesus macaques, transgenic Middle East respiratory syndrome coronavirus (MERS-CoV) was first isolated from a man in Saudi Arabia in 2012, and MERS-CoV infections have now been reported in >20 countries. 76,79 Originally called human coronavirus-EMC/2012, the virus was renamed MERS-CoV by the International Committee on Taxonomy of Viruses. 20,67 In humans, MERS-CoV is 1 of 6 coronaviruses that cause respiratory disease; however, it is currently the only known pathogenic human lineage C betacoronavirus. 31,68 MERS-CoV infections in humans range from asymptomatic to progressive fatal pneumonia with occasional renal or multiorgan failure. 44,52 To date, published autopsy data from fatal human cases are not available, and the exact route of viral transmission to and among humans is unknown. Additionally, there are currently no approved MERS-CoV-specific countermeasures. Thus, development of animal models to study the pathology and pathogenesis of MERS-CoV, the routes of viral transmission, and the efficacy of treatments and vaccines is critical. Here, we review the current state of knowledge on MERS-CoV infections in humans and potential animal reservoirs for the virus and provide an overview and analysis of animal models of MERS-CoV infection.

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Section: Rhesus Macaquesmentioning

confidence: 95%

“…22,69 Viral antigen in the lung was exclusively present in areas of pneumonia. 22,77 Viral RNA was not present in blood or any visceral organs, including the kidney. 22,77 The transient respiratory disease that developed in MERS-CoV-infected rhesus macaques models human cases of mild MERS-CoV infections.…”

Section: Rhesus Macaquesmentioning

confidence: 98%

A Comparative Review of Animal Models of Middle East Respiratory Syndrome Coronavirus Infection

2016

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“…In vitro activity of interferon was further enhanced by the addition of ribavirin [30]. Recently, animal studies utilizing Rhesus Macaque monkeys infected with MERS-CoV were published [31][32][33]. Using intratracheal, ocular, oral and intranasal inoculation of MERS-CoV, Rhesus macaques developed a transient lower respiratory tract infection and had histopathologic changes of the disease and developed neutralizing antibodies [33].…”

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confidence: 99%

What are our pharmacotherapeutic options for MERS-CoV?

Al‐Tawfiq

Memish

2014

Expert Review of Clinical Pharmacology

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“…We next tried to detect MERS-CoV replication in these lesions using real-time RT-PCR. We used 2 primer combinations to detect ORF1 transcripts (viral RNA and mRNA) and ORF5 subgenomic mRNA (13). This assay can detect at least 100 copies of the specific target per reaction.…”

Section: Resultsmentioning

confidence: 99%

Non Susceptibility of Neonatal and Adult Rats against the Middle East Respiratory Syndrome Coronavirus

et al. 2016

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SUMMARY:The present study examined the susceptibility of rats to the Middle East respiratory syndrome coronavirus (MERS-CoV) and determined whether this animal is a suitable model for MERSCoV infection. Immunohistochemical analysis identified dipeptidyl peptidase 4 (DPP4), a known receptor for MERS-CoV on type I pneumocytes from infected rats. Whereas adult rats developed antibodies against MERS-CoV spike protein after intranasal inoculation, there was no evidence of viral replication in the lungs of adult, young, or neonatal rats after intranasal inoculation with MERS-CoV. In addition, human DPP4-expressing rat kidney fibroblasts, but not rat DPP4-expressing cells, were susceptible to MERS-CoV. Taken together, these results suggest that the rat is not a useful animal model for studying MERS-CoV infection.

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Middle East respiratory syndrome coronavirus (MERS-CoV) causes transient lower respiratory tract infection in rhesus macaques

Cited by 285 publications

References 29 publications

A Comparative Review of Animal Models of Middle East Respiratory Syndrome Coronavirus Infection

A Comparative Review of Animal Models of Middle East Respiratory Syndrome Coronavirus Infection

What are our pharmacotherapeutic options for MERS-CoV?

Non Susceptibility of Neonatal and Adult Rats against the Middle East Respiratory Syndrome Coronavirus

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