title: Infection with MERS-CoV causes lethal pneumonia in the common marmoset.
abstract: The availability of a robust disease model is essential for the development of countermeasures for Middle East respiratory syndrome coronavirus (MERS-CoV). While a rhesus macaque model of MERS-CoV has been established, the lack of uniform, severe disease in this model complicates the analysis of countermeasure studies. Modeling of the interaction between the MERS-CoV spike glycoprotein and its receptor dipeptidyl peptidase 4 predicted comparable interaction energies in common marmosets and humans. The suitability of the marmoset as a MERS-CoV model was tested by inoculation via combined intratracheal, intranasal, oral and ocular routes. Most of the marmosets developed a progressive severe pneumonia leading to euthanasia of some animals. Extensive lesions were evident in the lungs of all animals necropsied at different time points post inoculation. Some animals were also viremic; high viral loads were detected in the lungs of all infected animals, and total RNAseq demonstrated the induction of immune and inflammatory pathways. This is the first description of a severe, partially lethal, disease model of MERS-CoV, and as such will have a major impact on the ability to assess the efficacy of vaccines and treatment strategies as well as allowing more detailed pathogenesis studies.
authors.affiliation: Disease Modeling and Transmission, Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratories, Hamilton, Montana, United States of America.
authors.forename: Darryl
authors.initials: D
authors.lastname: Falzarano
authors.affiliation: Disease Modeling and Transmission, Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratories, Hamilton, Montana, United States of America.
authors.forename: Emmie
authors.initials: E
authors.lastname: de Wit
authors.affiliation: Rocky Mountain Veterinary Branch, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratories, Hamilton, Montana, United States of America.
authors.forename: Friederike
authors.initials: F
authors.lastname: Feldmann
authors.affiliation: Department of Microbiology, University of Washington, Seattle, Washington, United States of America.
authors.forename: Angela L
authors.initials: AL
authors.lastname: Rasmussen
authors.affiliation: Department of Microbiology, University of Washington, Seattle, Washington, United States of America.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Okumura
authors.affiliation: Department of Microbiology, University of Washington, Seattle, Washington, United States of America.
authors.forename: Xinxia
authors.initials: X
authors.lastname: Peng
authors.affiliation: Department of Microbiology, University of Washington, Seattle, Washington, United States of America.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Thomas
authors.affiliation: Virus Ecology Unit, Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratories, Hamilton, Montana, United States of America.
authors.forename: Neeltje
authors.initials: N
authors.lastname: van Doremalen
authors.affiliation: Disease Modeling and Transmission, Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratories, Hamilton, Montana, United States of America.
authors.forename: Elaine
authors.initials: E
authors.lastname: Haddock
authors.affiliation: Rocky Mountain Veterinary Branch, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratories, Hamilton, Montana, United States of America.
authors.forename: Lee
authors.initials: L
authors.lastname: Nagy
authors.affiliation: Rocky Mountain Veterinary Branch, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratories, Hamilton, Montana, United States of America.
authors.forename: Rachel
authors.initials: R
authors.lastname: LaCasse
authors.affiliation: Department of Immunology and Microbial Science, Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California, United States of America.
authors.forename: Tingting
authors.initials: T
authors.lastname: Liu
authors.affiliation: Department of Immunology and Microbial Science, Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California, United States of America.
authors.forename: Jiang
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Department of Biochemistry, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, United States of America.
authors.forename: Jason S
authors.initials: JS
authors.lastname: McLellan
authors.affiliation: Rocky Mountain Veterinary Branch, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratories, Hamilton, Montana, United States of America.
authors.forename: Dana P
authors.initials: DP
authors.lastname: Scott
authors.affiliation: Department of Microbiology, University of Washington, Seattle, Washington, United States of America.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Katze
authors.affiliation: Disease Modeling and Transmission, Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratories, Hamilton, Montana, United States of America; Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Heinz
authors.initials: H
authors.lastname: Feldmann
authors.affiliation: Virus Ecology Unit, Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratories, Hamilton, Montana, United States of America.
authors.forename: Vincent J
authors.initials: VJ
authors.lastname: Munster
mesh_terms: D000818:Animals; D002144:Callithrix; D018352:Coronavirus Infections / Q000473:pathology* / Q000821:virology; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D008297:Male; D065207:Middle East Respiratory Syndrome Coronavirus; D011024:Pneumonia, Viral / Q000473:pathology* / Q000821:virology; D060888:Real-Time Polymerase Chain Reaction