title: An Acute Immune Response to Middle East Respiratory Syndrome Coronavirus Replication Contributes to Viral Pathogenicity.
abstract: Middle East respiratory syndrome coronavirus (MERS-CoV) was first identified in a human with severe pneumonia in 2012. Since then, infections have been detected in >1500 individuals, with disease severity ranging from asymptomatic to severe, fatal pneumonia. To elucidate the pathogenesis of this virus and investigate mechanisms underlying disease severity variation in the absence of autopsy data, a rhesus macaque and common marmoset model of MERS-CoV disease were analyzed. Rhesus macaques developed mild disease, and common marmosets exhibited moderate to severe, potentially lethal, disease. Both nonhuman primate species exhibited respiratory clinical signs after inoculation, which were more severe and of longer duration in the marmosets, and developed bronchointerstitial pneumonia. In marmosets, the pneumonia was more extensive, with development of severe airway lesions. Quantitative analysis showed significantly higher levels of pulmonary neutrophil infiltration and higher amounts of pulmonary viral antigen in marmosets. Pulmonary expression of the MERS-CoV receptor, dipeptidyl peptidase 4, was similar in marmosets and macaques. These results suggest that increased virus replication and the local immune response to MERS-CoV infection likely play a role in pulmonary pathology severity. Together, the rhesus macaque and common marmoset models of MERS-CoV span the wide range of disease severity reported in MERS-CoV-infected humans, which will aid in investigating MERS-CoV disease pathogenesis.
authors.affiliation: Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, NIH, Rocky Mountain Laboratories, Hamilton, Montana; Department of Comparative Pathobiology, Purdue University, West Lafayette, Indiana.
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Baseler
authors.affiliation: Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, NIH, Rocky Mountain Laboratories, Hamilton, Montana.
authors.forename: Darryl
authors.initials: D
authors.lastname: Falzarano
authors.affiliation: Rocky Mountain Veterinary Branch, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, NIH, Rocky Mountain Laboratories, Hamilton, Montana.
authors.forename: Dana P
authors.initials: DP
authors.lastname: Scott
authors.affiliation: Rocky Mountain Veterinary Branch, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, NIH, Rocky Mountain Laboratories, Hamilton, Montana.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Rosenke
authors.affiliation: Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, NIH, Rocky Mountain Laboratories, Hamilton, Montana.
authors.forename: Tina
authors.initials: T
authors.lastname: Thomas
authors.affiliation: Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, NIH, Rocky Mountain Laboratories, Hamilton, Montana.
authors.forename: Vincent J
authors.initials: VJ
authors.lastname: Munster
authors.affiliation: Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, NIH, Rocky Mountain Laboratories, Hamilton, Montana.
authors.forename: Heinz
authors.initials: H
authors.lastname: Feldmann
authors.affiliation: Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, NIH, Rocky Mountain Laboratories, Hamilton, Montana. Electronic address: emmie.dewit@nih.gov.
authors.forename: Emmie
authors.initials: E
authors.lastname: de Wit
mesh_terms: D000818:Animals; D000956:Antigens, Viral / Q000032:analysis / Q000097:blood*; D002144:Callithrix; D018352:Coronavirus Infections / Q000276:immunology* / Q000821:virology; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008168:Lung / Q000276:immunology / Q000473:pathology; D008253:Macaca mulatta; D016676:Macrophages, Alveolar / Q000145:classification; D008297:Male; D065207:Middle East Respiratory Syndrome Coronavirus / Q000276:immunology* / Q000472:pathogenicity / Q000502:physiology; D009504:Neutrophils / Q000276:immunology; D011024:Pneumonia, Viral / Q000276:immunology*; D011817:Rabbits; D019562:Viral Load; D014774:Virulence; D014779:Virus Replication / Q000276:immunology*
chemical_list: D000956:Antigens, Viral; D018819:Dipeptidyl Peptidase 4