Infection with MERS-CoV Causes Lethal Pneumonia in the Common Marmoset

PLoS Pathogens

Jason S. McLellan¹  Tingting Liu²  Jiang Zhu²  Vincent J. Munster³  Michael G. Katze⁴  Matthew J. Thomas⁴  Angela L. Rasmussen⁴  Xinxia Peng⁴  Atsushi Okumura⁴  Elaine Haddock⁵  Emmie de Wit⁵  Heinz Feldmann⁵  Darryl Falzarano⁵  Friederike Feldmann⁶  Lee Nagy⁶  Rachel LaCasse⁶  Dana P. Scott⁶  Neeltje van Doremalen⁷ 

[1] Department of Biochemistry, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, United States of America;Department of Immunology and Microbial Science, Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California, United States of America;Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba, Canada;Department of Microbiology, University of Washington, Seattle, Washington, United States of America;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;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;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

关键词: Coronaviruses;    Marmosets;    Pneumonia;    Respiratory infections;    Viral load;    Macaque;    RNA extraction;    Rhesus monkeys;   

DOI  :  10.1371/journal.ppat.1004250

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY