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Infection with MERS-CoV causes lethal pneumonia in the common marmoset

Darryl Falzarano1, Emmie de Wit1, Friederike Feldmann2

  • 1Disease 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.

Plos Pathogens
|August 22, 2014
PubMed

Insights

A new common marmoset model for Middle East respiratory syndrome coronavirus (MERS-CoV) infection causes severe pneumonia. This severe MERS-CoV disease model is crucial for developing effective vaccines and treatments.

Area of Science:

  • Virology
  • Infectious Diseases
  • Animal Models

Background:

  • A robust disease model is critical for developing Middle East respiratory syndrome coronavirus (MERS-CoV) countermeasures.
  • Existing rhesus macaque models exhibit variable disease severity, hindering countermeasure analysis.

Purpose of the Study:

  • To evaluate the common marmoset as a susceptible and responsive model for MERS-CoV infection.
  • To establish a severe, partially lethal MERS-CoV disease model for pathogenesis and therapeutic studies.

Main Methods:

  • Computational modeling predicted MERS-CoV spike glycoprotein and human dipeptidyl peptidase 4 receptor interactions.
  • Common marmosets were inoculated via combined intratracheal, intranasal, oral, and ocular routes.
  • Disease progression, viral loads, lung pathology, and host immune responses were assessed.

Main Results:

  • Most marmosets developed progressive, severe pneumonia, with some requiring euthanasia.
  • Extensive lung lesions and high viral loads were observed in all necropsied animals.
  • Viremia and induction of immune and inflammatory pathways were detected via RNAseq.

Conclusions:

  • The common marmoset provides a valuable, severe, and partially lethal disease model for MERS-CoV.
  • This model will significantly advance the assessment of MERS-CoV vaccines and therapeutics.
  • It facilitates detailed studies into MERS-CoV pathogenesis.

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