African green monkey model of Middle East respiratory syndrome coronavirus (MERS-CoV) infection

      Purpose: Middle East Respiratory Syndrome Coronavirus (MERS-CoV) is a highly pathogenic zoonosis that emerged in 2012, causing lethal respiratory disease in approximately 35% of human cases. MERS-CoV continues to emerge on the Arabian Peninsula with the possibility of travel-exported cases to other regions of the world including prior confirmed cases in the Republic of Korea, the United States, England, France, and China. Currently, there are no specific countermeasures for MERS-CoV that have proven efficacious at ameliorating disease. Animal models that recapitulate severe MERS disease signs are needed to support development of therapeutics or vaccines to protect vulnerable populations.
      Methods & Materials: For initial development of a MERS-CoV primate model, twelve African green monkeys (AGMs) were exposed to 103, 104, or 105 PFU target doses of aerosolized MERS-CoV. Disease progression was followed with daily health observations, weights, body temperatures, blood and throat swab collection.
      Results: In this study, infection of the 103 PFU dose group was associated with minimal disease signs in AGMs, including lack of fever, lower viral titers and minimal clinical scores over 28 days of observation post-exposure to MERS-CoV. In contrast, the 104 PFU dose and especially the 105 PFU dose were associated with significantly more observable disease signs of MERS-CoV infection, although all AGMs survived for the 28 day duration of the study.
      Conclusion: Clinical symptoms of MERS in humans range from asymptomatic to severe respiratory syndrome and death. Severe cases of MERS present initially as fever, cough and shortness of breath, but progress to more severe respiratory symptoms including end-stage lung disease. Although biological factors including advanced age (>65 years) and comorbidities are associated with severe MERS disease in humans, few animal models exist that demonstrate biomarkers of severity in MERS-CoV infection as end-points for therapeutic testing. This study is the first to describe dose-dependent effects of highly pathogenic coronavirus infection of primates and uses a route of infection (aerosol) more relevant to MERS-CoV transmission in humans. Aerosol exposure of AGMs at higher doses may provide a lethal model of MERS in African green monkeys with potential utility in therapeutic development and viral pathogenesis studies.