Abstract

Emerging coronaviruses are a global public health threat because of the potential for person-to-person transmission and high mortality rates. Middle East respiratory syndrome coronavirus (MERS-CoV) emerged in 2012, causing lethal respiratory disease in »35% of cases. Primate models of coronavirus disease are needed to support development of therapeutics, but few models exist that recapitulate severe disease. For initial development of a MERS-CoV primate model, 12 African green monkeys were exposed to 103, 104, or 105 PFU target doses of aerosolized MERS-CoV. We observed a dose-dependent increase of respiratory disease signs, although all 12 monkeys survived for the 28-day duration of the study. This study describes dose-dependent effects of MERS-CoV infection of primates and uses a route of infection with potential relevance to MERS-CoV transmission. Aerosol exposure of African green monkeys might provide a platform approach for the development of primate models of novel coronavirus diseases.

Highlights

  • Since 2002, three novel coronaviruses have emerged into human populations, causing severe respiratory disease: severe acute respiratory syndrome coronavirus (SARS-CoV) during 2002–2004; Middle East respiratory syndrome coronavirus (MERS-CoV), starting in 2012; and most recently, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), starting in 2019 [1,2]

  • Novel coronaviruses from the Betacoronavirus genus have emerged into the human population 3 separate times in

  • During the emergence of SARS-CoV and MERS-CoV, spillover into human populations was driven by an intermediate animal reservoir in closer proximity to humans [9,31]

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Summary

Introduction

Since 2002, three novel coronaviruses have emerged into human populations, causing severe respiratory disease: severe acute respiratory syndrome coronavirus (SARS-CoV) during 2002–2004; Middle East respiratory syndrome coronavirus (MERS-CoV), starting in 2012; and most recently, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), starting in 2019 [1,2]. To determine whether exposure of AGMs to aerosolized MERS-CoV results in observable disease signs that recapitulate MERS disease observed in human cases, physical observations of AGMs were performed, including calculation of respiratory rates (Figure 2, panels A, B) and clinical scores (Figure 2, panels B–D).

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