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A Murine Model of Dengue Virus-induced Acute Viral Encephalitis-like Disease
Published on: April 28, 2019
Transmission dynamics of MERS-CoV in a transgenic human DPP4 mouse model
Neeltje van Doremalen1, Trenton Bushmaker1, Robert J Fischer1
1Division of Intramural Research, Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA.
Abstract:
Since 2002, three novel coronavirus outbreaks have occurred: severe acute respiratory syndrome coronavirus (SARS-CoV-1), Middle East respiratory syndrome coronavirus (MERS-CoV), and SARS-CoV-2. A better understanding of the transmission potential of coronaviruses will result in adequate infection control precautions and an early halt of transmission within the human population. Experiments on the stability of coronaviruses in the environment, as well as transmission models, are thus pertinent.Here, we show that transgenic mice expressing human DPP4 can be infected with MERS-CoV via the aerosol route. Exposure to 5 × 106 TCID50 and 5 × 104 TCID50 MERS-CoV per cage via fomites resulted in transmission in 15 out of 20 and 11 out of 18 animals, respectively. Exposure of sentinel mice to donor mice one day post inoculation with 105 TCID50 MERS-CoV resulted in transmission in 1 out of 38 mice via direct contact and 4 out of 54 mice via airborne contact. Exposure to donor mice inoculated with 104 TCID50 MERS-CoV resulted in transmission in 0 out of 20 pairs via direct contact and 0 out of 5 pairs via the airborne route. Our model shows limited transmission of MERS-CoV via the fomite, direct contact, and airborne routes. The hDPP4 mouse model will allow assessment of the ongoing evolution of MERS-CoV in the context of acquiring enhanced human-to-human transmission kinetics and will inform the development of other transmission models.
Insights
A new mouse model shows limited transmission of Middle East respiratory syndrome coronavirus (MERS-CoV) via fomites, direct contact, and airborne routes. This model aids in understanding MERS-CoV evolution and human-to-human transmission potential.
Area of Science:
- Virology
- Infectious Diseases
- Animal Models
Background:
- Three novel coronavirus outbreaks (SARS-CoV-1, MERS-CoV, SARS-CoV-2) since 2002 highlight the need to understand transmission.
- Understanding coronavirus transmission is crucial for effective infection control and preventing widespread outbreaks.
- Environmental stability and transmission modeling are key to managing coronavirus spread.
Purpose of the Study:
- To investigate the transmission potential of Middle East respiratory syndrome coronavirus (MERS-CoV) in a novel animal model.
- To assess MERS-CoV transmission via fomites, direct contact, and airborne routes.
- To establish a human dipeptidyl peptidase 4 (hDPP4) transgenic mouse model for studying MERS-CoV evolution and transmission.
Main Methods:
- Transgenic mice expressing human DPP4 (hDPP4) were infected with MERS-CoV.
- Exposure to MERS-CoV-infected donor mice via fomites, direct contact, and airborne routes was evaluated.
- Sentinel mice were used to assess transmission from infected donor mice.
Main Results:
- Transgenic mice expressing hDPP4 were susceptible to MERS-CoV infection via the aerosol route.
- Limited transmission was observed via fomites (15/20 and 11/18 animals), direct contact (1/38 mice), and airborne routes (4/54 mice).
- Higher MERS-CoV doses resulted in limited transmission, while lower doses showed no transmission via direct or airborne contact.
Conclusions:
- The hDPP4 mouse model demonstrates limited MERS-CoV transmission through fomites, direct contact, and airborne routes.
- This model is valuable for assessing MERS-CoV evolution, particularly in acquiring enhanced human-to-human transmission.
- Findings will inform the development of future MERS-CoV transmission models and intervention strategies.
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