Transmission dynamics of MERS-CoV in a transgenic human DPP4 mouse model

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 inf...

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Main Authors: Neeltje van Doremalen, Trenton Bushmaker, Robert J. Fischer, Atsushi Okumura, Dania M. Figueroa Acosta, Rebekah J. McMinn, Michael Letko, Dana Scott, Greg Saturday, Vincent J. Munster
Format: Article
Language:English
Published: Nature Portfolio 2024-08-01
Series:npj Viruses
Online Access:https://doi.org/10.1038/s44298-024-00048-y
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author Neeltje van Doremalen
Trenton Bushmaker
Robert J. Fischer
Atsushi Okumura
Dania M. Figueroa Acosta
Rebekah J. McMinn
Michael Letko
Dana Scott
Greg Saturday
Vincent J. Munster
author_facet Neeltje van Doremalen
Trenton Bushmaker
Robert J. Fischer
Atsushi Okumura
Dania M. Figueroa Acosta
Rebekah J. McMinn
Michael Letko
Dana Scott
Greg Saturday
Vincent J. Munster
author_sort Neeltje van Doremalen
collection DOAJ
description 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.
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spelling doaj-art-e7d22fcd180a4218891eaaca9b2cfed12025-08-20T03:06:00ZengNature Portfolionpj Viruses2948-17672024-08-01211810.1038/s44298-024-00048-yTransmission dynamics of MERS-CoV in a transgenic human DPP4 mouse modelNeeltje van Doremalen0Trenton Bushmaker1Robert J. Fischer2Atsushi Okumura3Dania M. Figueroa Acosta4Rebekah J. McMinn5Michael Letko6Dana Scott7Greg Saturday8Vincent J. Munster9Division of Intramural Research, Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of HealthDivision of Intramural Research, Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of HealthDivision of Intramural Research, Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of HealthPaul G. Allen School for Global Health, Washington State UniversityDivision of Intramural Research, Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of HealthDivision of Intramural Research, Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of HealthDivision of Intramural Research, Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of HealthDivision of Intramural Research, Rocky Mountain Veterinary Branch, National Institute of Allergy and Infectious Diseases, National Institutes of HealthDivision of Intramural Research, Rocky Mountain Veterinary Branch, National Institute of Allergy and Infectious Diseases, National Institutes of HealthDivision of Intramural Research, Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of HealthAbstract 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.https://doi.org/10.1038/s44298-024-00048-y
spellingShingle Neeltje van Doremalen
Trenton Bushmaker
Robert J. Fischer
Atsushi Okumura
Dania M. Figueroa Acosta
Rebekah J. McMinn
Michael Letko
Dana Scott
Greg Saturday
Vincent J. Munster
Transmission dynamics of MERS-CoV in a transgenic human DPP4 mouse model
npj Viruses
title Transmission dynamics of MERS-CoV in a transgenic human DPP4 mouse model
title_full Transmission dynamics of MERS-CoV in a transgenic human DPP4 mouse model
title_fullStr Transmission dynamics of MERS-CoV in a transgenic human DPP4 mouse model
title_full_unstemmed Transmission dynamics of MERS-CoV in a transgenic human DPP4 mouse model
title_short Transmission dynamics of MERS-CoV in a transgenic human DPP4 mouse model
title_sort transmission dynamics of mers cov in a transgenic human dpp4 mouse model
url https://doi.org/10.1038/s44298-024-00048-y
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