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An Acute Immune Response to Middle East Respiratory Syndrome Coronavirus Replication Contributes to Viral Pathogenicity

Middle East respiratory syndrome coronavirus (MERS-CoV) was first identified in a human with severe pneumonia in 2012. Since then, infections have been detected in >1500 individuals, with disease severity ranging from asymptomatic to severe, fatal pneumonia. To elucidate the pathogenesis of this...

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Autores principales: Baseler, Laura J., Falzarano, Darryl, Scott, Dana P., Rosenke, Rebecca, Thomas, Tina, Munster, Vincent J., Feldmann, Heinz, de Wit, Emmie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Investigative Pathology 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4816712/
https://www.ncbi.nlm.nih.gov/pubmed/26724387
http://dx.doi.org/10.1016/j.ajpath.2015.10.025
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author Baseler, Laura J.
Falzarano, Darryl
Scott, Dana P.
Rosenke, Rebecca
Thomas, Tina
Munster, Vincent J.
Feldmann, Heinz
de Wit, Emmie
author_facet Baseler, Laura J.
Falzarano, Darryl
Scott, Dana P.
Rosenke, Rebecca
Thomas, Tina
Munster, Vincent J.
Feldmann, Heinz
de Wit, Emmie
author_sort Baseler, Laura J.
collection PubMed
description Middle East respiratory syndrome coronavirus (MERS-CoV) was first identified in a human with severe pneumonia in 2012. Since then, infections have been detected in >1500 individuals, with disease severity ranging from asymptomatic to severe, fatal pneumonia. To elucidate the pathogenesis of this virus and investigate mechanisms underlying disease severity variation in the absence of autopsy data, a rhesus macaque and common marmoset model of MERS-CoV disease were analyzed. Rhesus macaques developed mild disease, and common marmosets exhibited moderate to severe, potentially lethal, disease. Both nonhuman primate species exhibited respiratory clinical signs after inoculation, which were more severe and of longer duration in the marmosets, and developed bronchointerstitial pneumonia. In marmosets, the pneumonia was more extensive, with development of severe airway lesions. Quantitative analysis showed significantly higher levels of pulmonary neutrophil infiltration and higher amounts of pulmonary viral antigen in marmosets. Pulmonary expression of the MERS-CoV receptor, dipeptidyl peptidase 4, was similar in marmosets and macaques. These results suggest that increased virus replication and the local immune response to MERS-CoV infection likely play a role in pulmonary pathology severity. Together, the rhesus macaque and common marmoset models of MERS-CoV span the wide range of disease severity reported in MERS-CoV–infected humans, which will aid in investigating MERS-CoV disease pathogenesis.
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spelling pubmed-48167122017-03-01 An Acute Immune Response to Middle East Respiratory Syndrome Coronavirus Replication Contributes to Viral Pathogenicity Baseler, Laura J. Falzarano, Darryl Scott, Dana P. Rosenke, Rebecca Thomas, Tina Munster, Vincent J. Feldmann, Heinz de Wit, Emmie Am J Pathol Regular Article Middle East respiratory syndrome coronavirus (MERS-CoV) was first identified in a human with severe pneumonia in 2012. Since then, infections have been detected in >1500 individuals, with disease severity ranging from asymptomatic to severe, fatal pneumonia. To elucidate the pathogenesis of this virus and investigate mechanisms underlying disease severity variation in the absence of autopsy data, a rhesus macaque and common marmoset model of MERS-CoV disease were analyzed. Rhesus macaques developed mild disease, and common marmosets exhibited moderate to severe, potentially lethal, disease. Both nonhuman primate species exhibited respiratory clinical signs after inoculation, which were more severe and of longer duration in the marmosets, and developed bronchointerstitial pneumonia. In marmosets, the pneumonia was more extensive, with development of severe airway lesions. Quantitative analysis showed significantly higher levels of pulmonary neutrophil infiltration and higher amounts of pulmonary viral antigen in marmosets. Pulmonary expression of the MERS-CoV receptor, dipeptidyl peptidase 4, was similar in marmosets and macaques. These results suggest that increased virus replication and the local immune response to MERS-CoV infection likely play a role in pulmonary pathology severity. Together, the rhesus macaque and common marmoset models of MERS-CoV span the wide range of disease severity reported in MERS-CoV–infected humans, which will aid in investigating MERS-CoV disease pathogenesis. American Society for Investigative Pathology 2016-03 /pmc/articles/PMC4816712/ /pubmed/26724387 http://dx.doi.org/10.1016/j.ajpath.2015.10.025 Text en © 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved. This document may be redistributed and reused, subject to certain conditions (http://www.elsevier.com/wps/find/authorsview.authors/supplementalterms1.0) .
spellingShingle Regular Article
Baseler, Laura J.
Falzarano, Darryl
Scott, Dana P.
Rosenke, Rebecca
Thomas, Tina
Munster, Vincent J.
Feldmann, Heinz
de Wit, Emmie
An Acute Immune Response to Middle East Respiratory Syndrome Coronavirus Replication Contributes to Viral Pathogenicity
title An Acute Immune Response to Middle East Respiratory Syndrome Coronavirus Replication Contributes to Viral Pathogenicity
title_full An Acute Immune Response to Middle East Respiratory Syndrome Coronavirus Replication Contributes to Viral Pathogenicity
title_fullStr An Acute Immune Response to Middle East Respiratory Syndrome Coronavirus Replication Contributes to Viral Pathogenicity
title_full_unstemmed An Acute Immune Response to Middle East Respiratory Syndrome Coronavirus Replication Contributes to Viral Pathogenicity
title_short An Acute Immune Response to Middle East Respiratory Syndrome Coronavirus Replication Contributes to Viral Pathogenicity
title_sort acute immune response to middle east respiratory syndrome coronavirus replication contributes to viral pathogenicity
topic Regular Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4816712/
https://www.ncbi.nlm.nih.gov/pubmed/26724387
http://dx.doi.org/10.1016/j.ajpath.2015.10.025
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