Small Animal Models for Human Metapneumovirus: Cotton Rat is More Permissive than Hamster and Mouse

Human metapneumovirus (hMPV) is the second most prevalent causative agent of pediatric respiratory infections worldwide. Currently, there are no vaccines or antiviral drugs against this virus. One of the major hurdles in hMPV research is the difficulty to identify a robust small animal model to accu...

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Main Authors: Yu Zhang, Stefan Niewiesk, Jianrong Li
Format: Article
Language:English
Published: MDPI AG 2014-07-01
Series:Pathogens
Subjects:
Online Access:http://www.mdpi.com/2076-0817/3/3/633
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author Yu Zhang
Stefan Niewiesk
Jianrong Li
author_facet Yu Zhang
Stefan Niewiesk
Jianrong Li
author_sort Yu Zhang
collection DOAJ
description Human metapneumovirus (hMPV) is the second most prevalent causative agent of pediatric respiratory infections worldwide. Currently, there are no vaccines or antiviral drugs against this virus. One of the major hurdles in hMPV research is the difficulty to identify a robust small animal model to accurately evaluate the efficacy and safety of vaccines and therapeutics. In this study, we compared the replication and pathogenesis of hMPV in BALB/c mice, Syrian golden hamsters, and cotton rats. It was found that BALB/c mice are not permissive for hMPV infection despite the use of a high dose (6.5 log10 PFU) of virus for intranasal inoculation. In hamsters, hMPV replicated efficiently in nasal turbinates but demonstrated only limited replication in lungs. In cotton rats, hMPV replicated efficiently in both nasal turbinate and lung when intranasally administered with three different doses (4, 5, and 6 log10 PFU) of hMPV. Lungs of cotton rats infected by hMPV developed interstitial pneumonia with mononuclear cells infiltrates and increased lumen exudation. By immunohistochemistry, viral antigens were detected at the luminal surfaces of the bronchial epithelial cells in lungs. Vaccination of cotton rats with hMPV completely protected upper and lower respiratory tract from wildtype challenge. The immunization also elicited elevated serum neutralizing antibody. Collectively, these results demonstrated that cotton rat is a robust small animal model for hMPV infection.
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spelling doaj.art-ae9b4c0c847a4eb2873eaa1cb7b5f6b32022-12-22T04:03:58ZengMDPI AGPathogens2076-08172014-07-013363365510.3390/pathogens3030633pathogens3030633Small Animal Models for Human Metapneumovirus: Cotton Rat is More Permissive than Hamster and MouseYu Zhang0Stefan Niewiesk1Jianrong Li2Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210, USADepartment of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210, USADepartment of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210, USAHuman metapneumovirus (hMPV) is the second most prevalent causative agent of pediatric respiratory infections worldwide. Currently, there are no vaccines or antiviral drugs against this virus. One of the major hurdles in hMPV research is the difficulty to identify a robust small animal model to accurately evaluate the efficacy and safety of vaccines and therapeutics. In this study, we compared the replication and pathogenesis of hMPV in BALB/c mice, Syrian golden hamsters, and cotton rats. It was found that BALB/c mice are not permissive for hMPV infection despite the use of a high dose (6.5 log10 PFU) of virus for intranasal inoculation. In hamsters, hMPV replicated efficiently in nasal turbinates but demonstrated only limited replication in lungs. In cotton rats, hMPV replicated efficiently in both nasal turbinate and lung when intranasally administered with three different doses (4, 5, and 6 log10 PFU) of hMPV. Lungs of cotton rats infected by hMPV developed interstitial pneumonia with mononuclear cells infiltrates and increased lumen exudation. By immunohistochemistry, viral antigens were detected at the luminal surfaces of the bronchial epithelial cells in lungs. Vaccination of cotton rats with hMPV completely protected upper and lower respiratory tract from wildtype challenge. The immunization also elicited elevated serum neutralizing antibody. Collectively, these results demonstrated that cotton rat is a robust small animal model for hMPV infection.http://www.mdpi.com/2076-0817/3/3/633human metapneumovirusanimal modelBALB/c miceSyrian golden hamsterscotton rats
spellingShingle Yu Zhang
Stefan Niewiesk
Jianrong Li
Small Animal Models for Human Metapneumovirus: Cotton Rat is More Permissive than Hamster and Mouse
Pathogens
human metapneumovirus
animal model
BALB/c mice
Syrian golden hamsters
cotton rats
title Small Animal Models for Human Metapneumovirus: Cotton Rat is More Permissive than Hamster and Mouse
title_full Small Animal Models for Human Metapneumovirus: Cotton Rat is More Permissive than Hamster and Mouse
title_fullStr Small Animal Models for Human Metapneumovirus: Cotton Rat is More Permissive than Hamster and Mouse
title_full_unstemmed Small Animal Models for Human Metapneumovirus: Cotton Rat is More Permissive than Hamster and Mouse
title_short Small Animal Models for Human Metapneumovirus: Cotton Rat is More Permissive than Hamster and Mouse
title_sort small animal models for human metapneumovirus cotton rat is more permissive than hamster and mouse
topic human metapneumovirus
animal model
BALB/c mice
Syrian golden hamsters
cotton rats
url http://www.mdpi.com/2076-0817/3/3/633
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AT stefanniewiesk smallanimalmodelsforhumanmetapneumoviruscottonratismorepermissivethanhamsterandmouse
AT jianrongli smallanimalmodelsforhumanmetapneumoviruscottonratismorepermissivethanhamsterandmouse