Modelling person-to-person transmission in an Enterovirus A71 orally infected hamster model of hand-foot-and-mouth disease and encephalomyelitis

Enterovirus A71 (EV-A71) causes hand-foot-and-mouth disease (HFMD), which may be complicated by fatal encephalomyelitis. Although fecal–oral or oral–oral routes are important in person-to-person transmission, how viral shedding and exposure may predispose individuals to infection remains unknown. We...

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Main Authors: Win Kyaw Phyu, Kien Chai Ong, Kum Thong Wong
Format: Article
Language:English
Published: Taylor & Francis Group 2017-01-01
Series:Emerging Microbes and Infections
Subjects:
Online Access:https://www.tandfonline.com/doi/10.1038/emi.2017.49
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author Win Kyaw Phyu
Kien Chai Ong
Kum Thong Wong
author_facet Win Kyaw Phyu
Kien Chai Ong
Kum Thong Wong
author_sort Win Kyaw Phyu
collection DOAJ
description Enterovirus A71 (EV-A71) causes hand-foot-and-mouth disease (HFMD), which may be complicated by fatal encephalomyelitis. Although fecal–oral or oral–oral routes are important in person-to-person transmission, how viral shedding and exposure may predispose individuals to infection remains unknown. We investigated person-to-person transmission by using a model of HFMD and encephalomyelitis based on EV-A71 oral infection of 2-week-old hamsters. Animals (index animals) infected with 104 50% cell culture infective doses of virus uniformly developed severe disease four days post-infection (dpi), whereas littermate contacts developed severe disease after six to seven days of exposure to index animals. Virus was detected in oral washes and feces at 3–4 dpi in index animals and at three to eight days after exposure to index animals in littermate contact animals. In a second experiment, non-littermate contact animals exposed for 8 or 12 h to index animals developed the disease six and four days post-exposure, respectively. Tissues from killed index and contact animals, studied by light microscopy, immunohistochemistry and in situ hybridization, exhibited mild inflammatory lesions and/or viral antigens/RNA in the squamous epithelia of the oral cavity, tongue, paws, skin, esophagus, gastric epithelium, salivary glands, lacrimal glands, central nervous system neurons, muscles (skeletal, cardiac and smooth muscles) and liver. Orally shed viruses were probably derived from infected oral mucosa and salivary glands, whereas fecal viruses may have derived from these sites as well as from esophageal and gastric epithelia. Asymptomatic seroconversion in exposed mother hamsters was demonstrated. Our hamster model should be useful in studying person-to-person EV-A71 transmission and how drugs and vaccines may interrupt transmission.Emerging Microbes & Infections (2017) 6, e62; doi:10.1038/emi.2017.49; published online 12 July 2017
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spelling doaj.art-72d8f99f00f24f8f971189de56c284132023-09-22T12:08:35ZengTaylor & Francis GroupEmerging Microbes and Infections2222-17512017-01-01611910.1038/emi.2017.49Modelling person-to-person transmission in an Enterovirus A71 orally infected hamster model of hand-foot-and-mouth disease and encephalomyelitisWin Kyaw Phyu0Kien Chai Ong1Kum Thong Wong2Department of Pathology, Faculty of MedicineUniversity of Malaya, Kuala Lumpur 50603, MalaysiaDepartment of Biomedical Science, Faculty of MedicineUniversity of Malaya, Kuala Lumpur 50603, MalaysiaDepartment of Pathology, Faculty of MedicineUniversity of Malaya, Kuala Lumpur 50603, MalaysiaEnterovirus A71 (EV-A71) causes hand-foot-and-mouth disease (HFMD), which may be complicated by fatal encephalomyelitis. Although fecal–oral or oral–oral routes are important in person-to-person transmission, how viral shedding and exposure may predispose individuals to infection remains unknown. We investigated person-to-person transmission by using a model of HFMD and encephalomyelitis based on EV-A71 oral infection of 2-week-old hamsters. Animals (index animals) infected with 104 50% cell culture infective doses of virus uniformly developed severe disease four days post-infection (dpi), whereas littermate contacts developed severe disease after six to seven days of exposure to index animals. Virus was detected in oral washes and feces at 3–4 dpi in index animals and at three to eight days after exposure to index animals in littermate contact animals. In a second experiment, non-littermate contact animals exposed for 8 or 12 h to index animals developed the disease six and four days post-exposure, respectively. Tissues from killed index and contact animals, studied by light microscopy, immunohistochemistry and in situ hybridization, exhibited mild inflammatory lesions and/or viral antigens/RNA in the squamous epithelia of the oral cavity, tongue, paws, skin, esophagus, gastric epithelium, salivary glands, lacrimal glands, central nervous system neurons, muscles (skeletal, cardiac and smooth muscles) and liver. Orally shed viruses were probably derived from infected oral mucosa and salivary glands, whereas fecal viruses may have derived from these sites as well as from esophageal and gastric epithelia. Asymptomatic seroconversion in exposed mother hamsters was demonstrated. Our hamster model should be useful in studying person-to-person EV-A71 transmission and how drugs and vaccines may interrupt transmission.Emerging Microbes & Infections (2017) 6, e62; doi:10.1038/emi.2017.49; published online 12 July 2017https://www.tandfonline.com/doi/10.1038/emi.2017.49Enterovirus A71hamster modelperson-to-person transmissionhand-foot-and-mouth diseaseencephalomyelitisimmunohistochemistry
spellingShingle Win Kyaw Phyu
Kien Chai Ong
Kum Thong Wong
Modelling person-to-person transmission in an Enterovirus A71 orally infected hamster model of hand-foot-and-mouth disease and encephalomyelitis
Emerging Microbes and Infections
Enterovirus A71
hamster model
person-to-person transmission
hand-foot-and-mouth disease
encephalomyelitis
immunohistochemistry
title Modelling person-to-person transmission in an Enterovirus A71 orally infected hamster model of hand-foot-and-mouth disease and encephalomyelitis
title_full Modelling person-to-person transmission in an Enterovirus A71 orally infected hamster model of hand-foot-and-mouth disease and encephalomyelitis
title_fullStr Modelling person-to-person transmission in an Enterovirus A71 orally infected hamster model of hand-foot-and-mouth disease and encephalomyelitis
title_full_unstemmed Modelling person-to-person transmission in an Enterovirus A71 orally infected hamster model of hand-foot-and-mouth disease and encephalomyelitis
title_short Modelling person-to-person transmission in an Enterovirus A71 orally infected hamster model of hand-foot-and-mouth disease and encephalomyelitis
title_sort modelling person to person transmission in an enterovirus a71 orally infected hamster model of hand foot and mouth disease and encephalomyelitis
topic Enterovirus A71
hamster model
person-to-person transmission
hand-foot-and-mouth disease
encephalomyelitis
immunohistochemistry
url https://www.tandfonline.com/doi/10.1038/emi.2017.49
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