Title Histopathological features and distribution of EV71 antigens and SCARB2 in human fatal cases and a mouse model of enterovirus 71 infection
Authors Yu, Pin
Gao, Zifen
Zong, Yuanyuan
Bao, Linlin
Xu, Lili
Deng, Wei
Li, Fengdi
Lv, Qi
Gao, Zhancheng
Xu, Yanfeng
Yao, Yanfeng
Qin, Chuan
Affiliation Chinese Acad Med Sci, Inst Lab Anim Sci, Beijing 100021, Peoples R China.
Peking Union Med Coll, Key Lab Human Dis Comparat Med, Minist Hlth, Comparat Med Ctr, Beijing 100021, Peoples R China.
Peking Univ, Hlth Sci Ctr, Dept Pathol, Beijing 100191, Peoples R China.
Shandong Univ, Shandong Prov Hosp, Dept Pathol, Jinan 250021, Peoples R China.
Peking Univ, Peoples Hosp, Dept Resp & Crit Care Med, Beijing 100044, Peoples R China.
Inst Lab Anim Sci, 5 Pan Jia Yuan Nan Li, Beijing 100021, Peoples R China.
Keywords Enterovirus 71
Hand
foot
and mouth disease
Pathology
Human cases
Mouse model
CENTRAL-NERVOUS-SYSTEM
SCAVENGER RECEPTOR B2
MOUTH-DISEASE
MOLECULAR EPIDEMIOLOGY
EVOLUTIONARY GENETICS
HAND
FOOT
CHILDREN
OUTBREAK
CHINA
Issue Date 2014
Publisher virus research
Citation VIRUS RESEARCH.2014,189,121-132.
Abstract Enterovirus 71 (EV71) is a neurotropic pathogen that causes hand, foot, and mouth disease. While infection is usually self-limiting, a minority of patients infected with EV71 develop severe neurological complications. In humans, EV71 has been reported to utilize the scavenger receptor class B, member 2 (SCARB2) as a receptor for infectious cellular entry. In this study, we define the pathological features of EV71-associated disease as well as the distribution of EV71 antigen and SCARB2 in human fatal cases and a mouse model. Histopathologically, human fatal cases showed severe central nervous system (CNS) changes, mainly in the brainstems, spinal cords, and thalamus. These patient further exhibited pulmonary edema and necrotic enteritis. Immunohistochemical analysis of human fatal cases demonstrated that EV71 antigen and SCARB2 were observed mainly in neurons, microglia cells and inflammatory cells in the CNS, and epithelial cells in the intestines. However, skeletal muscle tissue was negative for EV71 antigen. In a mouse model of EV71 infection, we observed massive necrotic myositis, different degrees of viral diseases in CNS, and extensive interstitial pneumonia. In mice, EV71 exhibits strong myotropism compared to the neurotropism seen in humans. EV71 antigen was detected in the spinal cord and brainstem of mice. However, there was no clear correlation between mouse SCARB2 and EV71 antigen distribution in the mouse model, consistent with previous results that SCARB2 functions as a receptor for EV71 in humans but not mice. The EV71-induced lesions seen in the mouse model resembled the pathological changes seen in human samples. These results increase our understanding of EV71 pathogenesis and will inform further work developing a mouse model for EV71 infection. (C) 2014 Elsevier B.V. All rights reserved.
URI http://hdl.handle.net/20.500.11897/189051
ISSN 0168-1702
DOI 10.1016/j.virusres.2014.05.006
Indexed SCI(E)
PubMed
Appears in Collections: 人民医院

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