title: The Preferential Infection of Astrocytes by Enterovirus 71 Plays a Key Role in the Viral Neurogenic Pathogenesis.
abstract: The pathological manifestations of fatal cases of human hand, foot, and mouth disease (HFMD) caused by enterovirus 71 (EV71) are characterized by inflammatory damage to the central nervous system (CNS). Here, the dynamic distribution of EV71 in the CNS and the subsequent pathological characteristics within different regions of neonatal rhesus macaque brain tissue were studied using a chimeric EV71 expressing green fluorescence protein. The results were compared with brain tissue obtained from the autopsies of deceased EV71-infected HFMD patients. These observations suggested that the virus was prevalent in areas around the blood vessels and nerve nuclei in the brain stem and showed a preference for astrocytes in the CNS. Interestingly, infected astrocytes within thein vivoandin vitrohuman and macaque systems exhibited increased expression of excitatory neurotransmitters and cytokines that also stimulated the neuronal secretion of the excitatory neurotransmitters noradrenalin and adrenalin, and this process most likely plays a role in the pathophysiological events that occur during EV71 infection.
authors.affiliation: Yunnan Key Laboratory of Vaccine Research and Development on Severe Infectious Diseases, Institute of Medical Biology, Chinese Academy of Medical Sciences, Peking Union Medical College Kunming, China.
authors.forename: Min
authors.initials: M
authors.lastname: Feng
authors.affiliation: Yunnan Key Laboratory of Vaccine Research and Development on Severe Infectious Diseases, Institute of Medical Biology, Chinese Academy of Medical Sciences, Peking Union Medical College Kunming, China.
authors.forename: Sujie
authors.initials: S
authors.lastname: Guo
authors.affiliation: Yunnan Key Laboratory of Vaccine Research and Development on Severe Infectious Diseases, Institute of Medical Biology, Chinese Academy of Medical Sciences, Peking Union Medical College Kunming, China.
authors.forename: Shengtao
authors.initials: S
authors.lastname: Fan
authors.affiliation: School of Forensic Medicine, Kunming Medical University Kunming, China.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Zeng
authors.affiliation: Yunnan Key Laboratory of Vaccine Research and Development on Severe Infectious Diseases, Institute of Medical Biology, Chinese Academy of Medical Sciences, Peking Union Medical College Kunming, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Yunnan Key Laboratory of Vaccine Research and Development on Severe Infectious Diseases, Institute of Medical Biology, Chinese Academy of Medical Sciences, Peking Union Medical College Kunming, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Liao
authors.affiliation: Yunnan Key Laboratory of Vaccine Research and Development on Severe Infectious Diseases, Institute of Medical Biology, Chinese Academy of Medical Sciences, Peking Union Medical College Kunming, China.
authors.forename: Jianbin
authors.initials: J
authors.lastname: Wang
authors.affiliation: Yunnan Key Laboratory of Vaccine Research and Development on Severe Infectious Diseases, Institute of Medical Biology, Chinese Academy of Medical Sciences, Peking Union Medical College Kunming, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Zhao
authors.affiliation: Yunnan Key Laboratory of Vaccine Research and Development on Severe Infectious Diseases, Institute of Medical Biology, Chinese Academy of Medical Sciences, Peking Union Medical College Kunming, China.
authors.forename: Lichun
authors.initials: L
authors.lastname: Wang
authors.affiliation: Yunnan Key Laboratory of Vaccine Research and Development on Severe Infectious Diseases, Institute of Medical Biology, Chinese Academy of Medical Sciences, Peking Union Medical College Kunming, China.
authors.forename: Yanchun
authors.initials: Y
authors.lastname: Che
authors.affiliation: Yunnan Key Laboratory of Vaccine Research and Development on Severe Infectious Diseases, Institute of Medical Biology, Chinese Academy of Medical Sciences, Peking Union Medical College Kunming, China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Yunnan Key Laboratory of Vaccine Research and Development on Severe Infectious Diseases, Institute of Medical Biology, Chinese Academy of Medical Sciences, Peking Union Medical College Kunming, China.
authors.forename: Na
authors.initials: N
authors.lastname: Ma
authors.affiliation: Yunnan Key Laboratory of Vaccine Research and Development on Severe Infectious Diseases, Institute of Medical Biology, Chinese Academy of Medical Sciences, Peking Union Medical College Kunming, China.
authors.forename: Longding
authors.initials: L
authors.lastname: Liu
authors.affiliation: Yunnan Key Laboratory of Vaccine Research and Development on Severe Infectious Diseases, Institute of Medical Biology, Chinese Academy of Medical Sciences, Peking Union Medical College Kunming, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Yue
authors.affiliation: Yunnan Key Laboratory of Vaccine Research and Development on Severe Infectious Diseases, Institute of Medical Biology, Chinese Academy of Medical Sciences, Peking Union Medical College Kunming, China.
authors.forename: Qihan
authors.initials: Q
authors.lastname: Li
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000821:virology*; D001921:Brain / Q000473:pathology / Q000821:virology*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D029821:Enterovirus A, Human / Q000254:growth & development / Q000302:isolation & purification / Q000502:physiology*; D004769:Enterovirus Infections / Q000821:virology*; D004837:Epinephrine / Q000378:metabolism; D006801:Humans; D008253:Macaca mulatta; D009638:Norepinephrine / Q000378:metabolism; D056189:Viral Tropism
chemical_list: D016207:Cytokines; D009638:Norepinephrine; D004837:Epinephrine
keywords: astrocytes; central nervous system (CNS); enterovirus 71 (EV71); neuron; pathogenesis