title: Enterovirus 71 infection causes severe pulmonary lesions in gerbils, meriones unguiculatus, which can be prevented by passive immunization with specific antisera.
abstract: Neurogenic pulmonary edema caused by severe brainstem encephalitis is the leading cause of death in young children infected by Enterovirus 71 (EV71). However, no pulmonary lesions have been found in EV71-infected transgenic or non-transgenic mouse models. Development of a suitable animal model is important for studying EV71 pathogenesis and assessing effect of therapeutic approaches. We had found neurological disorders in EV71-induced young gerbils previously. Here, we report severe pulmonary lesions characterized with pulmonary congestion and hemorrhage in a gerbil model for EV71 infection. In the EV71-infected gerbils, six 21-day-old or younger gerbils presented with a sudden onset of symptoms and rapid illness progression after inoculation with 1×105.5 TCID50 of EV71 via intraperitoneal (IP) or intramuscular (IM) route. Respiratory symptoms were observed along with interstitial pneumonia, pulmonary congestion and extensive lung hemorrhage could be detected in the lung tissues by histopathological examination. EV71 viral titer was found to be peak at late stages of infection. EV71-induced pulmonary lesions, together with severe neurological disorders were also observed in gerbils, accurately mimicking the disease process in EV71-infected patients. Passive transfer with immune sera from EV71 infected adult gerbils with a neutralizing antibody (GMT=89) prevented severe pulmonary lesion formation after lethal EV71 challenge. These results establish this gerbil model as a useful platform for studying the pathogenesis of EV71-induced pulmonary lesions, immunotherapy and antiviral drugs.
authors.affiliation: Key Lab of Vaccine against Hemorrhagic Fever with Renal Syndrome, Zhejiang Province Center for Disease Prevention and Control, Hangzhou, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Xu
authors.affiliation: Key Lab of Vaccine against Hemorrhagic Fever with Renal Syndrome, Zhejiang Province Center for Disease Prevention and Control, Hangzhou, China.
authors.forename: Ping-Ping
authors.initials: PP
authors.lastname: Yao
authors.affiliation: Key Lab of Vaccine against Hemorrhagic Fever with Renal Syndrome, Zhejiang Province Center for Disease Prevention and Control, Hangzhou, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Xia
authors.affiliation: Key Lab of Vaccine against Hemorrhagic Fever with Renal Syndrome, Zhejiang Province Center for Disease Prevention and Control, Hangzhou, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Qian
authors.affiliation: Key Lab of Vaccine against Hemorrhagic Fever with Renal Syndrome, Zhejiang Province Center for Disease Prevention and Control, Hangzhou, China.
authors.forename: Zhang-Nv
authors.initials: ZN
authors.lastname: Yang
authors.affiliation: Key Lab of Vaccine against Hemorrhagic Fever with Renal Syndrome, Zhejiang Province Center for Disease Prevention and Control, Hangzhou, China.
authors.forename: Rong-Hui
authors.initials: RH
authors.lastname: Xie
authors.affiliation: Key Lab of Vaccine against Hemorrhagic Fever with Renal Syndrome, Zhejiang Province Center for Disease Prevention and Control, Hangzhou, China.
authors.forename: Yi-Sheng
authors.initials: YS
authors.lastname: Sun
authors.affiliation: Key Lab of Vaccine against Hemorrhagic Fever with Renal Syndrome, Zhejiang Province Center for Disease Prevention and Control, Hangzhou, China.
authors.forename: Hang-Jing
authors.initials: HJ
authors.lastname: Lu
authors.affiliation: Key Lab of Vaccine against Hemorrhagic Fever with Renal Syndrome, Zhejiang Province Center for Disease Prevention and Control, Hangzhou, China.
authors.forename: Zi-Ping
authors.initials: ZP
authors.lastname: Miao
authors.affiliation: Key Lab of Vaccine against Hemorrhagic Fever with Renal Syndrome, Zhejiang Province Center for Disease Prevention and Control, Hangzhou, China.
authors.forename: Chan
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Pathology, First Municipal Hospital of Hangzhou, Hangzhou, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Li
authors.affiliation: The First Affiliated Hospital, Zhejiang University, Hangzhou, China.
authors.forename: Wei-Feng
authors.initials: WF
authors.lastname: Liang
authors.affiliation: Hangzhou Sixth People's Hospital, Hangzhou, China.
authors.forename: Xiao-Xiao
authors.initials: XX
authors.lastname: Huang
authors.affiliation: Key Lab of Vaccine against Hemorrhagic Fever with Renal Syndrome, Zhejiang Province Center for Disease Prevention and Control, Hangzhou, China.
authors.forename: Shi-Chang
authors.initials: SC
authors.lastname: Xia
authors.affiliation: Key Lab of Vaccine against Hemorrhagic Fever with Renal Syndrome, Zhejiang Province Center for Disease Prevention and Control, Hangzhou, China.
authors.forename: Zhi-Ping
authors.initials: ZP
authors.lastname: Chen
authors.affiliation: Key Lab of Vaccine against Hemorrhagic Fever with Renal Syndrome, Zhejiang Province Center for Disease Prevention and Control, Hangzhou, China.
authors.forename: Jian-Min
authors.initials: JM
authors.lastname: Jiang
authors.affiliation: Key Lab of Vaccine against Hemorrhagic Fever with Renal Syndrome, Zhejiang Province Center for Disease Prevention and Control, Hangzhou, China.
authors.forename: Yan-Jun
authors.initials: YJ
authors.lastname: Zhang
authors.affiliation: Key Lab of Vaccine against Hemorrhagic Fever with Renal Syndrome, Zhejiang Province Center for Disease Prevention and Control, Hangzhou, China.
authors.forename: Ling-Ling
authors.initials: LL
authors.lastname: Mei
authors.affiliation: Key Lab of Vaccine against Hemorrhagic Fever with Renal Syndrome, Zhejiang Province Center for Disease Prevention and Control, Hangzhou, China.
authors.forename: She-Lan
authors.initials: SL
authors.lastname: Liu
authors.affiliation: Key Lab of Vaccine against Hemorrhagic Fever with Renal Syndrome, Zhejiang Province Center for Disease Prevention and Control, Hangzhou, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Gu
authors.affiliation: Wenzhou Medical University, Wenzhou, China.
authors.forename: Zhi-Yao
authors.initials: ZY
authors.lastname: Xu
authors.affiliation: Jiaxing Center for Disease Control and Prevention, Jiaxing, China.
authors.forename: Xiao-Fei
authors.initials: XF
authors.lastname: Fu
authors.affiliation: Key Lab of Vaccine against Hemorrhagic Fever with Renal Syndrome, Zhejiang Province Center for Disease Prevention and Control, Hangzhou, China.
authors.forename: Zhi-Yong
authors.initials: ZY
authors.lastname: Zhu
authors.affiliation: Key Lab of Vaccine against Hemorrhagic Fever with Renal Syndrome, Zhejiang Province Center for Disease Prevention and Control, Hangzhou, China.
authors.forename: Han-Ping
authors.initials: HP
authors.lastname: Zhu
mesh_terms: D000818:Animals; D002648:Child; D004195:Disease Models, Animal; D029821:Enterovirus A, Human / Q000276:immunology*; D004769:Enterovirus Infections / Q000276:immunology* / Q000821:virology; D005849:Gerbillinae / Q000276:immunology* / Q000821:virology; D006801:Humans; D007106:Immune Sera / Q000276:immunology*; D007116:Immunization, Passive / Q000379:methods; D008168:Lung / Q000276:immunology / Q000821:virology; D008171:Lung Diseases / Q000276:immunology* / Q000821:virology; D009422:Nervous System Diseases / Q000276:immunology / Q000821:virology
chemical_list: D007106:Immune Sera