title: Delivery of human EV71 receptors by adeno-associated virus increases EV71 infection-induced local inflammation in adult mice.
abstract: Enterovirus71 (EV71) is now recognized as an emerging neurotropic virus in Asia and one major causative agent of hand-foot-mouth diseases (HFMD). However potential animal models for vaccine development are limited to young mice. In this study, we used an adeno-associated virus (AAV) vector to introduce the human EV71 receptors P-selectin glycoprotein ligand-1 (hPSGL1) or a scavenger receptor class-B member-2 (hSCARB2) into adult ICR mice to change their susceptibility to EV71 infection. Mice were administered AAV-hSCARB2 or AAV-hPSGL1 through intravenous and oral routes. After three weeks, expression of human SCARB2 and PSGL1 was detected in various organs. After infection with EV71, we found that the EV71 viral load in AAV-hSCARB2- or AAV-hPSGL1-transduced mice was higher than that of the control mice in both the brain and intestines. The presence of EV71 viral particles in tissues was confirmed using immunohistochemistry analysis. Moreover, inflammatory cytokines were induced in the brain and intestines of AAV-hSCARB2- or AAV-hPSGL1-transduced mice after EV71 infection but not in wild-type mice. However, neurological disease was not observed in these animals. Taken together, we successfully infected adult mice with live EV71 and induced local inflammation using an AAV delivery system.
authors.affiliation: National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan, Miaoli 35053, Taiwan.
authors.forename: Hung-Bo
authors.initials: HB
authors.lastname: Hsiao
authors.affiliation: National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan, Miaoli 35053, Taiwan.
authors.forename: Ai-Hsiang
authors.initials: AH
authors.lastname: Chou
authors.affiliation: National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan, Miaoli 35053, Taiwan.
authors.forename: Su-I
authors.initials: SI
authors.lastname: Lin
authors.affiliation: National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan, Miaoli 35053, Taiwan.
authors.forename: Shu-Pei
authors.initials: SP
authors.lastname: Lien
authors.affiliation: National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan, Miaoli 35053, Taiwan.
authors.forename: Chia-Chyi
authors.identifier: 0000-0002-6257-0389
authors.initials: CC
authors.lastname: Liu
authors.affiliation: National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan, Miaoli 35053, Taiwan ; Graduate Institute of Immunology, China Medical University, Taichung 40402, Taiwan.
authors.forename: Pele
authors.identifier: 0000-0003-4197-7160
authors.initials: P
authors.lastname: Chong
authors.affiliation: Institutes of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan ; Graduate Institute of Microbiology, National Taiwan University, Taipei 10051, Taiwan.
authors.forename: Chih-Yeh
authors.identifier: 0000-0003-1970-9776
authors.initials: CY
authors.lastname: Chen
authors.affiliation: Institutes of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan.
authors.forename: Mi-Hua
authors.initials: MH
authors.lastname: Tao
authors.affiliation: National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan, Miaoli 35053, Taiwan ; Graduate Institute of Immunology, China Medical University, Taichung 40402, Taiwan.
authors.forename: Shih-Jen
authors.identifier: 0000-0002-8736-1452
authors.initials: SJ
authors.lastname: Liu
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D001923:Brain Chemistry; D002460:Cell Line; D016207:Cytokines / Q000032:analysis; D000229:Dependovirus / Q000235:genetics*; D004770:Enterovirus / Q000235:genetics*; D049452:Green Fluorescent Proteins / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000235:genetics*; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000737:chemistry; D051907:Lysosomal Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D051116:Receptors, Scavenger / Q000235:genetics / Q000378:metabolism; D014162:Transfection / Q000379:methods*
chemical_list: D016207:Cytokines; D051907:Lysosomal Membrane Proteins; D008562:Membrane Glycoproteins; C084882:P-selectin ligand protein; D051116:Receptors, Scavenger; C074299:SCARB2 protein, human; D049452:Green Fluorescent Proteins