title: Human SCARB2 transgenic mice as an infectious animal model for enterovirus 71.
abstract: Enterovirus 71 (EV71) and coxsackievirus (CVA) are the most common causative factors for hand, foot, and mouth disease (HFMD) and neurological disorders in children. Lack of a reliable animal model is an issue in investigating EV71-induced disease manifestation in humans, and the current clinical therapies are symptomatic. We generated a novel EV71-infectious model with hSCARB2-transgenic mice expressing the discovered receptor human SCARB2 (hSCARB2). The challenge of hSCARB2-transgenic mice with clinical isolates of EV71 and CVA16 resulted in HFMD-like and neurological syndromes caused by E59 (B4) and N2838 (B5) strains, and lethal paralysis caused by 5746 (C2), N3340 (C4), and CVA16. EV71 viral loads were evident in the tissues and CNS accompanied the upregulated pro-inflammatory mediators (CXCL10, CCL3, TNF-α, and IL-6), correlating to recruitment of the infiltrated T lymphocytes that result in severe diseases. Transgenic mice pre-immunized with live E59 or the FI-E59 vaccine was able to resist the subsequent lethal challenge with EV71. These results indicate that hSCARB2-transgenic mice are a useful model for assessing anti-EV71 medications and for studying the pathogenesis induced by EV71.
authors: Institute of Infectious Disease and Vaccinology, National Health Research Institutes, Zhunan, Miaoli County, Taiwan.
authors: Yi-Wen
authors: YW
authors: Lin
authors: Shu-Ling
authors: SL
authors: Yu
authors: Hsiao-Yun
authors: HY
authors: Shao
authors: Hsiang-Yin
authors: HY
authors: Lin
authors: Chia-Chyi
authors: CC
authors: Liu
authors: Kuang-Nan
authors: KN
authors: Hsiao
authors: Ebenezer
authors: E
authors: Chitra
authors: Yueh-Liang
authors: YL
authors: Tsou
authors: Hsuen-Wen
authors: HW
authors: Chang
authors: Charles
authors: C
authors: Sia
authors: Pele
authors: P
authors: Chong
authors: Yen-Hung
authors: YH
authors: Chow
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D003384:Coxsackievirus Infections / Q000235:genetics / Q000276:immunology; D004195:Disease Models, Animal; D004770:Enterovirus / Q000235:genetics / Q000276:immunology; D029821:Enterovirus A, Human / Q000235:genetics* / Q000276:immunology; D004769:Enterovirus Infections / Q000235:genetics / Q000276:immunology; D005838:Genotype; D006232:Hand, Foot and Mouth Disease / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007249:Inflammation / Q000276:immunology; D051907:Lysosomal Membrane Proteins / Q000235:genetics* / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D051116:Receptors, Scavenger / Q000235:genetics* / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology; D014709:Vero Cells
chemical_list: D051907:Lysosomal Membrane Proteins; D051116:Receptors, Scavenger; C074299:SCARB2 protein, human