title: A new animal model containing human SCARB2 and lacking stat-1 is highly susceptible to EV71.
abstract: Enterovirus 71 (EV71) is a major threat to children worldwide. Children infected with EV71 could develop subclinical infection and hand-foot-and -mouth disease (HFMD). In severe cases, patients could develop encephalitis, paralysis, pulmonary edema, and death. A more user-friendly and robust animal model is essential to investigating EV71 pathogenesis. Here, we established a hybrid (hSCARB2(+/+)/stat-1(-/-)) mouse strain from crossbreeding SCARB2 transgenic and stat-1 KO mice, and compared the susceptibilities to EV71 infection and pathogenesis between parental and hybrid mice. Virus-encoded VP1 protein can be detected in the streaking nerve fibers in brain and spinal cord. This hybrid mouse strain at 2-week-old age can still be infected with different genotypes of EV71 at 1000-fold lower titer via an ip route. Infected hybrid mice developed earlier onset of CNS disease, paralysis, and death at a higher incidence. These advantages of this novel model meet the urgent need from the scientific community in basic and preclinical research in therapeutics and pathogenesis.
authors: Taiwan International Graduate Program (TIGP) in Molecular Medicine, National Yang-Ming University and Academia Sinica, Taipei, Taiwan.|Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.|Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei, Taiwan.
authors: An-Ting
authors: AT
authors: Liou
authors: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.|Institute of Microbiology and Immunology, National Yang-Ming University, Taipei, Taiwan.
authors: Szu-Yao
authors: SY
authors: Wu
authors: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
authors: Chun-Che
authors: CC
authors: Liao
authors: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
authors: Ya-Shu
authors: YS
authors: Chang
authors: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.|Institute of Microbiology and Immunology, National Yang-Ming University, Taipei, Taiwan.
authors: Chih-Shin
authors: CS
authors: Chang
authors: Taiwan International Graduate Program (TIGP) in Molecular Medicine, National Yang-Ming University and Academia Sinica, Taipei, Taiwan.|Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
authors: Chiaho
authors: C
authors: Shih
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D029821:Enterovirus A, Human / Q000235:genetics / Q000378:metabolism*; D004769:Enterovirus Infections / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D006801:Humans; D051907:Lysosomal Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008822:Mice, Transgenic; D051116:Receptors, Scavenger / Q000235:genetics / Q000378:metabolism; D050794:STAT1 Transcription Factor / Q000172:deficiency*
chemical_list: D051907:Lysosomal Membrane Proteins; D051116:Receptors, Scavenger; C074299:SCARB2 protein, human; D050794:STAT1 Transcription Factor; C494080:Stat1 protein, mouse