A new animal model containing human SCARB2 and lacking stat-1 is highly susceptible to EV71

• Published in: Scientific reports 2016-08, Vol.6 (1), p.31151-31151, Article 31151
• Main Authors: Liou, An-Ting, Wu, Szu-Yao, Liao, Chun-Che, Chang, Ya-Shu, Chang, Chih-Shin, Shih, Chiaho
• Format: Article
• Language: English
• Subjects: 631/326/421; 692/420/254; Animals; Central nervous system; Children; Disease Models, Animal; Edema; Encephalitis; Enterovirus A, Human - genetics; Enterovirus A, Human - metabolism; Enterovirus Infections - genetics; Enterovirus Infections - metabolism; Enterovirus Infections - pathology; Genotypes; Hand-foot-and-mouth disease; Humanities and Social Sciences; Humans; Lysosomal Membrane Proteins - genetics; Lysosomal Membrane Proteins - metabolism; Mice, Transgenic; multidisciplinary; Paralysis; Pathogenesis; Receptors, Scavenger - genetics; Receptors, Scavenger - metabolism; Science; Science (multidisciplinary); Spinal cord; Stat1 protein; STAT1 Transcription Factor - deficiency; Subclinical infection; Transgenic mice; VP1 protein
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep31151

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.