title: Genomic and immunologic factors associated with viral pathogenesis in a lethal EV71 infected neonatal mouse model.
abstract: Hand, foot and mouth disease (HFMD) caused by enterovirus 71 (EV71) has emerged as a major health problem in China and worldwide. The present study aimed to understand the virological features of EV71 and host responses resulting from EV71 infection. Six different EV71 strains were isolated from HFMD patients with severe or mild clinical symptoms, and were analyzed for pathogenicity in vitro and in vivo. The results demonstrated that the six virus strains exhibited similar cytopathogenic effects on susceptible MA104 cells. However, marked differences in histological and immunopathological changes were observed when mice were inoculated with the different virus strains. Thus, the viruses studied were divided into two groups, highly or weakly pathogenic. Two representative virus strains, JN200804 and JN200803 (highly and weakly pathogenic, respectively) were studied further to investigate pathogenicity-associated factors, including genetic mutations and immunopathogenesis. The present study has demonstrated that highly pathogenic strains have stable genome and amino acid sequences. Notably, the present study demonstrated that a highly pathogenic strain induced a significant increase of the bulk CD4 T cell levels at 3 days post‑inoculation. In conclusion, the current study demonstrates that genomic and immunologic factors may be responsible for the multiple tissue damage caused by highly pathogenic EV71 infection.
authors.affiliation: Key Laboratory of Rare and Uncommon Diseases, Department of Microbiology, Institute of Basic Medicine, Shandong Academy of Medical Sciences, Jinan, Shandong 250062, P.R. China.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Yue
authors.affiliation: Key Laboratory of Rare and Uncommon Diseases, Department of Microbiology, Institute of Basic Medicine, Shandong Academy of Medical Sciences, Jinan, Shandong 250062, P.R. China.
authors.forename: Peng
authors.initials: P
authors.lastname: Li
authors.affiliation: Key Laboratory of Rare and Uncommon Diseases, Department of Microbiology, Institute of Basic Medicine, Shandong Academy of Medical Sciences, Jinan, Shandong 250062, P.R. China.
authors.forename: Nannan
authors.initials: N
authors.lastname: Song
authors.affiliation: Key Laboratory of Rare and Uncommon Diseases, Department of Microbiology, Institute of Basic Medicine, Shandong Academy of Medical Sciences, Jinan, Shandong 250062, P.R. China.
authors.forename: Bingqing
authors.initials: B
authors.lastname: Li
authors.affiliation: Key Laboratory of Rare and Uncommon Diseases, Department of Microbiology, Institute of Basic Medicine, Shandong Academy of Medical Sciences, Jinan, Shandong 250062, P.R. China.
authors.forename: Zhihui
authors.initials: Z
authors.lastname: Li
authors.affiliation: Key Laboratory of Rare and Uncommon Diseases, Department of Microbiology, Institute of Basic Medicine, Shandong Academy of Medical Sciences, Jinan, Shandong 250062, P.R. China.
authors.forename: Yuqi
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Key Laboratory of Rare and Uncommon Diseases, Department of Microbiology, Institute of Basic Medicine, Shandong Academy of Medical Sciences, Jinan, Shandong 250062, P.R. China.
authors.forename: Weidong
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Division of Molecular and Gene Therapies, Griffith Health Institute and School of Medical Science, Griffith University, Gold Coast, Queensland 4215, Australia.
authors.forename: Ming Q
authors.initials: MQ
authors.lastname: Wei
authors.affiliation: Department of Comprehensive Internal Medicine, Jinan Children's Hospital, Jinan, Shandong 250022, P.R. China.
authors.forename: Zhongtao
authors.initials: Z
authors.lastname: Gai
authors.affiliation: Key Laboratory of Rare and Uncommon Diseases, Department of Microbiology, Institute of Basic Medicine, Shandong Academy of Medical Sciences, Jinan, Shandong 250062, P.R. China.
authors.forename: Hong
authors.initials: H
authors.lastname: Meng
authors.affiliation: Department of Neurology, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai 200127, P.R. China.
authors.forename: Jiwen
authors.initials: J
authors.lastname: Wang
authors.affiliation: Key Laboratory of Rare and Uncommon Diseases, Department of Microbiology, Institute of Basic Medicine, Shandong Academy of Medical Sciences, Jinan, Shandong 250062, P.R. China.
authors.forename: Lizeng
authors.initials: L
authors.lastname: Qin
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D002648:Child; D004195:Disease Models, Animal; D029821:Enterovirus A, Human / Q000235:genetics* / Q000276:immunology* / Q000302:isolation & purification; D005260:Female; D006232:Hand, Foot and Mouth Disease / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D006801:Humans; D008297:Male; D051379:Mice