title: Galectin-3 and Its Genetic Variation rs4644 Modulate Enterovirus 71 Infection.
abstract: Galectin-3, a chimeric type β-galactoside-binding protein, is known to modulate viral infection; however, its role in enterovirus 71 (EV71) infection has not been investigated. We generated galectin-3 null rhabdomyosarcoma (RD) cells and evaluated whether EV71 infection would be affected. In galectin-3 null cells, the released and intracellular EV71 viral loads were suppressed after 24 h of infection, and cell death rates were significantly lower, while cell proliferation remained unaltered. In addition, RD cells expressing a nonsynonymous genetic variant of galectin-3, rs4644 (LGALS3 +191C/A, P64H), produced lower virus titers than those with wild-type galectin-3 (C allele). To clarify whether the in vitro viral load reduction correlates with clinical severity, we enrolled children with laboratory-confirmed EV71 infection. Since hyperglycemia is an indicator of severe EV71 infection in children, 152 of 401 enrolled children had glucose examinations at admission, and 59 subjects had serum glucose levels ≥ 150 mg/dL. In comparison to the rs4644 AA genotype (2.2 ± 0.06 log10 mg/dL), serum glucose levels during EV71 infection were higher in patients with CC (2.4 ± 0.17 log10 mg/dL, p = 0.03) and CA (2.4 ± 0.15 log10 mg/dL, p = 0.02) genotypes, respectively. These findings suggest that the rs4644 AA genotype of galectin-3 might exert a protective effect. In summary, galectin-3 affects EV71 replication in our cellular model and its variant, rs4644, is associated with hyperglycemia in the clinical setting. The underlying mechanism and its potential therapeutic application warrant further investigation.
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.|Department of Pediatrics, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan.|Ph.D. Program in Translational Medicine, National Taiwan University and Academia Sinica, Taipei, Taiwan.
authors.forename: Wen-Chan
authors.initials: WC
authors.lastname: Huang
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
authors.forename: Hung-Lin
authors.initials: HL
authors.lastname: Chen
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
authors.forename: Huan-Yuan
authors.initials: HY
authors.lastname: Chen
authors.affiliation: School of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Kuan-Po
authors.initials: KP
authors.lastname: Peng
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.|Institute of Epidemiology and Preventive Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Yungling
authors.initials: Y
authors.lastname: Lee
authors.affiliation: Department of Pediatrics, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Li-Min
authors.initials: LM
authors.lastname: Huang
authors.affiliation: Department of Pediatrics, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Luan-Yin
authors.initials: LY
authors.lastname: Chang
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.|Department of Dermatology, University of California Davis, Sacramento, California, United States of America.
authors.forename: Fu-Tong
authors.initials: FT
authors.lastname: Liu
mesh_terms: D000483:Alleles; D001786:Blood Glucose / Q000032:analysis; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D002675:Child, Preschool; D029821:Enterovirus A, Human / Q000302:isolation & purification / Q000502:physiology*; D004769:Enterovirus Infections / Q000150:complications / Q000473:pathology*; D005260:Female; D037502:Galectin 3 / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism*; D005787:Gene Frequency; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D006943:Hyperglycemia / Q000209:etiology; D007223:Infant; D008297:Male; D012720:Severity of Illness Index; D019562:Viral Load; D014779:Virus Replication
chemical_list: D001786:Blood Glucose; D037502:Galectin 3