Galectin-3 and Its genetic variation rs4644 modulate enterovirus 71 infection

Wen Chan Huang, Hung Lin Chen, Huan Yuan Chen, Kuan Po Peng, Yungling Lee, Li Min Huang, Luan Yin Chang, Fu-Tong Liu

Research output: Contribution to journalArticle

5 Scopus citations

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 ô 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.

Original languageEnglish (US)
Article numbere0168627
JournalPLoS One
Volume11
Issue number12
DOIs
StatePublished - Dec 1 2016

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

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    Huang, W. C., Chen, H. L., Chen, H. Y., Peng, K. P., Lee, Y., Huang, L. M., Chang, L. Y., & Liu, F-T. (2016). Galectin-3 and Its genetic variation rs4644 modulate enterovirus 71 infection. PLoS One, 11(12), [e0168627]. https://doi.org/10.1371/journal.pone.0168627