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Galectin-3 and Its Genetic Variation rs4644 Modulate Enterovirus 71 Infection.

Galectin-3 and Its Genetic Variation rs4644 Modulate Enterovirus 71 Infection.
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Huang WC, Chen HL, Chen HY, Peng KP, Lee Y, Huang LM, Chang LY, Liu FT,


Huang WC, Chen HL, Chen HY, Peng KP, Lee Y, Huang LM, Chang LY, Liu FT, (click to view)

Huang WC, Chen HL, Chen HY, Peng KP, Lee Y, Huang LM, Chang LY, Liu FT,

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PloS one 2016 12 2111(12) e0168627 doi 10.1371/journal.pone.0168627

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.

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