Huang Wen-Chan, Chen Hung-Lin, Chen Huan-Yuan, Peng Kuan-Po, Lee Yungling, Huang Li-Min, Chang Luan-Yin, Liu Fu-Tong
Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
Department of Pediatrics, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan.
PLoS One. 2016 Dec 21;11(12):e0168627. doi: 10.1371/journal.pone.0168627. eCollection 2016.
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.
半乳糖凝集素-3是一种嵌合型β-半乳糖苷结合蛋白，已知其可调节病毒感染；然而，其在肠道病毒71型（EV71）感染中的作用尚未得到研究。我们构建了半乳糖凝集素-3基因敲除的横纹肌肉瘤（RD）细胞，并评估EV71感染是否会受到影响。在半乳糖凝集素-3基因敲除的细胞中，感染24小时后，释放的和细胞内的EV71病毒载量受到抑制，细胞死亡率显著降低，而细胞增殖保持不变。此外，表达半乳糖凝集素- rs4644（LGALS3 +191C/A，P64H）非同义基因变体的RD细胞产生的病毒滴度低于野生型半乳糖凝集素-3（C等位基因）的细胞。为了阐明体外病毒载量降低是否与临床严重程度相关，我们招募了实验室确诊为EV71感染的儿童。由于高血糖是儿童严重EV71感染的一个指标，401名入组儿童中有152名在入院时进行了血糖检查，59名受试者的血清葡萄糖水平≥150mg/dL。与rs4644 AA基因型（2.2±0.06 log10 mg/dL）相比，EV71感染期间CC基因型（2.4±0.17 log10 mg/dL, p = .03）和CA基因型（2.4±0.15 log10 mg/dL, p = .02）患者的血清葡萄糖水平更高。这些发现表明，半乳糖凝集素-3的rs4644 AA基因型可能具有保护作用。总之，在我们建立的细胞模型中，半乳糖凝集素-3影响EV71复制，其变体rs4644与临床环境中的高血糖相关。其潜在机制及其潜在的治疗应用值得进一步研究。
