Glucose-6-phosphate dehydrogenase deficiency enhances enterovirus 71 infection

Abstract

Variations in the cellular microenvironment affect the host's susceptibility to pathogens. Using glucose-6-phosphate dehydrogenase (G6PD)-deficient fibroblasts as a model, this study demonstrated that the cellular redox status affects infectivity as well as the outcome of enterovirus 71 (EV71) infection. Compared with their normal counterparts, G6PD-deficient cells supported EV71 replication more efficiently and showed greater cytopathic effect and loss of viability. Mechanistically, viral infection led to increased oxidative stress, as indicated by increased dichlorofluorescein fluorescence and a diminished ratio of glutathione (GSH) to its disulfide form (GSSG), with the effect being greater in G6PD-deficient cells. Exogenous expression of active G6PD in the deficient cells, which increased the intracellular GSH : GSSG ratio, suppressed the generation of viral progeny. Consistent with this, treatment with N-acetylcysteine offered resistance to EV71 propagation and a cytoprotective effect on the infected cells. These findings support the notion that G6PD status, and thus redox balance, is an important determinant of enteroviral infection.

Recent Advances in Research on Human Enterovirus 71

“…This haplotype has very low frequency in Caucasian populations but 17-35% frequency in Asian populations [7]. In addition, in vitro ana lysis suggests that glucose-6-phophate dehydrogenase deficiency enhances HEV71 infection [8]. A Taiwanese group demonstrated that children with severe forms of HEV71 encephalitis were significantly more likely to possess a specific cytotoxic T lymphocyte antigen haplotype (CTLA-4) than children who developed mild HEV71 infections [9].…”

Glucose 6-phosphate dehydrogenase deficiency enhances germ cell apoptosis and causes defective embryogenesis in Caenorhabditis elegans

“…5, 6, 7, 8, 9 However, during the past decade, accumulating evidence has demonstrated that G6PD deficiency also affects nucleated cells 10, 11, 12, 13, 14 and cellular pathophysiological events, including dysregulated cell proliferation, accelerated cellular senescence, enhanced susceptibility to viral infection, and impaired embryonic development. 15, 16 G6PD is essential for normal cell growth and survival. For example, G6PD-deficient fibroblasts exhibit retarded growth and premature senescence.…”

Relapse of hand foot and mouth disease: Are we at more risk?

“…[1] Another proposed factor is glucose-6-phophate dehydrogenase deficiency. [2] Age in the range of 6 month to 3 years,[3] fever ≥ 3 days, fever peak ≥ 38.5°C and history of lethargy were also correlated with poor prognosis. [4] On the other hand, older age of the patient was associated with higher risk of EV71 infection.…”