Why the study?
Does acid beta-glucosidase 1 (GBA1) prevent EV71 infection in preclinical models?
Does acid beta-glucosidase 1 (GBA1) prevent EV71 infection in preclinical models?
Acid beta-glucosidase 1 (GBA1) demonstrates antiviral activity against enterovirus 71 by interfering with the SCARB2 receptor, suggesting a potential novel therapeutic target for hand, foot and mouth disease.
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GBA1 may inform EV71 antiviral strategies in models; leaves open human translation for hand-foot-mouth disease.
Enterovirus 71 (EV71) is a causative agent of hand, foot and mouth disease (HFMD). EV71 causes fever, rash, diarrhoea and, in some cases, acute encephalopathy/encephalitis, which can be fatal. No specific treatment is currently available for EV71 infection. Here, we conducted a cDNA library screen and identified acid β-glucosidase 1 (GBA1; also known as β-glucocerebrosidase) as an EV71 resistance factor. The anti-EV71 function of GBA1 was verified by gene transduction and knockdown experiments. Cerezyme, a molecular drug used to treat Gaucher's disease and having recombinant human GBA1 as the active ingredient, protected against EV71 infection. The anti-EV71 activity of GBA1 was bimodal: endogenous GBA1 restricted cell surface expression levels of scavenger receptor class B, member 2 (SCARB2), also known as lysosomal integral membrane protein 2 (LIMP-2), and exogenous recombinant GBA1 interfered with EV71 to interact with SCARB2 outside the cell. Thus, our findings suggest that GBA1 may represent a novel molecular target for the treatment of EV71 infection.
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Nakata et al. (2017) studied this question.
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