title: Antiviral activity of acid beta-glucosidase 1 on enterovirus 71, a causative agent of hand, foot and mouth disease.
abstract: 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.
authors.affiliation: Department of Infectious Diseases, Osaka Prefectural Institute of Public Health, 3-69 Nakamichi-1chome, Higashinari-ku, Osaka 537-0025, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Nakata
authors.affiliation: AIDS Research Center, National Institute of Infectious Diseases, Toyama 1-23-1 Shinjuku-ku, Tokyo 162-8640, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Takeda
authors.affiliation: Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Tanaka
authors.affiliation: Animal Health Biotechnology, Temasek Life Sciences Laboratory, National University of Singapore, 1 Research Link, 117604, Singapore.
authors.forename: Jimmy
authors.initials: J
authors.lastname: Kwang
authors.affiliation: National Hospital Organization, Nagoya Medical Center, 4-1-1 Sannomaru, Naka-ku, Nagoya 460-0001, Japan.|Department of Infectious Diseases, Osaka Prefectural Institute of Public Health, 3-69 Nakamichi-1chome, Higashinari-ku, Osaka 537-0025, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Komano
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology*; D002460:Cell Line; D029821:Enterovirus A, Human / Q000276:immunology* / Q000502:physiology*; D005962:Glucosylceramidase / Q000494:pharmacology*; D006232:Hand, Foot and Mouth Disease / Q000821:virology; D006801:Humans; D051907:Lysosomal Membrane Proteins / Q000378:metabolism; D051116:Receptors, Scavenger / Q000378:metabolism; D011991:Receptors, Virus / Q000378:metabolism; D053585:Virus Attachment
chemical_list: D000998:Antiviral Agents; D051907:Lysosomal Membrane Proteins; D051116:Receptors, Scavenger; D011991:Receptors, Virus; C074299:SCARB2 protein, human; D005962:Glucosylceramidase