1887

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.

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2017-04-01
2021-10-26
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References

  1. Frydenberg A, Starr M. Hand, foot and mouth disease. Aust Fam Physician 2003; 32:594–595[PubMed]
    [Google Scholar]
  2. Racaniello V. Picornaviridae: the viruses and their replication. In Howley P, Knipe DM. (editors) Fields Virology, 6th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2013 pp 453–489
    [Google Scholar]
  3. Mcminn PC. An overview of the evolution of enterovirus 71 and its clinical and public health significance. FEMS Microbiol Rev 2002; 26:91–107 [View Article][PubMed]
    [Google Scholar]
  4. Ho M, Chen ER, Hsu KH, Twu SJ, Chen KT et al. An epidemic of enterovirus 71 infection in Taiwan. Taiwan Enterovirus Epidemic Working Group. N Engl J Med 1999; 341:929–935 [View Article][PubMed]
    [Google Scholar]
  5. Ahmad K. Hand, foot, and mouth disease outbreak reported in Singapore. Lancet 2000; 356:1338 [View Article][PubMed]
    [Google Scholar]
  6. Fujimoto T, Chikahira M, Yoshida S, Ebira H, Hasegawa A et al. Outbreak of central nervous system disease associated with hand, foot, and mouth disease in Japan during the summer of 2000: detection and molecular epidemiology of enterovirus 71. Microbiol Immunol 2002; 46:621–627 [View Article][PubMed]
    [Google Scholar]
  7. Shekhar K, Lye MS, Norlijah O, Ong F, Looi LM et al. Deaths in children during an outbreak of hand, foot and mouth disease in Peninsular Malaysia – clinical and pathological characteristics. Med J Malaysia 2005; 60:297–304[PubMed]
    [Google Scholar]
  8. Luo Z, Dong X, Li Y, Zhang Q, Kim C et al. PolyC-binding protein 1 interacts with 5'-untranslated region of enterovirus 71 RNA in membrane-associated complex to facilitate viral replication. PLoS One 2014; 9:e87491 [View Article][PubMed]
    [Google Scholar]
  9. Nishimura Y, Shimojima M, Tano Y, Miyamura T, Wakita T et al. Human P-selectin glycoprotein ligand-1 is a functional receptor for enterovirus 71. Nat Med 2009; 15:794–797 [View Article][PubMed]
    [Google Scholar]
  10. Yamayoshi S, Yamashita Y, Li J, Hanagata N, Minowa T et al. Scavenger receptor B2 is a cellular receptor for enterovirus 71. Nat Med 2009; 15:798–801 [View Article][PubMed]
    [Google Scholar]
  11. Lin YW, Yu SL, Shao HY, Lin HY, Liu CC et al. Human SCARB2 transgenic mice as an infectious animal model for enterovirus 71. PLoS One 2013; 8:e57591 [View Article][PubMed]
    [Google Scholar]
  12. Carlow DA, Gossens K, Naus S, Veerman KM, Seo W et al. PSGL-1 function in immunity and steady state homeostasis. Immunol Rev 2009; 230:75–96 [View Article][PubMed]
    [Google Scholar]
  13. Reczek D, Schwake M, Schröder J, Hughes H, Blanz J et al. LIMP-2 is a receptor for lysosomal mannose-6-phosphate-independent targeting of β-glucocerebrosidase. Cell 2007; 131:770–783 [View Article][PubMed]
    [Google Scholar]
  14. Balreira A, Gaspar P, Caiola D, Chaves J, Beirão I et al. A nonsense mutation in the LIMP-2 gene associated with progressive myoclonic epilepsy and nephrotic syndrome. Hum Mol Genet 2008; 17:2238–2243 [View Article][PubMed]
    [Google Scholar]
  15. Fujii K, Nagata N, Sato Y, Ong KC, Wong KT et al. Transgenic mouse model for the study of enterovirus 71 neuropathogenesis. Proc Natl Acad Sci USA 2013; 110:14753–14758 [View Article][PubMed]
    [Google Scholar]
  16. Huang PN, Lin JY, Locker N, Kung YA, Hung CT et al. Far upstream element binding protein 1 binds the internal ribosomal entry site of enterovirus 71 and enhances viral translation and viral growth. Nucleic Acids Res 2011; 39:9633–9648 [View Article][PubMed]
    [Google Scholar]
  17. Tsou YL, Lin YW, Chang HW, Lin HY, Shao HY et al. Heat shock protein 90: role in enterovirus 71 entry and assembly and potential target for therapy. PLoS One 2013; 8:e77133 [View Article][PubMed]
    [Google Scholar]
  18. Dahl N, Lagerström M, Erikson A, Pettersson U, Type Gdisease III. Gaucher disease type III (Norrbottnian type) is caused by a single mutation in exon 10 of the glucocerebrosidase gene. Am J Hum Genet 1990; 47:275–278[PubMed]
    [Google Scholar]
  19. Zimran A, Gelbart T, Westwood B, Grabowski GA, Beutler E. High frequency of the Gaucher disease mutation at nucleotide 1226 among Ashkenazi jews. Am J Hum Genet 1991; 49:855–859[PubMed]
    [Google Scholar]
  20. Aharon-Peretz J, Rosenbaum H, Gershoni-Baruch R. Mutations in the glucocerebrosidase gene and Parkinson's disease in Ashkenazi Jews. N Engl J Med 2004; 351:1972–1977 [View Article][PubMed]
    [Google Scholar]
  21. Deegan PB, Cox TM. Imiglucerase in the treatment of Gaucher disease: a history and perspective. Drug Des Devel Ther 2012; 6:81–106 [View Article][PubMed]
    [Google Scholar]
  22. Blanz J, Groth J, Zachos C, Wehling C, Saftig P et al. Disease-causing mutations within the lysosomal integral membrane protein type 2 (LIMP-2) reveal the nature of binding to its ligand beta-glucocerebrosidase. Hum Mol Genet 2010; 19:563–572 [View Article][PubMed]
    [Google Scholar]
  23. Yamayoshi S, Koike S. Identification of a human SCARB2 region that is important for enterovirus 71 binding and infection. J Virol 2011; 85:4937–4946 [View Article][PubMed]
    [Google Scholar]
  24. Xing W, Liao Q, Viboud C, Zhang J, Sun J et al. Hand, foot, and mouth disease in China, 2008-12: an epidemiological study. Lancet Infect Dis 2014; 14:308–318 [View Article][PubMed]
    [Google Scholar]
  25. Yoshida T, Kawano Y, Sato K, Ando Y, Aoki J et al. A CD63 mutant inhibits T-cell tropic human immunodeficiency virus type 1 entry by disrupting CXCR4 trafficking to the plasma membrane. Traffic 2008; 9:540–558 [View Article][PubMed]
    [Google Scholar]
  26. Yamayoshi S, Iizuka S, Yamashita T, Minagawa H, Mizuta K et al. Human SCARB2-dependent infection by coxsackievirus A7, A14, and A16 and enterovirus 71. J Virol 2012; 86:5686–5696 [View Article][PubMed]
    [Google Scholar]
  27. Komano J, Miyauchi K, Matsuda Z, Yamamoto N. Inhibiting the Arp2/3 complex limits infection of both intracellular mature vaccinia virus and primate lentiviruses. Mol Biol Cell 2004; 15:5197–5207 [View Article][PubMed]
    [Google Scholar]
  28. Shimizu N, Tanaka A, Mori T, Ohtsuki T, Hoque A et al. A formylpeptide receptor, FPRL1, acts as an efficient coreceptor for primary isolates of human immunodeficiency virus. Retrovirology 2008; 5:52 [View Article]
    [Google Scholar]
  29. Aoki T, Miyauchi K, Urano E, Ichikawa R, Komano J. Protein transduction by pseudotyped lentivirus-like nanoparticles. Gene Ther 2011; 18:936–941 [View Article][PubMed]
    [Google Scholar]
  30. Takeda S, Kanbayashi D, Kurata T, Yoshiyama H, Komano J. Enhanced susceptibility of B lymphoma cells to measles virus by Epstein-Barr virus type III latency that upregulates CD150/signaling lymphocytic activation molecule. Cancer Sci 2014; 105:211–218 [View Article][PubMed]
    [Google Scholar]
  31. Tanaka A, Takeda S, Kariya R, Matsuda K, Urano E et al. A novel therapeutic molecule against HTLV-1 infection targeting provirus. Leukemia 2013; 27:1621–1627 [View Article][PubMed]
    [Google Scholar]
  32. Jović M, Kean MJ, Szentpetery Z, Polevoy G, Gingras AC et al. Two phosphatidylinositol 4-kinases control lysosomal delivery of the Gaucher disease enzyme, β-glucocerebrosidase. Mol Biol Cell 2012; 23:1533–1545 [View Article][PubMed]
    [Google Scholar]
  33. Jinno-Oue A, Tanaka A, Shimizu N, Mori T, Sugiura N et al. Inhibitory effect of chondroitin sulfate type E on the binding step of human T-cell leukemia virus type 1. AIDS Res Hum Retroviruses 2013; 29:621–629 [View Article][PubMed]
    [Google Scholar]
  34. Shimizu N, Tanaka A, Mori T, Ohtsuki T, Hoque A et al. A formylpeptide receptor, FPRL1, acts as an efficient coreceptor for primary isolates of human immunodeficiency virus. Retrovirology 2008; 5:52 [View Article][PubMed]
    [Google Scholar]
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