The binding of a monoclonal antibody to the apical region of SCARB2 blocks EV71 infection

Xuyuan Zhang , Pan Yang , Nan Wang , Jialong Zhang , Jingyun Li , Hao Guo , Xiangyun Yin , Zihe Rao , Xiangxi Wang , Liguo Zhang

Protein Cell ›› 2017, Vol. 8 ›› Issue (8) : 590 -600.

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Protein Cell ›› 2017, Vol. 8 ›› Issue (8) : 590 -600. DOI: 10.1007/s13238-017-0405-7
RESEARCH ARTICLE
RESEARCH ARTICLE

The binding of a monoclonal antibody to the apical region of SCARB2 blocks EV71 infection

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Abstract

Entero virus 71 (EV71) causes hand, foot, and mouth disease (HFMD) and occasionally leads to severe neurological complications and even death. Scavenger receptor class B member 2 (SCARB2) is a functional receptor for EV71, that mediates viral attachment, internalization, and uncoating. However, the exact binding site of EV71 on SCARB2 is unknown. In this study, we generated a monoclonal antibody (mAb) that binds to human but not mouse SCARB2. It is named JL2, and it can effectively inhibit EV71 infection of target cells. Using a set of chimeras of human and mouse SCARB2, we identified that the region containing residues 77–113 of human SCARB2 contributes significantly to JL2 binding. The structure of the SCARB2-JL2 complex revealed that JL2 binds to the apical region of SCARB2 involving α-helices 2, 5, and 14. Our results provide new insights into the potential binding sites for EV71 on SCARB2 and the molecular mechanism of EV71 entry.

Keywords

SCARB2 / EV71 / monoclonal antibody / HFMD / receptor

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Xuyuan Zhang, Pan Yang, Nan Wang, Jialong Zhang, Jingyun Li, Hao Guo, Xiangyun Yin, Zihe Rao, Xiangxi Wang, Liguo Zhang. The binding of a monoclonal antibody to the apical region of SCARB2 blocks EV71 infection. Protein Cell, 2017, 8(8): 590-600 DOI:10.1007/s13238-017-0405-7

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References

[1]

AdamsPD, AfoninePV, BunkocziG, ChenVB, DavisIW, EcholsN, HeaddJJ, HungLW, KapralGJ, Grosse-KunstleveRW (2010) PHENIX: a comprehensive Python-based system for macromolecular structure solution.Acta Crystallogr Sect D66:213–221

[2]

CantonJ, NeculaiD, GrinsteinS(2013) Scavenger receptors in homeostasis and immunity.Nat Rev Immunol13:621–634

[3]

ChanKP, GohKT, ChongCY, TeoES, LauG, LingAE (2003) Epidemic hand, foot and mouth disease caused by human enterovirus 71, Singapore.Emerg Infect Dis9:78–85

[4]

ChenP, SongZ, QiY, FengX, XuN, SunY, WuX, YaoX, MaoQ, LiX (2012) Molecular determinants of enterovirus 71 viral entry: cleft around GLN-172 on VP1 protein interacts with variable region on scavenge receptor B 2.J Biol Chem287:6406–6420

[5]

ChoHK, LeeNY, LeeH, KimHS, SeoJW, HongYM, LeeSJ, LeeSW, CheonDS, HongJY (2010) Enterovirus 71-associated hand, foot and mouth diseases with neurologic symptoms, a university hospital experience in Korea, 2009.Korean J Pediatr53:639–643

[6]

ChuaKB, KasriAR (2011) Hand foot and mouth disease due to enterovirus 71 in Malaysia.Virol Sin26:221–228

[7]

ChuaKB, ChuaBH, LeeCS, ChemYK, IsmailN, KiyuA, KumarasamyV (2007) Genetic diversity of enterovirus 71 isolated from cases of hand, foot and mouth disease in the 1997, 2000 and 2005 outbreaks, Peninsular Malaysia.Malays J Pathol29:69–78

[8]

DangM,WangX,WangQ,WangY, LinJ, SunY, LiX, ZhangL, LouZ, WangJ (2014) Molecular mechanism of SCARB2-mediated attachment and uncoating of EV71.Protein Cell5:692–703

[9]

DeLano, W.L. (2002). The PyMOL molecular graphics system.

[10]

EmsleyP, CowtanK (2004) Coot: model-building tools for molecular graphics.Acta Crystallogr Sect D60:2126–2132

[11]

FanX, JiangJ, LiuY, HuangX, WangP, LiuL, WangJ, ChenW, WuW, XuB (2013) Detection of human enterovirus 71 and Coxsackievirus A16 in an outbreak of hand, foot, and mouth disease in Henan Province, China in 2009.Virus Genes46:1–9

[12]

FujiiK, NagataN, SatoY, OngKC, WongKT, YamayoshiS, ShimanukiM, ShitaraH, TayaC, KoikeS (2013) Transgenic mouse model for the study of enterovirus 71 neuropathogenesis.Proc Natl Acad Sci USA110:14753–14758

[13]

GaoM, DuanH, LiuJ, ZhangH, WangX, ZhuM, GuoJ, ZhaoZ, MengL, PengY (2014) The multi-targeted kinase inhibitor sorafenib inhibits enterovirus 71 replication by regulating IRESdependent translation of viral proteins.Antivir Res106:80–85

[14]

HoM, ChenER, HsuKH, TwuSJ, ChenKT, TsaiSF, WangJR, ShihSR (1999) An epidemic of enterovirus 71 infection in Taiwan. Taiwan Enterovirus Epidemic Working Group.N Engl J Med341:929–935

[15]

HosoyaM, KawasakiY, SatoM, HonzumiK, KatoA, HiroshimaT, IshikoH, SuzukiH (2006) Genetic diversity of enterovirus 71 associated with hand, foot and mouth disease epidemics in Japan from 1983 to 2003.Pediatr Infect Dis J25:691–694

[16]

KimSJ, KimJH, KangJH, KimDS, KimKH, KimKH, KimYH, ChungJY, BinJH, JungDE (2013) Risk factors for neurologic complications of hand, foot and mouth disease in the Republic of Korea, 2009.J Korean Med Sci28:120–127

[17]

LeeKY, LeeMS, KimDB (2016) Neurologic manifestations of enterovirus 71 infection in Korea.J Korean Med Sci31:561–567

[18]

LinYW, LinHY, TsouYL, ChitraE, HsiaoKN, ShaoHY, LiuCC, SiaC, ChongP, ChowYH (2012) Human SCARB2-mediated entry and endocytosis of EV71.PLoS ONE7:e30507

[19]

LinYW, YuSL, ShaoHY, LinHY, LiuCC, HsiaoKN, ChitraE, TsouYL, ChangHW, SiaC (2013) Human SCARB2 transgenic mice as an infectious animal model for enterovirus 71.PLoS ONE8:e57591

[20]

LiuMY, LiuW, LuoJ, LiuY, ZhuY, BermanH, WuJ (2011) Characterization of an outbreak of hand, foot, and mouth disease in Nanchang, China in 2010.PLoS ONE6:e25287

[21]

MatthewsBW (1968) Solvent content of protein crystals.J Mol Biol33:491–497

[22]

McCoyAJ, Grosse-KunstleveRW, AdamsPD, WinnMD, StoroniLC, ReadRJ (2007) Phaser crystallographic software.J Appl Crystallogr40:658–674

[23]

McMinnPC (2002) An overview of the evolution of enterovirus 71 and its clinical and public health significance.FEMS Microbiol Rev26:91–107

[24]

MizutaK, AokiY, MatobaY, YahagiK, ItagakiT, KatsushimaF, KatsushimaY, ItoS, HongoS, MatsuzakiY (2014) Molecular epidemiology of enterovirus 71 strains isolated from children in Yamagata, Japan, between 1990 and 2013.J Med Microbiol63:1356–1362

[25]

NeculaiD, SchwakeM, RavichandranM, ZunkeF, CollinsRF, PetersJ, NeculaiM, PlumbJ, LoppnauP, PizarroJC (2013) Structure of LIMP-2 provides functional insights with implications for SR-BI and CD36.Nature504:172–176

[26]

NijhuisM, van MaarseveenN, SchuurmanR, VerkuijlenS, de VosM, HendriksenK, van LoonAM (2002) Rapid and sensitive routine detection of all members of the genus enterovirus in different clinical specimens by real-time PCR.J Clin Microbiol40:3666–3670

[27]

OoiMH, WongSC, PodinY, AkinW, del SelS, MohanA, ChiengCH, PereraD, ClearD, WongD(2007) Human enterovirus 71 disease in Sarawak, Malaysia: a prospective clinical, virological, and molecular epidemiological study.Clin Infect Dis44:646–656

[28]

OoiMH, WongSC, LewthwaiteP, CardosaMJ, SolomonT (2010) Clinical features, diagnosis, and management of enterovirus 71.Lancet Neurol9:1097–1105

[29]

OtwinowskiZ, MinorW (1997) Processing of X-ray diffraction data collected in oscillation mode.Methods Enzymol276:307–326

[30]

SandersSA, HerreroLJ, McPhieK, ChowSS, CraigME, DwyerDE, RawlinsonW, McMinnPC (2006) Molecular epidemiology of enterovirus 71 over two decades in an Australian urban community.Arch Virol151:1003–1013

[31]

SatoC, SyojiM, UekiY, SatoY, OkimuraY, SaitoN, KikuchiN, YagiT, NumakuraH (2006) Isolation of enterovirus 71 from patients with hand, foot and mouth disease in a local epidemic on March 2006, in Miyagi prefecture, Japan.Jpn J Infect Dis59:348

[32]

VegaMA, RodriguezF, SeguiB, CalesC, AlcaldeJ, SandovalIV (1991a) Targeting of lysosomal integral membrane protein LIMP II. The tyrosine-lacking carboxyl cytoplasmic tail of LIMP II is sufficient for direct targeting to lysosomes.J Biol Chem266:16269–16272

[33]

VegaMA, Segui-RealB, GarciaJA, CalesC, RodriguezF, VanderkerckhoveJ, SandovalIV (1991b) Cloning, sequencing, and expression of a cDNA encoding rat LIMP II, a novel 74-kDa lysosomal membrane protein related to the surface adhesion protein CD36.J Biol Chem266:16818–16824

[34]

WangY, ZouG, XiaA, WangX, CaiJ, GaoQ, YuanS, HeG, ZhangS, ZengM (2015) Enterovirus 71 infection in children with hand, foot, and mouth disease in Shanghai, China: epidemiology, clinical feature and diagnosis.Virol J12:83

[35]

WangX, ZhuL, DangM, HuZ, GaoQ, YuanS, SunY, ZhangB, RenJ, KotechaA(2017) Potent neutralization of hepatitis A virus reveals a receptor mimic mechanism and the receptor recognition site.Proc Natl Acad Sci USA114:770–775

[36]

WuY, YeoA, PhoonMC, TanEL, PohCL, QuakSH, ChowVT (2010) The largest outbreak of hand; foot and mouth disease in Singapore in 2008: the role of enterovirus 71 and coxsackievirus A strains.Int J Infect Dis14:e1076–1081

[37]

YamayoshiS, KoikeS (2011) Identification of a human SCARB2 region that is important for enterovirus 71 binding and infection.J Virol85:4937–4946

[38]

YamayoshiS, YamashitaY, LiJ, HanagataN, MinowaT, TakemuraT, KoikeS (2009) Scavenger receptor B2 is a cellular receptor for enterovirus 71.Nat Med15:798–801

[39]

YamayoshiS, FujiiK, KoikeS (2012) Scavenger receptor b2 as a receptor for hand, foot, and mouth disease and severe neurological diseases.Front Microbiol3:32

[40]

YamayoshiS, OhkaS, FujiiK, KoikeS (2013) Functional comparison of SCARB2 and PSGL1 as receptors for enterovirus 71.J Virol87:3335–3347

[41]

YamayoshiS, FujiiK, KoikeS (2014) Receptors for enterovirus 71.Emerg Microbes Infect3:e53

[42]

ZhangQ, MacDonaldNE, SmithJC, CaiK, YuH, LiH, LeiC (2014) Severe enterovirus type 71 nervous system infections in children in the Shanghai region of China: clinical manifestations and implications for prevention and care.Pediatr Infect Dis J33:482–487

[43]

ZhouX, FanG, XiaW, HeF, HuM, NiX, ZhangY, ChenH (2013) Molecular epidemiology of human enterovirus 71 strains in the Nanchang region of China in 2011.Jpn J Infect Dis66:149–150

[44]

ZhouS, LiuQ, WuX, ChenP, WuX, GuoY, LiuS, LiangZ, FanC, WangY (2016) A safe and sensitive enterovirus A71 infection model based on human SCARB2 knock-in mice.Vaccine34:2729–2736

[45]

ZouXN, ZhangXZ, WangB, QiuYT (2012) Etiologic and epidemiologic analysis of hand, foot, and mouth disease in Guangzhou city: a review of 4,753 cases.Braz J Infect Dis16:457–465

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