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

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

doi:10.1007/s13238-017-0405-7

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.

Highlights

Hand, foot, and mouth disease (HFMD) is a common viral illness that usually affects infants and children younger than 5 years old (Ooi et al, 2010)
In the 293-hSCARB2 cells, which stably expressed human Scavenger receptor class B member 2 (SCARB2) on the cell surface, we showed that JL2 could bind to SCARB2 without permeabilization (Fig. 1B)
With serial dilution of JL2, we showed that the binding of JL2 to 293-hSCARB2 increased from 0.01 μg/mL and plateaued at a concentration of 2 μg/mL (Fig. 1C)

Summary

Introduction

Foot, and mouth disease (HFMD) is a common viral illness that usually affects infants and children younger than 5 years old (Ooi et al, 2010). Both Entero virus 71 (EV71) and Coxsackie A virus type 16 (CA16) are common causative agents (Fan et al, 2013; Kim et al, 2013; Zou et al, 2012). EV71 infection is a serious public health problem across the AsianPacific region

Methods

Results

Conclusion