Cellular Receptors for Human Enterovirus Species A

Yorihiro Nishimura,Hiroyuki Shimizu

doi:10.3389/fmicb.2012.00105

Abstract

Human enterovirus species A (HEV-A) is one of the four species of HEV in the genus Enterovirus in the family Picornaviridae. Among HEV-A, coxsackievirus A16 (CVA16) and enterovirus 71 (EV71) are the major causative agents of hand, foot, and mouth disease (HFMD). Some other types of HEV-A are commonly associated with herpangina. Although HFMD and herpangina due to HEV-A are common febrile diseases among infants and children, EV71 can cause various neurological diseases, such as aseptic meningitis and fatal encephalitis. Recently, two human transmembrane proteins, P-selectin glycoprotein ligand-1 (PSGL-1) and scavenger receptor class B, member 2 (SCARB2), were identified as functional receptors for EV71 and CVA16. In in vitro infection experiments using the prototype HEV-A strains, PSGL-1 and SCARB2 could be responsible for the specific receptors for EV71 and CVA16. However, the involvement of both receptors in the in vitro and in vivo infections of clinical isolates of HEV-A has not been clarified yet. To elucidate a diverse array of the clinical outcome of HEV-A-associated diseases, the identification and characterization of HEV-A receptors may provide useful information in understanding the HEV-A pathogenesis at a molecular level.

Highlights

The genus Enterovirus within family Picornaviridae, nonenveloped viruses with a single-stranded RNA genome of positive polarity, is comprised of more than 100 serotypes (Pallansch and Roos, 2007)
Higher viral titers were found for coxsackievirus A2 (CVA2) and CVA7 in L-P-selectin glycoprotein ligand-1 (PSGL-1).1 cells compared with those in L-bsd cells, replication was not affected by KPL1. These results suggest that CVA2 and CVA7 may infect to L-PSGL-1.1 cells in an alternative pathway via PSGL-1 or glycosylated PSGL-1, without the interaction between enterovirus 71 (EV71)-PB and the N-terminal region of PSGL-1 recognized by KPL1
It is possible that Human enterovirus species A (HEV-A) strains other than EV71 require adaptive mutations for efficient replication in L-PSGL-1.1 cells

Summary

Cellular receptors for human enterovirus species A

Among HEV-A, coxsackievirus A16 (CVA16) and enterovirus 71 (EV71) are the major causative agents of hand, foot, and mouth disease (HFMD). HFMD and herpangina due to HEV-A are common febrile diseases among infants and children, EV71 can cause various neurological diseases, such as aseptic meningitis and fatal encephalitis. In in vitro infection experiments using the prototype HEV-A strains, PSGL-1 and SCARB2 could be responsible for the specific receptors for EV71 and CVA16. The involvement of both receptors in the in vitro and in vivo infections of clinical isolates of HEV-A has not been clarified yet. To elucidate a diverse array of the clinical outcome of HEV-A-associated diseases, the identification and characterization of HEV-A receptors may provide useful information in understanding the HEV-A pathogenesis at a molecular level

INTRODUCTION

Nishimura and Shimizu

CONCLUSION