Endocytosis of Integrin-Binding Human Picornaviruses

Abstract

Picornaviruses that infect humans form one of the largest virus groups with almost three hundred virus types. They include significant enteroviral pathogens such as rhino-, polio-, echo-, and coxsackieviruses and human parechoviruses that cause wide range of disease symptoms. Despite the economic importance of picornaviruses, there are no antivirals. More than ten cellular receptors are known to participate in picornavirus infection, but experimental evidence of their role in cellular infection has been shown for only about twenty picornavirus types. Three enterovirus types and one parechovirus have experimentally been shown to bind and use integrin receptors in cellular infection. These include coxsackievirus A9 (CV-A9), echovirus 9, and human parechovirus 1 that are among the most common and epidemic human picornaviruses and bind to αV-integrins via RGD motif that resides on virus capsid. In contrast, echovirus 1 (E-1) has no RGD and uses integrin α2β1 as cellular receptor. Endocytosis of CV-A9 has recently been shown to occur via a novel Arf6- and dynamin-dependent pathways, while, contrary to collagen binding, E-1 binds inactive β1 integrin and enters via macropinocytosis. In this paper, we review what is known about receptors and endocytosis of integrin-binding human picornaviruses.

Differential permissivity of human cerebrovascular endothelial cells to enterovirus infection and specificities of serotype EV-A71 in crossing an in vitro model of the human blood–brain barrier

“…Most EV strains occupied a central position in the susceptibility spectrum of hCMEC/D3 cells, notably the E-6, E-13 and E-30 strains, and intratypic variations may be related to individual genetic differences amongst genogroups and sub-genogroups. A wide range of cellular receptors has been observed in human EVs (reviewed by Merilahti et al, 2012). Although we did not examine the binding processes of EVs to the hCMEC/D3 cell surface, there is a large body of earlier experimental evidence to suggest that the intertypic variations in hCMEC/D3 susceptibility to EVs can be attributed to their propensity for using a wide range of receptors and internalization processes (Coyne et al, 2007;Bozym et al, 2010;Ylipaasto et al, 2010).…”

Role of Heparan Sulfate in Cellular Infection of Integrin-Binding Coxsackievirus A9 and Human Parechovirus 1 Isolates

“…Structural proteins form the icosahedral capsid, which mediates virus binding to different cellular receptors [ 15 ]. CV-A9 and HPeV-1 carry an RGD motif in their capsid structure and utilize integrins as their receptors [ 16 ]. They are significant human pathogens causing infections in gastrointestinal, respiratory and central nervous systems [ 16 , 17 ].…”

“…CV-A9 and HPeV-1 carry an RGD motif in their capsid structure and utilize integrins as their receptors [ 16 ]. They are significant human pathogens causing infections in gastrointestinal, respiratory and central nervous systems [ 16 , 17 ]. Both CV-A9 and HPeV-1 bind in vitro to integrins [ 18 – 21 ].…”

Plaque2.0—A High-Throughput Analysis Framework to Score Virus-Cell Transmission and Clonal Cell Expansion

“…For example, herpes, measles or polio virus use nectins [ 19 – 22 ], hepatitis C virus uses claudin and occludin (for review, see [ 23 ]). HRV-A16 binds to ICAM-1 (intercellular adhesion molecule [ 1 , 24 ]), HAdV-C2 and coxsackie virus use coxsackie virus adenovirus receptor (CAR), desmoglein or CD46, and adenovirus, rotavirus, herpes virus and a variety of picornaviruses take advantage of integrins (reviewed in [ 25 , 26 , 27 ]). For some of these cell adhesion receptors, it is known that they not just bind to the virus but also induce conformational changes in the bound virus and thereby prime the virus for further steps of entry, uncoating and infection [ 28 – 30 ].…”