Limits...
Receptors for enterovirus 71.

Yamayoshi S, Fujii K, Koike S - Emerg Microbes Infect (2014)

Bottom Line: This mouse model facilitates the in vivo investigation of many issues related to EV71.These molecules also contribute to viral infection in vitro either by interacting with SCARB2 or independently of SCARB2.However, the cooperative effects of these receptors, and their contribution to EV71 pathogenicity in vivo, remain to be elucidated.

View Article: PubMed Central - PubMed

Affiliation: Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, The University of Tokyo , Tokyo 108-8639, Japan.

ABSTRACT
Enterovirus 71 (EV71) is one of the major causative agents of hand, foot and mouth disease (HFMD). Occasionally, EV71 infection is associated with severe neurological diseases, such as acute encephalitis, acute flaccid paralysis and cardiopulmonary failure. Several molecules act as cell surface receptors that stimulate EV71 infection, including scavenger receptor B2 (SCARB2), P-selectin glycoprotein ligand-1 (PSGL-1), sialylated glycan, heparan sulfate and annexin II (Anx2). SCARB2 plays critical roles in attachment, viral entry and uncoating, and it can facilitate efficient EV71 infection. The three-dimensional structures of the mature EV71 virion, procapsid and empty capsid, as well as the exofacial domain of SCARB2, have been elucidated. This structural information has greatly increased our understanding of the early steps of EV71 infection. Furthermore, SCARB2 plays essential roles in the development of EV71 neurological disease in vivo. Adult mice are not susceptible to infection by EV71, but transgenic mice that express human SCARB2 become susceptible to EV71 infection and develop similar neurological diseases to those found in humans. This mouse model facilitates the in vivo investigation of many issues related to EV71. PSGL-1, sialylated glycan, heparan sulfate and Anx2 are attachment receptors, which enhance viral infection by retaining the virus on the cell surface. These molecules also contribute to viral infection in vitro either by interacting with SCARB2 or independently of SCARB2. However, the cooperative effects of these receptors, and their contribution to EV71 pathogenicity in vivo, remain to be elucidated.

No MeSH data available.


Related in: MedlinePlus

Schematic showing the process of enterovirus uncoating. The mature virion (left) comprises 60 copies each of VP1, VP2, VP3 and VP4, and agenomic RNA. The virion is captured by its cognate receptor on the target cell surface and then internalized. The Ig-like domain in PVR, CAR and ICAM-1 binds to the canyon of the virus and induces a conformational change. The A-particle (middle) comprises 60 copies each of VP1, VP2 and VP3, together with the genomic RNA. The A-particle increases in diameter by approximately 4% and has a large hole near the two- and three-fold axes. The N-terminus of VP1 is externalized and anchors the virus to the membrane, where extruded VP4s associate to form a channel through the membrane. The viral RNA is then released from the hole close to the two-fold axis and enters the cell cytoplasm. Minor group human rhinoviruses bind to LDLR family members and the conformational change of the virionis induced by the low endosomal pH. The resulting empty capsid (right) comprises 60 copies each of VP1, VP2 and VP3. CAR, coxsackie-adenovirus receptor; ICAM-1, intercellular adhesion molecule-1; LDLR, low-density lipoprotein receptor.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4126179&req=5

fig1: Schematic showing the process of enterovirus uncoating. The mature virion (left) comprises 60 copies each of VP1, VP2, VP3 and VP4, and agenomic RNA. The virion is captured by its cognate receptor on the target cell surface and then internalized. The Ig-like domain in PVR, CAR and ICAM-1 binds to the canyon of the virus and induces a conformational change. The A-particle (middle) comprises 60 copies each of VP1, VP2 and VP3, together with the genomic RNA. The A-particle increases in diameter by approximately 4% and has a large hole near the two- and three-fold axes. The N-terminus of VP1 is externalized and anchors the virus to the membrane, where extruded VP4s associate to form a channel through the membrane. The viral RNA is then released from the hole close to the two-fold axis and enters the cell cytoplasm. Minor group human rhinoviruses bind to LDLR family members and the conformational change of the virionis induced by the low endosomal pH. The resulting empty capsid (right) comprises 60 copies each of VP1, VP2 and VP3. CAR, coxsackie-adenovirus receptor; ICAM-1, intercellular adhesion molecule-1; LDLR, low-density lipoprotein receptor.

Mentions: The mature virions of enteroviruses have an icosahedral shell with T=1 (quasi-T=3) symmetry; 60 copies each of VP1, VP2, VP3 and VP4; and a single-stranded RNA genome of approximately 7500 bases. VP1, VP2 and VP3 comprise wedge-shaped eight-stranded β-barrels.19 An overview of enterovirus infection is presented in Figure 1. Virus infection is initiated by attachment to a cellular receptor on the surface of a susceptible cell, followed by internalization and uncoating.20 A variety of enterovirus receptors play critical roles in these steps, such as the poliovirus receptor (PVR), coxsackie-adenovirus receptor and intercellular adhesion molecule-1 that is major group human rhinovirus receptor. These receptors all possess an immunoglobulin (Ig)-like fold. The Ig-like domains of these receptors bind to the depression around the five-fold axis, which is called a canyon. These receptors also mediate the internalization of the virus–receptor complex. Finally, the binding of the virus to the receptor triggers a conformational change in the native virion, resulting in an altered (A)-particle, which sediments at ca 135S by sucrose gradient centrifugation, lacks VP4, and harbors an externalized VP1 N-terminus. The externalized N-termini of VP1 anchors to the cell membrane and the extruded VP4s associate to form a channel through the membrane.21,22,23,24 The viral RNA is then released from a hole near the two-fold axis.25,26 The virion then becomes an ‘empty capsid', which sediments at ca 80S. Minor group human rhinoviruses bind to receptors that belong to the low-density lipoprotein receptor family:27,28,29 the low-density lipoprotein receptor binds to a star-shaped mesa on the five-fold axes, and does not induce a conformational change. After internalization of the virus, a conformational change is induced by the low endosomal pH.30 The early events during infection by other picornaviruses have been clarified, whereas those related to EV71 remain poorly understood. Recently, the three-dimensional structure of the EV71 virion was reported,31,32,33,34 and several research groups have identified molecules that enhance either the attachment of EV71 to cells or the establishment of infection,35,36,37,38,39 including sialylated glycans, heparan sulfate, annexin II (Anx2), P-selectin glycoprotein ligand-1 (PSGL-1) and scavenger receptor B2 (SCARB2) (Table 1).


Receptors for enterovirus 71.

Yamayoshi S, Fujii K, Koike S - Emerg Microbes Infect (2014)

Schematic showing the process of enterovirus uncoating. The mature virion (left) comprises 60 copies each of VP1, VP2, VP3 and VP4, and agenomic RNA. The virion is captured by its cognate receptor on the target cell surface and then internalized. The Ig-like domain in PVR, CAR and ICAM-1 binds to the canyon of the virus and induces a conformational change. The A-particle (middle) comprises 60 copies each of VP1, VP2 and VP3, together with the genomic RNA. The A-particle increases in diameter by approximately 4% and has a large hole near the two- and three-fold axes. The N-terminus of VP1 is externalized and anchors the virus to the membrane, where extruded VP4s associate to form a channel through the membrane. The viral RNA is then released from the hole close to the two-fold axis and enters the cell cytoplasm. Minor group human rhinoviruses bind to LDLR family members and the conformational change of the virionis induced by the low endosomal pH. The resulting empty capsid (right) comprises 60 copies each of VP1, VP2 and VP3. CAR, coxsackie-adenovirus receptor; ICAM-1, intercellular adhesion molecule-1; LDLR, low-density lipoprotein receptor.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4126179&req=5

fig1: Schematic showing the process of enterovirus uncoating. The mature virion (left) comprises 60 copies each of VP1, VP2, VP3 and VP4, and agenomic RNA. The virion is captured by its cognate receptor on the target cell surface and then internalized. The Ig-like domain in PVR, CAR and ICAM-1 binds to the canyon of the virus and induces a conformational change. The A-particle (middle) comprises 60 copies each of VP1, VP2 and VP3, together with the genomic RNA. The A-particle increases in diameter by approximately 4% and has a large hole near the two- and three-fold axes. The N-terminus of VP1 is externalized and anchors the virus to the membrane, where extruded VP4s associate to form a channel through the membrane. The viral RNA is then released from the hole close to the two-fold axis and enters the cell cytoplasm. Minor group human rhinoviruses bind to LDLR family members and the conformational change of the virionis induced by the low endosomal pH. The resulting empty capsid (right) comprises 60 copies each of VP1, VP2 and VP3. CAR, coxsackie-adenovirus receptor; ICAM-1, intercellular adhesion molecule-1; LDLR, low-density lipoprotein receptor.
Mentions: The mature virions of enteroviruses have an icosahedral shell with T=1 (quasi-T=3) symmetry; 60 copies each of VP1, VP2, VP3 and VP4; and a single-stranded RNA genome of approximately 7500 bases. VP1, VP2 and VP3 comprise wedge-shaped eight-stranded β-barrels.19 An overview of enterovirus infection is presented in Figure 1. Virus infection is initiated by attachment to a cellular receptor on the surface of a susceptible cell, followed by internalization and uncoating.20 A variety of enterovirus receptors play critical roles in these steps, such as the poliovirus receptor (PVR), coxsackie-adenovirus receptor and intercellular adhesion molecule-1 that is major group human rhinovirus receptor. These receptors all possess an immunoglobulin (Ig)-like fold. The Ig-like domains of these receptors bind to the depression around the five-fold axis, which is called a canyon. These receptors also mediate the internalization of the virus–receptor complex. Finally, the binding of the virus to the receptor triggers a conformational change in the native virion, resulting in an altered (A)-particle, which sediments at ca 135S by sucrose gradient centrifugation, lacks VP4, and harbors an externalized VP1 N-terminus. The externalized N-termini of VP1 anchors to the cell membrane and the extruded VP4s associate to form a channel through the membrane.21,22,23,24 The viral RNA is then released from a hole near the two-fold axis.25,26 The virion then becomes an ‘empty capsid', which sediments at ca 80S. Minor group human rhinoviruses bind to receptors that belong to the low-density lipoprotein receptor family:27,28,29 the low-density lipoprotein receptor binds to a star-shaped mesa on the five-fold axes, and does not induce a conformational change. After internalization of the virus, a conformational change is induced by the low endosomal pH.30 The early events during infection by other picornaviruses have been clarified, whereas those related to EV71 remain poorly understood. Recently, the three-dimensional structure of the EV71 virion was reported,31,32,33,34 and several research groups have identified molecules that enhance either the attachment of EV71 to cells or the establishment of infection,35,36,37,38,39 including sialylated glycans, heparan sulfate, annexin II (Anx2), P-selectin glycoprotein ligand-1 (PSGL-1) and scavenger receptor B2 (SCARB2) (Table 1).

Bottom Line: This mouse model facilitates the in vivo investigation of many issues related to EV71.These molecules also contribute to viral infection in vitro either by interacting with SCARB2 or independently of SCARB2.However, the cooperative effects of these receptors, and their contribution to EV71 pathogenicity in vivo, remain to be elucidated.

View Article: PubMed Central - PubMed

Affiliation: Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, The University of Tokyo , Tokyo 108-8639, Japan.

ABSTRACT
Enterovirus 71 (EV71) is one of the major causative agents of hand, foot and mouth disease (HFMD). Occasionally, EV71 infection is associated with severe neurological diseases, such as acute encephalitis, acute flaccid paralysis and cardiopulmonary failure. Several molecules act as cell surface receptors that stimulate EV71 infection, including scavenger receptor B2 (SCARB2), P-selectin glycoprotein ligand-1 (PSGL-1), sialylated glycan, heparan sulfate and annexin II (Anx2). SCARB2 plays critical roles in attachment, viral entry and uncoating, and it can facilitate efficient EV71 infection. The three-dimensional structures of the mature EV71 virion, procapsid and empty capsid, as well as the exofacial domain of SCARB2, have been elucidated. This structural information has greatly increased our understanding of the early steps of EV71 infection. Furthermore, SCARB2 plays essential roles in the development of EV71 neurological disease in vivo. Adult mice are not susceptible to infection by EV71, but transgenic mice that express human SCARB2 become susceptible to EV71 infection and develop similar neurological diseases to those found in humans. This mouse model facilitates the in vivo investigation of many issues related to EV71. PSGL-1, sialylated glycan, heparan sulfate and Anx2 are attachment receptors, which enhance viral infection by retaining the virus on the cell surface. These molecules also contribute to viral infection in vitro either by interacting with SCARB2 or independently of SCARB2. However, the cooperative effects of these receptors, and their contribution to EV71 pathogenicity in vivo, remain to be elucidated.

No MeSH data available.


Related in: MedlinePlus