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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

Crystal structure of SCARB2. The crystal structure of the SCARB2 ectodomain (PDB: 4F7B) was determined by X-ray diffraction. The important amino acid region responsible for binding to EV71 (amino acids 142–204)56 is shown in yellow. Arrows represent β-strands and tubes represent α-helices. Black, red and blue sticks and balls represent the carbohydrate chains.
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fig3: Crystal structure of SCARB2. The crystal structure of the SCARB2 ectodomain (PDB: 4F7B) was determined by X-ray diffraction. The important amino acid region responsible for binding to EV71 (amino acids 142–204)56 is shown in yellow. Arrows represent β-strands and tubes represent α-helices. Black, red and blue sticks and balls represent the carbohydrate chains.

Mentions: Recently, the crystal structure of the SCARB2 ectodomain was elucidated.55 In contrast to PVR and coxsackie-adenovirus receptor, SCARB2 lacks an Ig-like fold, but comprises an anti-parallel β-barrel with many short α-helical segments. There are two α-helices at the bottom of the β-barrel fold, i.e., α1 and α15, which are connected to the N-terminal and C-terminal transmembrane regions, respectively (Figure 3). The head region at the top comprises a three α-helix bundle (which is formed by α-helices 4, 5 and 7), two other short helices (α2 and α14) and the β7 strand. Nine N-glycosylation sites are present in SCARB2, but the carbohydrate chains are localized in the middle or lower regions (the head region is free of carbohydrate chains). The binding site of β-glucocerebrosidase, the natural ligand of SCARB2, has been mapped to this head region. Mutagenesis and model reconstitution studies using other members of the CD36 family suggest that this apical face also acts as the binding site for their respective ligands.


Receptors for enterovirus 71.

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

Crystal structure of SCARB2. The crystal structure of the SCARB2 ectodomain (PDB: 4F7B) was determined by X-ray diffraction. The important amino acid region responsible for binding to EV71 (amino acids 142–204)56 is shown in yellow. Arrows represent β-strands and tubes represent α-helices. Black, red and blue sticks and balls represent the carbohydrate chains.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig3: Crystal structure of SCARB2. The crystal structure of the SCARB2 ectodomain (PDB: 4F7B) was determined by X-ray diffraction. The important amino acid region responsible for binding to EV71 (amino acids 142–204)56 is shown in yellow. Arrows represent β-strands and tubes represent α-helices. Black, red and blue sticks and balls represent the carbohydrate chains.
Mentions: Recently, the crystal structure of the SCARB2 ectodomain was elucidated.55 In contrast to PVR and coxsackie-adenovirus receptor, SCARB2 lacks an Ig-like fold, but comprises an anti-parallel β-barrel with many short α-helical segments. There are two α-helices at the bottom of the β-barrel fold, i.e., α1 and α15, which are connected to the N-terminal and C-terminal transmembrane regions, respectively (Figure 3). The head region at the top comprises a three α-helix bundle (which is formed by α-helices 4, 5 and 7), two other short helices (α2 and α14) and the β7 strand. Nine N-glycosylation sites are present in SCARB2, but the carbohydrate chains are localized in the middle or lower regions (the head region is free of carbohydrate chains). The binding site of β-glucocerebrosidase, the natural ligand of SCARB2, has been mapped to this head region. Mutagenesis and model reconstitution studies using other members of the CD36 family suggest that this apical face also acts as the binding site for their respective ligands.

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