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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

EV71 infection mediated by SCARB2 and other receptors. SCARB2 delivers β-GC from the ER to the lysosomes under physiological conditions. SCARB2 is abundant in the lysosomal and endosomal compartments, and it also shuttles to the plasma membrane where it encounters EV71. After binding the virus on the cell surface, the virus–receptor complex is internalized via the clathrin-mediated endocytosis pathway. In the endosome or lysosome, where the pH is low, the virus initiates a conformational change that leads to uncoating. PSGL-1 can bind EV71 and internalize via caveolin-mediated endocytosis, but PSGL-1 cannot initiate uncoating. Anx2, heparan sulfate, and sialylated glycans can also bind EV71. However, the mechanism of internalization and uncoating is unknown. They may deliver EV71 to SCARB2 or they may establish infections via their own mechanisms. β-GC, β-glucocerebrosidase; ER, endoplasmic reticulum.
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fig2: EV71 infection mediated by SCARB2 and other receptors. SCARB2 delivers β-GC from the ER to the lysosomes under physiological conditions. SCARB2 is abundant in the lysosomal and endosomal compartments, and it also shuttles to the plasma membrane where it encounters EV71. After binding the virus on the cell surface, the virus–receptor complex is internalized via the clathrin-mediated endocytosis pathway. In the endosome or lysosome, where the pH is low, the virus initiates a conformational change that leads to uncoating. PSGL-1 can bind EV71 and internalize via caveolin-mediated endocytosis, but PSGL-1 cannot initiate uncoating. Anx2, heparan sulfate, and sialylated glycans can also bind EV71. However, the mechanism of internalization and uncoating is unknown. They may deliver EV71 to SCARB2 or they may establish infections via their own mechanisms. β-GC, β-glucocerebrosidase; ER, endoplasmic reticulum.

Mentions: SCARB2 (also known as lysosomal integral membrane protein II, LGP85, or CD36b like-2) belongs to the CD36 family, which includes CD36 and scavenger receptor B, member 1 (SR-BI and its splice variant SR-BII).49 SCARB2 is a type III double-transmembrane protein, which comprises 478 amino acids, a large exofacial domain (an extracellular domain when SCARB2 is presented at the cell surface or a luminal domain when presented in the endosomal compartment), and short cytoplasmic domains at the amino- and carboxy-termini (Figure 2).49 SCARB2 participates in membrane transportation and in the reorganization of the endosomal/lysosomal compartment.50,51,52 The best-known physiological function of SCARB2 is mediation of β-glucocerebrosidase delivery from the endoplasmic reticulum to lysosomes.53 Thus, the majority of SCARB2 is localized in the lysosomal membrane. Yamayoshi et al.37,54 showed that SCARB2 on the cell surface binds to EV71; the EV71 is then internalized, possibly as a SCARB2–EV71 complex. These observations suggest that (at least) a small proportion of SCARB2 molecules shuttle between the endosomal/lysosomal compartments and the plasma membrane, where they act as EV71 receptors (Figure 2).


Receptors for enterovirus 71.

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

EV71 infection mediated by SCARB2 and other receptors. SCARB2 delivers β-GC from the ER to the lysosomes under physiological conditions. SCARB2 is abundant in the lysosomal and endosomal compartments, and it also shuttles to the plasma membrane where it encounters EV71. After binding the virus on the cell surface, the virus–receptor complex is internalized via the clathrin-mediated endocytosis pathway. In the endosome or lysosome, where the pH is low, the virus initiates a conformational change that leads to uncoating. PSGL-1 can bind EV71 and internalize via caveolin-mediated endocytosis, but PSGL-1 cannot initiate uncoating. Anx2, heparan sulfate, and sialylated glycans can also bind EV71. However, the mechanism of internalization and uncoating is unknown. They may deliver EV71 to SCARB2 or they may establish infections via their own mechanisms. β-GC, β-glucocerebrosidase; ER, endoplasmic reticulum.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig2: EV71 infection mediated by SCARB2 and other receptors. SCARB2 delivers β-GC from the ER to the lysosomes under physiological conditions. SCARB2 is abundant in the lysosomal and endosomal compartments, and it also shuttles to the plasma membrane where it encounters EV71. After binding the virus on the cell surface, the virus–receptor complex is internalized via the clathrin-mediated endocytosis pathway. In the endosome or lysosome, where the pH is low, the virus initiates a conformational change that leads to uncoating. PSGL-1 can bind EV71 and internalize via caveolin-mediated endocytosis, but PSGL-1 cannot initiate uncoating. Anx2, heparan sulfate, and sialylated glycans can also bind EV71. However, the mechanism of internalization and uncoating is unknown. They may deliver EV71 to SCARB2 or they may establish infections via their own mechanisms. β-GC, β-glucocerebrosidase; ER, endoplasmic reticulum.
Mentions: SCARB2 (also known as lysosomal integral membrane protein II, LGP85, or CD36b like-2) belongs to the CD36 family, which includes CD36 and scavenger receptor B, member 1 (SR-BI and its splice variant SR-BII).49 SCARB2 is a type III double-transmembrane protein, which comprises 478 amino acids, a large exofacial domain (an extracellular domain when SCARB2 is presented at the cell surface or a luminal domain when presented in the endosomal compartment), and short cytoplasmic domains at the amino- and carboxy-termini (Figure 2).49 SCARB2 participates in membrane transportation and in the reorganization of the endosomal/lysosomal compartment.50,51,52 The best-known physiological function of SCARB2 is mediation of β-glucocerebrosidase delivery from the endoplasmic reticulum to lysosomes.53 Thus, the majority of SCARB2 is localized in the lysosomal membrane. Yamayoshi et al.37,54 showed that SCARB2 on the cell surface binds to EV71; the EV71 is then internalized, possibly as a SCARB2–EV71 complex. These observations suggest that (at least) a small proportion of SCARB2 molecules shuttle between the endosomal/lysosomal compartments and the plasma membrane, where they act as EV71 receptors (Figure 2).

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