Enterovirus A71 does not meet the uncoating receptor SCARB2 at the cell surface

Area of Science:

• Virology
• Cell Biology
• Molecular Biology

Background:

• Enterovirus A71 (EV-A71) infection relies on cellular receptors.
• P-selectin glycoprotein ligand-1 (PSGL-1) and scavenger receptor class B member 2 (SCARB2) are known EV-A71 receptors.
• Previous studies suggested cell surface expression of these receptors.

Purpose of the Study:

• To investigate the precise roles of PSGL-1 and SCARB2 in EV-A71 entry.
• To determine the cell surface expression of SCARB2 in different cell types.
• To elucidate the stage at which SCARB2 interacts with EV-A71.

Main Methods:

• Analysis of SCARB2 expression in Jurkat cells (cytoplasmic vs. cell surface).
• Utilizing PSGL-1 and SCARB2 knockout cells to assess infection and attachment.
• Examining SCARB2 expression and function in various EV-A71-susceptible cell lines (e.g., RD cells).

Main Results:

• SCARB2 was found intracellularly, not on the surface of Jurkat cells.
• EV-A71 attachment to Jurkat cells required PSGL-1, while infection needed both PSGL-1 and SCARB2.
• SCARB2 was absent from the surface of RD cells and other susceptible lines, indicating an alternative attachment receptor.
• SCARB2 is crucial for infection but not attachment in these cells, localizing to lysosomes/late endosomes for virion uncoating.

Conclusions:

• EV-A71 attachment and internalization likely involve a cell surface receptor distinct from SCARB2.
• SCARB2's essential role in EV-A71 infection occurs post-internalization, within lysosomes/late endosomes.
• The interaction between EV-A71 and SCARB2 is intracellular, facilitating acid-dependent virion uncoating.