Syndecan 2 proteoglycan serves as a hepatitis B virus cell attachment receptor

Area of Science:

• Hepatology and Virology
• Cell Biology
• Molecular Medicine

Background:

• Hepatitis B virus (HBV) infection relies on cell surface receptors for entry.
• Human apolipoprotein E (apoE) and low-density lipoprotein receptor (LDLR) are implicated in HBV infection.
• Heparan sulfate proteoglycans (HSPGs), including syndecans and glypicans, are known HBV attachment receptors.

Purpose of the Study:

• To identify and characterize novel cell attachment receptors involved in HBV infection.
• To investigate the role of syndecan-2 (SDC2) in mediating HBV entry into hepatocytes.

Main Methods:

• Small interfering RNA (siRNA) to silence SDC2 expression.
• Gene knockout of SDC2 in hepatocytes.
• Ectopic expression of SDC2 to restore function.
• Validation using primary human hepatocytes.
• Assessment of HBV preS1 and apoE binding and HBV attachment.

Main Results:

• SDC2 acts as a cell attachment receptor promoting HBV infection.
• Silencing or knocking out SDC2 significantly reduced HBV infection susceptibility.
• Ectopic SDC2 expression fully restored HBV infection in deficient cells.
• SDC2 deficiency decreased HBV preS1 and apoE binding to hepatocytes.
• SDC2 facilitates HBV attachment to the hepatocyte surface.

Conclusions:

• SDC2 is a critical cell attachment receptor for Hepatitis B virus.
• SDC2 promotes HBV infection by interacting with viral envelope proteins apoE and preS1.
• Targeting SDC2 may offer a novel strategy to inhibit HBV infection.