Lipoprotein lipase mediates hepatitis C virus (HCV) cell entry and inhibits HCV infection

Area of Science:

• Virology
• Cell Biology
• Biochemistry

Background:

• Hepatitis C virus (HCV) cell entry mechanisms are not fully understood.
• CD-81 and SR-BI are known HCV receptors, but HCV in patient sera is lipoprotein-associated.
• The role of lipoproteins in HCV infection requires further investigation.

Purpose of the Study:

• To elucidate the role of lipoprotein lipase (LPL) in hepatitis C virus (HCV) cell entry.
• To investigate the mechanism by which LPL influences HCV infectivity.

Main Methods:

• Investigated LPL's role in mediating HCV binding and internalization using various cell types.
• Assessed the necessity of LPL's dimeric structure and catalytic activity for HCV uptake.
• Evaluated the effect of exogenous LPL, anti-LPL antibodies, and LPL inhibitors on HCV infection in vitro.
• Examined the impact of anti-apolipoprotein B (ApoB) antibodies on HCV infection.

Main Results:

• Lipoprotein lipase (LPL) mediates the binding and internalization of HCV by bridging virus-associated lipoproteins to cell surface heparan sulfate proteoglycans (HSPG).
• LPL's dimeric structure and enzymatic activity are essential for this HCV uptake process.
• Exogenous LPL unexpectedly inhibits HCV infection in vitro, an effect dependent on LPL activity and blocked by anti-ApoB antibodies.
• LPL appears to mediate a non-productive uptake of HCV, similar to hepatic clearance of triglyceride-rich lipoproteins (TRL).

Conclusions:

• Lipoprotein lipase (LPL) plays a dual role in HCV infection, mediating cell entry while also inhibiting productive infection.
• LPL-mediated HCV uptake is analogous to TRL clearance, suggesting a mechanism for non-productive virus entry.
• These findings offer new insights into HCV cell entry and suggest LPL as a potential modulator of HCV infectivity in vivo.