Table 1.
Role of the major apolipoproteins in the HCV life cycle.
| Name | Physiological role | Role in HCV life cycle | Reference |
|---|---|---|---|
| ApoA-I (exchangeable apolipoprotein) | Structural role: major component of HDL | Structural role: component of the LVP | (12, 15, 19, 49, 50) |
| HDL metabolism: involved in HDL maturation by activating LCAT | HCV morphogenesis: redundantly participate in the production of infectious HCV particles | ||
| Reverse cholesterol transport: from peripheral tissues to liver through interaction with SR-BI and ABCA1 (cholesterol efflux) | |||
| ApoB-100 (non exchangeable apolipoprotein) | Structural role: major component of VLDL and LDL | Structural role: major component of the LVP | (12, 15, 19, 33, 34, 41, 42, 49) |
| Triglyceride transport: involved in VLDL synthesis and clearance through interaction with LDLR | HCV entry: mediates LVP binding through interaction with SR-BI | ||
| Cholesterol transport: transfer of LDL-cholesterol in cells through LDLR | HCV morphogenesis: LVP synthesis and secretion | ||
| ApoC-I (exchangeable apolipoprotein) | Structural role: component of VLDL and HDL | Structural role: component of the LVP | (12, 15, 19, 35) |
| HDL metabolism: LCAT activator | HCV entry: enhance HCV infectivity through complex interaction with SR-BI | ||
| ApoC-II (exchangeable apolipoprotein) | Structural role: component of VLDL and HDL | Structural role: component of the LVP | (12, 15, 19, 37) |
| Triglyceride metabolism: LPL activator | HCV entry: physiological HCV entry inhibitor by activating LPL | ||
| HCV morphogenesis: redundantly participate in the production of infectious HCV particles | |||
| ApoC-III (exchangeable polipoprotein) | Structural role: component of VLDL and HDL | Structural role: component of the LVP | (12, 15, 19, 38) |
| Triglyceride metabolism: LPL inhibitor | HCV entry: enhance HCV entry by inhibiting LPL | ||
| HCV morphogenesis: redundantly participate in the production of infectious HCV particles | |||
| ApoE (exchangeable apolipoprotein) | Structural role: major component of VLDL and HDL | Structural role: major component of the LVP | (12, 15, 19, 23–34, 43–61) |
| Triglyceride transport: involved in VLDL synthesis and clearance trough interaction with HSPG, LRP1, and LDLR | HCV entry: mediates LVP binding through interaction with HSPG, LDLR, and SR-BI. Involved in cell-to-cell transmission | ||
| HDL metabolism: involved in reverse cholesterol transport | HCV morphogenesis: crucial role in HCV assembly by interaction with NS5A, E1, and E2, necessary for the production and maturation of infectious HCV particles | ||
ABCA1, ATP-binding cassette A1; Apo, apolipoprotein; HDL, high-density lipoprotein; HSPG, heparan sulfate proteoglycan; LCAT, lecithin cholesterol acyltransferase; LDL, low-density lipoprotein; LDLR, low-density lipoprotein receptor; LPL, lipoprotein lipase; LRP1, LDLR-related protein 1; LVP, lipo-viro-particle; SR-BI, scavenger receptor class B type I; VLDL, very-low-density lipoprotein; HCV, hepatitis C virus.