In vitro interaction between hepatitis C virus (HCV) envelope glycoprotein E2 and serum lipoproteins (LPs) results in enhanced cellular binding of both HCV E2 and LPs.
Hepatitis C virus (HCV) particles in serum associate with lipoproteins (LPs), and the low-density lipoprotein receptor (LDLr) has been implicated in virus attachment and entry into cells. To clarify the basis of interactions between virus and LPs, we determined whether HCV interacts with human LPs via its envelope glycoprotein E2. The binding of serum-derived virus-like particles, HCV E2, and HCV E2-LP complexes to CD81 and LDLr was studied. Incubation of HCV E2 protein with human and bovine LPs (very low density, low density, and high density) enhanced the binding of both HCV E2 and LPs to CD4+ lymphoblastoid (MOLT-4) cells, foreskin fibroblasts, and hepatocytes. The binding of HCV E2 to MOLT-4 cells was not enhanced when it was preincubated with lipid-free apoprotein B, which suggests that E2 interacts with the lipid moiety of human lipoproteins. The LP interaction was specific for HCV E2--incubation of HIV gp120 with LPs did not enhance gp120 binding to MOLT-4 cells. The enhanced HCV E2 binding required expression of both human CD81 and LDLr. These data suggest that HCV E2 associates with LDL and that the resulting complex enhances binding of both ligands to cells, which may contribute to the finding that HCV-infected individuals have significantly lower levels of LDL than control subjects.
Wunschmann
Sabina
S
Department of Internal Medicine, Iowa City Veterans Administration Medical Center, University of Iowa College of Medicine, Iowa City, IA 52242, USA.
Muller
Hubert M
HM
Stipp
Christopher S
CS
Hemler
Martin E
ME
Stapleton
Jack T
JT
D015703:Antigens, CD / Q000502:physiology; D004797:Enzyme-Linked Immunosorbent Assay; D016174:Hepacivirus / Q000472:pathogenicity / Q000502:physiology*; D006526:Hepatitis C / Q000276:immunology*; D006801:Humans; D066298:In Vitro Techniques; D008074:Lipoproteins / Q000502:physiology; D011973:Receptors, LDL / Q000502:physiology; D060225:Tetraspanin 28; D014759:Viral Envelope Proteins / Q000502:physiology*
D015703:Antigens, CD; C554798:CD81 protein, human; D008074:Lipoproteins; D011973:Receptors, LDL; D060225:Tetraspanin 28; D014759:Viral Envelope Proteins; C091015:glycoprotein E2, Hepatitis C virus