Antibodies against hepatitis C virus-like particles and viral clearance in acute and chronic hepatitis C.
We recently described the efficient assembly of hepatitis C virus (HCV) structural proteins into HCV-like particles (HCV-LPs) in insect cells. These noninfectious HCV-LPs have similar morphologic and biophysical properties as putative virions isolated from HCV-infected humans and can induce a broadly directed immune response in animal models. The HCV envelope proteins of HCV-LPs are presumably presented in a native, virion-like conformation and may therefore interact with antienvelope antibodies directed against conformational epitopes. In this study, HCV-LPs were used as capture antigens in an enzyme-linked immunosorbent assay (ELISA) to detect and quantify antibodies against HCV structural proteins in patients with acute and chronic hepatitis C. High titers of anti-HCV-LP antibodies were detected in patients chronically infected with HCV genotypes 1 to 6. In contrast to individuals with chronic hepatitis C, patients with acute self-limited hepatitis C displayed only a transient and weak seroreactivity against HCV-LPs. Patients with chronic HCV infection successfully treated with interferon demonstrated a gradual decline of anti-HCV-LP titers during or subsequent to viral clearance. Sustained interferon responders were characterized by significantly higher pretreatment levels of anti-HCV-LP antibodies as compared with nonresponders (P =.0001). In conclusion, HCV infection is associated with limited humoral immunity against the envelope proteins present on the HCV-LPs. An HCV-LP-based ELISA may be a useful diagnostic tool to distinguish acute hepatitis C from chronic HCV infection with exacerbation, and to predict viral clearance in response to interferon.
Baumert
T F
TF
Department of Medicine II, University of Freiburg Medical School, Germany. tbaumert@ukl.uni-freiberg.de
Wellnitz
S
S
Aono
S
S
Satoi
J
J
Herion
D
D
Tilman Gerlach
J
J
Pape
G R
GR
Lau
J Y
JY
Hoofnagle
J H
JH
Blum
H E
HE
Liang
T J
TJ
D000208:Acute Disease; D000998:Antiviral Agents / Q000627:therapeutic use; D004797:Enzyme-Linked Immunosorbent Assay; D016174:Hepacivirus / Q000276:immunology* / Q000302:isolation & purification*; D006526:Hepatitis C / Q000188:drug therapy / Q000276:immunology* / Q000821:virology; D018937:Hepatitis C Antibodies / Q000032:analysis*; D019698:Hepatitis C, Chronic / Q000188:drug therapy / Q000276:immunology* / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use; D014771:Virion / Q000276:immunology*
D000998:Antiviral Agents; D018937:Hepatitis C Antibodies; D016898:Interferon-alpha