Peptide immunogen mimicry of putative E1 glycoprotein-specific epitopes in hepatitis C virus.
Hepatitis C virus (HCV) accounts for most cases of acute and chronic non-A and non-B hepatitis with serious consequences that may lead to hepatocellular carcinoma. The putative envelope glycoproteins (E1 and E2) of HCV probably play a role in the pathophysiology of the virus. In order to map the immunodominant domains of the E1 glycoprotein, two epitopes from amino acid residues 210 to 223 (P1) and 315 to 327 (P2) were predicted from the HCV sequence. Immunization of mice with the synthetic peptides conjugated to bovine serum albumin induced an antibody response, and the antisera immunoprecipitated the E1 glycoprotein (approximately 33 kDa) of HCV expressed by recombinant vaccinia virus. A panel of HCV-infected human sera was also tested with the synthetic peptides by enzyme-linked immunosorbent assay for epitope-specific responses. Of 38 infected serum samples, 35 (92.1%) demonstrated a spectrum of reactivity to the P2 peptide. On the other hand, only 17 of 38 (44.7%) serum samples were reactive to the P1 peptide. Strains of HCV exhibit a striking genomic diversity. The predicted P1 epitope showed localization in the sequence-variable region, and the P2 epitope localized in a highly conserved domain. Results from this study suggest that the E1 glycoprotein of HCV contains at least two potential antigenic epitopes. Synthetic peptides corresponding to these epitopes and antisera to these peptides may serve as the monospecific immunological reagents to further determine the role of E1 glycoprotein in HCV infection.
Ray
R
R
Division of Infectious Diseases and Immunology, St. Louis University Health Sciences Center, Missouri 63110.
Khanna
A
A
Lagging
L M
LM
Meyer
K
K
Choo
Q L
QL
Ralston
R
R
Houghton
M
M
Becherer
P R
PR
D000595:Amino Acid Sequence; D016174:Hepacivirus / Q000276:immunology*; D006508:Hepatitis Antibodies / Q000096:biosynthesis / Q000276:immunology; D006526:Hepatitis C / Q000276:immunology; D006801:Humans; D007106:Immune Sera; D016056:Immunodominant Epitopes / Q000276:immunology*; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000276:immunology*
C087035:E1 protein, Hepatitis C virus; D006508:Hepatitis Antibodies; D007106:Immune Sera; D016056:Immunodominant Epitopes; D010455:Peptides; D014759:Viral Envelope Proteins