Immune response to GOR, a marker for non-A, non-B hepatitis and its correlation with hepatitis C virus infection

Abstract

Recently, identification and molecular cloning of a host cellular gene designated GOR from chimpanzees experimentally infected with non-A, non-B hepatitis (NANBH) agent was reported. It was further demonstrated that there is a close association between the immune response to an antigenic peptide of GOR (GOR2) and NANBH. In order to define the specificity of the immune response, in the present study we have identified an additional epitope in the GOR gene sequence, upstream from GOR2, and studied its correlation with the immune response to hepatitis C virus (HCV) in NANBH patients. An enzyme-linked immunoassay (EIA) was developed which utilizes synthetic peptides designated spGOR346 and spGOR2 as the serological target for the detection of anti-GOR antibodies in patient serum samples from various hepatic and non-hepatic disease categories. GOR peptides identified 80-90% of the NANBH samples that were positive for HCV C100-3 and about 70% of the NANBH samples that were positive by Abbott prototype second-generation HCV antibody assay. Among a normal donor population(s), only 2-3% of the samples were positive for antibodies to GOR sequences, whereas from the patient categories unrelated to viral hepatitis as well as various nonhepatic diseases, the immune response to both GOR peptides was closely associated with the presence of antibodies to HCV. The data indicate that antibodies to GOR is a marker associated with NANBH.

Serum Immunoglobulin G Antibodies to the GOR Autoepitope Are Present in Patients with Occult Hepatitis C Virus (HCV) Infection despite Lack of HCV-Specific Antibodies

“…The frequency of anti-GOR IgG in patients with occult HCV infection was significantly lower than the 63.6% GOR IgG antibody reactivity found in patients with chronic hepatitis C, which is similar to the frequency reported by several authors in patients with overt HCV infection (10,12,14,16,21). Also, anti-GOR levels were greater in patients with chronic hepatitis C than in patients with occult HCV infection.…”

“…Thus, despite the repeated absence of serum anti-HCV antibodies as determined by commercial immunoassays, anti-GOR IgG could be found in patients with occult HCV infection. Most studies have detected anti-GOR reactivity only in HCV-seropositive patients (6,9,14,15,21,31). However, a few reports identified anti-HCVnegative individuals who tested positive for anti-GOR (9,14), including blood donors (7,33), although those studies did not exclude the presence of occult HCV infection.…”

“…The detection of antibodies to the GOR47-1 autoepitope (anti-GOR) was first described in sera from non-A, non-B hepatitis cases (16). Since then, several studies have shown that the presence of anti-GOR is almost restricted to anti-HCV-positive individuals (14,15). The sequence of the GOR (GOR47-1) epitope has partial homology with the HCVencoded core protein sequence (17); both sequences show high degrees of conservation of residues essential for antibody binding (34).…”

Serological reactivity and viral genotypes in hepatitis C virus infection

“…In the present study, we examined the sera of patients infected with different HCV genotypes to evaluate whether they behave differently when tested with currently available anti-HCV immunoblotting assays. In addition, the sera were examined for the presence of anti-GOR antibody (9, 10), which has been proposed as a marker of HCV infection severity (8). As the GOR epitope is a nuclear antigen that shares a short amino acid sequence with the core protein of HCV, anti-GOR antibodies are believed to represent HCV-induced autoantibodies (10).…”