glycoprotein-e2--hepatitis-c-virus and Acute-Disease

In view of the high rate of chronicity of acute hepatitis C and the low efficacy of interferon (IFN) treatment in advanced liver disease, it may be beneficial to treat patients during the acute phase of the infection. Here we assessed the effects of variable-dose IFNalpha-2b treatment in haemodialysis patients with acute hepatitis C virus (HCV) infection, and identified factors that may predict response to this therapy. The study population included 67 patients, but 14 were excluded due to side-effects or because they were lost to follow-up. Seventeen patients who received no specific treatment were used as controls (Group 1). Sixteen and 20 patients received low-(3 MU) and high-dose (6-10 MU) IFNalpha-2b three times weekly for 3 months (Groups 2 and 3, respectively). Virological end-of-treatment response (ETR) was observed in 1 (5.6%), 13 (56.5%), and 17 (65.4%) patients in Groups 1, 2, and 3, respectively, and virological sustained response (SR) was observed in 1 (5.6%), 6 (26.1%), and 13 (50%) patients in the three groups. The rates of virological ETR and SR in the treated groups were significantly higher than those of the control group (P < 0.01 for all comparisons). In multivariate logistic regression analysis, single stranded confirmational polymorphysm (SSCP) band number (P=0.02) was the only factor that was significantly associated with virological SR. In conclusion, IFN-alpha treatment initiated during the acute phase of HCV infection is associated with a higher rate of virological ETR and SR. This study suggested that quasispecies heterogeneity has predictive value with regard to virological SR.

Topics: 5' Untranslated Regions; Acute Disease; Adult; Antiviral Agents; Female; Genotype; Hepacivirus; Hepatitis C; Humans; Interferon alpha-2; Interferon-alpha; Male; Middle Aged; Polymerase Chain Reaction; Polymorphism, Single-Stranded Conformational; Predictive Value of Tests; Recombinant Proteins; Renal Dialysis; RNA, Viral; Treatment Outcome; Viral Envelope Proteins

The extremely high rate of chronicity to hepatitis C virus (HVC) infection suggests an inefficient immune response. The humoral immune response to HCV was evaluated in 60 patients with chronic HCV infection and in 12 patients acutely infected with HCV.. A number of recombinant HCV antigens including the core, envelope 2 (E2), nonstructural (NS) 3, NS4, and NS5 proteins, and NS4a and E2-HVR-1 peptides were used in enzyme-linked immunoassays.. Immunoglobulin (Ig) G antibody responses to these viral antigens, except for the HCV core, were highly restricted to the IgG1 isotype. The prevalence of antibodies of the IgG1 isotype specific for the HCV core, E2, E2-HVR1, NS3 (helicase domain), NS4, and NS5 antigens was 97%, 98%, 28%, 88%, 33%, and 68%, respectively. Antibodies of the IgG3 isotype specific for E2, E2-HVR-1, NS3, NS4, and NS5 were detected in a minority of serum samples. The IgG2 and IgG4 isotypes were rarely if ever detected. Furthermore, antibody responses to HCV viral antigens were of relatively low titer and, with the exception of anti-HCV core, were delayed in appearance until the chronic phase of infection.. The IgG1 restriction, low titer, and delayed appearance of antibody responses elicited during HCV infection suggest that the immunogenicity of HCV proteins is limited in the context of natural infection. Inasmuch as recombinant HCV viral antigens perform as relatively normal immunogens in small animals, we suggest that the defective humoral immune responses during HCV infection may be attributable to an "immune avoidance" strategy.

Topics: Acute Disease; Antibody Formation; Enzyme-Linked Immunosorbent Assay; Hepatitis C; Hepatitis C Antigens; Hepatitis C, Chronic; Humans; Immunoglobulin G; Kinetics; Viral Core Proteins; Viral Envelope Proteins

Hepatitis C virus (HCV) can be cleared naturally in a subset of individuals. However, the asymptomatic nature of acute HCV infection makes the study of the early immune response and defining the correlates of protection challenging. Despite this, there is now strong evidence implicating the humoral immune response, specifically neutralising antibodies, in determining the clearance or chronicity outcomes of primary HCV infection. In general, immunoglobulin G (IgG) plays the major role in viral neutralisation. However, there are limited investigations of anti-HCV envelope protein 2 (E2) isotypes (IgM, IgG, IgA) and IgG subclasses (IgG1-4) in early HCV infection. In this study, using a rare cohort of 14 very recently HCV-infected individuals (4-45 days) with varying disease outcome (

Topics: Acute Disease; Adult; Antibodies, Neutralizing; Antibody Formation; Binding Sites, Antibody; Female; Hepacivirus; Hepatitis C; Hepatitis C Antibodies; Humans; Immunity, Humoral; Immunoglobulin G; Immunoglobulin M; Longitudinal Studies; Male; Prospective Studies; Viral Envelope Proteins; Young Adult

Broadly neutralizing antibodies have been associated with spontaneous clearance of the hepatitis C infection as well as viral persistence by immune escape. Further study of neutralizing antibody epitopes is needed to unravel pathways of resistance to virus neutralization, and to identify conserved regions for vaccine design. All reported broadly neutralizing antibody (BNAb) epitopes in the HCV Envelope (E2) glycoprotein were identified. The critical contact residues of these epitopes were mapped onto the linear E2 sequence. All publicly available E2 sequences were then downloaded and the contact residues within the BNAb epitopes were assessed for the level of conservation, as well as the frequency of occurrence of experimentally-proven resistance mutations. Epitopes were also compared between two sequence datasets obtained from samples collected at well-defined time points from acute (<180days) and chronic (>180days) infections, to identify any significant differences in residue usage. The contact residues for all BNAbs were contained within 3 linear regions of the E2 protein sequence. An analysis of 1749 full length E2 sequences from public databases showed that only 10 out of 29 experimentally-proven resistance mutations were present at a frequency >5%. Comparison of subtype 1a viral sequences obtained from samples collected during acute or chronic infection revealed significant differences at positions 610 and 655 with changes in residue (p<0.05), and at position 422 (p<0.001) with a significant difference in variability (entropy). The majority of experimentally-described escape variants do not occur frequently in nature. The observed differences between acute and chronically isolated sequences suggest constraints on residue usage early in infection.

Topics: Acute Disease; Amino Acid Sequence; Antibodies, Monoclonal; Antibodies, Neutralizing; Epitope Mapping; Epitopes; Gene Expression; Hepacivirus; Hepatitis C Antibodies; Hepatitis C, Chronic; Humans; Immune Evasion; Models, Molecular; Mutation Rate; Protein Structure, Secondary; Viral Envelope Proteins

Hepatitis C virus (HCV) envelope genes encoding glycoproteins E1 and E2 exhibits a high degree of variability that gives rise to differing phenotypic traits; including alterations in receptor-binding affinity and immune recognition and escape. This study aims to elucidate the relationship of the evolutionary patterns for HCV envelope glycoproteins to viral persistence.. HCV quasispecies were characterized in specimens collected every two to six months from a cohort of acutely HCV-infected subjects. We evaluated two individuals who spontaneously cleared viremia and three individuals with persistent viremia by cloning 33 1-kb amplicons that spanned E1 and the 5' half of E2; including hypervariable region 1 (HVR1). To detect representative variants for sequencing thirty-three cloned cDNAs representing each specimen were assessed by a method that combined analysis of a single-stranded conformational polymorphism (SSCP) method and heteroduplex analysis (HDA). For each patient, the rates of both synonymous and nonsynonymous substitutions for the E1, HVR1 and E2 regions outside HVR1 were evaluated. The amino acid sequences and predicted antigenic profiles were analyzed.. The genetic diversity within HVR1 was consistently higher than that in the E1 and E2 regions outside HVR1 in individuals with persistent viremia, but did not change markedly over time in those with clearance of viremia. For individuals with persistent viremia, the rate of nonsynonymous substitutions within the HVR1 region predominated and gradually increased, compared to that in the E1 and E2 regions outside HVR1. By contrast, the rates of both nonsynonymous and synonymous substitutions for the E1 and E2 regions, including HVR1, were consistently lower in individuals with clearance of viremia. HVR1 had a higher antigenic variable and lower positive charge in subjects with persistent viremia. All cysteine residues and N-linked glycosylation sites, some of which were known to play a major role in protein folding and others play a role in HCV entry, were 100% conserved among the sequenced cloned cDNAs from the two outcome groups.. HCV persistence may be associated with positive selection pressures on HVR1, rather than functional constraints in the envelope region.

Topics: Acute Disease; Adult; Amino Acid Sequence; Evolution, Molecular; Female; Hepacivirus; Hepatitis C; Heteroduplex Analysis; Humans; Male; Molecular Sequence Data; Polymorphism, Single-Stranded Conformational; Viral Envelope Proteins

Hepatitis C virus (HCV) causes persistent infection in most patients. To clarify the mechanisms underlying establishment of this persistent infection, nucleotide sequences of the E1/E2 region were characterized in 5 patients with acute and chronic HCV infection. We used direct DNA sequencing methods to identify the major sequence of HCV in each patient. Each HCV genome displayed a high frequency of nucleotide sequence variation in the hypervariable region (HVR) of E2. However, patient-specific conserved nucleotide sequences were identified in the E1/E2 region during the course of infection and conserved the higher-order protein structure. In the acute phase HCV infection, amino acid substitution in HVR-1 as the monthly rate of amino acids substitution per site (%) between each point exceeded 10.2%. In the chronic phase HCV infection, a significantly lower rate of amino acid substitution was observed in patients. The host immune responses to HVR-1 of each HCV isolates from all clinical courses were characterized using synthetic peptides and ELISA. One chronic patient serum (genotype 1b) did not react at all to its own HVR-1 peptides, however another patient (genotype 2b) reacted to all clinical course. These results indicated that HVR-1 might not always exhibit neutralizing epitopes of HCV infection. The sequence variation in HVR-1 may instead indicate the existence of various clones in acute phase infection and the adaption of these clones is thought to have caused persistent and chronic infection in each patient.

Topics: Acute Disease; Adult; Aged; Amino Acid Sequence; Amino Acid Substitution; Base Sequence; Chronic Disease; Female; Genetic Variation; Genotype; Hepacivirus; Humans; Male; Middle Aged; Molecular Sequence Data; Sequence Analysis, DNA; Viral Envelope Proteins; Viral Proteins

The factors leading to spontaneous clearance of hepatitis C virus (HCV) or to viral persistence are elusive. Understanding virus-host interactions that enable acute HCV clearance is key to the development of more effective therapeutic and prophylactic strategies. Here, using a sensitive neutralization assay based on infectious HCV pseudoparticles (HCVpp), we have studied the kinetics of humoral responses in a cohort of acute-phase patients infected during a single nosocomial outbreak in a hemodialysis center. The 17 patients were monitored for the spontaneous outcome of HCV infection for 6 months before a treatment decision was made. Blood samples were taken frequently (15 +/- 4 per patient). Phylogenetic analysis of the predominant virus(es) revealed infection by only one of two genotype 1b strains. While all patients seroconverted, their sera induced two opposing effects in HCVpp infection assays: inhibition and facilitation. Furthermore, the ability of sera to facilitate or inhibit infection correlated with the presence of either infecting HCV strain and divided the patients into two groups. In group 1, the progressive emergence of a relatively strong neutralizing response correlated with a fluctuating decrease in high initial viremia, leading to control of viral replication. Patients in group 2 failed to reduce viremia within the acute phase, and no neutralizing responses were detected despite seroconversion. Strikingly, sera of group 2, as well as naive sera, facilitated infection by HCVpp displaying HCV glycoproteins from different genotypes and strains, including those retrieved from patients. These results provide new insights into the mechanisms of viral persistence and immune control of viremia.

Topics: Acute Disease; Adult; Aged; Alanine Transaminase; Amino Acid Sequence; Cohort Studies; Female; Genotype; Hepacivirus; Hepatitis C; Hepatitis C Antibodies; Humans; Male; Middle Aged; Molecular Sequence Data; Sequence Alignment; Time Factors; Viral Envelope Proteins; Viremia; Virus Replication

We identified 15 patients with acute hepatitis C (AHC) among 29 healthy volunteers participating in 2 consecutive pharmacokinetics studies. Molecular techniques were used to determine the relatedness of viral strains, whereas clinical and virologic follow-up was started to establish the course and outcome of the acute infection. After presentation, serum liver enzymes and HCV RNA were monitored weekly for 4 months, then monthly for at least 12 months. Liver biopsy was performed 6 to 12 months after AHC diagnosis. Phylogenetic analysis of coding regions for the envelope glycoproteins E1 and E2 was performed. At presentation, all 15 patients tested HCV RNA-positive and had HCV genotype 2c. Phylogenetic analysis indicated a common source of infection. Fourteen patients agreed to be followed prospectively. Infection resolved spontaneously in 8 patients, HCV RNA becoming undetectable by 4 to 5 months after the presumed time of infection in 5 of them and by 8, 13, and 24 months in the remaining 3. Six patients developed chronic infection. Liver biopsies performed in 9 subjects who were HCV RNA-positive 6 months after AHC diagnosis revealed that the prevalent histologic finding was lobular inflammation. In conclusion, our homogeneous cohort showed a wide spectrum of clinical, virologic and histologic features, and, more importantly, short-term outcome differed noticeably despite the common source of infection.

Topics: Acute Disease; Adult; Disease Outbreaks; DNA, Viral; Female; Follow-Up Studies; Health Personnel; Hepacivirus; Hepatitis C; Humans; Liver; Male; Middle Aged; Pharmacokinetics; Phylogeny; RNA, Viral; Viral Envelope Proteins

We analyzed sequences of hypervariable region 1 (HVR1) of hepatitis C virus (HCV) in six chimpanzees, experimentally infected with a single HCV inoculum, to clarify the correlation between HVR1 mutation and antibodies to HVR1. Two chimpanzees had been immunized with synthetic HVR1 peptides before HCV inoculation. All six animals became infected with HCV but cleared the infection within the acute phase. The major HVR1 sequences in longitudinal sera were unchanged in animals both with and without anti-HVR1 antibodies. Additionally, sequences of HVR1 variants in each chimpanzee converged after 11 to 19 weeks. The data show that anti-HVR1 antibodies are unlikely to drive variation in HVR1.

Topics: Acute Disease; Amino Acid Sequence; Animals; Hepatitis C; Hepatitis C Antibodies; Molecular Sequence Data; Pan troglodytes; RNA, Viral; Viral Envelope Proteins

Infection with hepatitis C virus (HCV) generally progresses to chronic disease, although a minority of patients appear to clear viremia spontaneously. In this investigation, serum samples were analyzed for virological parameters, serum alanine aminotransferase (ALT) levels, and neutralizing antibody response against pseudotyped vesicular stomatitis virus (VSV) generated using chimeric envelope glycoprotein 1 (E1) or 2 (E2) of HCV. Testing of sequential serum samples that were collected beginning at the onset of acute-phase disease demonstrated intermittent viremia, elevated ALT levels, and detectable neutralization activity against VSV in 9 of 10 patients. Serum neutralization activity did not exhibit a correlation with the genotype of the infecting HCV or with virus load. On the other hand, patients with chronic HCV infection consistently had detectable amounts of virus present but no significant variation in ALT levels, and serum samples from a majority (>90%) of patients failed to show detectable neutralization activity.

Topics: Acute Disease; Adolescent; Adult; Alanine Transaminase; Chronic Disease; Female; Hepatitis C; Hepatitis C Antibodies; Humans; Male; RNA, Viral; Vesicular stomatitis Indiana virus; Viral Envelope Proteins

The antibody profile to various proteins of hepatitis C virus (HCV) was studied in 113 patients positive for HCV RNA in various disease statuses of hepatitis C (HC). A single peptide (E2/NS1, aa 413-436 of HCV polyprotein) chosen from a conserved region at the C-terminus of the hypervariable region (HVR) HVR1 of HCV was found to be sufficient for reliable diagnosis of the infection, even in the acute phase. Six hundred and one suspected HC cases and 200 voluntary blood donors were tested by this peptide. The sensitivity of detection of HCV antibodies by this peptide did not increase with addition of peptides from other HCV proteins. Our results clearly demonstrate that antibodies to HCV envelope proteins occur in a higher percentage of the infected population than those to other proteins. This emphasizes the necessity of using representative sequences from HCV envelope proteins in diagnostic immunoassays of this viral infection.

Topics: Acute Disease; Amino Acid Sequence; Case-Control Studies; Epitopes; Hepacivirus; Hepatitis C; Hepatitis C Antibodies; Hepatitis C, Chronic; Humans; Immunoenzyme Techniques; Molecular Sequence Data; Sequence Homology, Amino Acid; Viral Envelope Proteins

CD8(+) cytotoxic T lymphocytes (CTL) are thought to control hepatitis C virus (HCV) replication and so we investigated why this response fails in persistently infected individuals. The HCV quasispecies in three persistently infected chimpanzees acquired mutations in multiple epitopes that impaired class I MHC binding and/or CTL recognition. Most escape mutations appeared during acute infection and remained fixed in the quasispecies for years without further diversification. A statistically significant increase in the amino acid replacement rate was observed in epitopes versus adjacent regions of HCV proteins. In contrast, most epitopes were intact when hepatitis C resolved spontaneously. We conclude that CTL exert positive selection pressure against the HCV quasispecies and the outcome of infection is predicted by mutations in class I MHC restricted epitopes.

Topics: Acute Disease; Amino Acid Sequence; Animals; Antigenic Variation; Cell Line; Epitopes; Follow-Up Studies; Hepacivirus; Hepatitis C; Hepatitis C Antigens; Hepatitis C, Chronic; Histocompatibility Antigens Class I; Molecular Sequence Data; Mutation; Pan troglodytes; Remission, Spontaneous; RNA, Viral; Sequence Alignment; Sequence Homology, Amino Acid; T-Lymphocytes, Cytotoxic; Viral Envelope Proteins; Viral Nonstructural Proteins

The mechanisms by which hepatitis C virus (HCV) induces chronic infection in the vast majority of infected individuals are unknown. Sequences within the HCV E1 and E2 envelope genes were analyzed during the acute phase of hepatitis C in 12 patients with different clinical outcomes. Acute resolving hepatitis was associated with relative evolutionary stasis of the heterogeneous viral population (quasispecies), whereas progressing hepatitis correlated with genetic evolution of HCV. Consistent with the hypothesis of selective pressure by the host immune system, the sequence changes occurred almost exclusively within the hypervariable region 1 of the E2 gene and were temporally correlated with antibody seroconversion. These data indicate that the evolutionary dynamics of the HCV quasispecies during the acute phase of hepatitis C predict whether the infection will resolve or become chronic.

Topics: Acute Disease; Adult; Aged; Antibodies, Viral; Disease Progression; Evolution, Molecular; Female; Genes, Viral; Genetic Variation; Hepacivirus; Hepatitis C; Hepatitis C Antibodies; Hepatitis C, Chronic; Humans; Male; Middle Aged; Molecular Sequence Data; Phylogeny; Prospective Studies; Selection, Genetic; Time Factors; Viral Envelope Proteins; Virus Replication

Topics: Acute Disease; Animals; Genetic Variation; Hepacivirus; Hepatitis C; Hepatitis C Antibodies; Humans; Lymphocytic Choriomeningitis; Lymphocytic choriomeningitis virus; Mice; Mutation; Neutralization Tests; T-Lymphocytes, Cytotoxic; Viral Envelope Proteins

Changes in the deduced amino acid sequence of the envelope 2 (E2) region of the GB virus C/hepatitis G virus (GBV-C/HGV) were analyzed to investigate whether or not the region contributes to persistent infection with the virus.. Eight patients with acute hepatitis C and 1 patient with acute hepatitis of unknown etiology were included in the study. GBV-C/HGV RNA was detected in 6 patients, including the patient with hepatitis of unknown origin. The nucleotide sequence of the E2 region of hepatitis C virus (HCV) and GBV-C/HGV was determined by direct sequencing of polymerase chain reaction products in 5 patients with HCV infection and in 6 patients with GBV-C/HGV infection twice during the period of early infection and several months or years later in each patient.. The mean substitution rate of the deduced amino acid sequence in the E2 region was over 100 times lower (p < 0.001) in GBV-C/HGV (0.01 +/- 0.04/month/100 sites) than in HCV (2.4 +/- 1.7/month/100 sites). The amino acid sequence of the loop domain of GBV-C/HGV-E2 did not change in any of the 6 patients. On the other hand, the sequence of the hypervariable region of HCV-E2 changed remarkably (5.9 +/- 4.3/month/100 sites). No amino acid substitution in the loop domain was observed in 7 additional patients who showed persistent GBV-C/HGV viremia for more than 2 years.. These results indicate that changes in the amino acid sequence of the E2 region are not involved in the mechanism of persistent GBV-C/HGV infection.

Topics: Acute Disease; Adult; Amino Acid Sequence; Amino Acid Substitution; Female; Flaviviridae; Hepacivirus; Hepatitis C; Hepatitis, Viral, Human; Humans; Male; Middle Aged; Molecular Sequence Data; Sequence Alignment; Sequence Analysis, Protein; Viral Envelope Proteins

Antibody response to the E2/NS1 protein of the hepatitis C virus (HCV) was studied in 26 patients with post-transfusion acute hepatitis C. Second-generation HCV (HCV-2) antibody, E2/NS1 antibody and HCV-RNA were measured in serial serum samples taken within 1 month and 3, 6 and 12 months after the onset of acute hepatitis C. The HCV genotype was also tested to study its clinical significance. Of 26 patients, eight showed normalization of alanine aminotransferase (ALT) and clearance of HCV-RNA (resolved group). In the remaining 18 patients, HCV viraemia and ALT abnormality (except one patient) continued for more than 3 years (unresolved group). Both HCV-2 and E2/NS1 antibodies were positive at least once in all patients. The prevalence of E2/NS1 antibody was significantly (P < 0.05) higher in the resolved group (88%) than in the unresolved group (39%) in the period within 1 month of onset; the prevalence was similar between the two groups thereafter. The prevalence of HCV-2 antibody did not differ between the two groups at any point. The HCV genotype was not related to the chronicity of acute hepatitis C. In conclusion, the E2/NS1 antibody appeared in all patients with acute hepatitis C and was associated with the clearance of HCV.

Topics: Acute Disease; Adult; Alanine Transaminase; Blood Transfusion; Case-Control Studies; Clinical Enzyme Tests; Enzyme-Linked Immunosorbent Assay; Female; Follow-Up Studies; Hepacivirus; Hepatitis C; Hepatitis C Antibodies; Humans; Male; Prevalence; RNA, Viral; Seroepidemiologic Studies; Time Factors; Viral Envelope Proteins; Viral Nonstructural Proteins

Epitopes of hypervariable region 1 (HVR1) were mapped by enzyme-linked immunosorbent assay using follow-up sera of patients, all of whom were infected with the same isolate of hepatitis C virus (HCV). Our results suggest that (i) an early appearance (up to month 13 postinfection) of antibodies directed to the N terminus of HVR1 is associated with acute self-limiting infections of HCV and (ii) isolate-independent antibodies which are mainly directed to the C terminus of HVR1 seem to persist in chronically infected patients. The relevance of HVR1-specific antibodies for neutralization was evaluated by characterization of a rabbit serum.

Topics: Acute Disease; Amino Acid Sequence; Animals; Chronic Disease; Epitope Mapping; Hepatitis C; Hepatitis C Antibodies; Humans; Molecular Sequence Data; Peptide Fragments; Rabbits; Viral Envelope Proteins

Acute and chronic Hepatitis C virus infections were investigated retrospectively in chimpanzees that had been infected from a single source. Anti-E1 and anti-E2 were detected in two of three chimpanzees with a chronic infection, but were first detected 1 to 2 years after inoculation. Sequence evolution of the E1 region in three animals over a period of 9 to 11 years revealed a mutation rate of 1.02 to 2.23 x 10(-3) base substitutions per site per year. The acute phase viremia levels in acute infections which resolved appeared to be at least 10-fold higher than during the acute phase of chronic infections. During chronic infections, the viral load fell rapidly after the acute phase and remained at very low levels for several years. After 4 to 6 years, the viral load and liver enzymes increased again, suggesting reactivation of the infection. There was no clear temporal relationship between sequence evolution of the E1 region, changes in viral load, and the production of antibodies to the envelope proteins.

Topics: Acute Disease; Animals; Base Sequence; Chronic Disease; Cloning, Molecular; DNA Primers; Evolution, Molecular; Female; Hepacivirus; Hepatitis C; Male; Pan troglodytes; Phylogeny; Polymerase Chain Reaction; RNA, Viral; Viral Envelope Proteins; Viremia

Antibody responses to the hepatitis C virus (HCV) envelope proteins E1 and E2 were analyzed using two original assays in sera from 86 patients in different stages of disease. A Western blot assay and an immunofluorescence assay (IFA) were developed using envelope proteins produced, respectively, in Escherichia coli and in CV1 cells infected with a recombinant SV40. As a third method, the INNO-LIA HCV Ab III assay including E2 synthetic peptides was used. Of 38 chronically infected patients positive for anti-E2 antibodies by IFA, 26 were positive in the Western blot assay (68%) and 25 in the INNO-LIA test (66%). Thus, the detection of anti-envelope antibodies is highly dependent on the antigen formulation, and a native glycosylated form of the proteins is probably needed for their efficient detection. This study shows that the antibody response to HCV envelope proteins depends on the phase of infection. A few acutely infected patients displayed a response to E1 or E2 (36% by Western blot, 7% by IFA), and these antibodies seem to develop in patients evolving toward chronicity. The high prevalence in chronically infected subjects (62% to E2 by Western blot, 90% by IFA), particularly in subjects with essential mixed cryoglobulinemia (68% and 100%), confirms that the resolution of infection involves more than these antibodies. The antienvelope response in patients treated with interferon was investigated, but no significant relationship was found between antibody level prior to treatment and the evolution of hepatitis. The detection of anti-envelope antibodies, therefore, is not predictive of the response to antiviral therapy.

Topics: Acute Disease; Animals; Cell Line; Chlorocebus aethiops; Chronic Disease; Cryoglobulinemia; Gene Expression; Hepacivirus; Hepatitis C; Hepatitis C Antibodies; Humans; Interferon alpha-2; Interferon-alpha; Recombinant Fusion Proteins; Recombinant Proteins; Viral Envelope Proteins