glycoprotein-e2--hepatitis-c-virus and Agammaglobulinemia

The question of whether viruses persist after apparent clearance of infection remains unanswered. Here, we describe a patient with hypogammaglobulinemia whose acute hepatitis C virus (HCV) infection appeared to resolve after receipt of interferon therapy, relapse immediately, and then clear spontaneously--only to relapse after receipt of corticosteroid therapy, and clear again, 8.5 years later. Sequencing indicated that the viruses detected during each relapse were virtually identical, with the hypervariable region 1 of E2 appearing to be monoclonal, which is typical of patients with hypogammaglobulinemia. Nonstructural 5A sequences exhibited quasispecies diversity initially but, after 8.5 years, had become monoclonal. The prolonged period of negativity for HCV RNA followed by relapse suggests that HCV may persist in apparent sustained viral responders.

Topics: Adrenal Cortex Hormones; Adult; Agammaglobulinemia; Alanine Transaminase; Amino Acid Sequence; Antiviral Agents; Female; Hepacivirus; Hepatitis C; Humans; Interferons; Mutation; Polymorphism, Genetic; Recurrence; RNA, Viral; Sequence Analysis, DNA; Sequence Homology; Viral Envelope Proteins; Viral Nonstructural Proteins

The N-terminal end of the hepatitis C virus (HCV) envelope glycoprotein E2 contains a stretch of 27 amino acids that exhibit increased variability. This hypervariable region 1 (HVR-1), as it is normally referred to, is thought to contain epitopes that come under humoral immune attack. In the present study, 10 patients (5 children and 5 adults) with humoral immune defects and chronic HCV infection were investigated, to see how HVR-1 sequences behave over time in these patients who are unable to produce antibodies. Amplicons of this region showed little or no variation at all over time, indicating that quasispecies variation in this region is driven by the host's humoral immune response.

Topics: Adolescent; Adult; Agammaglobulinemia; Amino Acid Sequence; Child; Common Variable Immunodeficiency; Complementarity Determining Regions; Female; Genetic Variation; Hepacivirus; Hepatitis C, Chronic; Humans; Male; Molecular Sequence Data; Sequence Analysis, DNA; Viral Envelope Proteins