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Sequential change of the hypervariable region of the hepatitis C virus genome in acute infection
N Sakamoto1, N Enomoto, M Kurosaki
1Second Department of Internal Medicine, Faculty of Medicine, Tokyo Medical and Dental University, Japan.
Insights
Hepatitis C virus (HCV) infection involves liver inflammation. The study tracked HCV
Area of Science:
- Virology
- Hepatology
- Molecular Biology
Background:
- Hepatitis C virus (HCV) infection causes persistent liver inflammation, often leading to end-stage liver disease.
- The E2/NS1 region of the HCV genome contains a hypervariable region (HVR) with significant diversity among isolates.
Observation:
- A longitudinal analysis of HVR alterations in three patients with acute HCV infection was performed.
- Plasma samples were collected over time, and HCV RNA was analyzed for HVR sequences.
- HCV RNA reappeared in patients about a year after initial clearance, with or without hepatitis worsening.
Findings:
- Significant amino acid substitutions in the HVR were observed between acute and recurrent phases of HCV infection.
- One case showed seven amino acid substitutions, while another had only 30% homology in the HVR between phases.
- The mutation rate of the HVR tended to accelerate as HCV infection progressed toward chronicity.
Implications:
- HVR alterations may be associated with the clinical course and progression of Hepatitis C virus infection.
- Understanding HVR dynamics could offer insights into HCV persistence and disease progression.
- Further research into HVR mutations may inform strategies for managing chronic HCV infection.
Abstract:
Hepatitis C virus (HCV) infection is characterized by persistence of liver inflammation that often leads to end-stage liver disease, although the mechanisms are not fully understood. A hypervariable region (HVR) has been reported in the E2/NS1 region of the HCV genome, in which striking diversity is found among different HCV isolates. To investigate the association of the HVR alterations with the clinical courses of HCV infection, a longitudinal analysis of the HVR in patients with acute HCV infection was carried out. Plasma samples were obtained at several times in three patients with acute hepatitis C. Plasma RNA was extracted and reverse transcribed, and DNA fragments that included the HVR were amplified by PCR. The sequences of the HVR were directly determined from the PCR products by the dideoxy chain termination method, from which amino acid sequences were deduced. In all cases, plasma HCV-RNA disappeared with the improvement of the initial alanine aminotransferase (ALT) elevation, but HCV-RNA reappeared about 1 year later with or without deterioration of the hepatitis. In a case of sporadic acute hepatitis, the HCV in the recurrent phase had seven amino acid substitutions in the HVR compared with that in the acute phase, although no amino acid changes were noted during the initial acute phase. In a case of posttransfusion hepatitis, a marked difference was observed between the acute and the recurrent phases, with an amino acid homology of 30% (8/27). The mutation rate of the HVR had a tendency to accelerate as the HCV infection progressed to the chronic stage.(ABSTRACT TRUNCATED AT 250 WORDS)