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Published on: July 16, 2012
Change of hypervariable region proteins of hepatitis C virus E2 in two infants
R Li1, K Sugiyama, K Goto
1Department of Pediatrics, Nagoya City University Medical School, Nagoya, Japan.
Insights
Hepatitis C virus (HCV) genetic diversity evolved differently in two infants after vertical transmission. Infant 2 showed higher mutation rates in the HCV E2 gene hypervariable region (HVR) compared to infant 1, with increased anti-HCV levels observed in both.
Area of Science:
- Virology
- Immunology
- Genetics
Background:
- Vertical transmission of Hepatitis C virus (HCV) can lead to chronic infection in infants.
- Understanding HCV genetic evolution in infants is crucial for predicting disease progression and immune response.
Purpose of the Study:
- To investigate the genetic drift of the HCV E2 gene hypervariable region (HVR) in two vertically infected infants.
- To compare viral evolution between infants and their mothers and between the two infant cases.
Main Methods:
- Analysis of five complementary DNA (cDNA) clones from each infant and their mothers.
- Sequencing and comparison of the HCV E2 gene hypervariable region (HVR).
- Monitoring of serum ALT levels, HCV-core protein activity, and anti-HCV antibody levels.
Main Results:
- HCV strains in infant 1 were initially identical to her mother's, while infant 2's strains differed significantly from her mother's.
- The mutation rate of HVR-1 proteins was 1.6 to 2-fold higher in infant 2 than in infant 1.
- HVR-1 mutation rates increased significantly from 6 months of age in both infants, coinciding with elevated anti-HCV levels.
Conclusions:
- Infant HCV infections exhibit distinct genetic evolutionary patterns.
- Increased HVR-1 mutation rates in infants may be linked to the development of adaptive immune responses, indicated by rising anti-HCV antibody levels.
Abstract:
Two infants vertically infected with hepatitis C virus (HCV) were followed-up from 3 or 4 months to 2.5 years of age. We analyzed five complementary DNA (cDNA) clones from each patient and compared the genetic drift of the HCV E2 gene hypervariable region (HVR) between the two infants and between the infants and their mothers within the two families. The HCV strains initially detected in infant 1 were identical to those found in her mother, while the HCV strains initially detected in infant 2 were very different from those of her mother. The mutation rate of HVR-1 proteins was higher in mother 1 than in mother 2, but was 1.6 to 2-fold higher in infant 2 than in infant 1 during the follow-up period. Serum ALT levels or serum HCV-core protein activity did not correlate with the mutation rates of HVR-1 proteins in either infant. However, the mutation rate of HVR-1 proteins significantly increased from 6 months of age in both infants, with concomitantly increased serum HCV antibody (anti-HCV) levels.
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