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Published on: July 16, 2012
Evolution in the hypervariable region of the hepatitis C virus in two infants infected by mother-to-infant
Tsutomu Ishii1, Hitoshi Ohto, Chikako Takeuchi
1Department of Pediatrics, Fukushima Medical School of Medicine, Fukushima, Japan. ishiit@fmu.ac.jp
Insights
Hepatitis C virus (HCV) quasispecies in infants evolved significantly over ten years post-transmission. Infant HCV evolution showed increased variability and shifts in hydrophobia profiles, similar to adults.
Area of Science:
- Virology
- Immunology
- Pediatrics
Background:
- Limited data exists on hepatitis C virus (HCV) quasispecies evolution in infants following mother-to-infant transmission.
- This study investigates the hypervariable region 1 (HVR1) of HCV in two mother-infant pairs over a decade.
Purpose of the Study:
- To analyze the long-term evolution of HCV quasispecies in infants infected via mother-to-infant transmission.
- To compare viral evolution patterns between infected infants and their mothers.
Main Methods:
- HCV RNA was extracted from serum samples of two mother-infant pairs.
- Ten cDNA clones of the HVR1 region were generated and analyzed for sequence variability, identity, and hydrophobia profiles.
- Phylogenetic studies were conducted to assess quasispecies evolution.
Main Results:
- Infant A exhibited higher sequence diversity and greater amino acid changes in HVR1 compared to Infant B.
- Phylogenetic analysis indicated more extensive quasispecies evolution in Infant A than in Infant B.
- Both infants displayed dynamic shifts in hydrophobia profiles within the HVR1 sequences.
Conclusions:
- HCV HVR1 evolution and quasispecies variability increase in infants with mother-to-infant transmission over a ten-year period.
- Elevated alanine aminotransferase (ALT) levels in infants may indicate the emergence of escape mutants and novel quasispecies.
- Findings suggest that infant HCV evolution mirrors patterns observed in adults.
Background:
There is little data on the evolution of hepatitis C virus (HCV) quasispecies in infants infected by mother-to-infant transmission during long-term follow up. The hypervariable region 1 (HVR1) of the HCV genome was investigated in two mother-infant pairs from birth to 7.6 and 10.2 years, respectively.
Methods:
Ten cDNA clones of HVR1 generated from HCV-RNA and extracted from serum samples of both pairs were analyzed. The sequences were compared with regard to variability, identity, and hydrophobia profile, and analyzed by phylogenetic studies.
Results:
The alanine aminotransferase (ALT) level was high with fluctuation in infant A and almost within the normal range in infant B. Sequence diversity was higher in infant A at 7.6 years than in infant B at 9.3 years (sequence identity with the mothers'; 69.3-70.7% vs 85.3-90.7% for nucleotides, and 48% vs 68-72% for amino acids, respectively). Compared to the first samples, amino acid changes greatly increased in infant A (35.2% at 4.9 years and 52% at 7.6 years), but not in infant B (4% at 5.6 years and 27.5% at 9.3 years). Phylogenetic studies revealed that quasispecies in infant A evolved to a greater extent than that in infant B. Hydrophobia profile analyses revealed that dynamic shifts between hydrophilia and hydrophobia occurred in both infants.
Conclusions:
As in adults, the evolution of HVR1 and variability of quasispecies increased in infants infected through mother-to-infant transmission for 10 years after birth. A large episode of ALT elevation suggested the emergence of escape mutants and the evolution of new quasispecies.
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