Evolution in the hypervariable region of the hepatitis C virus in two infants infected by mother-to-infant transmission.
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.
Ishii
Tsutomu
T
Department of Pediatrics, Fukushima Medical School of Medicine, Fukushima, Japan. ishiit@fmu.ac.jp
Ohto
Hitoshi
H
Takeuchi
Chikako
C
Ariga
Hiromichi
H
Hirai
Shigeru
S
Ujiie
Niro
N
Suzuki
Hitoshi
H
Okamoto
Hiroaki
H
D000410:Alanine Transaminase / Q000097:blood; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D022801:Complementarity Determining Regions / Q000235:genetics; D019143:Evolution, Molecular; D005260:Female; D005500:Follow-Up Studies; D016174:Hepacivirus / Q000235:genetics*; D006526:Hepatitis C / Q000635:transmission* / Q000821:virology; D006801:Humans; D007223:Infant; D018445:Infectious Disease Transmission, Vertical; D008297:Male; D010802:Phylogeny; D012367:RNA, Viral; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors
D022801:Complementarity Determining Regions; D012367:RNA, Viral; D000410:Alanine Transaminase