Evaluation of the G145R Mutant of the Hepatitis B Virus as a Minor Strain in Mother-to-Child Transmission

PLoS One. 2016 Nov 3;11(11):e0165674. doi: 10.1371/journal.pone.0165674. eCollection 2016.

Abstract

The role of the hepatitis B virus (HBV) mutant G145R, with a single change in amino acid 145 of the surface protein, as a minor population remains unknown in mother-to-child transmission. The minor strain as well as the major strain of the G145R mutant were evaluated in three cohorts using a locked nucleic acid probe-based real-time PCR. The breakthrough cohort consisted of children who were born to HBV carrier mothers and became HBV carriers despite immnoprophylaxis (n = 25). The control cohort consisted of HBV carriers who had no history of receiving the hepatitis B vaccine, hepatitis B immunoglobulin or antiviral treatment (n = 126). The pregnant cohort comprised pregnant women with chronic HBV infection (n = 31). In the breakthrough cohort, 6 showed positive PCR results (major, 2; minor, 4). In the control cohort, 13 showed positive PCR results (major, 0; minor, 13). HBeAg-positive patients were prone to have the G145R mutant as a minor population. Deep sequencing was performed in a total of 32 children (PCR positive, n = 13; negative, n = 19). In the breakthrough cohort, the frequency of the G145R mutant ranged from 0.54% to 6.58%. In the control cohort, the frequency of the G145R mutant ranged from 0.42% to 4.1%. Of the 31 pregnant women, 4 showed positive PCR results (major, n = 0; minor, n = 4). All of the pregnant women were positive for HBeAg and showed a high viral load. Three babies born to 3 pregnant women with the G145R mutant were evaluated. After the completion of immunoprophylaxis, 2 infants became negative for HBsAg. The remaining infant became negative for HBsAg after the first dose of HB vaccine. G145R was detected in one-fourth of the children with immunoprophylaxis failure. However, the pre-existence of the G145R mutant as a minor population in pregnant women does not always cause breakthrough infection in infants.

MeSH terms

  • Adolescent
  • Adult
  • Amino Acid Substitution / genetics
  • Base Sequence
  • Child
  • Child, Preschool
  • DNA, Viral / genetics
  • Female
  • Hepatitis B Antibodies / immunology*
  • Hepatitis B Surface Antigens / genetics*
  • Hepatitis B Surface Antigens / immunology
  • Hepatitis B Vaccines / immunology
  • Hepatitis B e Antigens / immunology*
  • Hepatitis B virus / genetics*
  • Hepatitis B, Chronic / transmission*
  • Hepatitis B, Chronic / virology
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Infant
  • Infectious Disease Transmission, Vertical*
  • Male
  • Middle Aged
  • Sequence Analysis, DNA
  • Vaccination
  • Viral Load / genetics
  • Young Adult

Substances

  • DNA, Viral
  • Hepatitis B Antibodies
  • Hepatitis B Surface Antigens
  • Hepatitis B Vaccines
  • Hepatitis B e Antigens

Grants and funding

This study was supported by JSPS KAKENHI (Grant-in- Aid for Scientific Research) grant number 15K09701.