A novel stop codon mutation within the hepatitis B surface gene is detected in the liver but not in the peripheral blood mononuclear cells of HIV-infected individuals with occult HBV infection

J Viral Hepat. 2013 Jan;20(1):42-9. doi: 10.1111/j.1365-2893.2012.01623.x. Epub 2012 Jun 1.

Abstract

To characterize occult HBV infection (OHB) in different compartments of HIV+ individuals. This retrospective study involved 38 consecutive HIV+ patients; 24 HBsAg negative (HBV-) and 14 HBsAg positive (HBV+). OHB was assessed in serum samples, liver tissue (LT) and peripheral blood mononuclear cells (PBMC) by genomic amplification of the partial S, X and precore/core regions. HBV genomic analysis was inferred by direct sequencing of PCR products. The intracellular HBV-DNA was measured by a quantitative real-time PCR. HBV+ patients were used as a control for HBV replication and genomic profile. In HBV- patients, HBV-DNA was undetectable in all serum samples, while it was found positive in 7/24 (29%) LT in which genotype D prevailed (57%). HBV-DNA was found in 6/7 (86%) PBMC of occult-positive and none of occult-negative LT. Significantly lower HBV-DNA load was present in both compartments in OHB+ with respect to the HBV+ group (LT: P = 0.002; PBMC: P = 0.026). In the occult-positive cases, HBV replication was significantly higher in LT than in PBMC (P = 0.028). A hyper-mutated S gene in PBMC and a nucleotide mutation at position C695 in LT that produces a translational stop codon at amino acid 181 of the HBs gene characterized OHB. In this group of HIV+ persons, OHB is frequent and exhibits lower replication levels than chronic HBV in the different compartments examined. HBV-DNA detection in PBMC may offer a useful tool to identify OHB in serum-negative cases. The novel HBs gene stop codon found in LT could be responsible for reduced production leading to undetectability of HBsAg.

MeSH terms

  • Adult
  • Amino Acid Sequence
  • Base Sequence
  • Codon, Nonsense
  • DNA Mutational Analysis
  • DNA, Viral / analysis
  • DNA, Viral / genetics
  • Female
  • Genome, Viral / genetics
  • Genotype
  • HIV Infections / complications*
  • HIV Infections / virology
  • Hepatitis B / complications
  • Hepatitis B / diagnosis*
  • Hepatitis B / virology
  • Hepatitis B Surface Antigens / blood
  • Hepatitis B Surface Antigens / genetics*
  • Hepatitis B virus / genetics*
  • Hepatitis B virus / isolation & purification
  • Humans
  • Leukocytes, Mononuclear / virology*
  • Liver / virology*
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Retrospective Studies
  • Sequence Alignment
  • Sequence Analysis, DNA
  • Viral Load
  • Virus Replication

Substances

  • Codon, Nonsense
  • DNA, Viral
  • Hepatitis B Surface Antigens