HBV whole-genome mutation profile in HIV-1/HBV coinfected patients in a long-term follow-up study

Infection. 2014 Aug;42(4):675-87. doi: 10.1007/s15010-014-0616-2. Epub 2014 Apr 4.

Abstract

Purpose: Human immunodeficiency virus (HIV-1)-infected patients frequently harbour hepatitis B and C viruses (HBV and HCV, respectively). Possible modifications of the natural history of hepatitis B may occur. The aim of this study was to characterise HBV diversity and evolutionary and mutational viral genome profiles in HIV-1/HBV coinfections.

Methods: HIV-1 and HBV markers determinations (Roche, FRG; Abbott, USA) and HBV genome-length retrospective analysis were performed in follow-up isolates from patients who were either stably HBsAg-negative with a low level of HBV DNA (occult hepatitis B infection, OBI) or HBsAg-positive with a high level of HBV DNA. Phylogenetic analysis (maximum likelihood method, MEGA5), statistical analysis and evolutionary rates calculation (d S/d N) were applied.

Results: Positive selection pressures in the PreS/S region and a significantly higher number of mutations in this region including the major hydrophilic region (MHR) and the "a" determinant were shown in HBsAg-negative (possibly OBI) compared to stably HBsAg-positive HIV-1/HBV subgenotypes D3/A2 coinfected patients. Mutants previously described in HIV-1/HBV coinfected patients were found. Known mutants Y100C, P127T and P120A associated to Y134H and S143T and new S mutants, which may potentially affect HBsAg expression and secretion and anti-HBs binding, were detected in baseline sera persisting up to the end of 9 years follow-up. Known mutations of BCP, Pre-C, C and X regions were also characterised. Natural mutants strictly known as being involved in diagnostic failure were not detected; however, numerous corresponding sites showed amino acid variations.

Conclusions: Evolutionary and genotypic differences observed, particularly in the PreS/S region, between HBsAg-negative (OBI) and HBsAg-positive HIV-1/HBV coinfected patients, may contribute, in association with mutations of other genomic regions, to the HBsAg-negative phenotype.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • DNA, Viral / chemistry
  • DNA, Viral / genetics*
  • Female
  • Follow-Up Studies
  • Genetic Variation
  • Genome, Viral*
  • Genotype
  • HIV Infections / complications*
  • Hepatitis B virus / classification*
  • Hepatitis B virus / genetics*
  • Hepatitis B virus / isolation & purification
  • Hepatitis B, Chronic / virology*
  • Humans
  • Male
  • Middle Aged
  • Mutation*
  • Phylogeny
  • Retrospective Studies
  • Sequence Analysis, DNA

Substances

  • DNA, Viral