Genomic variability associated with the presence of occult hepatitis B virus in HIV co-infected individuals.
Occult hepatitis B virus (O-HBV) infection is characterized by the presence of HBV DNA without detectable hepatitis B surface antigen (HBV DNA+/HBsAg-) in the serum. Although O-HBV is more prevalent during HBV/HIV co-infection, analysis of HBV mutations in co-infected patients is limited. In this preliminary study, HBV PreSurface (PreS) and surface (S) regions were amplified from 33 HIV-positive patient serum samples - 27 chronic HBV (C-HBV) and six O-HBV infections. HBV genotype was determined by phylogenetic analysis, while quasispecies diversity was quantified for the PreS, S and overlapping polymerase regions. C-HBV infections harboured genotypes A, D and G, compared to A, E, G and one mixed A/G infection for O-HBV. Interestingly, nonsynonymous-synonymous mutation values indicated positive immune selection in three regions for O-HBV vs one for C-HBV. Sequence analysis further identified new O-HBV mutations, in addition to several previously reported mutations within the HBsAg antigenic determinant. Several of these O-HBV mutations likely contribute to the lack of detectable HBsAg in O-HBV infection by interfering with detection in serologic assays, altering antigen secretion and/or decreasing replicative fitness.
Martin
C M
CM
Department of Internal Medicine, Division of Digestive Diseases, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA.
Welge
J A
JA
Shire
N J
NJ
Rouster
S D
SD
Shata
M T
MT
Sherman
K E
KE
Blackard
J T
JT
D000328:Adult; D001483:Base Sequence; D015331:Cohort Studies; D004279:DNA, Viral / Q000737:chemistry / Q000235:genetics; D014644:Genetic Variation; D005838:Genotype; D006678:HIV / Q000276:immunology*; D015658:HIV Infections / Q000150:complications* / Q000276:immunology / Q000821:virology; D006509:Hepatitis B / Q000150:complications* / Q000276:immunology / Q000821:virology; D006514:Hepatitis B Surface Antigens / Q000235:genetics / Q000276:immunology*; D006515:Hepatitis B virus / Q000235:genetics / Q000276:immunology*; D006801:Humans; D008875:Middle Aged; D008969:Molecular Sequence Data; D010802:Phylogeny; D010865:Pilot Projects; D016133:Polymerase Chain Reaction; D011446:Prospective Studies; D012194:RNA-Directed DNA Polymerase / Q000737:chemistry / Q000235:genetics; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D015678:Viral Structural Proteins / Q000737:chemistry / Q000235:genetics; D055815:Young Adult
D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens; D015678:Viral Structural Proteins; D012194:RNA-Directed DNA Polymerase