title: 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.
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.
authors.affiliation: Department of Clinical Medicine, University of Bologna, Bologna, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Cassini
authors.forename: M S
authors.initials: MS
authors.lastname: De Mitri
authors.forename: D
authors.initials: D
authors.lastname: Gibellini
authors.forename: L
authors.initials: L
authors.lastname: Urbinati
authors.forename: S
authors.initials: S
authors.lastname: Bagaglio
authors.forename: G
authors.initials: G
authors.lastname: Morsica
authors.forename: M
authors.initials: M
authors.lastname: Domenicali
authors.forename: G
authors.initials: G
authors.lastname: Verucchi
authors.forename: M
authors.initials: M
authors.lastname: Bernardi
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D001483:Base Sequence; D018389:Codon, Nonsense; D004252:DNA Mutational Analysis; D004279:DNA, Viral / Q000032:analysis / Q000235:genetics; D005260:Female; D016679:Genome, Viral / Q000235:genetics; D005838:Genotype; D015658:HIV Infections / Q000150:complications* / Q000821:virology; D006509:Hepatitis B / Q000150:complications / Q000175:diagnosis* / Q000821:virology; D006514:Hepatitis B Surface Antigens / Q000097:blood / Q000235:genetics*; D006515:Hepatitis B virus / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000821:virology*; D008099:Liver / Q000821:virology*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D012189:Retrospective Studies; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D019562:Viral Load; D014779:Virus Replication
chemical_list: D018389:Codon, Nonsense; D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens