HBV whole-genome mutation profile in HIV-1/HBV coinfected patients in a long-term follow-up study.
OBJECTIVE
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.
Department of Infectious, Parasitic and Immune-mediated Diseases (MIPI), Istituto Superiore di Sanità, Viale Regina Elena 299, 00161, Rome, Italy.
S
S
Taffon
D
D
Genovese
M
M
Blasi
P
P
Pierotti
A
A
Degli Esposti
S
S
Catone
P
P
Chionne
B
B
Pulimanti
A
A
Candido
S
S
Dettori
M E
ME
Tosti
C
C
Argentini
F
F
Mazzotta
M
M
Rapicetta
D000328:Adult; D004279:DNA, Viral / Q000737:chemistry / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D014644:Genetic Variation; D016679:Genome, Viral; D005838:Genotype; D015658:HIV Infections / Q000150:complications*; D006515:Hepatitis B virus / Q000145:classification* / Q000235:genetics* / Q000302:isolation & purification; D019694:Hepatitis B, Chronic / Q000821:virology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010802:Phylogeny; D012189:Retrospective Studies; D017422:Sequence Analysis, DNA
D004279:DNA, Viral