Retrospective characterization of the S open reading frame of HBV isolated from children with membranous nephropathy treated with interferon-alpha2b.
BACKGROUND
A causal relationship exists between HBV infection and membranous nephropathy. The association is especially close in Black children in sub-Saharan Africa. Interferon-alpha2b is commonly used to treat this condition, but is effective in only 30-40% of patients. The reason for the poor response is unknown. The objective of this study was to determine if mutations in the surface gene of HBV isolated from Black children with HBV-associated membranous nephropathy before, during and after interferon treatment, have any effect on treatment response and vice versa.


METHODS
HBV DNA was extracted from a responder, a reverter and a non-responder before and after initiation of 16 weeks of interferon-alpha2b treatment. The preS1/preS2/S region was amplified, cloned and sequenced.


RESULTS
The preS2 region was the most variable in the reverter and the non-responder, and the S region was the most variable in the non-responder. Phylogenetic analysis showed that the viral population dynamics between the responder and the reverter/non-responder strains differed as a result of mutations in the surface gene.


CONCLUSIONS
The presence of mutations in the S region of HBV could be used as predictive markers to differentiate interferon-alpha2b responders from non-responders provided that detailed analysis of further genomes confirms our findings.
Gous
Natasha
N
Hepatitis Virus Diversity Research Programme (formerly MRC/CANSA/University Molecular Hepatology Research Unit), Department of Internal Medicine, University of the Witwatersrand, Johannesburg, South Africa.
Bhimma
Rajendra
R
Kew
Michael
M
Kramvis
Anna
A
D017954:Africa South of the Sahara / Q000208:ethnology; D000998:Antiviral Agents / Q000627:therapeutic use*; D002648:Child; D004279:DNA, Viral / Q000032:analysis / Q000235:genetics; D005819:Genetic Markers; D015433:Glomerulonephritis, Membranous / Q000188:drug therapy* / Q000208:ethnology / Q000209:etiology; D006514:Hepatitis B Surface Antigens / Q000032:analysis / Q000235:genetics*; D006515:Hepatitis B virus / Q000187:drug effects / Q000235:genetics*; D019694:Hepatitis B, Chronic / Q000150:complications / Q000188:drug therapy / Q000821:virology*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D009154:Mutation; D016366:Open Reading Frames; D010802:Phylogeny; D011498:Protein Precursors / Q000032:analysis / Q000235:genetics*; D011994:Recombinant Proteins; D012189:Retrospective Studies; D017422:Sequence Analysis, DNA; D017211:Treatment Failure
D000998:Antiviral Agents; D004279:DNA, Viral; D005819:Genetic Markers; D006514:Hepatitis B Surface Antigens; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011498:Protein Precursors; D011994:Recombinant Proteins; C050806:presurface protein 1, hepatitis B surface antigen; C050807:presurface protein 2, hepatitis B surface antigen