Mutations in surface and polymerase gene of chronic hepatitis B patients with coexisting HBsAg and anti-HBs.
OBJECTIVE
To investigate the clinical significance and presence of mutations in the surface (S) and overlapping polymerase gene of hepatitis B patients with coexisting HBsAg and anti-HBs.


METHODS
Twenty-three patients with chronic hepatitis B were studied. Of the 23 patients, 11 were both positive for hepatitis B virus (HBV) surface antigen (HBsAg) and antibody to HBV surface antigen (anti-HBs), 12 were negative for anti-HBs while positive for HBsAg. DNA was extracted from 200 muL serum of the patients. Nucleotide of the surface and overlapping polymerase gene from HBV-infected patients was amplified by PCR, and the PCR products were sequenced.


RESULTS
Forty-one mutations were found within the surface gene protein of HBV in 15 patients (10 with coexisting HBsAg and anti-HBs). Six (14.6%) out of 41 mutations were located at "alpha " determinant region in 5 patients (4 positive for HBsAg and anti-HBs). Eleven mutations (26.8%) occurred in the downstream or upstream of "alpha " determinant region. Lamivudine (LMV)-selected mutations were found in three patients who developed anti-HBs, which occurred in amino acid positions (196, 198, 199) of the surface protein and in YMDD motif (M204I/V) of the polymerase protein simultaneously. Presence of these mutations did not relate to changes in ALT and HBV DNA levels.


CONCLUSIONS
Besides mutations in the "alpha " deter-minant region, mutations at downstream or upstream of the "alpha " determinant region may contribute to the development of anti-HBs. These mutations do not block the replicating competency of HBV in the presence of high titer of anti-HBs.
Lu
Hai-Ying
HY
Department of Infectious Diseases, Peking University First Hospital, Beijing 100034, China. zeng@bjmu.edu.cn
Zeng
Zheng
Z
Xu
Xiao-Yuan
XY
Zhang
Nai-Lin
NL
Yu
Min
M
Gong
Wei-Bo
WB
D000328:Adult; D020816:Amino Acid Motifs / Q000235:genetics; D000596:Amino Acids / Q000032:analysis / Q000235:genetics; D004279:DNA, Viral / Q000235:genetics; D005260:Female; D015967:Gene Expression Regulation, Viral / Q000235:genetics; D015684:Gene Products, pol / Q000235:genetics*; D005807:Genes, Overlapping / Q000235:genetics; D005814:Genes, Viral / Q000235:genetics; D006510:Hepatitis B Antibodies / Q000235:genetics*; D006514:Hepatitis B Surface Antigens / Q000235:genetics*; D006515:Hepatitis B virus / Q000235:genetics / Q000276:immunology; D019694:Hepatitis B, Chronic / Q000235:genetics* / Q000276:immunology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*
D000596:Amino Acids; D004279:DNA, Viral; D015684:Gene Products, pol; D006510:Hepatitis B Antibodies; D006514:Hepatitis B Surface Antigens; C066027:P protein, Hepatitis B virus