Identification of a novel pre-S2 mutation in a subgroup of chronic carriers with spontaneous clearance of hepatitis B virus surface antigen.
OBJECTIVE
The aim of the present study was to investigate whether spontaneous seroclearance of hepatitis B surface antigen (HBsAg) in patients with chronic hepatitis B could be attributed to the presence of pre-S/S gene mutations.


METHODS
Of 34 hepatitis B virus (HBV) carriers who experienced spontaneous seroclearance of HBsAg, 30 were still seropositive for HBV DNA. The serum samples of these carriers were subjected to sequence analysis.


RESULTS
A novel pre-S2 mutation, G149R, was found in nine (group I) but not in 17 (group II) patients carrying HBV DNA with intact pre-S/S reading frames. In the remaining four patients (group III), only aberrant pre-S/S transcripts were found in their sera. Distinct patterns of amino acid substitutions specific to group I and II patients were identified. Superinfection by hepatitis C or D virus occurred predominantly in group II patients (P = 0.019). Superinfection by HBV of a different genotype occurred predominantly in patients without hepatitis C or D virus superinfection (P = 0.013). Site-directed mutagenesis experiments showed that secretion of HBsAg was not defective in the pre-S2 G149R mutant.


CONCLUSIONS
In a particular subgroup (group I) of patients, seroclearance of HBsAg was not caused by superinfection of other hepatitis viruses, nor was it caused by failure of HBsAg secretion or detection. Instead, a yet unrecognized mechanism associated with emergence of a novel pre-S2 mutation is responsible.
Yeh
Chau-Ting
CT
Liver Research Unit, Chang Gung Memorial Hospital and Chang Gung University School of Medicine, Taipei, Taiwan. catyeh@ms14.hinet.net
Chang
Mei-Hui
MH
Lai
Hsin-Yu
HY
Chang
Ming-Ling
ML
Chu
Chia-Ming
CM
Liaw
Yun-Fan
YF
D000328:Adult; D000368:Aged; D019943:Amino Acid Substitution; D002353:Carrier State / Q000821:virology*; D004279:DNA, Viral / Q000235:genetics; D005260:Female; D005838:Genotype; D006514:Hepatitis B Surface Antigens / Q000097:blood* / Q000235:genetics*; D006515:Hepatitis B virus / Q000235:genetics; D019694:Hepatitis B, Chronic / Q000821:virology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D011498:Protein Precursors / Q000235:genetics*; D016364:Reading Frames; D020539:Sequence Analysis, Protein; D015163:Superinfection / Q000821:virology
D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens; D011498:Protein Precursors; C050807:presurface protein 2, hepatitis B surface antigen