[The change of HBV nucleotide sequence during Adefovir dipivoxil treatment].
OBJECTIVE
To study the change of HBV nucleotide sequence during Adefovir dipivoxil treatment.


METHODS
Serum samples were collected from 4 patients (numbers 228, 229, 230 and 233) with chronic hepatitis B (CHB) treated with PMEA. PCR amplification of full-length genomes, total genome clone, and sequencing and linkage of the HBV viruses were done with the serum samples collected before the therapy, and again on the 28th week, 52nd week and on the 92nd week of the therapy. Gene types and serum types were studied according to the HBV DNA sequence. The related biological information was analyzed, including the homogeneity and heterogeneity of the HBV DNA sequence before and during PMEA therapy, and variance of amino acids coded by HBV sequence.


RESULTS
The gene types and serum types of HBV of the 4 patients were determined. Patient 228 was gene type C/serum type adrq+. Patient 229 was complex gene type B and C/complex serum type adw2 and adrq+. Patients 230 and 233 were both serum type adw2. The homogeneity of total gene sequence was 97.5% - 99.8% in one group of patients and 90.6% - 100% between groups in variant patients. The base mutation quantity of 52W was significantly higher than that of 28W and 92W. There was a common site of hotspot congregating mutation that existed in the P region. The target of PMEA was located in the P region encoding reverse transcriptase, which was generally very conservative. Therefore the mutations in this region were very significant. This might affect the activity of reverse transcriptase, leading to resistance to PMEA.


CONCLUSIONS
We discovered some unusual aminophenol variations in the HBV genomes, which most probably are related to the HBV mutation that resulted in the developing resistance to PMEA.
Lu
Jian-xi
JX
Central Laboratory, Third Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, China.
Xie
Dong-ying
DY
Xu
Qi-huan
QH
Zhu
Ming-fen
MF
Chen
Wei
W
Li
Li
L
Li
Gang
G
D000225:Adenine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use; D004279:DNA, Viral / Q000235:genetics*; D005260:Female; D006515:Hepatitis B virus / Q000235:genetics*; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D008297:Male; D063065:Organophosphonates / Q000627:therapeutic use*; D017354:Point Mutation; D017422:Sequence Analysis, DNA
D000998:Antiviral Agents; D004279:DNA, Viral; D063065:Organophosphonates; D000225:Adenine; C106812:adefovir dipivoxil