Hepatitis B virus X-DNA. A serum marker for early detection of resistance development during lamivudine therapy.
HBV genome replication intermediates blocked at early stages of minus strand synthesis have been identified in a study on circulating DNA and RNA during short-term lamivudine therapy. This suggested that the inhibition of HBV replication processes in the liver are mirrored in the blood. Levels of circulating HBV mRNA remained largely unaffected. Here we followed therapy with two patients (patients 1 and 2) up to stages without apparent replication. As in the earlier study, DNA segments produced successively during replication were used as targets for quantitative PCR: X (early minus strand), C (completed minus strand), and preC (nascent plus strand). Corresponding RNA was quantified by RT/PCR. Polyadenylated viral RNA were assayed as full-length (f) and as truncated (tr) RNAs. Blocked X-region intermediates persisted for about one year. After a period of undetectable HBV DNA viral replication resumed in patient 1 because of the emergence of drug-resistant mutants and in patient 2 because of the discontinuation of therapy. In the former case, X-region intermediates reappeared first, then C- and, finally, preC-region intermediates. Stopping therapy, in contrast, led to a simultaneous reappearance of all three types of intermediates. At low replication levels or its absence, trRNA represented the only polyadenylated viral RNA. Apparently, HBV serum nucleic acid markers allow a study of replication and transcription separately. Specifically, it is concluded (1) that PCR assays for monitoring lamivudine therapy must target the X-gene region and (2) that in the absence of HBV replication, trRNA may constitute a serum marker for HBV expression.
Department of Pathology, Tangdu Hospital, The Fourth Military Medical University, Xi'an, China. zhwlyh@fmmu.edu.cn
Wei
W
Zhang
Yan-Hong
YH
Li
Shao-Jun
SJ
Zhu
Yan
Y
Zhang
Li
L
Gong
Shu-Mei
SM
Wang
Hans Jörg
HJ
Hacker
Claus Hobe
CH
Schröder
Dong-Sheng
DS
Cheng
Ying-Ming
YM
Feng
D000328:Adult; D015415:Biomarkers / Q000097:blood*; D004279:DNA, Viral / Q000097:blood* / Q000235:genetics; D024882:Drug Resistance, Viral / Q000235:genetics*; D005260:Female; D006515:Hepatitis B virus / Q000235:genetics*; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use*; D008297:Male; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D014779:Virus Replication
D015415:Biomarkers; D004279:DNA, Viral; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine