Patterns of circulating hepatitis B virus serum nucleic acids during lamivudine therapy.
We examined whether lamivudine treatment, in addition to the rapid decline of HBV serum DNA described in a large number of laboratories, causes changes in composition and amount of discernable circulating viral DNA and RNA. Nucleic acids were extracted from serial serum samples of a patient infected chronically and treated with lamivudine for 14 weeks. Three sequence segments of the HBV genome synthesized successively during replication, X, C, and X-preC, were analyzed by competitive PCR and RT/PCR. In addition, RNA was examined for differential polyadenylation. Before treatment, identical DNA copy numbers (10(9)/ml) were found in all three segments. C segment DNA displayed the expected rapid decline. X-preC, a target contiguous only on plus-strand DNA behaved similarly. In contrast, the X segment DNA copy numbers showed a less pronounced decrease remaining at higher values (10(7)/ml) than the C and X-preC segment (both about 2 x 10(5)/ml) at the end of therapy. X segment RNA displayed a persisting copy number of about 10(7)/ml, while C and X-preC RNA decreased to about 10(5) copies/ml. Polyadenylated HBV RNA, full-length and truncated, persisted initially at 10(5) but decreased to 10(4) to 10(3) copies/ml at the end of treatment. The major conclusions are the actual numbers of virus particles during lamivudine therapy can only be assessed via X segment DNA, since it is reverse transcribed first, and Lamivudine induced coexistence of DNA and RNA for the C and X segment at similar levels indicates drug-arrested intermediates of reverse transcribed HBV DNA minus-strand. Packaged RNA lacks a poly(A) tail whereas polyadenylated RNA is likely not packaged.
Zhang
Wei
W
Department of Virus-Host Interactions, Deutsches Krebsforschungszentrum Heidelberg, Germany.
Hacker
Hans Jörg
HJ
Tokus
Mehmet
M
Bock
Thomas
T
Schröder
Claus H
CH
D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use; D004279:DNA, Viral / Q000097:blood*; D006515:Hepatitis B virus / Q000187:drug effects* / Q000235:genetics* / Q000502:physiology; D019694:Hepatitis B, Chronic / Q000188:drug therapy / Q000821:virology*; D006801:Humans; D019259:Lamivudine / Q000494:pharmacology* / Q000627:therapeutic use; D012367:RNA, Viral / Q000097:blood*
D000998:Antiviral Agents; D004279:DNA, Viral; D012367:RNA, Viral; D019259:Lamivudine