Identification of a new variant in the YMDD motif of the hepatitis B virus polymerase gene selected during lamivudine therapy.
A new hepatitis B virus variant selected during lamivudine treatment was detected, in which the methionine (rtM204) in the so-called YMDD motif in the C domain of the catalytic site of the polymerase gene was replaced by a serine (rtM204S). This change simultaneously resulted in a tyrosine-195 into valine variant (sY195V) in the surface protein HBsAg. The detection of this YSDD variant was initially observed, after an increase of HBV DNA levels, by sequencing of amplification products from day 586. A specific RFLP assay was developed that could identify 10% of YSDD-containing variants in the virus pool, which enabled detection of this new variant virus at day 506. However, by cloning several PCR products and sequencing individual recombinant clones, the mutation was first identified at day 477, before a significant increase of HBV DNA was observed in serum. The mutation was followed by a leucine to methionine change at position 180 (rtL180M). The consequences of this mutation for disease management and diagnostic strategies are discussed.
Niesters
Hubert G M
HGM
DE Man
Robert A
RA
Department of Virology and *Gastroenterology, University Hospital Rotterdam, Rotterdam, The Netherlands.
Pas
Suzan D
SD
Fries
Edwin
E
Osterhaus
Albert D M E
ADME
D000410:Alanine Transaminase / Q000097:blood; D001483:Base Sequence; D004279:DNA, Viral / Q000097:blood / Q000235:genetics; D004259:DNA-Directed DNA Polymerase / Q000187:drug effects / Q000235:genetics*; D006515:Hepatitis B virus / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics; D019694:Hepatitis B, Chronic / Q000097:blood / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D019259:Lamivudine / Q000009:adverse effects / Q000627:therapeutic use*; D008969:Molecular Sequence Data; D012150:Polymorphism, Restriction Fragment Length; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D012641:Selection, Genetic; D017422:Sequence Analysis, DNA
D004279:DNA, Viral; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; D000410:Alanine Transaminase; D004259:DNA-Directed DNA Polymerase