Comparisons of the HBV and HIV polymerase, and antiviral resistance mutations.
The antiviral treatment of chronic hepatitis B is limited by the selection of antiviral resistance mutations. Primary resistance to lamivudine occurs at rtM2041/V in the C Domain of the polymerase. Recently, resistance to adefovir has also been described in the D Domain at rtN236T. The treatment of patients with resistant virus without complete suppression can lead to the further selection of compensatory mutations. Thus, to gain an understanding of the hepatitis B virus (HBV) polymerase and also mutations associated with resistance, a three-dimensional model of the HBV reverse transcriptase core region based on homology with human immunodeficiency virus (HIV) was created. A comparative analysis of the HIV polymerase and the model of HBV polymerase was performed. In addition, the antiviral resistance mutations including potential compensatory mutations were mapped to determine their effect on the HBV polymerase model, especially in the nucleotide binding site.
Bartholomeusz
Angeline
A
Victorian Infectious Diseases Reference Laboratory, North Melbourne, Victoria, Australia. angeline@mh.org.au
Tehan
Benjamin G
BG
Chalmers
David K
DK
D000595:Amino Acid Sequence; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology; D001483:Base Sequence; D024882:Drug Resistance, Viral; D054303:HIV Reverse Transcriptase / Q000737:chemistry* / Q000235:genetics; D006515:Hepatitis B virus / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics; D019694:Hepatitis B, Chronic / Q000821:virology; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D012194:RNA-Directed DNA Polymerase / Q000737:chemistry* / Q000235:genetics
D000998:Antiviral Agents; D054303:HIV Reverse Transcriptase; D012194:RNA-Directed DNA Polymerase