VARIANTS OF HEPATITIS B VIRUS WITH RESISTANCE TO ANTI-VIRAL NUCLEOSIDE AGENTS AND APPLICATIONS THEREOF

摘要

The present invention relates generally to viral variants exhibiting reduced sensitivity to particular agents and/or reduced interactivity with immunological reagents. More particularly, the present invention is directed to hepatitis B virus (HBV) variants exhibiting complete or partial resistance to nucleoside or nucleotide analogs and/or reduced interactivity with antibodies to viral surface components including reduced sensitivity to these antibodies. The present invention further contemplates assays for detecting such viral variants, which assays are useful in monitoring anti-viral therapeutic regimens and in developing new or modified vaccines directed against viral agents and in particular HBV variants. The present invention also contemplates the use of the viral variants to screen for and/or develop or design agents capable of inhibiting infection, replication and/or release of the virus.

主权项

1. An isolated Hepatitis B virus (HBV) variant wherein said variant comprises a nucleotide mutation resulting in an amino acid addition, substitution and/or deletion in a protein encoded by said variant and wherein said variant exhibits decreased sensitivity to one or more nucleoside or nucleotide analogs selected from the list consisting of ADV, LMV, TFV and FTC wherein said HBV variant comprises a mutation in the gene encoding a DNA polymerase at a codon selected from the list consisting of rtN53, rtY54, rtL180, rtT181, rtT184, rtM204, rtN236, rtY124, rtH126, rtT128, rtS135, rtL180, rtS202, rtM204, rtH248, rtI53, rtS54, rtN122, rtM145, rtL180, rtM204, rtM250, rtN53, rtS85, rtS116, rtD134, rtN139, rtQ149, rtA181, rtS219, rtI233, rtN236 or rtM250 and/or a mutation in the gene encoding a surface antigen selected from a mutation at a codon selected from the list consisting of stT45, sL173, sL175, sI195, sT118, sP120, sP127, sI195, sT114, sI195, sS204, sI208, sS210, sV14, sG130, sM133, sW172, sS204 or sS210.