Variants of hepatitis B virus with resistance to anti-viral nucleoside agents and applications thereof

摘要

Disclosed is an isolated Hepatitis B virus (HBV) variant comprising amino acid co-mutations within a reverse transcriptase (rt) of a DNA polymerase conferring resistance to at least two nucleoside or nucleotide analogs said co-mutations comprising an amino acid substitution, addition or deletion of an Alanine (A) at amino acid residue number 181 (rtA181), an Isoleucine (I) at amino acid residue number 233 (rtI233), an Asparagine (N) at amino acid residue number 236 (rtN236) and a Methionine (M) at amino acid residue number 250 (rtM250) of the rt of the DNA polymerase.