Viral variants with altered susceptibility to nucleoside analogs and uses thereof

A method for determining whether a hepatitis B virus (“test virus”) from a human patient would exhibit reduced sensitivity to entecavir relative to a wild-type HBV, the method comprising:

• screening a nucleic acid molecule from the test virus with entecavir-resistance mutations, wherein the nucleic acid molecule comprises a nucleic acid sequence that encodes a reverse transcriptase domain of a DNA polymerase, the mutations being combinations of mutations selected from the group consisting of:
• (i) mutations at codon positions 180, 184, 202 and 204;
• and
• (ii) mutations at codon positions 180, 204, and 250;
• wherein codon positions 180, 184, 202, 204 and 250 correspond to positions 106, 110, 128, 130 and 176, respectively, of SEQ ID NO:2;
• wherein the mutation at codon position 180 is a substitution to methionine and the mutation at codon position 204 is a substitution to isoleucine or valine, and
• wherein the presence of the mutations corresponding to combination (i) or (ii) indicates that the test virus would exhibit reduced sensitivity to entecavir.