Viral variants
AssigneeMelbourne Health
InventorsAngeline Bartholomeusz, Margaret Littlejohn, Anna Ayres, Stephen Locarnini
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Abstract
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 variants exhibiting complete or partial resistance to nucleoside analogues and/or reduced interactivity with antibodies to viral surface components including reduced sensitivity. The present invention further contemplates assays for detecting such viral variants which assays are useful in monitoring anti-viral therapeutic regimes and in developing new or modified vaccines directed against viral agents and in particular hepatitis B virus variants.
Claims1
A method for determining the potential for an HBV to exhibit reduced sensitivity to a nucleoside analogue, said method comprising isolating DNA or corresponding mRNA from said HBV and screening for one or more mutation(s) in the nucleotide sequence encoding HBV DNA polymerase resulting in at least one amino acid substitution in the D domain of said DNA polymerase wherein the presence of such a mutation is an indication of the likelihood of resistance to said nucleoside analogue, wherein said one or more mutation(s) is selected from the group consisting of N584S, N584K, S/H584N/K, R588K, N/Q 584H, K587R in the following sequence:
- Z47Z48GIHLNPZ49KTKR (SEQ ID NO:9)
- wherein Z47 is S or D;
- Z48 is L or V, and Z49 is N or Q, wherein the notation defines a codon number position of HBV genotype with reference to codon 550 being methionine in the YMDD motif, the letter(s) proceeding the number in the notation of the mutation being at least one wild-type or permutation amino acid at said codon number position, and the letter(s) subsequent to the number in the notation being at least one post-mutation amino acid at said codon number position, wherein Z47 is codon number position 576 of the HBV genotype.
Dependencies are inferred from the claim text.