Viral variants and methods for detecting same
AssigneeMelbourne Health
InventorsStephen A. LOCARNINI, Angeline I. Bartholomguez, Thein T. Aye, Robert A. de Man
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Abstract
The present invention relates generally to viral variants exhibiting reduced interactivity with immunological reagents. More particularly, the present invention is directed to hepatitis B variants exhibiting complete or partial resistance to nucleoside analogs and/or reduced interactivity with antibodies to viral surface components. The present invention further contemplates assays for detecting such viral variants which assays are useful in monitoring anti-viral therapeutic agents.
Claims17
An isolated HBV mutant, comprising one or more mutations in the gene encoding the HBV polymerase resulting in decreased sensitivity to a nucleoside analogue compared to a wild-type HBV, wherein said mutation(s) result(s) in at least one amino acid addition, substitution and/or deletion in the A domain corresponding to amino acid residues 421-436 of a wild-type HBV polymerase and/or in the D domain corresponding to amino acid residues 576-588 of a wild-type HBV polymerase and/or in the E domain corresponding to amino acid residues 592-600 of a wild-type HBV polymerase, or in a region proximal thereto.
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, deletion and/or addition in the D domain or E domain or a region proximal thereto of said DNA polymerase wherein the presence of such a mutation is an indication of the likelihood of resistance to said nucleoside analogue.
A method for determining whether an HBV isolate encodes a variant DNA polymerase, said method comprising determining the amino acid sequence of its DNA polymerase directly or via a nucleotide sequence and comparing same to the amino acid sequence below (SEQ ID NO:29):
- DOMAIN A
- 421 430 440 450
- SNDLSWLSLD VSAAFYHIPPL HPAAMPHLLIV GSSGLSDRYVA
- 460 470 480 490
- RLSSTNSRNNI*N NYHQHYGR***DNLH DNSYCSRNQLYVS LLMLLYKQTYFGRW
- DOMAIN B
- 500 510 520 530
- KLHLYLSAHPIIV LGFRKILPMGVG GLSPFLLAQF TSAICLASVMVTRCR
- DOMAIN C
- 540 550 560
- AFFPHCLVAVFSAY MDDVLMVLGAKRST VGQEHLSRESFLFYTAAS
- DOMAIN D DOMAIN E
- 570 580 590 600
- VITCNSFVLLSDLVGI HLNPNQKTKRW GYSLNFMGYVII G
- where the presence of a different amino acid from the consensus sequence in the D or E domain indicates a putative HBV mutant.
A method for determining whether an HBV isolate encodes a variant DNA polymerase said method comprising determining the amino acid sequence of the A domain (corresponding to amino acid residues 421-436) or a region proximal thereto (corresponding to amino acid residues 437-456) directly or via a nucleotide sequence and comparing same to the A domain or the region proximal thereto of the following amino acid sequence (SEQ ID NO:29):
- DOMAIN A
- 421 430 440 450
- SNDLSWLSLD VSAAFYHIPPL HPAAMPHLLIV GSSGLSDRYVA
- 460 470 480 490
- RLSSTNSRNNI*N NYHQHYGR***DNLH DNSYCSRNQLYVS LLMLLYKQTYFGRW
- DOMAIN B
- 500 510 520 530
- KLHLYLSAHPIIV LGFRKILPMGVG GLSPFLLAQF TSAICLASVMVTRCR
- DOMAIN C
- 540 550 560
- AFFPHCLVAVFSAY MDDVLMVLGAKRST VGQEHLSRESFLFYTAAS
- DOMAIN D DOMAIN E
- 570 580 590 600
- VITCNSFVLLSDLVGI HLNPNQKTKRW GYSLNFMGYVII G
Dependencies are inferred from the claim text.