hbv genotyping/hbv drug resistance ymdd mutation · activity of hbv polymerase during viral...
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HBV Genotyping/HBV Drug Resistance
YMDD Mutation
Introduction - HBV
There are about 350 million persons chronically infected
with HBV worldwide. Chronic carrier rate in India is 4.7%
Chronic HBV infection is associated with a wide range of
clinical manifestations, from an asymptomatic carrier status
with a normal liver histology to severe and chronic liver
disease, including cirrhosis and hepatocellular carcinoma
(HCC).
The virus relies on error-prone reverse transcriptase during
the replicative process due to which mutant viral genomes
are found frequently.
Reverse transcriptase
A reverse transcriptase, also known as RNA-dependent DNA
polymerase, is a DNA polymerase enzyme that transcribes
single-stranded RNA into single-stranded DNA
The enzyme is encoded and used by reverse-transcribing
viruses, which use the enzyme during the process of
replication
Without reverse transcriptase, the viral genome would not be
able to incorporate into the host cell, resulting in the failure of
the ability to replicate
HBV Genotypes:
• HBV is been classified into 8 genotypes (A-H) based on an
intergroup divergence of 8% or more in the complete
nucleotide sequence.
Significance of HBV Genotyping
• HBV genotype C is associated with more severe liver diseases than genotype B.
• Patients infected with genotype D appear to have a higher incidence of HCC, a higher risk for HBV recurrence, and a higher mortality rate after liver transplantation than patients with genotype A.
• Patients with HBV genotypes C and D have a lower response rate to treatment with IFN-a compared to those with genotypes A and B.
• Genotype may also influence the emergence of lamivudine resistance mutations, which appear to be more strongly associated with genotype A than genotype D.
• Therefore, HBV genotyping is of great importance in guiding treatment, improving vaccination, and controlling liver diseases.
HBVDR
• Lamivudine, Telbivudine, Adefovir and Emtricitabine are nucleotide/nucleoside analogues that target the reverse transcriptase activity of HBV polymerase during viral replication.
• Nucleotide/Nucleoside analogue therapy allows safe, long term supression of hepatitis B virus and is a major milestone in the treatment of chronic hepatitis B.
• Early detection of emerging HBV drug resistance mutations helps to monitor lamivudine treatment, and improves therapeutic decision making like use of adefovir rescue therapy.
Amino Acid SLC DNA codons
Isoleucine I ATT, ATC, ATA
Leucine L CTT, CTC, CTA, CTG, TTA, TTG
Valine V GTT, GTC, GTA, GTG
Phenylalanine F TTT, TTC
Methionine M ATG
Cysteine C TGT, TGC
Alanine A GCT, GCC, GCA, GCG
Glycine G GGT, GGC, GGA, GGG
Proline P CCT, CCC, CCA, CCG
Threonine T ACT, ACC, ACA, ACG
Serine S TCT, TCC, TCA, TCG, AGT, AGC
Tyrosine Y TAT, TAC
Tryptophan W TGG
Glutamine Q CAA, CAG
Asparagine N AAT, AAC
Histidine H CAT, CAC
Glutamic acid E GAA, GAG
Aspartic acid D GAT, GAC
Lysine K AAA, AAG
Arginine R CGT, CGC, CGA, CGG, AGA, AGG
Stop codons Stop TAA, TAG, TGA
Y I D D
YMDD – YIDD/ YVDD
YMDD test report @Metropolis
HBVDR test report @Metropolis
HBVDR test report @Metropolis
HBV Genotyping/ HBV-DR
HBV DNA Extn
(Serum/ Plasma)
Nested PCR
(Polymerase Gene) Gel Electrophoresis
HBVG Analysis
(Viral Genotyping Tool)
PCR Sequencing
HBV-DR Analysis
(Mutation Detection)