Antiviral therapies: focus on hepatitis B reverse transcriptase.
Antiviral therapies: focus on hepatitis B reverse transcriptase.
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DOI：
10.1016/j.biocel.2012.04.006
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发表时间：
2012-07
期刊：
影响因子：
--
通讯作者：
Sarafianos SG
中科院分区：
文献类型：
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作者：
Michailidis E;Kirby KA;Hachiya A;Yoo W;Hong SP;Kim SO;Folk WR;Sarafianos SG
乙型肝炎病毒（Hepatitis B Virus，HBV）是人类最严重的肝脏疾病的病原体。虽然疫苗的可用性减少了新的HBV感染的数量，但疫苗并没有使已经慢性感染该病毒的约3.5亿人受益。FDA批准用于治疗B型肝炎的大多数药物靶向逆转录酶（RT或P基因产物），并且是抑制病毒复制的核苷RT抑制剂（NRTI）。然而，针对单一靶标的长期单一疗法导致病毒耐药性的出现。HBV基因型差异影响NRTI耐药性，由于S（表面抗原）和P基因的阅读框部分重叠，影响病毒表面的基因组差异也可能改变病毒聚合酶序列、功能和药物敏感性。本综述的范围是评估HBV基因型变异对NRTIs耐药性发展的影响。在不同基因型之间变化的一些RT残基位于突变并产生NRTI抗性的残基附近。这些氨基酸之间的相互作用可以帮助解释HBV基因型对抗病毒治疗期间NRTI耐药性的发展的影响，并可能有助于设计改进的治疗策略。
Hepatitis B virus (HBV) is the etiologic agent of mankind’s most serious liver disease. While the availability of a vaccine has reduced the number of new HBV infections, the vaccine does not benefit the approximately 350 million people already chronically infected by the virus. Most of the drugs approved by the FDA for the treatment of hepatitis B target the reverse transcriptase (RT or P gene product) and are nucleoside RT inhibitors (NRTIs) that suppress viral replication. However, prolonged monotherapies directed against a single target result in the emergence of viral resistance. HBV genotypic differences affect NRTI resistance, and because the reading frames of the S (surface antigen) and P genes partially overlap, genomic differences that affect the surface of the virus may also alter the viral polymerase sequence, function and drug susceptibility. The scope of this review is to assess the effects of HBV genotypic variation on the development of drug resistance to NRTIs. Some RT residues that vary among different genotypes are in the vicinity of residues that mutate and give rise to NRTI resistance. Interactions between these amino acids can help explain the effect of HBV genotype on the development of NRTI resistance during antiviral therapies, and might help in the design of improved therapeutic strategies.