Antiviral therapies: Focus on hepatitis B reverse transcriptase.

StephenW

Int J Biochem Cell Biol. 2012 Apr 16. [Epub ahead of print]
Antiviral therapies: Focus on hepatitis B reverse transcriptase.Michailidis E, Kirby KA, Hachiya A, Yoo W, Hong SP, Kim SO, Folk WR, Sarafianos SG.
SourceChristopher S. Bond Life Sciences Center, Department of Molecular Microbiology & Immunology, University of Missouri, Columbia, MO 65211, USA.

AbstractHepatitis 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.
Copyright © 2012. Published by Elsevier Ltd.

StephenW

生物化学与细胞生物学。 2012年4月16日。 [出处提前打印]
抗病毒治疗乙肝逆转录焦点。
，柯比KA michailidisé，一蜂屋，柳W，香港SP，金苏，民歌西铁，Sarafianos神光。
源

克里斯托弗·邦德与生命科学中心，分子微生物学与免疫学，密苏里大学，哥伦比亚，密苏里州65211，美国系。


摘要


B型肝炎病毒（HBV）是对人类最严重的肝脏疾病的病原体。虽然疫苗的可用性，减少了一些新的乙肝病毒感染，疫苗并不能惠及约350万已长期受病毒感染的人。逆转录酶（RT或P基因产物）和大多数药物通过FDA批准用于治疗乙肝的目标是核苷逆转录酶抑制剂（NRTI）抑制病毒复制。然而，长期单一疗法针对单一目标的结果中出现的病毒抗性。 HBV基因型差异影响NRTI的阻力，因为在S的阅读框（表面抗原）和P基因部分重叠，影响表面的病毒基因组的差异也可能改变病毒聚合酶序列，功能和药敏。本次审查的范围是耐药NRTI的发展，以评估HBV基因型差异的影响。一些不同基因型不同的RT残留在附近的残基突变引起NRTI的阻力。这些氨基酸之间的相互作用可以帮助解释HBV基因型对NRTI的阻力在抗病毒治疗的发展的影响，并可能有助于设计更好的治疗策略。

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