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首页> 外文期刊>Hepatology: Official Journal of the American Association for the Study of Liver Diseases >Defective hepatitis B virus DNA is not associated with disease status but is reduced by polymerase mutations associated with drug resistance.
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Defective hepatitis B virus DNA is not associated with disease status but is reduced by polymerase mutations associated with drug resistance.

机译：乙型肝炎病毒DNA的缺陷与疾病状况无关，但与耐药性相关的聚合酶突变可减少这种缺陷。

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摘要

Defective hepatitis B virus DNA (dDNA) is reverse-transcribed from spliced hepatitis B virus (HBV) pregenomic messenger RNA (pgRNA) and has been identified in patients with chronic HBV (CH-B). The major 2.2-kb spliced pgRNA encodes a novel HBV gene product, the hepatitis B splice protein (HBSP) via a deletion and frame shift within the polymerase. Although spliced RNA and HBSP expression have been associated with increased HBV DNA levels and liver fibrosis, the role of dDNA in HBV-associated disease is largely undefined. Our aims were to (1) compare the relative proportions of dDNA (% dDNA) in a range of HBV-infected serum samples, including patients with human immunodeficiency virus (HIV)/HBV coinfection and HBV-monoinfected persons with differing severities of liver disease, and (2) determine the effect of mutations associated with drug resistance on defective DNA production. Defective DNA was detected in 90% of persons with CH-B. There was no significant difference in the relative abundance of dDNA between the monoinfected and HIV/HBV-coinfected groups. We also found no association between the % dDNA and alanine aminotransferase, hepatitis B e antigen status, HBV DNA levels, fibrosis levels, compensated or decompensated liver cirrhosis, genotype, or drug treatment. However, the % dDNA was significantly lower in individuals infected with lamivudine-resistant (LMV-R) HBV compared with wild-type HBV (P < 0.0001), indicating that antiviral drug resistance alters the balance between defective and genomic length DNA in circulation. Experiments in vitro using HBV encoding LMV-R mutations confirmed these results. CONCLUSION: Our results identified no association between dDNA and parameters associated with disease status and suggested that the relative abundance of dDNA is largely dependent on the integrity of the HBV polymerase and is unrelated to the severity of liver disease.
机译：有缺陷的乙型肝炎病毒DNA（dDNA）从剪接的乙型肝炎病毒（HBV）前基因组信使RNA（pgRNA）中逆转录，并已在慢性HBV（CH-B）患者中得到鉴定。 2.2kb的主要剪接pgRNA通过聚合酶内的缺失和移码来编码新型HBV基因产物，即乙型肝炎剪接蛋白（HBSP）。尽管剪接的RNA和HBSP表达与HBV DNA水平升高和肝纤维化有关，但dDNA在HBV相关疾病中的作用尚不清楚。我们的目标是（1）比较一系列HBV感染的血清样本中dDNA的相对比例（％dDNA），包括患有人类免疫缺陷病毒（HIV）/ HBV合并感染的患者和患有严重肝病严重程度不同的HBV单一感染者（2）确定与耐药相关的突变对缺陷DNA产生的影响。在90％的CH-B患者中检测到DNA缺陷。在单感染和HIV / HBV合并感染组之间，dDNA的相对丰度没有显着差异。我们还发现％dDNA与丙氨酸转氨酶，乙型肝炎e抗原状态，HBV DNA水平，纤维化水平，代偿性或代偿性肝硬化，基因型或药物治疗之间没有关联。但是，与野生型HBV相比，拉米夫定抗性（LMV-R）HBV感染的个体中dDNA的百分比显着降低（P <0.0001），这表明抗病毒药物耐药性改变了循环中缺陷和基因组长度DNA之间的平衡。使用编码LMV-R突变的HBV进行的体外实验证实了这些结果。结论：我们的结果未发现dDNA与疾病状态相关参数之间存在关联，并提示dDNA的相对丰度很大程度上取决于HBV聚合酶的完整性，而与肝病的严重程度无关。

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