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标题: E抗原转换后DNA水平降主要由于cccDNA水平降低 [打印本页]

作者: 肝胆速递    时间: 2012-9-1 15:23     标题: E抗原转换后DNA水平降主要由于cccDNA水平降低

本帖最后由 肝胆速递 于 2012-9-23 00:39 编辑

PLoS One. 2012;7(7):e36349. Epub 2012 Jul 20.
Hepatitis B Viral DNA Decline at Loss of HBeAg Is Mainly Explained by Reduced cccDNA Load - Down-Regulated Transcription of PgRNA Has Limited Impact.E抗原转换后DNA水平降主要由于cccDNA水平降低,pgRNA转录下调影响有限

Malmström S, Larsson SB, Hannoun C, Lindh M.
Source

Department of Infectious Diseases, University of Gothenburg, Gothenburg, Sweden.
Abstract
BACKGROUND:

Quantification of hepatitis B virus (HBV) DNA and surface antigen (HBsAg) serum levels have become increasingly important for the assessment of clinical stage and response to treatment for chronic hepatitis B. Effective immune clearance results in reduction of viremia by 4-5 log units and HBsAg levels by 2 log, but these processes are not well understood. Thus, it is uncertain to what extent mechanisms that inhibit transcription of the pregenomic RNA (pgRNA), an RNA intermediate, contribute to suppression of viremia. Likewise, it is unclear if transcriptional regulation is important for the excessive production of surface antigen (HBsAg) that is a hallmark of HBV infection.
METHODS:

HBV RNA and cccDNA were quantified in 19 liver biopsies from patients with chronic HBV infection, as well as in transfected Huh7.5 cells and in PLC/PRF/5 cells carrying integrated HBV genome.
RESULTS:

Patients negative for HBeAg had 2.15 log lower levels of cccDNA in liver tissue, 4.84 log lower serum levels of HBV DNA and 1.45 log lower serum levels of HBsAg, than HBeAg-positive patients. The pgRNA in liver tissue correlated strongly with cccDNA (R(2) = 0.87, p<0.0001) and HBV DNA levels in serum (R(2) = 0.81, p<0.0001), whereas S-RNA correlated strongly with cccDNA (R(2) = 0.65, p<0.0001) and HBsAg levels (R(2) = 0.57, p = 0.0003). The S-RNA/pgRNA ratio was higher in HBeAg-negative patients (ratio 40 vs. 3, p = 0.01) and in PLC/PRF/5 cells, and was in transfected Huh7.5 cells not influenced by mutations in the HBV core promoter.
CONCLUSION:

The reduction of viremia that is observed after loss of HBeAg was mainly explained by reduced cccDNA load in the liver, whereas the contribution of down-regulation of pgRNA transcription was relatively small. Enhanced transcription of S-RNA does not explain excessive production of HBsAg.



作者: 肝胆速递    时间: 2012-9-1 15:23

公共科学图书馆之一。 2012年7(7):e36349。 EPUB 2012年7月20日。
在HBeAg消失的B型肝炎病毒DNA下降主要是解释降低cccDNA的负载 - 下调的转录PgRNA的影响有限。
的马尔姆斯特伦S,C,林德M.拉尔森SB,哈农


传染病,哥德堡,瑞典哥德堡大学的学系。
抽象
背景:

定量分析乙型肝炎病毒(HBV)DNA与表面抗原(HBsAg)血清水平已成为越来越重要的评估,临床分期和治疗慢性乙型肝炎有效的免疫清除病毒血症减少4-5个对数单位HBsAg和2记录的水平,但这些处理过程并不了解。因此,它是不定的何种程度上抑制转录前基因组RNA(pgRNA),一个RNA中间体的机制,有助于抑制病毒血症。同样的,目前还不清楚过量生产的特点是HBV感染的表面抗原(HBsAg),如果转录调控是非常重要的。
方法:

HBV RNA进行定量与cccDNA在慢性HBV感染的患者,以及在的转Huh7.5细胞PLC/PRF/5细胞整合型HBV基因组,在19个肝活检。
结果:

对于HBeAg阴性患者的肝组织中的cccDNA的水平低2.15日志,4.84日志降低血清HBV DNA水平为1.45日志降低血清中的HBsAg水平低于HBeAg阳性患者。 pgRNA强相关的肝组织cccDNA水平(R(2)= 0.87,P <0.0001)和(R(2)= 0.81,P <0.0001)血清HBV DNA水平,而S-RNA相关坚决与cccDNA水平(R (2)= 0.65,P <0.0001),HBsAg水平(R(2)= 0.57,P = 0.0003)。 S-RNA/pgRNA比明显高于HBeAg阴性患者(比为40比3,P = 0.01)和PLC/PRF/5细胞,并在的转Huh7.5细胞乙肝病毒核心基因突变不会影响子。
结论:

HBeAg消失后观察到的病毒血症的减少主要说明通过降低在肝脏中的共价闭合环状DNA的负载,而下调pgRNA转录的贡献是相对小的。增强的S-RNA的转录并不能说明乙肝表面抗原的过度生产。
作者: 肝胆速递    时间: 2012-9-1 15:26

全篇论文都可以在这里找到:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3401194/?tool=pubmed





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