Microbiome Biomarkers: One Step Closer in NAFLD Cirrhosis.
Microbiome Biomarkers: One Step Closer in NAFLD Cirrhosis.
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微生物组生物标志物：NAFLD 肝硬化又近了一步。
DOI：
10.1002/hep.31660
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发表时间：
2021
期刊：
影响因子：
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通讯作者：
Huttenhower,Curtis
中科院分区：
文献类型：
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作者：
Simon,TraceyG;Chan,AndrewT;Huttenhower,Curtis
我们的研究表明，与血清HBV DNA相比，血清HBV RNA rtM204I/V突变的出现通常是延迟的，并且在持续的NA治疗下，两者最终都将成为接近100%的突变形式。(1)一般来说，由于病毒聚合酶缺乏校对活性，HBV突变主要发生在基因组前RNA （pgRNA）逆转录为宽松环状DNA （rcDNA）的过程中。(2)携带rtM204I/V的rcDNA可在病毒粒子内分泌感染新肝细胞或再循环进入细胞核，合成突变型共价闭合环状DNA (cccDNA)，转录突变型pgRNA。因此，从理论上讲，突变型HBV RNA和cccDNA的出现滞后于突变型rcDNA，直到野生型cccDNA转换完成。廖博士假设了两种情况，即在NAs治疗下，肝内野生型pgRNA优先直接分泌，而突变型pgRNA优先转化为突变型rcDNA然后释放。第一种情况可能是基于他们发表的NA治疗后HepAD38细胞细胞外HBV DNA减少和细胞外HBV RNA增加。(3)然而，由于CHB患者的pgRNA转录模板与HepAD38细胞中的pgRNA转录模板不同，因此在CHB患者中没有得到同样的观察结果。对于后一种情况，目前尚不清楚突变体pgRNA反转录和随后的rcDNA病毒粒子分泌效率是否优于突变体pgRNA分泌；因此，主要路线
Our study demonstrated that the emergence of serum HBV RNA rtM204I/V mutation was generally delayed compared with that of serum HBV DNA, and both of them would ultimately become nearly 100% mutant forms under continuous NA therapy.(1) Generally, HBV mutations occurred primarily during the reverse transcription of pregenomic RNA (pgRNA) into relaxed circular DNA (rcDNA) due to viral polymerase lacking proofreading activity.(2) The rcDNA carrying rtM204I/V could be secreted in virion to infect new hepatocyte or recycled into nucleus, synthesizing mutant covalently closed circular DNA (cccDNA) and then transcribing mutant pgRNA. Hence, theoretically, the appearance of mutant HBV RNA and cccDNA lags behind mutant rcDNA until the wild-type cccDNA turnover is completed. Dr. Liao postulated two scenarios that, under NAs therapy, the intrahepatic wild-type pgRNA would be preferentially secreted directly, while the mutant pgRNA is preferentially converted to mutant rcDNA and then released. The first scenario might be based on their publication showing a decrease of extracellular HBV DNA and increase of extracellular HBV RNA in HepAD38 cells following NA treatment.(3) However, such observation has not been reproduced in patients with CHB, whose pgRNA transcription template was different from that in HepAD38 cells. Regarding the latter scenario, it is not known whether the efficiency of mutant pgRNA reverse transcription and subsequent rcDNA virion secretion is superior to mutant pgRNA secretion; thus, the major route