病毒准种增加,口服核苷治疗治疗HBeAg阳性转阴的患者

StephenW

http://www.journal-of-hepatology.eu/article/S0168-8278%2812%2900748-9/abstract?elsca1=etoc&elsca2=email&elsca3=0168-8278_201302_58_2&elsca4=gastroenterology
Increased viral quasispecies evolution in HBeAg seroconverter patients treated with oral nucleoside therapy
病毒准种增加,口服核苷治疗治疗HBeAg阳性转阴的患者
Yan Cheng,    Stephane Guindon    ,    Allen Rodrigo    ,    Seng Gee Lim

Background & Aims

Increased viral diversity and evolution appear to be a pre-HBeAg-seroconversion feature in spontaneous and interferon-treated seroconverters. The aim of this study was to examine the viral evolution pattern in nucleoside analogue related HBeAg-seroconversion.

Methods

This was a case control study consisting of ten lamivudine-treated HBeAg-seroconverters and ten lamivudine-treated non-seroconverters as matching controls. All patients in this study were followed as long as 6years after starting lamivudine, and cases had three serum time points before HBeAg-seroconversion while controls had three matching serum time points. Nested PCR, cloning and sequencing of HBV precore/core gene were performed. Sequences were aligned with Clustal X 2.0. Phylogenetic trees were constructed and viral diversity, evolutionary rates and patterns of positive selection were evaluated.
Results

After starting lamivudine treatment, HBV viral diversity increased in both seroconverters and non-seroconverters, but seroconverters showed a significantly higher level of viral diversity that persisted over time by 2.1-fold (p=0.009). The increased viral diversity correlated with reduced HBV DNA levels (p<0.001). Lamivudine-treated seroconverters had significant reduced HBV DNA concurrent with increased viral diversity after starting treatment (p=0.001, compared to non-seroconverters, and resembled those of interferon-seroconverters published previously). There was evidence of positive selection in seroconverters with significantly increased amino acid changes compared to non-seroconverters (p<0.001), occurring in recognized T-cell and B-cell epitopes.

Conclusions

Lamivudine-treated HBeAg-seroconverters showed a higher viral diversity than non-seroconverters, and the pattern resembled that of interferon-treated seroconverters. The findings strengthen the evidence that increased viral diversity is strongly associated with HBeAg-seroconversion.

StephenW

背景与目的

增加病毒的多样性和进化出现在自发和干扰素处理的血清转化是一个预HBeAg的血清转换功能。本研究的目的是研究病毒的演化模式，在核苷类似物相关的HBeAg血清学转换。
方法

这是一个由10拉米夫定治疗的HBeAg血清转化和十拉米夫定治疗非血清转化为匹配控件的病例对照研究。在这项研究中所有患者随访，只要6年后开始拉米夫定，有三例血清e抗原血清转换的时间点之前，而对照组有三个匹配的血清时间点。巢式PCR，HBV前C / C基因的克隆与序列分析。序列与应用Clustal X 2.0。构建了系统进化树和病毒的多样性，正选择的进化速率和模式进行了评价。
结果

开始拉米夫定治疗后，HBV病毒的多样性增加，同时血清转化和非血清转化，，但血清转化显示，病毒多样性的一个显着更高水平的2.1倍（P = 0.009），随着时间的推移，坚持。增加病毒的多样性与降低HBV DNA水平（P <0.001）。拉米夫定治疗血清转化后开始治疗（P = 0.001，与非血清转化相比，有显着的降低HBV DNA的同时，增加病毒的多样性和相似的干扰素 - 血清转化公布以前）。积极的选择有证据表明，在血清转化显着增加氨基酸的变化相比，非血清转化（P <0.001），发生在公认的T细胞和B细胞表位。
结论

拉米夫定治疗的HBeAg血清转化表现出较高的病毒多样性比非血清转化，而图案相似的干扰素处理的血清转化。调查结果加强的证据表明，增加病毒的多样性是紧密联系在一起的HBeAg血清学转换。