病毒进化的患者病毒学突破的动态模式与核苷/核苷酸类似物

StephenW

Mol Med Rep. 2015 Nov 19. doi: 10.3892/mmr.2015.4577. [Epub ahead of print]
Evaluation of the dynamic pattern of viral evolution in patients with virological breakthrough during treatment with nucleoside/nucleotide analogs by ultra‑deep pyrosequencing.Chen S1, Wu J1, Gu E1, Shen Y2, Wang F1, Zhang W1.
Author information

• 1Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai 200040, P.R. China.
• 2Institute of Biomedical Sciences, Fudan University, Shanghai 200032, P.R. China.
  

AbstractVirological breakthrough is a clinical manifestation in patients infected with chronic hepatitis B (CHB), who undergo treatment with nucleoside/nucleotide analogs (NUCs). The current understanding of the underlying mechanism of virological breakthrough is limited. Ultra‑deep pyrosequencing (UDPS) is a novel and powerful tool used to investigate minor viral variants and viral evolution. The present study used UDPS to investigate the viral evolution pattern during virological breakthrough in patients with CHB treated with NUCs. A total of 12 patients who experienced virological breakthrough were recruited in the present study. During the treatment with lamivudine, adefovir was added as a rescue therapy when virological breakthrough emerged, and the therapy was continued until week 96. Serum samples from each patient were collected at different time points for UDPS analysis. Treatment with lamivudine resulted in an increased rate of the viral mutations, rtM204V/I, rtL180M and rtL80I. Virological breakthrough was accompanied by significant rtM204I/V substitutions in eight of the patients. A total of three types of rt204 mutation, associated with virological breakthrough, were observed, including YIDD variant‑dominated, YVDD variant‑dominated and YMDD wild‑type‑dominated virological breakthrough. YVDD variants reverted to the wild‑type following the adefovir add‑on rescue therapy, although the YIDD variants remained dominant following the combination therapy. The mechanism underlying virological breakthrough was revealed to be complex and associated with the rapid replication of mutated variants. UDPS analysis, therefore, provided a useful tool to investigate the dynamic evolution pattern of hepatitis B virus.

StephenW

分子医学众议员2015年19月DOI：10.3892 / mmr.2015.4577。 [打印EPUB提前]
病毒进化的患者病毒学突破的动态模式与核苷/核苷酸类似物治疗的超深焦磷酸测序过程评价。
陈S1，吴J1，顾E1，沉Y2，王F1，张W1。
作者信息

    复旦大学教研室传染病，华山医院，上海200040，中国公关。
    复旦大学2中国科学院生物医学科学学院，上海200032，中国公关。

抽象

病毒学突破是一种临床表现的感染慢性乙型肝炎（CHB）患者，谁接受治疗的核​​苷/核苷酸类似物（NUCs）。病毒学突破的基本机制目前的了解是有限的。超深焦磷酸测序（UDPS）是用于研究次要病毒变异体和病毒进化一种新颖的和强大的工具。使用UDPS本研究调查期间的慢性乙肝患者有NUCs治疗病毒学突破病毒的演化模式。共有谁经历病毒学突破12例患者被招募在​​本研究中。期间拉米夫定治疗，阿德福韦加入作为救援治疗时病毒学突破出现，该疗法持续进行，直到从每个病人周96.收集血清样品在用于UDPS分析不同时间点。治疗拉米夫定导致病毒突变，rtM204V / I，rtL180M和rtL80I率增加。病毒学突破是伴随着显著rtM204I / V置换的病人八强。一共有三种类型rt204突变，与病毒学突破相关，观察，其中YIDD变异为主，YVDD变异主导和YMDD野生型为主的病毒学突破。 YVDD变体恢复到野生型继阿德福韦附加抢救性治疗，虽然YIDD变体仍然占主导地位的下列组合治疗。基本病毒学突破机制显露是复杂和突变的变种迅速复制有关。 UDPS分析，因此，提供一个有用的工具来调查乙型肝炎病毒的动态演变图案。