Convergence and coevolution of Hepatitis B virus drug resistance

StephenW

[This is a very technical paper on HBV virus mutation and drug resistance. Interested readers may download and read the whole paper.
这是对乙肝病毒变异和耐药性的技术论文。有兴趣的读者可以下载和阅读整份论文]

ARTICLE
nature communicati ons | 3:789 | DOI: 10.1038/ncomms1794 | www.nature.com/naturecommunications
© 2012 Macmillan Publishers Limited. All rights reserved.
Received 15 Nov 2011 | Accepted 19 Mar 2012 | Published 17 Apr 2012
DOI: 10.1038/ncomms1794
Treatment with lamivudine of patients infected with hepatitis B virus (HBV) results in a high rate of drug resistance, which is primarily associated with the rtM204I/V substitution in the HBV reverse transcriptase domain. Here we show that the rtM204I/V substitution, although essential, is insufficient for establishing resistance against lamivudine. The analysis of 639 HBV whole-genome sequences obtained from 11 patients shows that rtM204I/V is independently acquired by more than one intra-host HBV variant, indicating the convergent nature of lamivudine resistance. The differential capacity of HBV variants to develop drug resistance suggests that fitness effects of drug-resistance mutations depend on the genetic structure of the HBV genome. An analysis of Bayesian networks that connect rtM204I/V to many sites of HBV proteins confirms that lamivudine resistance is a complex trait encoded by the entire HBV genome rather than by a single mutation. These findings have implications for public health and offer a more general framework for understanding drug resistance.
1 Molecular Epidemiology and Bioinformatics Laboratory, Division of Viral Hepatitis, Center for Disease Control and Prevention, Atlanta 30329, Georgia, USA. 2 Department of Internal Medicine, Division of Gastroenterology and Hepatology, University of Michigan Health System, Ann Arbor, Michigan 48109, USA. Correspondence and requests for materials should be addressed to H.T. (email: [email protected]).

咬牙硬挺

没有新药的消息吗

StephenW

回复 咬牙硬挺 的帖子

在EASL2012没有. 谣言吉利德可进行二期临床试验，其GS9620（TLR7的激动剂）.

咬牙硬挺

新药研发进入瓶颈期了