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HIV-1逆转录酶突变率的测定、其可能的变构效应及其对耐药性的影响。

The Determination of HIV-1 RT Mutation Rate, Its Possible Allosteric Effects, and Its Implications on Drug Resistance.

作者信息

Yeo Joshua Yi, Goh Ghin-Ray, Su Chinh Tran-To, Gan Samuel Ken-En

机构信息

Antibody & Product Development Lab, Bioinformatics Institute, Agency for Science, Technology and Research (A*STAR), Singapore 138671, Singapore.

p53 Laboratory, Agency for Science, Technology and Research (A*STAR), Singapore 138648, Singapore.

出版信息

Viruses. 2020 Mar 9;12(3):297. doi: 10.3390/v12030297.

Abstract

The high mutation rate of the human immunodeficiency virus type 1 (HIV-1) plays a major role in treatment resistance, from the development of vaccines to therapeutic drugs. In addressing the crux of the issue, various attempts to estimate the mutation rate of HIV-1 resulted in a large range of 10-10 errors/bp/cycle due to the use of different types of investigation methods. In this review, we discuss the different assay methods, their findings on the mutation rates of HIV-1 and how the locations of mutations can be further analyzed for their allosteric effects to allow for new inhibitor designs. Given that HIV is one of the fastest mutating viruses, it serves as a good model for the comprehensive study of viral mutations that can give rise to a more horizontal understanding towards overall viral drug resistance as well as emerging viral diseases.

摘要

人类免疫缺陷病毒1型(HIV-1)的高突变率在从疫苗开发到治疗药物等治疗抗性方面起着主要作用。在解决问题的关键时,由于使用了不同类型的研究方法,各种估计HIV-1突变率的尝试导致了10-10个错误/碱基对/循环的大范围结果。在这篇综述中,我们讨论了不同的检测方法、它们关于HIV-1突变率的发现,以及如何进一步分析突变位置的变构效应以进行新的抑制剂设计。鉴于HIV是突变最快的病毒之一,它是全面研究病毒突变的良好模型,这可以使人们对整体病毒耐药性以及新出现的病毒性疾病有更全面的了解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c329/7150816/ebca1dc79e60/viruses-12-00297-g001.jpg

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