The distinct contributions of fitness and genetic barrier to the development of antiviral drug resistance

被引:38
|
作者
Goette, Matthias [1 ,2 ,3 ]
机构
[1] McGill Univ, Dept Microbiol & Immunol, Montreal, PQ H3A 2B4, Canada
[2] McGill Univ, Dept Biochem, Montreal, PQ H3G 1Y6, Canada
[3] McGill Univ, Dept Med, Div Expt Med, Montreal, PQ H3A 1A3, Canada
基金
加拿大健康研究院;
关键词
HIV-1; REVERSE-TRANSCRIPTASE; CROSS-RESISTANCE; MUTATIONAL BIAS; NS5A INHIBITOR; VIRUS; PROTEASE; FIDELITY; REPLICATION; INFECTION; VARIANTS;
D O I
10.1016/j.coviro.2012.08.004
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
The selection of resistance to antiviral drugs depends on multiple parameters, including the genetic barrier that is often broadly defined as the number of mutations required to overcome drug selective pressure. In this review, it is intended to assess the roles of genetic barrier and viral fitness at various stages of the selection process. Several examples in the fields of HIV and HCV drug resistance show that the two parameters are distinct and independent. An analogy to the concept of kinetic versus thermodynamic control of chemical reactions supports a more narrow definition of the genetic barrier as the kinetic obstacle for the generation of genetic changes required to overcome selective pressure.
引用
收藏
页码:644 / 650
页数:7
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