Founder effects in the assessment of HIV polymorphisms and HLA allele associations
Founder effects in the assessment of HIV polymorphisms and HLA allele associations
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DOI：
10.1126/science.1131528
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发表时间：
2007-03-16
期刊：
影响因子：
56.9
通讯作者：
Korber, Bette
中科院分区：
文献类型：
--
作者：
Bhattacharya, Tanmoy;Daniels, Marcus;Korber, Bette
逃避T细胞介导的免疫反应影响了快速进化的病毒（如HIV）的持续进化。通过应用统计方法，占病毒序列之间的系统发育关系，我们表明，病毒谱系的影响，而不是免疫逃逸往往解释明显的人类白细胞抗原（HLA）介导的免疫逃逸突变定义的旧的分析方法。系统发生学方法识别免疫易感位置的准确性大大提高，我们用这些方法识别的关联得到了实验验证。这种方法对于理解宿主免疫对病原体进化的影响和定义包含在疫苗抗原中的相关变体具有实际意义。
Escape from T cell-mediated immune responses affects the ongoing evolution of rapidly evolving viruses such as HIV. By applying statistical approaches that account for phylogenetic relationships among viral sequences, we show that viral lineage effects rather than immune escape often explain apparent human leukocyte antigen (HLA)-mediated immune-escape mutations defined by older analysis methods. Phylogenetically informed methods identified immune-susceptible locations with greatly improved accuracy, and the associations we identified with these methods were experimentally validated. This approach has practical implications for understanding the impact of host immunity on pathogen evolution and for defining relevant variants for inclusion in vaccine antigens.