HIV evolution: CTL escape mutation and reversion after transmission
HIV evolution: CTL escape mutation and reversion after transmission
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DOI：
10.1038/nm992
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发表时间：
2004-03-01
期刊：
影响因子：
82.9
通讯作者：
Goulder, PJR
中科院分区：
文献类型：
--
作者：
Leslie, AJ;Pfafferott, KJ;Goulder, PJR
患者体内的HIV进化反映了强大的选择压力驱动病毒逃避细胞毒性t淋巴细胞（CTL）识别。这种患者内逃逸突变的积累是否转化为人群水平上的HIV进化尚未得到评估。我们研究了来自B支和c支流行病的300多名患者，重点研究了人类白细胞抗原（HLA）等位基因HLA- b57和HLA- b5801，这些等位基因与HIV的长期控制有关，因此可能对病毒施加强大的选择压力。在hlab57 /5801阳性受试者的急性感染中，CTL反应主导了逃逸突变的阳性选择，该突变在传播到hla - b57 /5801阴性个体后恢复为野生型。相比之下，表位内的第二个逃逸突变在传播后保持不变。这些数据表明，艾滋病毒内部逃逸突变的积累过程并非不可避免。复杂的表位和残基特异性选择力，包括ctl介导的正选择压力和病毒介导的纯化选择，协同作用在群体水平上塑造HIV进化。
Within-patient HIV evolution reflects the strong selection pressure driving viral escape from cytotoxic T-lymphocyte (CTL) recognition. Whether this intrapatient accumulation of escape mutations translates into HIV evolution at the population level has not been evaluated. We studied over 300 patients drawn from the B- and C-clade epidemics, focusing on human leukocyte antigen (HLA) alleles HLA-B57 and HLA-B5801, which are associated with long-term HIV control and are therefore likely to exert strong selection pressure on the virus. The CTL response dominating acute infection in HLAB57/5801-positive subjects drove positive selection of an escape mutation that reverted to wild-type after transmission to HLA-B57/5801-negative individuals. A second escape mutation within the epitope, by contrast, was maintained after transmission. These data show that the process of accumulation of escape mutations within HIV is not inevitable. Complex epitope- and residue-specific selection forces, including CTL-mediated positive selection pressure and virus-mediated purifying selection, operate in tandem to shape HIV evolution at the population level.