Rapid HIV-1 Disease Progression in Individuals Infected with a Virus Adapted to Its Host Population.
Rapid HIV-1 Disease Progression in Individuals Infected with a Virus Adapted to Its Host Population.
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DOI：
10.1371/journal.pone.0150397
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Iwamoto A
中科院分区：
文献类型：
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作者：
Katoh J;Kawana-Tachikawa A;Shimizu A;Zhu D;Han C;Nakamura H;Koga M;Kikuchi T;Adachi E;Koibuchi T;Gao GF;Brumme ZL;Iwamoto A
基于宿主表达的人类白细胞抗原（HLA）I类等位基因，HIV-1逃避CTL是可预测的。因此，在宿主群体中循环的HIV-1序列将携带对该群体的HLA等位基因特异性的逃逸突变。从理论上讲，这应该会增加逃逸突变传播到表达限制性HLA等位基因的人的频率，从而损害宿主对进入的HIV-1毒株的免疫力。然而，感染含有免疫逃逸突变的HIV-1的临床影响尚未得到最终证实。日本人口的特点是有限的HLA多样性，这推动了人口水平的HIV适应：例如，>60%的日本人表达HLA-A*24：02及其相关的Nef-Y135 F逃逸突变代表了人口共识。因此，日本是研究这一现象的理想人群。在这里，我们结合联合收割机遗传学和免疫学分析，以确定A*24：02阳性的个人可能已经感染了Y135 F-含有HIV-1。在约5年的随访中，这些个体与推断已感染野生型HIV-1的个体相比，表现出显著较低的CD 4计数。我们的研究结果支持一个显着的负面临床影响的病原体适应宿主的压力在人口水平。
HIV-1 escape from CTL is predictable based on the Human Leukocyte Antigen (HLA) class I alleles expressed by the host. As such, HIV-1 sequences circulating in a population of hosts will harbor escape mutations specific to the HLA alleles of that population. In theory, this should increase the frequency of escape mutation transmission to persons expressing the restricting HLA allele, thereby compromising host immunity to the incoming HIV-1 strain. However, the clinical impact of infection with HIV-1 containing immune escape mutations has not conclusively been demonstrated. Japan’s population features limited HLA diversity which is driving population-level HIV adaptation: for example, >60% of Japanese express HLA-A*24:02 and its associated Nef-Y135F escape mutation represents the population consensus. As such, Japan is an ideal population in which to examine this phenomenon. Here, we combine genetic and immunological analyses to identify A*24:02-positive individuals likely to have been infected with Y135F-containing HIV-1. Over a ~5 year follow-up, these individuals exhibited significantly lower CD4 counts compared to individuals inferred to have been infected with wild-type HIV-1. Our results support a significant negative clinical impact of pathogen adaptation to host pressures at the population level.