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Insights from host genomics into HIV infection and disease: Identification of host targets for drug development

机译:宿主基因组学对HIV感染和疾病的见解:确定药物开发的宿主靶标

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摘要

HIV susceptibility and disease progression show a substantial degree of individual heterogeneity, ranging from fast progressors to long-term non progressors or elite controllers, that is, subjects that control infection in the absence of therapy. Recent years have seen a significant increase in understanding of the host genetic determinants of susceptibility to HIV infection and disease progression, driven in large part by candidate gene studies, genome-wide association studies, genome-wide transcriptome analyses, and large-scale functional screens. These studies have identified common variants in host loci that clearly influence disease progression, characterized the scale and dynamics of gene and protein expression changes in response to infection, and provided the first comprehensive catalogue of genes and pathways involved in viral replication. This review highlights the potential of host genomic influences in antiviral therapy by pointing to promising novel drug targets but also providing the basis of the identification and validation of host mechanisms that might be susceptible targets for novel antiviral therapies.
机译:HIV易感性和疾病进展显示出很大程度的个体异质性,从快速进展者到长期的非进展者或精英控制者,即在没有治疗的情况下控制感染的受试者。近年来,对宿主对艾滋病毒感染和疾病进展易感性的遗传决定因素的理解有了显着提高,这在很大程度上是由候选基因研究,全基因组关联研究,全基因组转录组分析和大规模功能筛选驱动的。这些研究已经确定了宿主基因座中的常见变异,这些变异明显影响疾病的进程,表征了响应感染的基因和蛋白质表达变化的规模和动态,并提供了涉及病毒复制的基因和途径的第一个综合目录。这篇综述通过指出有希望的新型药物靶标突出了宿主基因组学在抗病毒治疗中的潜力,同时也为鉴定和验证可能是新型抗病毒治疗易感靶标的宿主机制提供了基础。

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