IrsiCaixa, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Spain.
Antiviral Res. 2013 Nov;100(2):473-86. doi: 10.1016/j.antiviral.2013.09.017. Epub 2013 Sep 29.
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.
HIV 的易感性和疾病进展表现出相当大的个体异质性,范围从快速进展者到长期非进展者或精英控制者,即未经治疗就能控制感染的受试者。近年来,人们对宿主遗传决定因素对 HIV 感染和疾病进展的易感性有了显著的理解,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展,描述了基因和蛋白质表达变化对感染的规模和动态,并提供了参与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前途的新型药物靶点,强调了宿主基因组影响抗病毒治疗的潜力,但也为鉴定和验证宿主机制提供了基础,这些宿主机制可能是新型抗病毒治疗的潜在靶点。