Laboratory of Genomic Diversity, SAIC-Frederick, Inc., National Cancer Institute at Frederick, Frederick, MD 21702, USA.
Trends Genet. 2010 Mar;26(3):119-31. doi: 10.1016/j.tig.2010.01.002. Epub 2010 Feb 10.
Twenty-five years after the discovery of HIV as the cause of AIDS there is still no effective vaccine and no cure for this disease. HIV susceptibility shows a substantial degree of individual heterogeneity, much of which can be conferred by host genetic variation. In an effort to discover host factors required for HIV replication, identify crucial pathogenic pathways, and reveal the full armament of host defenses, there has been a shift from candidate-gene studies to unbiased genome-wide genetic and functional studies. However, the number of securely identified host factors involved in HIV disease remains small, explaining only approximately 15-20% of the observed heterogeneity - most of which is attributable to human lymphocyte antigen (HLA) variants. Multidisciplinary approaches integrating genetic epidemiology to systems biology will be required to fully understand virus-host interactions to effectively combat HIV/AIDS.
在发现 HIV 是艾滋病的病因 25 年后,仍然没有有效的疫苗,也无法治愈这种疾病。HIV 的易感性表现出很大程度的个体异质性,其中大部分可以归因于宿主遗传变异。为了发现 HIV 复制所需的宿主因素,确定关键的致病途径,并揭示宿主防御的全部武器,人们已经从候选基因研究转向了无偏基因组范围的遗传和功能研究。然而,已确定的参与 HIV 疾病的宿主因素的数量仍然很少,仅能解释观察到的异质性的约 15-20%——其中大部分归因于人类淋巴细胞抗原(HLA)变体。为了充分了解病毒-宿主相互作用,有效对抗 HIV/AIDS,需要整合遗传流行病学和系统生物学的多学科方法。