Dissecting the HIV-specific immune response: a systems biology approach.
Dissecting the HIV-specific immune response: a systems biology approach.
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DOI：
10.1097/coh.0b013e32834ddb0e
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发表时间：
2012-01
影响因子：
4.1
通讯作者：
Sékaly RP
中科院分区：
文献类型：
--
作者：
Peretz Y;Cameron C;Sékaly RP
几个独特的艾滋病毒感染者或艾滋病毒耐药人群多年来一直在研究，试图描绘保护的相关性。虽然已经提出了几种机制，但仍缺乏旨在将不同机制整合为一个综合模型的研究。目前的系统生物学方法强调统一独立数据集的重要性，提供了促进假设制定和测试的工具，并通过定义疾病期间扰动的分子网络来指导我们发现新的治疗靶点。本综述将集中在目前的研究结果，利用系统生物学技术，以确定相关的保护艾滋病毒疾病的进展和抗感染的独特的个人群体，以及在非人灵长类动物模型的SIV感染。使用系统生物学技术和数据分析工具，本文所述的研究已经发现，涉及存活、细胞周期、炎症和氧化应激的途径一致地起作用以限制由慢性免疫激活引起的病理。这种情况有利于效应淋巴细胞的存活，并限制了病毒颗粒在HIV精英控制者、暴露未感染个体和SIV感染的天然宿主中的传播。系统和计算生物学工具通过统一独立的观察结果和为我们提供新的分子靶点，明显扩大了我们对艾滋病发病机制的理解。这些分子特征有可能揭示HIV疾病中保护的相关性，并在个性化医疗时代确定治疗疗效和/或失败的预测特征。
Several unique HIV-infected or HIV-resistant cohorts have been studied over the years to try and delineate the correlates of protection. Although several mechanisms have been put forward, studies aiming to integrate the different mechanisms into a comprehensive model are still lacking. Current systems biology approaches emphasize the importance of unifying independent datasets, provide tools that facilitate hypothesis formulation and testing, and direct us toward uncovering novel therapeutic targets by defining molecular networks perturbed during disease. This review will focus on the current findings that utilized systems biology techniques in order to identify correlates of protection from HIV disease progression and resistance to infection in unique cohorts of individuals as well as in nonhuman primate models of SIV infection. Using systems biology technologies and data analysis tools, the studies described herein have found that pathways implicated in survival, cell cycling, inflammation, and oxidative stress work in unison to limit pathology caused by chronic immune activation. This situation favors the survival of effector lymphocytes and limits the dissemination of viral particles in HIV elite controllers, exposed-uninfected individuals, and natural hosts of SIV infection. Systems and computational biology tools have clearly expanded our understanding of HIV pathogenesis by unifying independent observations and by giving us novel molecular targets to pursue. These molecular signatures have the potential to uncover correlates of protection in HIV disease and, in the era of personalized medicine, to determine predictive signatures of treatment efficacy and/or failure.