Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA; Department of Virology, National Veterinary Research Institute, Pulawy, Poland.
Proteomics Clin Appl. 2008 Oct;2(10-11):1498-507. doi: 10.1002/prca.200780114. Epub 2008 Sep 10.
HIV-1 infection of the brain commonly leads to cognitive impairments (CIs). In its most severe form, HIV-1 associated dementia (HAD) is associated with advanced immune suppression and debilitating loss of memory, behavioral, and motor functions. Despite significant research activities, diagnosis remains one of exclusion. Bioimaging, neuropsychological testing, and viral and immune biomarkers serve to support but not define a diagnosis of HIV-1 associated CI. This is timely and required as brain injury triggered by HIV-1 can be controlled, in part, by antiretroviral medicines. The recent development of proteomics has opened new ways to study viral-host interactions which may provide new insight into treatment and disease monitoring. To this end, we developed a proteomics platform for HIV-1 associated CI biomarker discovery and used it to perform a pilot study for sera-associated HAD proteins. A 2-DE map of a serum proteome was focused on differentially expressed proteins. Differential expression of two proteins was validated by Western blot tests identifying afamin and ceruloplasmin as a potential biomarkers for CI associated with advanced HIV-1 infection.
HIV-1 对大脑的感染通常会导致认知障碍(CIs)。在其最严重的形式中,HIV-1 相关痴呆症(HAD)与晚期免疫抑制和记忆、行为和运动功能的严重丧失有关。尽管开展了大量研究活动,但诊断仍然是排除性的。生物成像、神经心理学测试以及病毒和免疫生物标志物可用于支持但不能确定 HIV-1 相关认知障碍的诊断。这是及时和必要的,因为 HIV-1 引发的脑损伤可以部分通过抗逆转录病毒药物来控制。蛋白质组学的最新发展为研究病毒-宿主相互作用开辟了新途径,这可能为治疗和疾病监测提供新的见解。为此,我们开发了一种用于 HIV-1 相关认知障碍生物标志物发现的蛋白质组学平台,并使用该平台对与 HIV-1 感染相关的血清 HAD 蛋白进行了一项试点研究。我们专注于血清蛋白质组的差异表达蛋白的 2-DE 图谱。通过 Western blot 测试验证了两种蛋白质的差异表达,鉴定出 afamin 和 ceruloplasmin 是与晚期 HIV-1 感染相关的认知障碍的潜在生物标志物。