Section of Infections of the Nervous System, National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda, MD, USA.
J Neurovirol. 2013 Feb;19(1):82-8. doi: 10.1007/s13365-012-0144-8. Epub 2013 Jan 18.
Despite major advances in the development of antiretroviral therapies, currently available treatments have no effect on the production of HIV-Tat protein once the proviral DNA is formed. Tat is a highly neurotoxic and neuroinflammatory protein, but its effects may be modulated by antibody responses against it. We developed an indirect enzyme-linked immunosorbent assay and measured anti-Tat antibody titers in CSF of a well characterized cohort of 52 HIV-infected and 13 control individuals. We successfully measured anti-Tat antibodies in CSF of HIV-infected individuals with excellent sensitivity and specificity, spanning a broad range of detection from 10,000 to over 100,000 relative light units. We analyzed them for relationship to cognitive function, CD4 cell counts, and HIV viral load. Anti-Tat antibody levels were higher in those without neurocognitive dysfunction than in those with HIV-associated neurocognitive dysfunction (HAND) and in individuals with lower CD4 cell counts and higher viral loads. We provide details of an assay which may have diagnostic, prognostic, or therapeutic implications for patients with HAND. Active viral replication may be needed to drive the immune response against Tat protein, but this robust immune response against the protein may be neuroprotective.
尽管在开发抗逆转录病毒疗法方面取得了重大进展，但一旦形成前病毒 DNA，目前可用的治疗方法对 HIV-Tat 蛋白的产生没有影响。Tat 是一种高度神经毒性和神经炎症蛋白，但它的作用可能可以通过针对它的抗体反应来调节。我们开发了一种间接酶联免疫吸附试验，并测量了来自 52 名 HIV 感染患者和 13 名对照个体的特征明确队列的 CSF 中的抗-Tat 抗体滴度。我们成功地测量了 HIV 感染个体的 CSF 中的抗-Tat 抗体，具有出色的灵敏度和特异性，检测范围很广，从 10,000 到超过 100,000 相对光单位。我们分析了它们与认知功能、CD4 细胞计数和 HIV 病毒载量的关系。无神经认知功能障碍的个体的抗-Tat 抗体水平高于 HIV 相关神经认知功能障碍（HAND）患者和 CD4 细胞计数较低、病毒载量较高的个体。我们提供了一种可能对 HAND 患者具有诊断、预后或治疗意义的检测方法的详细信息。针对 Tat 蛋白的免疫反应可能需要活跃的病毒复制来驱动，但针对该蛋白的这种强大免疫反应可能具有神经保护作用。
