Burgos Javier S, Ramirez Carlos, Sastre Isabel, Valdivieso Fernando
Lab CX340, Centro de Biología Molecular, Universidad Autónoma de Madrid, Cantoblanco, 28049 Madrid, Spain.
J Virol. 2006 Jun;80(11):5383-7. doi: 10.1128/JVI.00006-06.
Herpes simplex virus type 1 (HSV-1) is neurotropic and enters a latent state lasting the lifetime of the host. This pathogen has recently been proposed as a risk factor for Alzheimer's disease (AD) in conjunction with apolipoprotein E4 (ApoE4). In a murine acute infection model, we showed that viral neuroinvasiveness depends directly on the overall ApoE dosage and especially on the presence of isoform ApoE4. If an interaction between ApoE and HSV-1 is involved in AD, it may occur during latency rather than during acute infection. Certainly, ApoE plays an important role in late-onset AD, i.e., at a time in life when the majority of people harbor HSV-1 in their nervous system. In the present work, wild-type, APOE knockout, APOE3, and APOE4 transgenic mice were used to analyze the influence of the ApoE profile on the levels of latent virus DNA. The knockout mice had significantly lower concentrations of the virus in the nervous system than the wild-type mice, while the APOE4 mice had very high levels in the brain compared to the APOE3 animals. ApoE4 seems to facilitate HSV-1 latency in the brain much more so than ApoE3. The APOE dosage correlated directly with the HSV-1 DNA concentration in the brain, strengthening the hypothesis that HSV-1, together with ApoE, might be involved in AD.
单纯疱疹病毒1型（HSV-1）具有嗜神经性，可进入潜伏状态并持续宿主一生。最近，这种病原体被认为是与载脂蛋白E4（ApoE4）相关的阿尔茨海默病（AD）的一个风险因素。在小鼠急性感染模型中，我们发现病毒的神经侵袭性直接取决于总的ApoE剂量，特别是ApoE4异构体的存在。如果ApoE与HSV-1之间的相互作用参与了AD的发生，那么这种相互作用可能发生在潜伏期间而非急性感染期间。当然，ApoE在晚发型AD中起着重要作用，即在大多数人神经系统中携带HSV-1的生命阶段。在本研究中，使用野生型、ApoE基因敲除、ApoE3和ApoE4转基因小鼠来分析ApoE谱对潜伏病毒DNA水平的影响。基因敲除小鼠神经系统中的病毒浓度明显低于野生型小鼠，而与ApoE3小鼠相比，ApoE4小鼠大脑中的病毒水平非常高。与ApoE3相比，ApoE4似乎更有助于HSV-1在大脑中潜伏。ApoE剂量与大脑中HSV-1 DNA浓度直接相关，这进一步支持了HSV-1与ApoE可能共同参与AD发病的假说。
