Increased proinflammatory cytokine and chemokine responses and microglial infection following inoculation with neural stem cells infected with polytropic murine retroviruses.
Increased proinflammatory cytokine and chemokine responses and microglial infection following inoculation with neural stem cells infected with polytropic murine retroviruses.
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DOI：
10.1016/j.virol.2006.06.016
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发表时间：
2006-10
期刊：
影响因子：
3.7
通讯作者：
K. Peterson;L. Evans;K. Wehrly;B. Chesebro
中科院分区：
文献类型：
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作者：
K. Peterson;L. Evans;K. Wehrly;B. Chesebro
促炎细胞因子和趋化因子通常在患有神经系统疾病如多发性硬化（MS）、HIV相关痴呆（HAD）和阿尔茨海默病（AD）的患者的脑组织中检测到。我们利用逆转录病毒诱导的神经系统疾病的小鼠模型来研究这些促炎反应如何促进神经发病机制。在以前的研究中，该模型，神经毒力和细胞因子和趋化因子的表达之间的相关性被发现。然而，目前尚不清楚这些细胞因子和趋化因子的诱导是否是对特定病毒包膜决定簇的反应，还是受大脑中病毒感染水平的调节。在目前的研究中，我们证明了多种多变性逆转录病毒诱导细胞因子和趋化因子mRNA表达后，在大脑中的病毒水平增加。多变性病毒的病毒水平增加也与神经发病机制增加相关。相反，亲嗜性逆转录病毒，FB29，不诱导细胞因子或趋化因子的mRNA表达或神经系统疾病，尽管病毒水平相似或高于多嗜性逆转录病毒。由于嗜多性和亲嗜性病毒利用不同的受体进入，这些受体可能在脑中诱导这些先天性免疫应答中发挥关键作用。
Proinflammatory cytokines and chemokines are often detected in brain tissue of patients with neurological diseases such as multiple sclerosis (MS), HIV-associated dementia (HAD) and Alzheimer's disease (AD). We have utilized a mouse model of retrovirus-induced neurological disease to examine how these proinflammatory responses contribute to neuropathogenesis. In previous studies with this model, a correlation was found between neurovirulence and cytokine and chemokine expression. However, it was unclear whether the induction of these cytokines and chemokines was in response to specific virus envelope determinants or was regulated by the level of virus infection in the brain. In the current study, we demonstrated that multiple polytropic retroviruses induced cytokine and chemokine mRNA expression following increased virus levels in the brain. Increased virus levels of polytropic viruses also correlated with increased neuropathogenesis. In contrast, the ecotropic retrovirus, FB29, did not induce cytokine or chemokine mRNA expression or neurological disease, despite virus levels either similar to or higher than the polytropic retroviruses. As polytropic and ecotropic viruses utilize different receptors for entry, these receptors may play a critical role in the induction of these innate immune responses in the brain.