Acyclovir or Aβ42 peptides attenuate HSV-1-induced miRNA-146a levels in human primary brain cells
Acyclovir or Aβ42 peptides attenuate HSV-1-induced miRNA-146a levels in human primary brain cells
复制标题
DOI：
10.1097/wnr.0b013e32833da51a
复制
发表时间：
2010-10-06
期刊：
影响因子：
1.7
通讯作者：
Hill, James M.
中科院分区：
文献类型：
--
作者：
Lukiw, Walter J.;Cui, Jian Guo;Hill, James M.
人类大脑中含有单纯疱疹病毒1型（HSV-1）DNA，通常在几十年的生命中保持静止。HSV-1与病毒性脑病和淀粉样β 42（A β 42）肽富集病变相关，这些病变是阿尔茨海默病神经病理学的特征。在这里，我们报告说，感染的人神经胶质细胞与HSV-1的原代共培养诱导不规则的肥大的人神经胶质细胞的细胞体，诱导HSV-1的DNA聚合酶，和上调的micro-RNA-146 a与改变的先天免疫反应。抗病毒药物阿昔洛韦或可溶性A β 42肽的存在显著减弱了这些神经病理学反应。在HSV-1感染的CV-1细胞的病毒空斑试验中也观察到A β 42肽的抑制作用。结果表明，可溶性A β 42肽可以通过简单的病毒隔离、病毒破坏或复杂的神经遗传机制灭活HSV-1对人脑细胞的攻击来引起非病理性和抗病毒作用。NeuroReport 21：922-927（C）2010年威科健康|利平科特威廉姆斯&威尔金斯。
Human brains harbor herpes simplex virus type-1 (HSV-1) DNA, which normally remains quiescent throughout many decades of life. HSV-1 is associated with viral encephalopathy and with the amyloid beta 42 (A beta 42) peptide-enriched lesions that characterize Alzheimer's disease neuropathology. Here we report that infection of human neuronal-glial cells in primary co-culture with HSV-1 induces an irregular hypertrophy of human neuronal-glial cell bodies, an induction of HSV-1 DNA polymerase, and an up-regulation of micro-RNA-146a associated with altered innate-immune responses. Presence of the antiviral acyclovir or soluble A beta 42 peptide significantly attenuated these neuropathological responses. The inhibitory effects of A beta 42 peptide were also observed in an HSV-1-infected CV-1 cell-based viral plaque assay. The results suggest that soluble A beta 42 peptide can invoke non-pathological and anti-viral effects through inactivation of an HSV-1 challenge to human brain cells by simple viral sequestration, viral destruction, or by complex neurogenetic mechanisms. NeuroReport 21:922-927 (C) 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins.