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• W2913532401 abstract "Herpes simplex virus type 1 (HSV-1) has the ability to replicate in neurons and glial cells and to produce encephalitis leading to neurodegeneration. Accumulated evidence suggests that nitric oxide (NO) is a key molecule in the pathogenesis of neurotropic virus infections. NO can exert both cytoprotective as well as cytotoxic effects in the central nervous system (CNS) depending on its concentration, time course exposure, and site of action. In this study, we used an in vitro model of HSV-1-infected primary neuronal and mixed glial cultures as well as an intranasal model of HSV-1 in BALB/c mice to elucidate the role of NO and nonapoptotic Fas signalling in neuroinflammation and neurodegeneration. We found that low, nontoxic concentration of NO decreased HSV-1 replication in neuronal cultures together with production of IFN-alpha and proinflammatory chemokines. However, in HSV-1-infected glial cultures, low concentrations of NO supported virus replication and production of IFN-alpha and proinflammatory chemokines. HSV-1-infected microglia downregulated Fas expression and upregulated its ligand, FasL. Fas signalling led to production of proinflammatory cytokines and chemokines as well as induced iNOS in uninfected bystander glial cells. On the contrary, NO reduced production of IFN-alpha and CXCL10 through nonapoptotic Fas signalling in HSV-1-infected neuronal cultures. Here, we also observed colocalization of NO production with the accumulation of β -amyloid peptide in HSV-1-infected neurons both in vitro and in vivo. Low levels of the NO donor increased accumulation of β -amyloid in uninfected primary neuronal cultures, while the NO inhibitor decreased its accumulation in HSV-1-infected neuronal cultures. This study shows for the first time the existence of a link between NO and Fas signalling during HSV-1-induced neuroinflammation and neurodegeneration." @default.
• W2913532401 created "2019-02-21" @default.
• W2913532401 creator A5023668575 @default.
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• W2913532401 date "2019-02-11" @default.
• W2913532401 modified "2023-10-01" @default.
• W2913532401 title "Nitric Oxide Influences HSV-1-Induced Neuroinflammation" @default.
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• W2913532401 doi "https://doi.org/10.1155/2019/2302835" @default.
• W2913532401 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6388346" @default.
• W2913532401 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30886672" @default.
• W2913532401 hasPublicationYear "2019" @default.
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