Neuroinflammatory responses may be dependent on the initiation of innate immune responses triggered by the stimulation of intrinsic brain cells by pathogen-associated molecular patterns (PAMPs), repeated structural motifs generated by microbes that are not normally found in the host or by debris from apoptotic or necrotic cells following injury. However, there is a lack of basic understanding of which cell types in the brain respond to stimulation of PRRs, as well as the pathways of neuroinflammation, neuroprotection and/or neuronal damage induced when these PRRs are activated on different cell types. Understanding the mechanism of PRR-induced activation of different cell types in the CNS is important for understanding viral pathogenesis as well as identifying potential pathways for therapeutic treatments. Our laboratory has focused on understanding the response of intrinsic brain cells following PRR activation or during virus infection and determining the downstream effects of innate immune activation on neuroinflammation and neuropathogenesis. In FY2015, we examined the neuroinflammatory response of astrocytes and microglia to endosomal TLR stimulation and identified unique gene expression for microglia and astrocytes. (Madeddu et al. PLoS One, 2015). We further examined these specific gene profiles in context of retroviral and bunyavirus infections in the CNS. These studies provide better tools for determining glial activation during viral infections of the CNS. In addition, we collaborated with investigators at Southern Illinois University to determine the role of specific protein kinases of Herpes Simplex Virus 1 (HSV-1) in the assembly and release of mature virions from cells (Gershburg et al. PLoS One 2015).
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