Submitting Campus
Daytona Beach
Department
Human Factors and Behavioral Neurobiology
Document Type
Article
Publication/Presentation Date
12-24-2018
Abstract/Description
West Nile virus (WNV) infection results in a spectrum of neurological symptoms, ranging from a benign fever to severe WNV neuroinvasive disease with high mortality. Many who recover from WNV neuroinvasive infection present with long-term deficits, including weakness, fatigue, and cognitive problems. While neurons are a main target of WNV, other cell types, especially astrocytes, play an important role in promoting WNV-mediated central nervous system (CNS) damage. Conversely, it has been shown that cultured primary astrocytes secrete high levels of interferons (IFNs) immediately after WNV exposure to protect neighboring astrocytes, as well as neurons. However, how intrinsic responses to WNV in specific cell types and different regions of the brain modify immune protection is not fully understood. Here, we used a mouse ex vivo spinal cord slice culture (SCSC) and cerebellar slice culture (CSC) models to determine the innate immune responses specific to the CNS during WNV infection. Slices were prepared from the spinal cord and cerebellar tissue of 7–9-day-old mouse pups. Four-day-old SCSC or CSC were infected with 1 × 103 or 1 × 105 PFU of WNV, respectively. After 12 h exposure to WNV and 3 days post-infection in normal growth media, the pooled slice cultures were processed for total RNA extraction and for gene expression patterns using mouse Affymetrix arrays. The expression patterns of a number of genes were significantly altered between the mock- and WNV-treated groups, both in the CSCs and SCSCs. However, distinct differences were observed when CSC data were compared with SCSC. CSCs showed robust induction of interferons (IFNs), IFN-stimulated genes (ISGs), and regulatory factors. Some of the antiviral genes related to IFN were upregulated more than 25-fold in CSCs as compared to mock or SCSC. Though SCSCs had twice the number of dysregulated genes, as compared CSCs, they exhibited a much-subdued IFN response. In addition, SCSCs showed astrogliosis and upregulation of astrocytic marker genes. In sum, our results suggest that early anti-inflammatory response to WNV infection in CSCs may be due to large population of distinct astrocytic cell types, and lack of those specialized astrocytes in SCSC may make spinal cord cells more susceptible to WNV damage. Further, the understanding of early intrinsic immune response events in WNV-infected ex vivo culture models could help develop potential therapies against WNV.
Publication Title
Brain Sciences
DOI
https://doi.org/10.3390/brainsci9010001
Publisher
MDPI
Grant or Award Name
NIGMS, including Mississippi INBRE (P20GM103476), Obesity, Cardiorenal and Metabolic Diseases- COBRE (P20GM104357), and Mississippi Center of Excellence in Perinatal Research (MS-CEPR)-COBRE (P20GM121334)
Scholarly Commons Citation
Brain Sci. 2019, 9, 1; doi:10.3390/brainsci9010001
Included in
Behavioral Neurobiology Commons, Immunity Commons, Molecular and Cellular Neuroscience Commons, Neurology Commons
Additional Information
Dr. Paul was not affiliated with Embry-Riddle Aeronautical University at the time this paper was published.