title: Astrocytes as targets for Venezuelan equine encephalitis virus infection.
abstract: Venezuelan equine encephalitis virus (VEE) produces an acute infection in humans and induces a well-characterized cytopathic effect in neurons of the central nervous system (CNS). However, little is known about the role of glial cells in response to VEE infection of the CNS. Our results demonstrate that VEE is capable of a productive infection in primary astrocyte cultures and that this infection is cytotoxic. Further, there were significant differences in the growth kinetics comparing virulent and attenuated strains of VEE. Additionally, VEE infection of astrocyte cultures induced gene expression of two neuro-immune modulators, tumor necrosis factor-alpha (TNF-alpha) and inducible nitric oxide synthase (iNOS). Assays for TNF-alpha protein and nitric oxide (NO) demonstrated high levels of TNF-alpha protein and low levels of NO in response to VEE infection of astrocytes. These observations suggest an important role of astrocytes in this virus-induced encephalitis, and that interactions between astrocytes, other glial cells, and neurons may be important in VEE pathogenesis. Such interactions, which could impact neuronal survival, may include loss of functional changes in astrocytes or, alternatively, their production of neurotoxic molecules.
authors.affiliation: Program in Neuroscience, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
authors.forename: B A
authors.initials: BA
authors.lastname: Schoneboom
authors.forename: M J
authors.initials: MJ
authors.lastname: Fultz
authors.forename: T H
authors.initials: TH
authors.lastname: Miller
authors.forename: L C
authors.initials: LC
authors.lastname: McKinney
authors.forename: F B
authors.initials: FB
authors.lastname: Grieder
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism / Q000821:virology*; D002478:Cells, Cultured; D004666:Encephalitis Virus, Venezuelan Equine / Q000472:pathogenicity / Q000502:physiology*; D004685:Encephalomyelitis, Venezuelan Equine / Q000473:pathology; D019001:Nitric Oxide Synthase / Q000032:analysis / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000378:metabolism; D014774:Virulence; D014779:Virus Replication
chemical_list: D014409:Tumor Necrosis Factor-alpha; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat