Role of Cytokines and Neurotrophins in the Central Nervous System in Venezuelan Equine Encephalitis Pathogenesis
UNIFORMED SERVICES UNIV OF THE HEALTH SCIENCES BETHESDA MD BETHESDA United States
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Venezuelan equine encephalitis virus VEE is a mosquito-borne alphavirus capable of causing acute febrile illness and encephalitis in man. Currently, there is no licensed vaccine to combat this human health threat and no treatment other than supportive therapy. The inflammatory immune response in the central nervous system CNS has been implicated as a contributing factor in a number of neurodegenerative disorders and encephalitic virus infections. The studies detailed here have attempted to elucidate the role of the cytokine and neurotrophin response in the CNS in response to VEE infection by characterizing the gene and protein expression of a number of proinflammatory and anti-inflammatory cytokines in primary astrocyte cultures as well as in the CNS of mice following infection with VEE strains of differing degrees of neurovirulence. Reverse transcription-polymerase chain reaction, RNase protection assays, and enzyme-linked immunosorbent assays were used to achieve this. Data revealed proinflammatory cytokines were significantly upregulated following infection with the virulent VEE, while neurotrophin were significantly upregulated following infection with the attenuated VEE. These findings may contribute to the goal of manipulating these immune responses for therapeutic benefit.