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Uniformed Services University of theHealth Sciences
1 E-mail: rmaheshwari{at}usuhs.mil
Venezuelan equine encephalitis (VEE) is an emerging infectious disease. VEE virus (VEEV) may cause lethal infection of the central nervous system in horses and humans. The mechanisms underlying the host immune response to VEEV infection in the brain are not fully understood. Toll-Like Receptors (TLR) recognize conserved microbial sequences and induce specific biological response in the form of proinflammatory cytokine induction. TLR expression in blood following VEEV infection has been reported in nonhuman primates and TLRs are also upregulated in brains of other alphavirus infected mouse. In this study, mice (3-5 weeks old) were infected with V3000, a neurovirulent strain of VEEV and gene expression of TLRs and their associated signaling molecules was evaluated. VEEV infection resulted in upregulation of TLR 1,2,3,7 and 9, chemokines, inflammatory cytokines, interferon, interferon regulatory factors and genes involved in signal transduction such as Mcp1, Cxcl10, IL12
/β, INF-β, IRF-1, IRF-7, Jun, Fos, MyD88, Nfkβ, Cd14 and Cd86. These results demonstrate the upregulation of TLR and associated signaling genes following VEEV infection of the brain with important implication for how VEEV induces inflammation and neurodegeneration.
Received 12 January 2009;
accepted 12 April 2009.
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