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Originally published as JGV in Press, 10.1099/vir.0.010280-0 on April 15, 2009 J Gen Virol 90 (2009), 1836-1847; DOI 10.1099/vir.0.010280-0

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Oligonucleotide array analysis of Toll-like receptors and associated signalling genes in Venezuelan equine encephalitis virus-infected mouse brain

Anuj Sharma1,2 and Radha K. Maheshwari1

1 Centre for Combat Casualty and Life Sustainment Research, Department of Pathology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA
2 Birla Institute of Technology and Science, Biological Sciences Group, Pilani 333031, India

Correspondence
Radha K. Maheshwari
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 (TLRs) recognize conserved microbial sequences and induce specific biological responses in the form of proinflammatory cytokine induction. TLR expression in blood following VEEV infection has been reported in non-human primates and TLRs are also upregulated in the brains of mice infected with other alphaviruses. 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 signalling molecules was evaluated. VEEV infection resulted in upregulation of TLR 1, 2, 3, 7 and 9, chemokines, inflammatory cytokines, interferon (IFN), IFN regulatory factors and genes involved in signal transduction such as Mcp1, Cxcl10, IL12{alpha}, IFN-β, IRF-1, IRF-7, Jun, Fos, MyD88, Nfkb, Cd14 and Cd86. These results demonstrate the upregulation of TLRs and associated signalling genes following VEEV infection of the brain, with important implications for how VEEV induces inflammation and neurodegeneration.

Six supplementary figures and two supplementary tables are available with the online version of this paper.







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