Intracerebral infection with dengue-3 virus induces meningoencephalitis and behavioral changes that precede lethality in mice

Background: dengue,one of the most important arboviral diseases of humans,may cause severe systemic disease. although dengue virus (denv) has been considered to be a non-neurotropic virus,dengue infection has been associated recently with a series of neurological syndromes,including encephalitis. in this work,we evaluated behavioral changes and inflammatory parameters in c57bl/6 mice infected with non-adapted dengue virus 3 (denv-3) genotype i.methods: c57bl/6 mice received 4 × 103pfu of denv-3 by an intracranial route. we evaluated the trafficking of leukocytes in brain microvasculature using intravital microscopy,and evaluated chemokine and cytokine profiling by an elisa test at 3 and 6 days post infection (p.i.). furthermore,we determined myeloperoxidase activity and immune cell populations,and also performed histopathological analysis and immunostaining for the virus in brain tissue.results: all animals developed signs of encephalitis and died by day 8 p.i. motor behavior and muscle tone and strength parameters declined at day 7 p.i. we observed increased leukocyte rolling and adhesion in brain microvasculature of infected mice at days 3 and 6 p.i. the infection was followed by significant increases in ifn-γ,tnf-α,ccl2,ccl5,cxcl1,and cxcl2. histological analysis showed evidence of meningoencephalitis and reactive gliosis. increased numbers of neutrophils,cd4+and cd8+t cells were detected in brain of infected animals,notably at day 6 p.i. cells immunoreactive for anti-ns-3 were visualized throughout the brain.conclusion: intracerebral infection with non-adapted denv-3 induces encephalitis and behavioral changes that precede lethality in mice. © 2011 amaral et al; licensee biomed central ltd.