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

Abstract：

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 4×10(3) PFU 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.

journal_name

J Neuroinflammation

journal_title

Journal of neuroinflammation

authors

Amaral DC,Rachid MA,Vilela MC,Campos RD,Ferreira GP,Rodrigues DH,Lacerda-Queiroz N,Miranda AS,Costa VV,Campos MA,Kroon EG,Teixeira MM,Teixeira AL

doi

10.1186/1742-2094-8-23

subject

Has Abstract

pub_date

2011-03-09 00:00:00

pages

issn

1742-2094

pii

1742-2094-8-23

journal_volume

pub_type

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