Email updates

Keep up to date with the latest news and content from BMC Proceedings and BioMed Central.

This article is part of the supplement: Infectious diseases of the nervous system: pathogenesis and worldwide impact

Open Access Poster presentation

Dengue virus pathogenesis in mouse central nervous system: studies on host response to dengue virus infection

Juliano Bordignon1, Christian Probst1, Ana Luiza P Mosimann1, Vanessa Stella1, Daniela Pavoni1, Greg Buck2, Paul Fawcett2, Silvio M Zanata3, Lucia Noronha4, Marco Krieger1 and Claudia Nunes Duarte dos Santos1*

Author Affiliations

1 Instituto Carlos Chagas/Fiocruz, Curitiba, Paraná, Brazil

2 Virginia Commonwealth University, Richmond, VA, USA

3 Universidade Federal do Paraná/UFPR, Curitiba, Paraná, Brazil

4 Pontifícia Universidade Católica do Paraná/PUCPR, Curitiba, Paraná, Brazil

For all author emails, please log on.

BMC Proceedings 2008, 2(Suppl 1):P8  doi:

The electronic version of this article is the complete one and can be found online at: http://www.biomedcentral.com/1753-6561/2/S1/P8


Published:23 September 2008

© 2008 Bordignon et al; licensee BioMed Central Ltd.

Poster presentation

Dengue virus (DENV) causes a self-limiting fever (DF) or severe hemorrhagic fever/shock-syndrome (DHF/DSS). Recently, clinical profile of DENV infection is changing, and neurological manifestations are becoming frequent. We previously demonstrated that mutations on E and NS3 proteins may account for DENV neurovirulence for mice. To validate the involvement of the observed mutations in the appearance of neurovirulent viral phenotypes, we constructed cDNA infectious clones encompassing the observed mutations. Aiming to determine host response to infection with neurovirulent and parental strains of DENV-1, we used a Mus musculus biochip (Virginia Commonwealth University) encompassing whole mouse genome. Newborn Swiss mice were infected intracerebraly with 8.000ffuC636 of FGA/89 (parental strain), FGA/NA a5c (neurovirulent strain) and mock. Animals infected with FGA/NA a5c show clinical signs of encephalitis around 9 days post-infection (dpi) and succumb to death (13.1 dpi ± 2.2), in contrast with animals infected with FGA/89 and mock. Kinetics of infection showed higher levels of viral RNA and progeny in FGA/NA a5c infected animals at 9 dpi. Microarray analyzes were carried out at 5, 6, 7 and 8 dpi in central nervous system (CNS) of mock, FGA/89 and FGA/NA a5c infected animals. Bioinformatic analysis revealed 149 genes up-regulated in CNS infection by DENV-1, at higher levels in animals infected with FGA/NA a5c. Analysis with the software Ingenuity Pathways Systems (IPA) showed that the main pathways modulated by DENV infection in the mouse CNS are IFN signaling, antigen presentation, complement cascades and protein ubiquitination. Additionally, 15 genes were selected by in silico analyses; of special interest are four genes encoding chemokines with chemoattractant activity, that are up-regulated following infection with the neurovirulent virus compared to parental virus. Nowadays we are performing the biological characterization of the selected genes and pathways.

Financial support

Fundação Araucária, Fiocruz and CNPq.