Viral-induced impairment of innate immune response and functional properties of cerebrovascular endothelial cells correlates with brain viral invasion.

Abstract

Event Abstract Back to Event Viral-induced impairment of innate immune response and functional properties of cerebrovascular endothelial cells correlates with brain viral invasion. Christian Bleau1, Mélanie Burnette1 and Lucie Lamontagne1* 1 Université du Québec à Montréal, Sciences Biologiques, Canada The blood-brain barrier (BBB) provides significant protection against brain invasion by hematogenous spread viruses but some have evolved strategies to bypass this primary endothelial cell (EC) barrier and induce neuropathogenesis. The role of BBB ECs in a rapid early anti-viral immunity limiting viral spread to the brain is largely unknown. Using mouse hepatitis viruses (MHVs) of different neurovirulence, we investigated the viral-induced innate response and structural dysfunctions of ECs according to viral permittivity. C57BL/6 mice were infected i.p. with the highly-neurotropic (L2-MHV3), mildly-neurotropic (MHV-A59) or the attenuated variant 51.6-MHV3 showing low tropism for ECs. Higher intracerebral levels of IFN-b, IL-6, TNF-a chemokines and TLR-2 and lowered ECs junctionnal protein mRNA expression, as assessed by qRT-PCR, correlating with viral nucleoprotein expression, were observed only in brain from L2-MHV3 infected mice. Using EC line Bend.3 as an in vitro BBB model, infection with L2-MHV3 provoked higher cytopathic effects, decreased IFN-b, IL-6, TNF-a and chemokine and transendothelial resistance, correlating with lower junctional protein mRNA expression when compared with lower virulent MHV-A59 and 51.6-MHV3. Such disorders in innate immunity and viral spreading induced by L2-MHV3 in EC depend on both TLR-2- and specific viral receptor-dependent endocytic ways used by L2-MHV3 than lower virulent viral strains. Our findings highlight the importance of innate immunity parameters and functions of BBB ECs that may prevent access of pathogenic neurotropic viruses to the brain. Acknowledgements This work was funded by NSERC-Canada. Keywords: Brain, Endothelial Cells, Coronavirus, blood brain barrier, Cytokines, TLR2 Conference: 15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013. Presentation Type: Abstract Topic: Host-pathogen interactions Citation: Bleau C, Burnette M and Lamontagne L (2013). Viral-induced impairment of innate immune response and functional properties of cerebrovascular endothelial cells correlates with brain viral invasion. . Front. Immunol. Conference Abstract: 15th International Congress of Immunology (ICI). doi: 10.3389/conf.fimmu.2013.02.00658 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 12 Jun 2013; Published Online: 22 Aug 2013. * Correspondence: Dr. Lucie Lamontagne, Université du Québec à Montréal, Sciences Biologiques, Montréal, Québec, H3C 3P8, Canada, lamontagne.lucie@uqam.ca Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Christian Bleau Mélanie Burnette Lucie Lamontagne Google Christian Bleau Mélanie Burnette Lucie Lamontagne Google Scholar Christian Bleau Mélanie Burnette Lucie Lamontagne PubMed Christian Bleau Mélanie Burnette Lucie Lamontagne Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.