Immunobiologie des infections virales

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Projects

From viral invasion to evasion: Interplay between virus and innate immune response
Our studies aim to decipher the early steps of a virus infection including those leading to the activation of the cellular innate immunity to unravel their contribution to the virus replication cycle and resulting pathology. Our two favorite viruses are the Mononegavirales measles virus (MeV) and Nipah virus (NiV). Despite strong similarities of their replication machinery, these two viruses diverge by NiV showing much higher pathogenicity than MeV in humans with lethality up to 80% for the former virus. The interaction with a cellular receptor is a key early event in viral pathogenesis and the outcome of MeV interaction with two different cell surface receptors, CD46 and CD150 is under study. CD46, is used also by human herpesvirus 6 (HHV-6) and both viruses may therefore share some common features in pathogenesis, associated to this common receptor usage. Downstream the virus entry, we analyze the interaction of the virus with known pathogen Pattern Recognition Receptors (PRR), including RIG-I and MDA5 and look for virus ability to induce inflammatory cytokines in vitro and in vivo in animal models. We are particularly interested in the viral interaction with the activation of NF-kB pathway, the main regulator of inflammatory responses. Application of three model viruses, MeV, NiV and HHV-6, all of them associated with the induction of neuropathology in humans, provides an important comparative research platform for the analysis of different aspects of viral pathogenesis and new anti-viral treatments. Finally, novel aspects of innate antiviral responses are searched in fruit bat model, natural reservoir of Nipah virus, where this infection, highly severe in the other species, is apparently asymptomatic.

Our projects combine approaches starting from the molecular level studies of virus-cell interaction, via cellular analysis up to the more integrative analysis of viral pathogenesis in the animal models. These studies may reveal the particular properties of virus interaction with the innate immune response, reflecting common and/or different features for RNA and DNA viruses and open new avenues to better understanding of viral pathogenesis.

Figure2 projet BH aout 2013

Figure: Schematic representation of the major scientific questions asked within the project. Numbers (Q1-5) correspond to the numbers of projects, Le, leader, containing the transcription and replication promoters; N, nucleoprotein; P, phosphoprotein; F, fusion protein, G, attachment protein; H, hemagglutinin; L, polymerase; V, C and W, nonstructural proteins; MeV, measles virus; NiV, Nipah virus; CD46 and CD150, MeV receptors, EphrinB2, NiV receptor.

 

Measles virus infection of the transgenic brain explant

 

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