Vesicular trafficking, Innate response and Viruses
How does the host sense viral infection? How do viruses adapt to the host responses?
Part 1 In human cells.
Upon sensing invading viruses, host cells can trigger signaling events that lead to the activation of an innate immune response. This antiviral response represents the first line of defense against many pathogens and is initiated by the recognition of pathogen-associated molecular patterns (PAMPs) by cellular pathogen recognition receptors (PRRs), including the toll-like receptors (TLRs). This induces the production of antiviral molecules such as interferons (IFNs), a broad range of interferon-stimulated genes (ISGs), and inflammatory cytokines. This first line of host response suppresses viral spread and jump-starts the adaptive immune response.
Paradoxical observations: virtually all viruses have evolved mechanism to evade the host antiviral response within the cells they infect. Nonetheless antiviral molecules are readily detected in infected humans.
How does the host circumvent such inhibition?
How are the infected cells detected by innate immune cells?
We are defining how infected cells are sensed by specialized innate immune cells, leading to an antiviral state. These innate immune cells include the plasmacytoid dendritic cells (pDCs), which can sense inflected cells but are not themselves permissive to viral infection thus this recognition leads to a robust antiviral response. Consistently, we revealed that the immunostimulatory signal is transmitted via non-infectious and/or non-canonical carriers (i.e., exosome and immature virions), which we called PAMP-carriers. Interestingly, sensing of the infected cells by innate immune cells require physical cell-cell contact. We are interested at defining this newly discovered aspect of the innate immunity.
Our viral models: Flavivirus (Dengue, West Nile, Zika virus), hepatitis C virus, and others (HTLV, Ebola).
Part 2 In cells of the vector of many viruses, the mosquito.
How does the vector react to viral infections?
How do viruses adapt to the host defense in the vector?
We aim at determining how is viral infection regulated by the mosquito antiviral responses. We are notably interested in the role of intra-cellular trafficking pathway (such as for example autophagy) in this response, as well as canonical defense pathways (such as RNA interference, Toll, IMD and Jak-stat signaling). In addition, we are studying the viral adaptations to these host defense mechanisms.
Our scientific interests gravitate around a main question: how does the vesicular trafficking regulate the innate response and viral spread?
Our research program thus gathers aspects of virology, immunology, and cell biology areas.
- We revealed a previously unsuspected mechanism of innate immunity in which exosomal export of viral RNA from infected cells serves as a host strategy to induce an innate response in cells whose innate signaling pathways are unopposed because they are not infected.
- We uncovered that the sensing of immature non-infectious particles produced by dengue virus infected cells induces an antiviral response by plasmacytoid dendritic cells.
- Agence Nationale de la Recherche (ANR-JCJC “EXAMIN”)
- European Community (H2020 – Horizon)
- EMBO Long-Term fellowship program
- Fondation pour la Recherche Médicale (FRM)
- Labex Ecofect
- Ligue Nationale Contre le Cancer (LNCC)
- Agence Nationale pour la Recherche contre le SIDA et les Hépatites Virales (ANRS)