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Centre d'Immunologie et des Maladies Infectieuses
UPMC UMRS CR7 - Inserm U1135 - CNRS ERL 8255

Immunobiology of Viral Infections and Antigen Presentation - Arnaud MORIS

Team members

Team research program

To fight infections, a tight coordination of innate and adaptive immunity is crucial. Viruses, such as HIV-1, Measles and CMV, have evolved means to manipulate host responses. In particular, they affect the functions of dendritic cells, which coordinates these two arms of immunity.
Our work, at the interface between immunology and virology, focuses on the interactions between viruses and antigen presenting cells, e.g. dendritic cells, macrophages and B cells. We characterize the cellular pathways involved in the presentation of viral antigens to CD4+ and CD8+ T cells and define potential escape mechanism developed by viruses. Our current work focuses on:

  • Studying the role of autophagy in viral replication (including HIV, MeV and CMV) and antigen presentation.
  • Defining novel sources of viral antigens from alternative reading frames: The example ASP, HIV-1 Antisense protein.
  • Dissecting the interactions of B cells and T follicular helper (Tfh) cells in HIV-1 infection.
  • Characterizing novel vaccine candidates.

November 2015 : Arnaud Moris, member of the Cimi-Paris team involved in european project H2020

Technical expertise

  • Flow Cytometry
  • Assessment of  T cell activation IFNɣ-ELISpot and ICCS,
  • Culture of primary cells (T cell clones, Dendritic cells, macrophages and B cells)
  • Assessment of B cell antigen specificity (B-cell Elispot and Flow cytometry)
  • Monitoring of autophagy using Confocal Imaging and Western Blotting.
  • Cloning and Production of Viruses (HIV, EBV) and Lentiviral vectors in L3 facilities

Main achievements

  • Definition of the multiple destinies of incoming HIV-1 particles in dendritic cells (DC): degradation in lysosomes leading to MHC-II antigen presentation (Moris, Blood 2006), transmission to CD4+ T cells, translocation to cytoplasm followed by proteosomal processing and MHC-I Ag presentation (Moris, Blood 2004), dissociation between the capacity of DC  to capture HIV and to present viral Ag (Rodriguez-Plata, J. Immuno 2012), evasion of the autophagic machinery leading to escape from viral degradation, Ag processing and to perturbation of innate signaling (Blanchet, Immunity 2010)
  • Characterization of a novel source of HIV Ag derived from HIV alternative reading frames (ARF). ARF-specific CTLs exert a selective pressure on HIV (Cardinaud, PlosPatho 2011) and during chronic infection, target the antisens protein of HIV-1 (ASP) (Bet, Retrovirology 2015).
  • Defining a novel function for the antiviral factor APOBEC-3G (A3G). A3G acts not only as an intrinsic antiviral factor, but also as an inducer of the adaptive immune system (Casartelli N, J. Exp. Med.  2010).
  • In vitro assessment of vaccine candidates, a prerequisite prior clinical development (Brandler, J.Virology 2010).

External funding (current)

  • ANR (2015-2018) : "Autovirim": L'autophagie dans l'immunité virale
  • ANRS (2015-2017) : Defining conserved alternative ORF in HIV-1 genome
  • ANRS (2014-2015) : Novel aspect of IgG2 antiviral functions
  • ANRS (2013-2015) : La protéine antisens ASP du VIH – Partner
  • ANRS (2012-2014) : T follicular helper cells in HIV-1 infection
  • Sidaction (2012-2013) : HIV and Autophagy
  • ANRS (2011-2012) : HIV and Autophagy
  • UPMC Emergence (2010-2013) : UPMC Autophagy & Immunity

Publications (PDF):

(2017 - 2016 - 2015 - 2014 - 2013)

23/10/17

Traductions :

Contact

cimi-paris @ upmc.fr

To see

Key words

Viral replication, Antigen presentation, MHC, Autophagy, Follicular T cells.

Fields of application

Viral infections, HIV, Immune responses, Vaccines strategies