Research Topics

Molecular virology and innate immunity

My scientific work revolves around three axes (i) Innate detection of viral RNAs /discrimination between self and non-self RNAs, (ii) viral strategies to escape innate detection, (iii) Loss of function mutations of MDA5 and increased susceptibility to viral infection.

  • (i) Innate detection of viral RNAs /discrimination between self and non-self RNAs: The innate immune response to pathogens is based on the discrimination between self-RNA and non-self-RNA. The main determinants of this detection for RNA viruses are specific pathogen-associated molecular patterns (PAMPs) of RNA, which are detected by dedicated cytoplasmic pattern recognition receptors (PRRs). We have particularly studied the viral molecular signatures detected by RIG-I which is part of the RIG-Like Receptor family as well as the mechanisms related to this detection and its regulation by LGP2.
  • (ii) viral strategies to escape innate detection: We have done a lot of work on viral strategies to escape or subvert innate immune responses. How influenza virus, arenaviruses, bunyaviruses managed to "play" with their molecular signature to escape detection by RIG-I. How paramyxoviruses combined different strategies to prevent the activation of type I IFNs and prevent the signaling of these IFNs.
  • (iii) Loss of function mutations of MDA5 and increased susceptibility to viral infection. Human respiratory syncytial virus (hRSV) is the leading cause of hospitalization for young children. We have shown that MDA5 mutants, identified in children with extreme susceptibility to respiratory RNA viruses, have lost their ability to be activated by various stimuli in cell culture (dsRNAs, viral infection) and in vitro (ATPase activity of purified proteins). We study in detail the molecular mechanisms of this loss of function as well as its capacity to act as a negative dominant in the case of heterozygotes.

Specific expertise

We have many useful viral tools to induce innate responses in different cell types.

Selected Publications

Anchisi, S., J. Guerra and D. Garcin (2015). "RIG-I ATPase activity and discrimination of self-RNA versus non-self-RNA." MBio 6(2): e02349

Anchisi, S., J. Guerra, G. Mottet-Osman and D. Garcin (2016). "Mismatches in the Influenza A Virus RNA Panhandle Prevent Retinoic Acid-Inducible Gene I (RIG-I) Sensing by Impairing RNA/RIG-I Complex Formation." J Virol 90(1): 586-590

Asgari, S., L. J. Schlapbach, S. Anchisi, C. Hammer, I. Bartha, T. Junier, G. Mottet-Osman, K. M. Posfay-Barbe, D. Longchamp, M. Stocker, S. Cordey, L. Kaiser, T. Riedel, T. Kenna, D. Long, A. Schibler, A. Telenti, C. Tapparel, P. J. McLaren, D. Garcin and J. Fellay (2017). "Severe viral respiratory infections in children with IFIH1 loss-of-function mutations." Proc Natl Acad Sci U S A 114(31): 8342-8347

Le, T. V., E. Mironova, D. Garcin and R. W. Compans (2011). "Induction of influenza-specific mucosal immunity by an attenuated recombinant Sendai virus." PLoS One 6(4): e18780

Marq, J. B., S. Hausmann, N. Veillard, D. Kolakofsky and D. Garcin (2011). "Short double-stranded RNAs with an overhanging 5' ppp-nucleotide, as found in arenavirus genomes, act as RIG-I decoys." J Biol Chem 286(8): 6108-6116

6 Nov 2020

Host response to pathogens