Olivier SCHWARTZ
Virus & Immunity Unit
Institut Pasteur 25-28 rue du docteur Roux, 75015 Paris
 
Research area of the Unit
 
Our work focuses on cellular and molecular aspects of HIV-1 replication, and on the mechanisms of recognition of HIV-infected cells by the immune system. Three close and complementary axes of research characterize our scientific activities. The first axis is aimed at understanding the impact of HIV-1 infection on the biology of the cells. The second axis consists of the study of viral spread, with a focus on cell-to-cell viral transfer and on the mechanisms of virological synapse formation. The aim of the third axis is a better understanding of the interplay between viruses and the immune system of the host. For both axes, we are combining basic and applied scientific questions.
 
Contribution to the programme
 
The first axis is aimed at understanding the impact of HIV-1 infection on the biology of T cells. We study the impairment of intracellular trafficking and signaling pathways in infected lymphocytes, and the effect of viral proteins on these processes.
The second axis concerns HIV-1 cell-to-cell spread. Direct cell-to-cell transfer represents a potent mode of viral propagation, which involves the formation of virological synapses between infected cells and recipients. We designed various assays (flow cytometry, confocal & scanning electron microscopy, live videomicroscopy…) to assess cell-to-cell viral transfer. We examine the role of cellular and viral proteins on viral cell-to-cell spread.
The aim of the third axis is a better knowledge of the interplay between viruses and the immune system. We are studying the interplay between HIV and type-I Interferons (IFN). We aim at determining how HIV infection triggers IFN production in various cell types. We are following the impact of IFNs on virus replication and antigen presentation. The tools that we have designed are also used to study, in cell cultures, the behavior of HIV candidate vaccines.
 
References over the past 5 years
1.      RoeschF, MezianeO, KulaA, NisoleS, PorrotF, MammanoF, FassatiA, MarcelloA, Benkirane M & Schwartz O Hyperthermia stimulates HIV-1 replication. Plos Pathogens in press
2.      Laguette N, Sobhian B, Casartelli N, Ringeard M, Chable-Bessia C, Ségéral E, Yatim A, Emiliani S, Schwartz O, and Benkirane M. 2011. SAMHD1 is the dendritic- and myeloid-cell-specific HIV-1 restriction factor counteracted by Vpx. Nature 474, 654-7.
3.      LepelleyA, LouisS, SourisseauM, PothlichetJ, SchilteC, ChaperotL, PlumasJ, RandallRE, Si-TaharM, MammanoF, AlbertML & SchwartzO. 2011. Innate sensing of HIV-infected cells. Plos Pathogens 7: e1001284.
4.      Casartelli N, Sourisseau M, Feldmann, J, Guivel-BenhassineF, Mallet A, Marcelin, AG, Guatelli J, SchwartzO. 2010. Tetherin restricts productive HIV Cell-To-Cell Transmission. Plos Pathogens 6, e1000955
5.      Schwartz, O., and Albert, M.L. 2010. Biology and pathogenesis of chikungunya virus. Nature Reviews Microbiology 8, 491-500.
6.      Casartelli N, Guivel-BenhassineF, BouziatR, Brandler S, SchwartzO and MorisA. 2010 The antiviral factor APOBEC-3G improves CTL recognition of HIV infected T cells. Journal of Experimental Medicine 207(1): 39-49
7.      Rudnicka, D., J. Feldmann, F. Porrot, S. Wietgrefe, S. Guadagnini, M. C. Prevost, J. Estaquier, A. Haase, N. Sol-Foulon, and O. Schwartz. 2009. Simultaneous HIV Cell-to-Cell Transmission To Multiple Targets Through Polysynapses. Journal of Virology 83:6234-46