Viral Trafficking, Restriction and Innate Signaling


          Our team is interested in the mechanisms that control host-virus interactions at the level of the infected cell. Viruses rely on cellular transport machineries to travel from their site of entry to their site of replication, assembly and egress, with speed and efficiency to avoid rapid overpowering by the cell’s innate immunity and degradation machineries. We study how viruses use these cellular transport machineries for intracellular trafficking, including nuclear import for viruses that replicate in the nucleus such as HIV, and conversely how the cell responds to viral infections by initiating efficient intrinsic and innate immunities. In particular, we seek to understand the cellular pathways that mediate host-innate immune response to viral infection, focusing on the molecular mechanisms triggering interferon response following viral infections. Our aims are to (i) identify the determinants of viral movement within cells, (ii) characterize new mediators of the antiviral activity of interferon, (iii) determine the role of post-translational modifications in the control of viral infections.

The team in November 2017

Team members



Lucas-Hourani M, Dauzonne D, Mulier-Lehmann H, Khiar S, Nisole S, Dairou J, Helynck O, Afonso P, Tangy F, Vidalain PO. An original chemical series of pyrimidine biosynthesis inhibitors that boost the antiviral interferon response. Antimicrob. Agents Chemother. 2017, 61(10): e00383-17.

Khiar S, Lucas-Hourani M, Nisole S, Smith N, Helynck O, Bourgine M, Ruffié C, Herbeuval JP, Munier-Lehmann H, Tangy F, Vidalain PO. Identification of a small molecule that primes the type I interferon response to cytosolic DNA. Sci Rep. 2017, 7(1):2561.

Smith N, Pietrancosta N, Davidson S, Dutrieux J, Chauveau L, Cutolo P, Dy M, Scott-Algara D, Manoury B, Zirafi O, McCort-Tranchepain I, Durroux T, Bachelerie F, Schwartz O, Münch J, Wack A, Nisole S, Herbeuval JP. Natural amines inhibit activation of human plasmacytoid dendritic cells through CXCR4 engagement. Nat Commun. 2017, 8:14253.


Smith N, Vidalain PO, Nisole S, Herbeuval JP. An efficient method for gene silencing in human primary plasmacytoid dendritic cells: silencing of the TLR7/IRF 7 pathway as a proof of concept. Sci Rep. 2016, 6:29891.

Maarifi G, Hannoun Z, Geoffroy MC, El Asmi F, Zarrouk K, Nisole S, Blondel D, Chelbi-Alix M. MxA mediates SUMO-induced resistance to Vesicular Stomatitis Virus. J Virol. 2016, 90(14):6598-610.

Portilho DM, Fernandez J, Ringeard M, Machado AK, Boulay A, Mayer M, Müller-Trutwin M, Beignon AS, Kirchhoff F, Nisole S, Arhel NJ. Endogenous TRIM5α function is regulated by SUMOylation and nuclear sequestration for efficient innate sensing in dendritic cells. Cell Reports. 2016, 14(2):355-69.

Portilho DM, Persson R, Arhel N. Role of non-motile microtubule-associated proteins in virus trafficking. Biomol Concepts. 2016, 7(5-6):283-292.

Maillet S, Nisole S. Daxx, un facteur de restriction virale à large spectre. Virologie, 2016, 20(5):261-72.

Maarifi G, Dianoux L, Nisole S, Chelbi-Alix MK. SUMO paralogs and interferon response. Med Sci (Paris). 2016, 32(2):141-3.



Dutrieux J, Maarifi G, Portilho DM, Arhel NJ, Chelbi-Alix MK, Nisole S. PML/TRIM19-dependent inhibition of retroviral reverse-transcription by Daxx. PLoS Pathog. 2015, 11(11):e1005280.

Fernandez J, Portilho DM, Danckaert A, Munier S, Becker A, Roux P, Zambo A, Shorte S, Jacob Y, Vidalain PO, Charneau P, Clavel F, Arhel NJ. Microtubule-associated proteins 1 (MAP1) promote human immunodeficiency virus type I (HIV-1) intracytoplasmic routing to the nucleus. J Biol Chem. 2015, 290(8):4631-46.

Maarifi G, Maroui MA, Dutrieux J, Dianoux L, Nisole S, Chelbi-Alix MK. SUMO promotes resistance to interferon. J Immunol. 2015, 195(5):2312-24.

Dutrieux J, Portilho DM, Arhel NJ, Hazan U, Nisole S. TRIM5α is a SUMO substrate. Retrovirology. 2015, 12:28.

Brantis-de-Carvalho CE, Maarifi G, Gonçalves Boldrin PE, Zanelli CF, Nisole S, Chelbi-Alix MK, Valentini SR. MxA interacts with and is modified by the SUMOylation machinery. Exp Cell Res. 2015, 330(1):151-63.

Kotera N, Dubost E, Milanole G, Doris E, Gravel E, Arhel N, Brotin T, Dutasta JP, Cochrane J, Mari E, Boutin C, Léonce E, Berthault P, Rousseau B. A doubly responsive probe for the detection of Cys4-tagged proteins. Chem Commun. 2015, 51(57):11482-4.

Blondel D, Maarifi G, Nisole S, Chelbi-Alix M. Resistance to Rhabdoviridae Infection and Subversion of Antiviral Responses. Viruses. 2015, 7:3675-702.



Zebboudj A, Maroui MA, Dutrieux J, Boukoffa C, Bourouba M, Chelbi-Alix MK, Nisole S. Sodium arsenite induces apoptosis and Epstein-Barr virus reactivation in lymphoblastoid cells. Biochimie. 2014, 107: 247-56.

El Asmi F, Maroui MA, Dutrieux J, Blondel D, Nisole S, Chelbi-Alix MK. Implication of PMLIV in both intrinsic and innate immunity. PLoS Pathog. 2014, 10(2):e1003975.

Maarifi G, Chelbi-Alix MK, Nisole S. PML control of cytokine signaling. Cytokine Growth Factor Rev. 2014, 25(5):551-61.

Maroui MA, El Asmi F, Dutrieux J, Chelbi-Alix M, Nisole S. Implication of PML nuclear bodies in intrinsic and innate immunity. Med Sci (Paris). 2014, 30(8-9): 765-71.



Gaudin R, de Alencar BC, Arhel N, Benaroch P. HIV trafficking in host cells: motors wanted! Trends Cell Biol. 2013, 23(12):652-62.

Nisole S, Maroui MA, Mascle XH, Aubry M, Chelbi-Alix. Differential roles of PML isoforms. Frontiers in Oncology. 2013, 3:125.



Di Nunzio F, Danckaert A, Fricke T, Perez P, Fernandez J, Perret E, Roux P, Shorte S, Charneau P, Diaz-Griffero F, Arhel NJ. Human nucleoporins promote HIV-1 docking at the nuclear pore, nuclear import and integration. PLoS One. 2012, 7(9):e46037.

Lelek M, Di Nunzio F, Henriques R, Charneau P, Arhel N, Zimmer C. Superresolution imaging of HIV in infected cells with FlAsH-PALM. Proc Natl Acad Sci U S A. 2012, 109(22):8564-9.

Valle-Casuso JC, Di Nunzio F, Yang Y, Reszka N, Lienlaf M, Arhel N, Perez P, Brass AL, Diaz-Griffero F. TNPO3 is required for HIV-1 replication after nuclear import but prior to integration and binds the HIV-1 core. J Virol. 2012, 86(10):5931-6.

Roesch F, Meziane O, Kula A, Nisole S, Porrot F, Anderson I, Mammano F, Fassati A, Marcello A, Benkirane M, Schwartz O. Hyperthermia stimulates HIV-1 replication. PLoS Pathog. 2012, 8(7):e1002792.

Di Nunzio F, Félix T, Arhel NJ, Nisole S, Charneau P, Beignon AS.  HIV-derived vectors for therapy and vaccination against HIV. Vaccine. 2012, 30:2499-509.



  • Fabien BLANCHET, IRIM, Montpellier
  • Nadir MECHTI, DIMNP, Montpellier


  • Jean-Philippe HERBEUVAL & Pierre-Olivier VIDALAIN, Faculté des Saints-Pères, Paris
  • Nicolas LEVEQUE & Charles BODET, CHU de Poitiers


  • Franck KIRCHHOFF, Institute of Molecular Virology, Ulm, Germany

Team leaders

Nathalie Arhel

CNRS Staff scientist
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Sébastien Nisole

INSERM Staff scientist
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At a glance

Organisme(s) modèle(s)

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Processus biologique étudié

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Techniques utilisées

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Applications médicales

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Institut de Recherche en Infectiologie de Montpellier
UMR 9004 - CNRS / UM
1919 route de Mende - 34293 Montpellier cedex 5