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
From left to right: J. Lagisquet, N. Arhel, C. Chamontin, J. Fernandez, S. Nisole, S. Maillet, A. Zebboudj.

Team members

EnregistrerEnregistrerEnregistrerEnregistrerEnregistrerEnregistrerEnregistrerEnregistrer

2018

- Maarifi G, Fernandez J, Portilho DM, Boulay A, Dutrieux, J, Oddos S, Butler-Browne G, Nisole SArhel NJ. RanBP2 regulates the anti-retroviral activity of TRIM5α by SUMOylation at a predicted phosphorylated SUMOylation motif. Commun Biol. 2018, 1:193.

- Nisole S. Usutu, that which does not kill us makes us stronger. Virologie. 2018, 22(5):231-2

- Hayek S, Bekaddour N, Besson L, Alves de Sousa R, Pietrancosta N, Viel S, Smith N, Jacob Y, Nisole S, Mandal R, Wishart DS, Walzer T, Herbeuval JP, Vidalain PO. Identification of primary natural killer cell modulators by chemical library screening with a luciferase based functional assay. SLAS Discovery. 2018, 2472555218797078.

2017

- 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.

2016

- 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 SArhel 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, a broad-spectrum viral restriction factor. 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.

2015

- 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.

2014

- 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.

2013

- 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.

2012

- 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 NJNisole S, Charneau P, Beignon AS.  HIV-derived vectors for therapy and vaccination against HIV. Vaccine. 2012, 30:2499-509.

 

Local

  • Sara SALINAS & Yannick SIMONIN, INSERM U1058, Montpellier
  • Nadir MECHTI, DIMNP, Montpellier
  • Matteo BONAZZI, IRIM, Montpellier

National

  • Jean-Philippe HERBEUVAL & Pierre-Olivier VIDALAIN, Faculté des Saints-Pères, Paris
  • Nicolas LEVEQUE & Charles BODET, CHU de Poitiers
  • Anne-Sophie BEIGNON, CEA Fontenay-aux-Roses

International

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

- December 2018: Nathalie Arhel and Sébastien Nisole are attending the Immunotherapies for Infectious Diseases congress in Lyon, France.



- October 2018: 
The VTRIS team at the IRIM's cooking contest.


from left to right: J. Fernandez, S. Maillet, G. Maarifi

- September 2018: Nathalie Arhel organizes a very stimulating workshop at Domaine de Verchant, with the support of ANR.



- June 2018:  Marie-France Martin has been awarded a 3-year Ph.D. grant from the Labex EpigenMed to study the innate immune response to arboviruses in human immune cells. Congratulation and welcome Marie-France!



- May 2018: Juliette Fernandez organizes Montpellier's first ever Young Research Apprentices symposium on behalf of the "Arbre des Connaissances" association. Teenagers were given the opportunity to discover lab work throughout their school year, then presented their results before their families and teachers during a friendly symposium held in the CNRS amphitheatre. A huge thank you to all IRIM teams who welcomed these budding scientists in their labs.



- April 2018: The VTRIS members join the IRIM team for the "Ruée des Fadas", an 8 km obstacle race.



- April 2018: The team welcomes Richard de Reuver, an Erasmus Master student from the Netherlands, who comes for a 6-month internship. Welcome Richard!



- February 2018: Nathalie Arhel and Sébastien Nisole are attending the "Viruses - Breakthroughs in Viral Replication" conference in Barcelona.


Can you find us?

- October 2017:
 The VTRIS team wins second prize for the 3-min video contest illustrating life at IRIM. We've got our sights set on first prize for next year's challenge -the highly coveted golden pipette!


Left picture, from left to right: S. Maillet, J. Fernandez, C. Chamontin, A. Zebboudj, J. Lagisquet
Right picture: S. Maillet and J. Fernandez 

- October 2017: The VTRIS team is happy to welcome two new members, Abderezak Zebboudj (postdoc) and Justine Lagisquet (Research assistant). Welcome Zak and Justine!



- September 2017: The VTRIS team welcomes Célia Chamontin who joins the team as a permanent research assistant (Montpellier University). We're happy to have you Célia!



- June 2017: Sarah Maillet obtains a 3-year Ph.D. grant from the ANRS to investigate the molecular mechanism of the inhibition of HIV-1 reverse-transcription by the cellular protein Daxx. Well done, Sarah!



- May 2017: The VTRIS team on its first escape game.


From left to right: S. Nisole, N. Arhel, C. Chamontin, J. Fernandez, S. Maillet

- April 2017: The VTRIS team participates in a giant human chain to spell the word "Science" in Montpellier's main square. We're in the second "C" of "Science" on this satellite picture.



- March 2017: Juliette Fernandez holds the Sidaction stand with Véronique in the IRIM lobby.

 
- January 2017:  VTRIS Lab-warming party!



- January 2017: Juliette Fernandez obtains a 3-year PhD grant from the Sidaction to develop new tools to investigate HIV nuclear import. Well done, Juliette!



- January 2017: Inauguration of the Viral Trafficking, Restriction and Innate Signaling laboratory (VTRIS) at IRIM, Montpellier.

Team leaders

Nathalie Arhel

CNRS Staff scientist



Sébastien Nisole

INSERM Staff scientist

EnregistrerEnregistrerEnregistrerEnregistrerEnregistrer

At a glance

The VTRIS team was created on January 1st 2017, following an international call for senior group leaders from the IRIM institute. It is supported by the regional excellence consortium (Labex) EpiGenMed.

EnregistrerEnregistrer

Funding

                            
EnregistrerEnregistrerEnregistrerEnregistrerEnregistrer

Contact us


     
   

   

Enregistrer

Enregistrer

Enregistrer

Enregistrer

Enregistrer

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

 

Enregistrer

Enregistrer

Enregistrer

Enregistrer

Enregistrer

Enregistrer