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 January 2019
Front, from left to right: F. Blanchet, N. Arhel, C. Chamontin, J. Lagisquet, G. Maarifi
Back, from left to right: S. Maillet, J. Fernandez, M-F. Martin, S. Nisole

Team members

  

Past members (VTRIS Alumni)

 Carla Alemany, Bachelor student (Montpellier University, France), 2020

 Lina Lapeyre, Master student (Montpellier University, France), 2020

 Anne-Claire Aurilio, Master student (Montpellier University, France), 2019-2020

 Justine Lagisquet, Research assistant, 2017-2019

 Willy Lutz, Bachelor student (Nîmes University, France), 2019

 Richard de Reuver, Master student Erasmus (Leiden University, The Netherlands), 2018

 Samah Sharif, Master student (Montpellier University, France), 2018

 Abderezak Zebboudj, Postdoc, 2017-2018
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Publications 2014-2020

2020

- Volcic M, Sparrer KMJ, Koepke L, Hotter D, Sauter D, Stürzel CM, Scherer M, Stamminger T, Hofmann TG, Arhel NJ, Wiesmüller L, Kirchhoff F. Vpu modulates DNA repair to suppress innate sensing and hyper-integration of HIV-1. Nat Microbiol. 2020, 5(10):1247-1261.

- Arhel NJ. Early HIV replication revisited. Nat Microbiol. 2020, 5(9):1065-1066.

- Clé M, Desmetz C, Barthelemy J, Martin MF, Constant O, Maarifi G, Foulongne V, Bolloré K, Glasson Y, De Bock F, Blaquiere M, Dehouck L, Pirot N, Tuaillon E, Nisole S, Najioullah F, Van de Perre P, Cabié A, Marchi N, Gosselet F, Simonin Y, Salinas S. Zika Virus Infection Promotes Local Inflammation, Cell Adhesion Molecule Upregulation, and Leukocyte Recruitment at the Blood-Brain Barrier. mBio. 2020, 11(4):e01183-20.

- Sa Ribero M, Jouvenet N, Dreux M, Nisole S. Interplay between SARS-CoV-2 and the type I interferon response. PLoS Pathog. 2020, 16(7):e1008737.

- Nisole S, Saulnier A, Gatignol A. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2): Should we target the virus, the cell or the disease? Virologie. 2020, 24(3):135-141.

- Maillet S, Fernandez J, Decourcelle M, El Koulali K, Blanchet FP, Arhel NJ, Maarifi G, Nisole S. Daxx inhibits HIV-1 reverse transcription and uncoating in a SUMO-dependent manner. Viruses. 2020, 12(6):E636.

- Burette M, Allombert J, Lambou K, Maarifi G, Nisole S, Di Russo Case E, Blanchet FP, Hassen-Khodja C, Cabantous S, Samuel J, Martinez E, Bonazzi M. Modulation of innate immune signaling by a Coxiella burnetii eukaryotic-like effector protein. PNAS 2020, 117(24):13708-13718.

- Fernandez J, Arhel NJ. HIV capsid and productive infection: taking steps in the right direction. Virologie. 2020, 24(2):88-98.

- Maarifi G, Czubala MA, Lagisquet J, Ivory MO, Fuchs K, Papin L, Birchall JC, Nisole S, Piguet V, Blanchet FP. Langerin (CD207) represents a novel interferon-stimulated gene in Langerhans cells. Cell Mol Immunol. 2020, 17(5):547-549.

- Martin MF, Nisole S. West Nile Virus restriction in mosquito and human cells: A virus under confinement. Vaccines. 2020, 8(2):E256.

- Maarifi G, Smith N, Nisole S. Interferon response: with great power comes great responsibility? Med Sci (Paris). 2020, 36(3):206-209.

- Fernandez J, Arhel NJ. Transportin-1 orchestrates HIV-1 uncoating and nuclear entry. Med Sci (Paris). 2020, 36(3):203-206.

2019

- Salinas S, Simonin Y, L'Ambert G, Nisole S. Autochthonous cases of Zika virus in metropolitan France: a new paradigm for this arbovirus? Virologie. 2019, 23(6):329-332.

- Maarifi G, Smith N, Maillet S, Moncorgé O, Chamontin C, Edouard J, Sohm F, Blanchet FP, Herbeuval JP, Lutfalla G, Levraud JP, Arhel NJNisole S. TRIM8 is required for virus-induced IFN response in human plasmacytoid dendritic cells. Sci Adv. 2019, 5(11):eaax3511.

- Hayek S, Pietrancosta N, Hovhannisyan AA, Alves de Sousa R, Bekaddour N, Ermellino L, Tramontano E, Arnould S, Sardet C, Dairou J, Diaz O, Lotteau V, Nisole S, Melikyan G, Herbeuval JP, Vidalain PO. Cerpegin-derived furo[3,4-c]pyridine-3,4(1H,5H)-diones enhance cellular response to interferons by de novo pyrimidine biosynthesis inhibition. Eur J Med Chem. 2019 Nov 6:111855.

- Fernandez J, Machado AK, Lyonnais S, Chamontin C, Gärtner K, Léger T, Henriquet C, Garcia C, Portilho DM, Pugnière M, Chaloin L, Muriaux D, Yamauchi Y, Blaise M, Nisole SArhel NJ. Transportin-1 binds to the HIV-1 capsid via a nuclear localization signal and triggers uncoating. Nat Microbiol. 2019 4(11):1840-1850.

- Smith N, Rodero MP, Bekaddour N, Bondet V, Ruiz-Blanco YB, Harms M, Mayer B, Badder-Meunier B, Quartier P, Bodemer C, Baudouin V, Dieudonné Y, Kirchhoff F, Garcia ES, Charbit B, Leboulanger N, Jahrsdörfer B, Richard Y, Korganow AS, Münch J, Nisole S, Duffy D and Herbeuval JP. Control of TLR7-mediated type I IFN signaling in pDCs through CXCR4 engagement—A new target for lupus treatment. Science Advances. 2019, 5(7):eaav9019.

- Shimauchi T, Caucheteux S, Finsterbusch K, Turpin J, Blanchet FP, Ladell K, Triantafilou K, Czubala M, Tatsuno K, Easter T, Ahmed Z, Bayliss R, Hakobyan S, Price DA, Tokura Y, Piguet V. Dendritic Cells Promote the Spread of Human T-Cell Leukemia Virus Type 1 via Bidirectional Interactions with CD4+ T Cells. J Invest Dermatol. 2019, 139(1):157-66.

- 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. 2019, 24(1):25-37.

Nisole S, Fernandez J, Maarifi G, Arhel NJ. SUMO regulates the capacity of TRIM5α to inhibit HIV-1. Med Sci (Paris). 2019, 35(2):106-109. 

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.

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.

- Czubala MA, Finsterbusch K, Ivory MO, Mitchell JP, Ahmed Z, Shimauchi T, Karoo ROS, Coulman SA, Gateley C, Birchall JC, Blanchet FP, Piguet V. TGFβ Induces a SAMHD1-Independent Post-Entry Restriction to HIV-1 Infection of Human Epithelial Langerhans Cells. J Invest Dermatol. 2016, 136(10):1981-1989.

- Coulon PG, Richetta C, Rouers A, Blanchet FP, Urrutia A, Guerbois M, Piguet V, Theodorou I, Bet A, Schwartz O, Tangy F, Graff-Dubois S, Cardinaud S, Moris A. HIV-Infected Dendritic Cells Present Endogenous MHC Class II-Restricted Antigens to HIV-Specific CD4+ T Cells. J Immunol. 2016, 197(2):517-32.

- Caucheteux SM, Mitchell JP, Ivory MO, Hirosue S, Hakobyan S, Dolton G, Ladell K, Miners K, Price DA, Kan-Mitchell J, Sewell AK, Nestle F, Moris A, Karoo RO, Birchall JC, Swartz MA, Hubbel JA, Blanchet FP, Piguet V. Polypropylene Sulfide Nanoparticle p24 Vaccine Promotes Dendritic Cell-Mediated Specific Immune Responses against HIV-1. J Invest Dermatol. 2016, 136(6):1172-81.

- 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.

- Chauhan S, Ahmed Z, Bradfute SB, Arko-Mensah J, Mandell MA, Won Choi S, Kimura T, Blanchet F, Waller A, Mudd MH, Jiang S, Sklar L, Timmins GS, Maphis N, Bhaskar K, Piguet V, Deretic V. Pharmaceutical screen identifies novel target processes for activation of autophagy with a broad translational potential. Nat Commun. 2015, 6:8620.

- Sagnier S, Daussy CF, Borel S, Robert-Hebmann V, Faure M, Blanchet FP, Beaumelle B, Biard-Piechaczyk M, Espert L. Autophagy restricts HIV-1 infection by selectively degrading Tat in CD4+ T lymphocytes. J Virol. 2015, 89(1):615-25.

- 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

- 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.

- Morgan AH, Hammond VJ, Sakoh-Nakatogawa M, Ohsumi Y, Thomas CP, Blanchet F, Piguet V, Kiselyov K, O'Donnell VB. A novel role for 12/15-lipoxygenase in regulating autophagy. Redox Biol. 2014, 4:40-47.

- Alfaisal J, Daussy CF, Blanchet FP, Espert L, Salinas S, Biard-Piechaczyk M. To eat or not to eat: the intricate relationship between autophagy and HIV-1. Current Topics in Virology. 2014, 12:23-51.

- Fielding CA, Aicheler R, Stanton RJ, Wang EC, Han S, Seirafian S, Davies J, McSharry BP, Weekes MP, Antrobus PR, Prod'homme V, Blanchet FP, Sugrue D, Cuff S, Roberts D, Davison AJ, Lehner PJ, Wilkinson GW, Tomasec P. Two novel human cytomegalovirus NK cell evasion functions target MICA for lysosomal degradation. PLoS Pathog. 2014, 10(5):e1004058.

- 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.

- 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.

Local

  • Sara SALINAS & Yannick SIMONIN, INSERM U1058, Montpellier
  • Nadir MECHTI & Georges LUTFALLA, DIMNP, Montpellier
  • Matteo BONAZZI, Caroline GOUJON & OLivier MONCORGE, IRIM, Montpellier
  • Sébastien LYONNAIS & Delphine MURIAUX, CEMIPAI, Montpellier

National

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

International

  • Franck KIRCHHOFF, Institute of Molecular Virology, Ulm, Germany
  • Yohei YAMAUCHI, Medical School, University of Bristol, UK
- November 2020: Congratulations to Sarah Maillet on a great remote PhD defense!



- July 2020:
Quentin Hertel obtains a 3-year Ph.D. fellowship from the competitive CBS2 doctoral school. Well done Quentin!! We are glad to keep you in the lab!



- June 2020: 
A big thanks to the ANR and the Region Occitanie for financing our project Alpha-CoV, which aims to implement a fast and reliable assay for the high-throughput screening of antiviral molecules active against SARS-CoV-2.

     

- March/April 2020:
The VTRIS team is staying in touch during lockdown.



- February 2020:
Juliette Fernandez receives the 2019 i-PhD trophy from Frédérique Vidal, Minister of Higher Education, Research and Innovation. Many congratulations, Juliette !!


The 29 laureates of the i-PhD trophy

- February 2020:
Nathalie Arhel and Sébastien Nisole are attending the Viruses - Novel Concepts in Virology conference in Barcelona.


Can you spot us?


Nathalie chairing the session "Viral genetics and evolution"


- November 2019: 
Many congratulations to the newly minted Dr Juliette Fernandez, who successfully defended her PhD! We’re all proud of you, Juliette!

      

- October 2019: 
Sébastien Nisole is Guest Editor of a Special Issue entitled "Intrinsic Antiviral Factors" to be published in Viruses. Submissions are now open and we are looking forward to your contributions!

Deadline: November 1, 2020

For further information please visit the website of the Special Issue:
https://www.mdpi.com/journal/viruses/special_issues/antiviral_factors



- September 2019:
 After 3 years of trying, the highly coveted IRIM golden pipette is ours...!!!
It came to us, our own, our love... our precioussss!!



The VTRIS team wins the IRIM 2019 photography contest with this photo:



The Making-of:



- September 2019: Triple combo after a summer of revisions: the VTRIS team has 3 papers currently in press... watch out our webpage for an update!



- July 2019:
Sarah Maillet, Célia Chamontin and Juliette Fernandez join the dIRIM Team for CNRS's 80th anniversary challenge.



- March 2019:
IRIM is well represented at the French virology meeting (Journées Francophones de Virologie) in Lyon. Juliette Fernandez presented our work on the role of TNPO1 in HIV-1 uncoating and nuclear import.



- March 2019:
Nathalie Arhel, Célia Chamontin and Sébastien Nisole join the IRIM Greyhound team for the relay marathon of Montpellier! 42.2km in 3h 53min.... well done greyhounds!!



- January 2019:
2019 starts off well for Fabien Blanchet, who obtained a 2-year grant from the ANRS to pursue his exciting research on HIV-1 restriction in Langerhans cells. Well done, Fabien!



- December 2018: 
Christmas came early this year with the arrival of a new PI in our team! Fabien Blanchet is a tenured INSERM researcher and specialist of myeloid cells, antiviral immunity and HIV biology. He is joining us together with Ghizlane Maarifi, postdoctoral fellow financed by ANRS. A warm welcome to you both, we're delighted to have you!



- 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 tenured researcher



Sébastien Nisole

INSERM tenured researcher

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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.

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Funding

                                  
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Contact us


     
   

   

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

 

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