Interferon and antiviral restriction

Our projects

Interferon is produced by infected cells following the detection of pathogenic viruses and bacteria and is the first line of defence against infection. Interferon induces the expression of several hundred genes, names interferon-stimulated genes (ISGs) both in infected and neighbouring cells. The products of the ISGs, in turn, allow the establishment of a so-called antiviral state, which is able to prevent, or at least limit, viral replication. Most viruses, including influenza A virus and the Human Immunodeficiency Virus type 1 (HIV-1), are highly sensitive to this antiviral state and unable to replicate efficiently in cells that have been pre-exposed to IFN.



The dynamin-like, high-molecular weight GTPases MX1 and MX2 play a significant role in the interferon-induced inhibition of viral replication. Human MX1 is a restriction factor of broad antiviral activity, able to inhibit a great diversity of RNA and DNA viruses at different stages of their life cycles. The activity of MX2 seems narrower and has so far been restricted to HIV-1 and some primate lentiviruses. MX2 prevents HIV-1 DNA nuclear import and integration. Both MX1 and MX2 seem to recognize and interact with key components of viral nucleoprotein complexes to prevent viral replication, however their detailed mechanisms of action remain to be understood. Other antiviral ISGs inhibiting HIV-1 and influenza A virus have been identified, however, our preliminary data show that additional genes remain to be identified. We have recently identified the short isoform of NCOA7, which is interferon-inducible, as a new antiviral factor preventing endocytosis-meditaed viral entry.

Our lab, named Interferon and antiviral restriction, which has been established in January 2015 at the CNRS institute of research on infection of Montpellier (IRIM, ex-CPBS), aims at identifying new cellular effectors of the antiviral state (using, among other approaches, whole-genome scale CRISPR/Cas9 screens) and at characterizing the molecular mechanisms involved in their antiviral activity.
 
Our main projects are the following:
  • Understanding the antiviral activity of MX and NCOA7 proteins
 
  • Physiological role and potential involvement in innate immune signalling of MX proteins
 
  • Identification and characterization of new interferon-induced, antiviral effectors against HIV-1 and influenza A virus and other human pathogenic viruses

Key words
Interferon, antiviral restriction, HIV-1, influenza A virus, innate immunity, signalling, genetic screens
 
 
 

 






From left to right : B. Bonaventure, J. McKellar, C. Goujon, C. André, S. Allahverdiyeva, O. Moncorgé, M. Tauziet, M. Arnould


Team members

Minibio: Caroline studied at at the Ecole Normale Supérieure (ENS) of Lyon. She did her Master's and PhD in Dr Jean-Luc Darlix’s laboratory (Inserm U412/U758; Sept. 2002-Jan. 2008), under the supervision of Dr Andrea Cimarelli. She studied the restriction of HIV-1 infection in human dendritic cells and discovered for the first time that HIV-2/SIV Vpx was able to relieve this block. She then did a long postdoc in Prof. Michael Malim’s laboratory at King’s College London (Feb. 2008-Dec. 2014), where she was awarded a Marie Curie Intra-European Fellowship to study the host cell responses to HIV-1 infection. She became interested in the relationships between HIV-1 and the interferon system and characterized in depth the interferon-induced restriction of HIV-1 infection. She notably identified human MX2 as one of the major interferon-stimulated genes preventing HIV-1 infection. In 2014, she was awarded the Andy Kaplan prize and obtained both an INSERM researcher permanent position and an ATIP-Avenir grant to move back to France and start her own group. She has been working at the CNRS IRIM institute (which was formerly called CPBS) in Montpellier since January 2015. She has obtained in 2016 grants from Sidaction and the ANRS. She has been awarded an ERC Starting Grant in 2017 to study the mechanisms of interferon-induced antiviral restriction and mechanisms (ANTIViR project).

Minibio: After working as the molecular biology group leader in a French biotech company (Aptanomics SA, Lyon) and as an engineer (IE) on HIV-1 translation at the Ecole Normale Supérieure of Lyon, Olivier did his PhD and a 2-year postdoc in Prof. Wendy Barclay’s laboratory, at Imperial College London. Olivier worked on the molecular basis of host range restriction of avian influenza polymerases in mammalian hosts. During his first post-doc, Olivier was part of the European consortium ANTIFLU, aiming at identifying new inhibitors of influenza virus replication. Olivier also studied MX1 protein activity against influenza A virus. Olivier has joined the lab in Feb. 2015, thanks to the support of the ANRS (2-year fellowship obtained by C. Goujon in connection with the ATIP-Avenir grant, and 1-year fellowship renewal obtained by O. Moncorgé). Olivier now works on the ERC ANTIViR project and leads the influenza 1 virus-related topics of the lab.

 


Minibio: Francisco studied engineering in molecular biotechnology at the Universidad de Chile where his work focused on the characterization of the pre-integration complex of the murine leukemia virus in Prof. Monica Acevedo´s laboratory. He then did his PhD in microbiology at the Universidad de Chile-Universidad de Santiago and worked in Prof. Ricardo Soto-Rifo's laboratory. His PhD thesis focused on the regulation of HIV-1 gene expression. Francisco has joined the lab in May 2019 and works on several aspects of the ERC ANTIViR project.




Minibio: Boris studied at the ENS of Lyon. After internships at Oxford university and Harvard Medical School, Boris joined the lab for his third Master internship in Feb. 2016. He has obtained the French government MNERT scholarship to do his PhD in the lab and has started in October 2016. Boris is applying powerful, whole-genome CRISPR/Cas9 screens to the identification of new HIV-1 inhibitors.



Minibio: Marine did a B.Eng. (DUT and Licence professionnelle, from La Rochelle and Montpellier university, respectively). She did a 4-months internship in the lab (Spring 2017) and was then recruited as a research assistant (AI) in July 2017. She has been recruited as an AI again in October 2017. Marine works with Caroline on the characterization of a new antiviral interferon-stimulated gene.


  • Joe McKellar - 1st year PhD student (Montpellier university)
After gaining a B.Sc. in Cellular Biology and Physiology from Limoges University, Joe did his Master at Montpellier University and a 6-month internship in the group. He then worked as a research assistant. He has obtained the French government MNERT scholarship to do his PhD in the lab and started in October 2018. Joe studies the mechanism of action of MX1 protein against influenza A virus under the supervision of Olivier.




SonaSona is from Azerbaidjan and has moved to Montpellier for her studies. She is currently doing a 6-month internship in the lab and is co-supervised by Caroline and Valérie Courgnaud (IGMM). Her project aims at validating the role of potential cofactors of MX2 antiviral protein that were identified by Valérie in genetic screens done in haploid cells.



Mary"Normalienne agrégée" (ENS-Cachan), Mary did her PhD thesis Paris XI university in immunology and has been teaching since then at the IUT of Montpellier. Mary has joigned the team in March 2019 and uses her expertise in biochemistry to study MX1 antiviral protein.







The interferon and antiviral restriction lab in March 2018


Spring 2018. From left to right: O. Moncorgé, W. Djilli, M. Tauziet, B. Bonaventure, C. Goujon, C. André, J. McKellar

The interferon and antiviral restriction lab in October 2017


The team at the IRIM Retreat 2017. From left to right: O. Moncorgé, B. Bonaventure, C. Goujon, M. Tauziet.

The interferon and antiviral restriction lab in July 2017

From left to right : R. Planès, C. Goujon, M. Tauziet, B. Bonaventure, O. Moncorgé, E. Partiot.

The interferon and antiviral restriction lab in September 2016

The team at the IRIM Retreat 2016. From left to right : B. Bonaventure, C. Goujon, O. Moncorgé, R. Planès.


Past team members

  • Charlotte Arpin-André, Research assistant (CNRS). Spring 2018- Spring 2019.
  • Timothée Lalo-Deltour - BSc (L3) student, Montpellier university. Summer 2018 (7 weeks). 
  • Wassila Djilli - Master (M2) student, Strasbourg university. January-June 2018 (5 months).
After a technical diploma followed by a B.Sc., Wassila was a Master student at Strasbourg University and did a 5-month internship in the group. Wassila worked with Boris on the identification and characterization of new interferon-induced HIV-1 inhibitors. Wassila is currently finalizing her training to become a biology teacher. 



  • Rémi Planès - Postdoc (Sidaction). Oct. 2015-Sept. 2017. Current email address: Remi.Planes(AT)ipbs.fr

Rémi did his PhD in Toulouse (INSERM U1043, CHU Purpan), under the supervision of Prof. E. Bahraoui. His thesis unravelled the role of HIV-1 Tat protein in TLR4 signalling. Rémi was then awarded a 1-year FRM fellowship to join Dr P. Guermonprez at the Centre for Molecular and Cellular Biology of Inflammation (CMCBI), King’s College London, where he studied the response of human dendritic cells to Plasmodium falciparum-infected red cells. Rémi was recently awarded a 2 year-fellowship by Sidaction to join the Interferon and antiviral restriction Lab and study the physiological role of MX2 and its potential involvement in innate immune signalling. Rémi worked in the lab from Oct. 2015 to Sept. 2017 and has now joined the lab of Etienne Meunier in Toulouse where he is studying the activation of the inflammasome by different pathogens.
  • Emma Partiot, Master (M1) student. Paris Diderot University. June-July 2017 (2 months).
  • Leila Makrini, CNRS research assistant (AI). December-June 2017 (6 months).
  • Marion Chateauraynaud, Master (M1) student. Montpellier university. Spring 2017 (2 months).
  • Antoine Rebendenne, BSc (L3) student. ENS-Cachan. Summer 2016 (2,5 months).
  • Océane Paris, Master (M1) student. Montpellier university. Spring 2016 (2 months).
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March 2019. Six lab members at the 'Journées Francophones de Virologie', ENS-Lyon and many other IRIM members!





November 2018. Publication in Nature Microbiology of our collaborative article with M. Malim's team (King's College London) describing a new antiviral ISG:

Doyle T., Moncorgé O., Bonaventure B., Pollpeter D., Lussignol M., Tauziet M., Apolonia L., Catanese M.T., Goujon C.# and Malim M.H.#. The interferon inducible isoform of NCOA7 inhibits endosome-mediated viral entry. Nature Microbiology, (12):1369-1376.
(# corresponding authors)

Link towards the 'Behind the paper' post from C. Goujon : Entry forbidden, a new antiviral ISG identified


June 2018. Joe McKellar, a Master student in the team, ranked 1st at the competitive exam from CBS2 to obtain the PhD scholarship from the French government (MRT).

Mars 2018 : Article featuring Caroline Goujon on the INSERM website.

September 2017 : After 2 years with us, Rémi Planès leaves the lab and moves back to Toulouse to start a new postdoc on the inflammasome. Best of luck for your future Rémi !



29th of September 2017: Farewell drinks and lunch at the IRIM.

July 2017: Caroline Goujon has been awarded an ERC Starting Grant for the ANTIViR project (Mechanisms of interferon-induced antiviral restriction and signalling)



July 2017: Celebration drinks at the institute for the accepted grants.


January 2017: Olivier Moncorgé has been awarded a 1-year renewal of his ANRS postdoctoral fellowship, to characterize new anti-HIV-1 inhibitors identified in whole-genome scale CRISPR/Cas9 genetic screens.


July 2016 : Caroline Goujon has obtained grants from Sidaction and the ANRS (for 2 and 3 years, respectively), for a collaborative project with Jean-Luc Battini (IRIM, ex-IGMM) and Valérie Courgnaud (IGMM) to identify MX2 cellular cofactors and other interferon-induced HIV-1 inhibitors using powerful genetic screens.



June 2016 : Boris Bonaventure, a Master student in the team, ranked 2nd at the competitive exam from CBS2 to obtain the PhD scholarship from the French government (MRT).


July 2015 : Rémi Planès has obtained a 2-year postdoctoral fellowship from Sidaction to join the team and study the potential role of human MX2 in innate immune signalling.

Main publications (C. Goujon)

# corresponding authors
* co-first authors
(bold: lab members)


2018


2016


2015


2014


2013


2012


 

Local

  • J.L. Battini, IRIM and V. Courgnaud, IGMM, Montpellier. Genetic screens in haploid cells.
  • L. Espert, IRIM, Montpellier. Autophagy and influenza.
  • L. Briant, IRIM, Montpellier. Identification of anti-arboviruses ISGs.
  • D. Muriaux, IRIM, Montpellier. Late phases of influenza A virus replication.

National

  • E. Ricci et P.E. Mangeot, CIRI, ENS Lyon. CRISPR/Cas9 genetic modification of primary cells using the Nanoblade techonology.
  • Mélanie Wencker, CIRI, Lyon. Potential modulation of immune responses by NCOA7 in mice.
  • Bernardo Reina San Martin, IGBMC, Strasbourg. Proteomics of HIV-1 reverse transcription complexes.

International

  • G. Kochs, Université de Freiburg, Allemagne. MX and innate immunity
  • M.H. Malim et T. Doyle, King's College London, Royaume-Uni. Characterization of a new ISG preventing endocytosis-mediated viral entry.
  • W.S. Barclay, Imperial College Lodon, Royaume-Uni. Study of influenza A virus.
  • Ke Peng, Research group of virus-host interactions, Wuhan Institute of Virology, Chinese Academy of Sciences, China. New dependency factors of HIV-1.

Team leader


Caroline Goujon

INSERM tenure researcher (CR1)

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At a glance

The interferon-induced antiviral state strongly inhibits viral replication in human cells, which means that our cells are capable of expressing powerful, natural antiviral inhibitors. Our team aims at understanding the mechanisms of the interferon-induced antiviral defences. Using powerful approaches (such as whole-genome CRISPR/Cas9 knock-out functional genetic screens), we aim at identifying new interferon-induced effectors, and then at characterizing their antiviral activity.

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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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