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, the Human Immunodeficiency Virus type 1 (HIV-1) and SARS-CoV-2, 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, including SARS-CoV-2

  • Identification of new antiviral compounds active against influenza virus and SARS-CoV-2

Since March 2020, we've also been studying SARS-CoV-2: we're chacterizing the inhibitory effect of interferons, identifying cellular regulators of replication through whole-genome CRISPR screens and screening molecules to help identify new therapeutical avenues.


Key words
Interferon, antiviral restriction, HIV-1, influenza A virus, SARS-CoV-2, innate immunity, signalling, genetic screens, CRISPR/Cas9
 
 
 

 


Eté 2020.
De gauche à droite: Francisco Garcia de Gracia, Olivier Moncorgé, Marine Tauziet, Joe McKellar, Mary Arnould, Ana Luise Chaves Valadão, Antoine Rebendenne, Boris Bonaventure.



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). In 2020, the lab obtained several fundings to work on SARS-CoV-2, MUSE (Montpellier university), from INSB, La fondation CNRS, the ANR-RACOVID, in order to identify and characterize anti-SARS-CoV-2 molecules, characterize the host cell responses to infection and identify the cellular regulators of viral replication through CRISPR screen. In 2020, C. Goujon has also been awarded a PRC ANR grant to study NCOA7's mechanism of action and role in vivo, in collaboration withe M. Blaise (IRIM) and M. Wencker (CIRI).

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 and FluAttack projects and leads the influenza 1 virus-related topics of the lab. Olivier also works on several SARS-CoV-2 projects.

 


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. He has identified DDX42 as a new intrinsic inhibitor of HIV-1 and other viruses.



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 - 2nd 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 and is specialized in cell bology and microscopy approaches.





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 strong expertise in biochemistry to study MX1, NCOA7 and DDX42 antiviral proteins, in close collaboration with M. Blaise (IRIM).





« Normalien agrégé » in Biochemistry and bioengineering from the Ecole Normale Supérieure Paris-Saclay (ex ENS Cachan), Antoine did his Master 2 in Fundamental Virology (Sorbonne University/Pasteur Institute).  After carrying out several internships both in France (in our team during summer 2016) but also in London (Imperial College London, UK) in 2017 and in New York (Rockefeller University, USA) en 2018-2019, Antoine came back to do his master’s thesis in our team. Under the supervision of Caroline, Antoine has worked on the characterisation of a new interferon-induced antiviral protein, NCOA7, and on SARS-CoV-2 since the end of the first lockdown. Antoine is now pursuing his PhD both in the team and with Mélanie Wencker (CIRI).



Ana Luisa Chaves Valadão, Research Engineer, ERC PoC FluAttack

Ana studied Biological Sciences at State University of Rio de Janeiro. She has a master degree in Parasitology from Oswaldo Cruz Foundation where she worked in the development of a bivalent vaccine against yellow fever and dengue viruses. During her PhD, she focused her research in the role of Processing Bodies and Stress Granules during HIV replicative cycle. She did an intership, still during her PhD, at Institute of Human Genetics, in Montpellier, under the supervision of Monsef Benkirane, when they were interested in unveilling the activation pathway of HIV restriction factor SAMHD1. She started a post-doc in Brazil, working with HIV-1 latency and antiviral compounds against Zika virus. During this period, she was also teaching Genetics and Evolution for undergratuating students at Federal University of Rio de Janeiro. In 2016, she joined again the Institute of Human Genetics, now as a post-doc in Nadine Laguette team, working with Cancer Related Inflammation (MSDAvenir fellowship). After two years of contract, she became the Research Engineer of Laguette’s group. Since April 2020, Ana has joined the Interferon and antiviral restriction lab to work on new antivirals against Flu (ERC PoC FluAttack Project), in collaboration with Olivier Moncorgé, and has also been involved in SARS-CoV-2 projects.

  
The Interferon and Antiviral Restriction Lab in December 2019.

From left to right: A. Rebendenne, M. Arnould, F. Garcia de Gracia, M. Tauziet, O. Moncorgé, B. Bonaventure, J. McKellar, and C. Goujon.



The interferon and antiviral restriction lab in July 2019


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

The interferon and antiviral restriction lab in March 2019


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


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/students

  • Laura Navar, AI CNRS. Spring 2020. L3 Pro student, IUT Montpellier.
  • Sona Allahverdiyeva. Spring 2019. Master (M2) student, Montpellier university. Sona is doing a PhD in virology in Amsterdam.
  • Charlotte Arpin-André, Research assistant (CNRS). Spring 2018- Spring 2019.
  • Timothée Lalo-Deltour - BSc (L3) student, Montpellier university. Summer 2018 (7 weeks).
  • Joe McKellar - Master (M2) student, Montpellier university (6 mois). Joe is doing his PhD in the lab. 
  • 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 & Paris Unversity. Summer 2016 (2,5 months) and Master (M2) student (8 months), now a PhD student in the team.
  • Océane Paris, Master (M1) student. Montpellier university. Spring 2016 (2 months).
  • Boris Bonaventure, Master (M2) student. Ecole Normale Supérieure de Lyon. Spring 2020 (3 months). Boris is finalizing his PhD in the team.
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October 2020: the first two preprints from the team are online!

The first preprint describes the identification of DDX42 as a broad antiviral inhibitor. Boris Bonaventure, in the team, performed whole-genome CRISPR screens which led to the identification of DDX42 as an intrinsic inhibitor of HIV-1, in various cell lines and primary cells. DDX42 inhibits viral DNA accumulation and is in close proximity with Capsid in infected cells. DDX42 is also capable of inhibiting retrotranspoition of Line-1 and infection with different retroviruses. Finally, we reveal that DDX42 is also a potent inhibitor of other pathogenic viruses, including SARS-CoV-2!
https://www.biorxiv.org/content/10.1101/2020.10.28.359356v1
All the team members participated in this work as well as Laurence Briant and Eric Bernard from IRIM (work on CHIKV) as well as Nathalie Gros from CEMIPAI (work on ZIKV). The library preparation and deep sequencing analysis was done by Hugues Parrinello and Stéphanie Rialle from Montpellier GenomiX.

In the second preprint, we have explored the host cell responses to SARS-CoV-2 both in primary human airway epithelia and in model cell lines. We observed a potent interferon induction, mainly due to sensing by MDA-5, but unable to control replication.
https://www.biorxiv.org/content/10.1101/2020.10.28.358945v1
This work was done in collaboration with cytokine specialists, Seb Nisole and Ghizlane Maarifi at the IRIM.

Below an image example acquired with a LSM880 microscope (Airyscan mode) of human airway epithelial cells (in green, Actin) infected by SARS-CoV-2 (red). Do admire the beauty of the ciliated cells seen from above for most of them ! Scale bar: 10 um, IF and image by Joe McKellar, infection by Olivier Moncorgé.



September 2020: First two ANR grants awarded to C. Goujon!
ANR RA-COVID for the CRISPR-TARGET-CoV project, aiming to identify new therapeutic targets against SARS-CoV-2, using whole-genome CRISPR screens, in collaboration with John Doench (Broad Institute, USA).
ANR PRC for the CAIPIRINAS (Control of type A Influenza virus Propagation and Immune Responses: Investigating the role of NCOA7-Alternative Start) project, in collaboration with M. Blaise and M. Wencker. This project aims to study NCOA4s mode of action in vitro, in cellulo and its role in vivo.



June 2020 : Antoine Rebendenne, 'normalien agrégé' from ENS-Paris Saclay awarded a PhD scholarship to do his PhD in the team.


Spring 2020 : Fundings obatined from MUSE, INSB and the Fondation CNRS for the team work on SARS-CoV-2


March 2020 : While France is under lockdown, IRIM members, including our team work on SARS-CoV-2 research. In our team, C. Goujon, O. Moncorgé and M. Tauziet are in the lab everyday and perform experiments to better understand this new virus and potentially identify antiviral molecules. A. Chaves Valadao joins the COVID-19 team in April 2020, and A. Rebendenne at the end of the first lockdown.



March-April 2020: Team members working on covid19. From left to right: Marine Tauziet in our moleculat biology lab, Olivier Moncorgé in our Cat2 and Cat3 labs (CEMIPAI), Caroline Goujon in the cat3.


January 2020 : an ERC Proof of Concept grant (from the 3rd call 2019) awarded to C. Goujon for the FluAttack project led by O. Moncorgé (link: ERC website)








August 2019. Two innovation grants obtained from 'la région Occitanie' : for the Antigrip Anticip project from the team and the Fongal Kombat Microbes project, led by Jean-Michel Bellanger (CEFE) in collaboration with Matteo Bonazzi's team and our team.






September 2019: Celebratory drinks for the Region grants.


June 2019. Boris Bonaventure awarded a 4th year for his PhD by La Fondation pour la Recherche Médicale (FRM).




March 2019. Six lab members at the 'Journées Francophones de Virologie', ENS-Lyon and many other IRIM members! And second best poster prize for Boris Bonaventure: congrats, Boris!





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 and recent preprints (C. Goujon)

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


2020



2018


2016


2015


2014


2013


2012


 

Local

  • J.L. Battini, IRIM and V. Courgnaud, IGMM, Montpellier. Genetic screens in haploid cells.
  • L. Chaloin. 3D model of MX proteins. Inhibitors of SARS-CoV-2.
  • M. Blaise. Structure-function analysis of NCOA7, DDX42 and MX proteins.
  • L. Espert, IRIM, Montpellier. Autophagy, innate responses and viruses
  • L. Briant, IRIM, Montpellier. Identification of anti-arboviruses ISGs. Inhibition of CHIKV by DDX42.
  • D. Muriaux & C. Favard, IRIM, Montpellier. MX interactions with lipids.
  • L. Picas, IRIM, Montpellier. MX interactions with lipids.
  • J.M. Bellanger, CEFE. Antiviral activity of mushroom extracts.
  • M. Moriel, CRBM. Inhibitors of SARS-CoV-2.

National

  • M. Wencker, CIRI, Lyon. Potential modulation of immune responses by NCOA7 in mice.
  • E. Ricci et P.E. Mangeot, CIRI, ENS Lyon. CRISPR/Cas9 genetic modification of primary cells using the Nanoblade techonology. Host responses to SARS-CoV-2.
  • B. Reina San Martin, IGBMC, Strasbourg. Proteomics of HIV-1 reverse transcription complexes.
  • E. Meunier and R. Planès, IPBS, Toulouse. Impact of NCOA7 on bacterial infections.
  • C. Cougoule, IPBS, Toulouse. Organoid infection with SARS-CoV-2.

International

  • G. Kochs, Freiburg university, Allemagne. MX and innate immunity
  • X. Saelens, Ghent university, Belgique. MX1 mode of action.
  • M.H. Malim, King's College London, Royaume-Uni. Early responses to HIV-1 infection.
  • 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.
  • J. Doench, Broad Institute, USA. CRISPR screens to identify SARS-CoV-2 regulators.

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



 


   

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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