Molecular and cellular virology
Jean Dubuisson graduated as a Doctor in Veterinary Medicine in 1984 from the University of Liège in Belgium, and he received his PhD degree in 1989 from the same university. Between 1985 and 1991, he studied viral pathogenesis of bovine herpesviruses. He did a post-doc between 1991 and 1994 at Washington University School of Medicine in St. Louis, Missouri, USA, working on Sindbis virus, yellow fever virus and hepatitis C virus. In 1994, he obtained a tenure position at CNRS and he started to develop his own group in France, at the Institut Pasteur de Lille. Since 1993, Jean Dubuisson has been working on hepatitis C virus. He has been a pioneer in studying hepatitis C virus entry and morphogenesis. Since 2014, his group is also developing research projects on coronaviruses and hepatitis E virus. In 2003, he received the Silver Medal Award from the CNRS and between 2005 and 2010, he was an HHMI (Howard Hughes Medical Institute) International Research Scholar.
The MCV team is dedicated to the study of positive-strand RNA viruses. The main objectives are to better understand how these viruses interact with their host at the cellular and molecular level and to identify new antiviral targets. The viral models are hepatitis C virus (HCV), hepatitis E virus (HEV) and coronaviruses. For more than 25 years, the team has been studying the HCV life cycle and it has contributed to the field by characterizing the biogenesis of HCV glycoproteins as well as their functions in virus entry and assembly. Members of the team have also characterized host factors involved in different steps of the viral life cycle. They have also contributed to the characterization of HCV entry with the help of new antiviral molecules identified in the laboratory. Although major progress has been achieved since the development of a cell culture system for HCV in 2005, many gaps remain in our understanding of the HCV life cycle. The team therefore continues to study this virus and more particularly its interaction with the lipid metabolism. In 2013, with the emergence of the Middle East Respiratory Syndrome coronavirus (MERS-CoV), the team has also decided to initiate new projects on coronaviruses, which now also include SARS-CoV-2, the causative agent of COVID-19. These emerging viruses are life threatening and there is currently no specific antiviral available to treat infected patients. The current objective is therefore to better understand the life cycle of these viruses and identify novel antiviral targets. From a more fundamental point of view, the team is more interested to better understand the molecular mechanisms leading to virus entry and assembly. Due to the accumulation of tools to study HCV, the team is also developing a program on HEV, another hepatotropic virus, and the objectives are to identify and characterize host factors involved in the life cycle of this virus and to better understand the biogenesis of the viral particle.
Hervouet K, Ferrié M, Ankavay M, Montpellier C, Camuzet C, Alexandre V, Dembélé A, Lecoeur C, Foe AT, Bouquet P, Hot D, Vausselin T, Saliou JM, Salomé-Desnoulez S, Vandeputte A, Marsollier L, Brodin P, Dreux M, Rouillé Y, Dubuisson J, Aliouat-Denis CM, Cocquerel L. An Arginine-Rich Motif in the ORF2 capsid protein regulates the hepatitis E virus lifecycle and interactions with the host cell. PLoS Pathog. 2022 Aug 25;18(8):e1010798. doi: 10.1371/journal.ppat.1010798.
Meister TL, Brüggemann Y, Nocke MK, Ulrich RG, Schuhenn J, Sutter K, Gömer A, Bader V, Winklhofer KF, Broering R, Verhoye L, Meuleman P, Vondran FWR, Camuzet C, Cocquerel L, Todt D, Steinmann E. A ribavirin-induced ORF2 single-nucleotide variant produces defective hepatitis E virus particles with immune decoy function. Proc Natl Acad Sci U S A. 2022 Aug 23;119(34):e2202653119. doi: 10.1073/pnas.2202653119.
Rebendenne A, Roy P, Bonaventure B, Chaves Valadão AL, Desmarets L, Arnaud-Arnould M, Rouillé Y, Tauziet M, Giovannini D, Touhami J, Lee Y, DeWeirdt P, Hegde M, Urbach S, Koulali KE, de Gracia FG, McKellar J, Dubuisson J, Wencker M, Belouzard S, Moncorgé O, Doench JG, Goujon C. Bidirectional genome-wide CRISPR screens reveal host factors regulating SARS-CoV-2, MERS-CoV and seasonal HCoVs. Nat Genet. 2022 Aug;54(8):1090-1102. doi: 10.1038/s41588-022-01110-2.
Lavie M, Dubuisson J, Belouzard S. SARS-CoV-2 Spike Furin Cleavage Site and S2' Basic Residues Modulate the Entry Process in a Host Cell-Dependent Manner. J Virol. 2022 Jul 13;96(13):e0047422. doi: 10.1128/jvi.00474-22.
Belouzard S, Machelart A, Sencio V, Vausselin T, Hoffmann E, Deboosere N, Rouillé Y, Desmarets L, Séron K, Danneels A, Robil C, Belloy L, Moreau C, Piveteau C, Biela A, Vandeputte D, Heumel S, Deruyter L, Dumont L, Leroux F, Engelmann I, Alidjinou EK, Hober D, Brodin P, Beghyn T, Trottein F, Déprez B, Dubuisson J. Large scale screening discovers clofoctol as an inhibitor of SARS-CoV-2 replication that reduces COVID-19-like pathology. PLoS Pathog, 2022, 18, e1010498
Metzger K, Bentaleb C, Hervouet K, Alexandre V, Montpellier C, Saliou JM, Ferrié M, Camuzet C, Rouillé Y, Lecoeur C, Dubuisson J, Cocquerel L, Aliouat-Denis CM. Processing and subcellular localization of the hepatitis E virus replicase: identification of candidate viral factories. Front Microbiol, 2022, 13, 828636
Meunier T, Desmarets L, Bordage S, Bamba M, Hervouet K, Rouillé Y, François N, Decossas M, Tra Bi FH, Lambert O, Dubuisson J, Belouzard B, Sahpaz S, Séron K. A photoactivable natural product with broad antiviral activity against enveloped viruses including highly pathogenic coronaviruses. Antimicrob Agents Chemother, 2022, 66, e01581-21
Eymieux S, Rouillé Y, Terrier O, Séron K, Blanchard E, Rosa-Calatrava M, Dubuisson J, Belouzard S, Roingeard P. Ultrastructural modifications induced by the SARS-CoV-2 in Vero cells: a kinetic analysis of viral factories formation, viral particle morphogenesis and virion release. Cell Mol Life Sci, 2021, 78, 3565-3576
Perrier A, Bonnin A, Desmarets L, Danneels A, Goffard A, Rouillé Y, Dubuisson J, Belouzard S. Identification of a novel TGN localization signal in the C-terminal domain of the MERS coronavirus M protein. J Biol Chem, 2019, 294, 14406-14421
Lavie M, Linna L, Moustafa RI, Belouzard S, Fukasawa M, Dubuisson J. Role of the cytosolic domain of occludin in trafficking and HCV infection. Traffic, 2019, 20, 753-773
Ankavay M, Montpellier C, Sayed IM, Saliou JM, Wychowski C, Saas L, Duvet S, Aliouat-Denis CM, Farhat R, de Masson d'Autume V, Meuleman P, Dubuisson J, Cocquerel L. New insights into the ORF2 capsid protein, a key player of the hepatitis E virus lifecycle. Sci Rep, 2019, 9, 6243
Sahuc ME, Sahli R, Rivière C, Pène V, Lavie M, Vandeputte A, Brodin P, Rosenberg AR, Dubuisson J, Ksouri R, Rouillé Y, Sahpaz S, Séron K. Dehydrojuncusol, a natural phenanthrene compound extracted from Juncus maritimus is a new inhibitor of hepatitis C virus replication. J Virol, 2019, 93, e02009-18
Lebsir N, Goueslain L, Farhat R, Callens N, Dubuisson J, Jackson CL, Rouillé Y. Functional and physical interaction between the Arf activator GBF1 and hepatitis C virus NS3 protein. J Virol, 2019, 93, e01459-18
Moustafa R, Haddad J, Linna L, Hanoulle X, Descamps V, Mesalam A, Baumert T, Duverlie G, Meuleman P, Dubuisson J, Lavie M. Functional study of the C-terminal part of hepatitis C virus E1 ectodomain. J Virol, 2018, 92, e00939-18
Farhat R, Ankavay M, Lebsir N, Gouttenoire J, Jackson CL, Wychowski C, Weber A, Moradpour D, Dubuisson J, Rouillé Y, Cocquerel L. (2018) Identification of GBF1 as a cellular factor required for Hepatitis E virus RNA replication. Cell Microbiol, 20, e12804
Montpellier C, Wychwoski C, Sayed IM, Meunier JC, Saliou JM, Ankavay M, Bull A, Pillez A, Abravanel F, Helle F, Brochot E, Drobecq H, Farhat R, Aliouat-Denis CM, Haddad J, Izopet J, Meuleman P, Goffard A, Dubuisson J, Cocquerel L. (2018) Hepatitis E Virus Lifecycle and Identification of 3 Forms of the ORF2 Capsid Protein. Gastroenterology, 154, 211-223