General
Dimitri LAVILLETTE 
Institut Pasteur of Shanghai, Chinese Academy of Sciences (IPS-CAS)
Email: dlaville@ips.ac.cn
Telephone: 021-54923190
Address: A326, B Building of New life science building, 320 Yueyang Road
Postcode: 200023

Research Areas

Emergence and geographical extension of dengue (DENV) and chikungunya (CHIKV) viruses increase simultaneous outbreaks and up to 12% of patients have been diagnosed to be co-infected. In addition, it was shown that the mosquitoes Aedes albopictus could carry and transmit simultaneously CHIKV and DENV. However, the pathology, as well as the epidemiology of a pathogen can be influence by the interactions between several infectious agents present within an organism. So far, there is no extensive report of DENV-CHIKV interactions. Our global objective is to characterize the coinfection of CHIKV with DENV in both mosquitoes and humans, at the cell and molecular levels.

Our preliminary data indicate that cells chronically infected with CHIKV showed higher permissiveness to DENV and had higher DENV production. Our project aims to explain this increased DENV replication but also, identify in a more global study, the host proteins and pathways that are modified by the presence of both arboviruses. We will identify the modified replication steps and the viral proteins involved using mosquito cells (Aim 1). We also aim to purify modified molecular complexes containing key CHIKV proteins using a systemic quantitative proteomic approach (Aim 2). In parallel, we will study co-infection in relevant human common target cell lines involved in pathogenesis (Aim 3).

Altogether, we will establish a more precise viral-host interaction pattern during DENV-CHIKV co-infection. This work might provide clues for the development of new antiviral compounds targeting common pathways.    

Education

          
2009 Habilitation à diriger les recherches  (HDR ; February 3rd).

Sept1997- Dec2000 PhD in Virology 
(Ecole Normale Supérieure, Lyon, FRANCE) under supervision of Dr François-Loïc COSSET.
Research project: Characterization of the membrane fusion  mechanism mediated by the envelope glycoprotein of Murine Leukemia virus.
Date of graduation: December 18th 2000

Sept1994-Sept1997 Master of Differentiation,
 Genetic and Immunology at the University Claude Bernard, Lyon, FRANCE

Sept1991-Jun1994 Bachelor of Science – Biochemistry.  
Dijon University, Dijon, FRANCE

Honors & Distinctions

                

Publications

   
Papers
49. New insights into the understanding of hepatitis C virus entry and cell-to-cell transmission by using the ionophore Monensin A. Fénéant L, Potel J, François C, Sané F, Douam F,  Belouzard S, Calland N, Vausselin T, Rouillé Y, DESCAMPS V, Baumert TF, Duverlie G, Lavillette D, Hober D,  Dubuisson J.D., Wychowski C.  J Virol.Accepted 2015-05-26.

48. Low cross-neutralization of hepatitis C correlates with liver disease in immunocompromized patients. Maurin, G; Halgand, B; Bruscella, P; Fresquet, J; Duclos-Vallée, J-C; Roque-Afonso, A-M; Cosset, F-L; Samuel, D; Féray, C*; Lavillette, D*. AIDS: June 2015 - Volume 29 - Issue 9 - p 1025–1033 DOI: 10.1097/QAD.0000000000000651

47. Murphy L, Varela M, Desloire S, Ftaich N, Murgia C, Golder M, Neil S, Spencer TE, Wootton SK, Lavillette D, Terzian C, Palmarini M, Arnaud F. The sheep tetherin paralog oBST2B blocks envelope glycoprotein incorporation into nascent retroviral virions. J Virol. 2015 Jan;89(1):535-44. doi: 10.1128/JVI.02751-14. Epub 2014 Oct 22

46. Girard-Gagnepain A, Amirache F, Costa C, Lévy C, Frecha C, Fusil F, Nègre D, Lavillette D, Cosset FL, Verhoeyen E. Baboon envelope pseudotyped lentiviral vectors outperform VSV-G pseudotyped lentiviral vectors for gene transfer into cytokine-stimulated and resting hematopoietic stem cells. Blood. 2014 Jun 20. pii: blood-2014-02-558163. (IF2012 9)

45. Cartier F, Marcq I, Douam F, Ossart C, Regnier A, Debuysscher V, Lavillette D, Bouhlal H. The Expression of the Hepatocyte SLAMF3 (CD229) Receptor Enhances the Hepatitis C Virus Infection. PLoS One. 2014 Jun 13;9(6):e99601. (IF2012 3,7)

44. Bocchetta S, Maillard P, Yamamoto M, Gondeau C, Douam F, Lebreton S, Lagaye S, Pol S, Helle F, Plengpanich W, Guérin M, Bourgine M, Michel ML, Lavillette D, Roingeard P, le Goff W, Budkowska A. Up-Regulation of the ATP-Binding Cassette Transporter A1 Inhibits Hepatitis C Virus Infection. PLoS One. 2014 Mar 19;9(3):e92140. (IF2012 3,7)

*43. Douam F, Dao Thi VL, Maurin G., Fresquet J., Mompelat D., Cosset FL and Lavillette D. A critical interaction between E1 and E2 glycoproteins determines binding and fusion properties of hepatitis C virus during cell entry. Hepatology. 2014 Mar;59(3):776-88 (IF2011 11,66).

42. Lévy C, Aerts L, Hamelin MÈ, Granier C, Szécsi J, Lavillette D, Boivin G, Cosset FL. Virus-like particle vaccine induces cross-protection against human metapneumovirus infections in mice. Vaccine. 2013 Jun 7;31(25):2778-85. (IF2011 3.458)

41. Vausselin T, Calland N, Belouzard S, Descamps V, Douam F, Helle F, François C, Lavillette D, Duverlie G, Wahid A, Fénéant L, Cocquerel L, Guérardel Y, Wychowski C, Biot C, Dubuisson J. The antimalarial ferroquine is an inhibitor of hepatitis C virus. Hepatology. 2013 Jan 24. (IF2011 11,66).

40. Dao Thi VL, Granier C, Zeisel MB, Guerin M, Mancip J, Granio O, Penin F, Lavillette D, Bartenschlager R, Baumert TF, Cosset FL, Dreux M. Characterization of hepatitis C virus particle sub-populations reveals multiple usage of the scavenger receptor BI for entry steps. J Biol Chem. 2012 Jul 5. 7;287(37):31242-57 (IF2011 5.11)

39. Molina-Jimenez F, Benedicto I, Dao Thi VL, Gondar V, Lavillette D, Marin JJ, Briz O, Moreno-Otero R, Aldabe R, Baumert TF, Cosset FL, Lopez-Cabrera M, Majano PL. Matrigel-embedded 3D culture of Huh-7 cells as a hepatocyte-like polarized system to study hepatitis C virus cycle. Virology. 2012 Mar 30;425(1):31-9. Epub 2012 Jan 24. (IF2011 3.35)

38. Boo I, Tewierik K, Douam F, Lavillette D, Poumbourios P, Drummer HE. Distinct roles in folding, CD81 receptor binding and viral entry for conserved histidine residues of hepatitis C virus glycoprotein E1 and E2. Biochem J. 2012 Apr 1;443(1):85-94. (IF2011 4.89)

37. Garrone P, Fluckiger AC, Mangeot PE, Gauthier E, Dupeyrot-Lacas P, Mancip J, Cangialosi A, Du Chéné I, Legrand R, Mangeot I, Lavillette D, Bellier B, Cosset FL, Tangy F, Klatzmann D, Dalba C. A prime-boost strategy using virus-like particles pseudotyped for HCV proteins triggers broadly neutralizing antibodies in macaques. Sci Transl Med. 2011 Aug 3;3(94):94ra71. (IF2011 .7,8)

*36. Maurin G, Fresquet J, Granio O, Wychowski C, Cosset FL and Lavillette D. Identification of interactions in the E1E2 heterodimer of Hepatitis C virus important for cell entry. J Biol Chem. 2011 Jul 8;286(27):23865-76. (IF2011 5.11)

35. Lupberger J, Zeisel MB, Xiao F, Thumann C, Fofana I, Zona L, Davis C, Mee CJ, Turek M, Gorke S, Royer C, Fischer B, Zahid MN, Lavillette D, Fresquet J, Cosset FL, Rothenberg SM, Pietschmann T, Patel AH, Pessaux P, Doffoël M, Raffelsberger W, Poch O, McKeating JA, Brino L, Baumert TF. EGFR and EphA2 are host factors for hepatitis C virus entry and possible targets for antiviral therapy. Nat Med. 2011 May;17(5):589-95. (IF2011 26,41)

*34. FL Cosset and D Lavillette. Cell entry of enveloped viruses. Advances in Genetics. 2011;73:121-83. (IF2011 3,9)

33. Teissier E, Zandomeneghi G, Loquet A, Lavillette D, Lavergne JP, Montserret R, Cosset FL, Böckmann A, Meier BH, Penin F, Pécheur EI. Mechanism of inhibition of enveloped virus membrane fusion by the antiviral drug arbidol. PLoS One. 2011 Jan 25;6(1):e15874. (IF2011 4.41)

*32. Pérot P*, Montgiraud C*, Lavillette D* and Mallet F. A comparative portrait of retroviral fusogens and syncytins. Cell Fusions book. 2011. pp 63-115, Springer.

31. Bonnafous P, Perrault M, Le Bihan O, Bartosch B, Lavillette D, Penin F, Lambert O, Pecheur EI Characterization of hepatitis C viral pseudoparticles by cryo-electron microscopy usingfunctionalized magnetic nanobeads.. J Gen Virol. 2010 Apr 7. (IF2011 3,36)

30. Pawlotsky JM, Cocquerel L, Durantel D, Lavillette D, Lerat H, Pécheur EI, Polyak SJ, Tautz N, Thimme R.  HCV research 20 years after discovery: a summary of the 16th international symposium on hepatitis C virus and related viruses. Gastroenterology. 2010 Jan;138(1):6-12.e1-2. Epub 2009 Nov 18. (IF2011 11,6)

29. Lin EH, Salon C, Brambilla E, Lavillette D, Szecsi J, Cosset FL, Coll JL. Fusogenic membrane glycoproteins induce syncytia formation and death in vitro and in vivo: a potential therapy agent for lung cancer. Cancer Gene Ther. 2010 Apr;17(4):256-65. 2009 Nov 6. (IF2011 2,8)

28. Trotard M, Lepère-Douard C, Régeard M, Piquet-Pellorce C, Lavillette D, Cosset FL, Gripon P, Le Seyec J. Kinases required in hepatitis C virus entry and replication highlighted by small interference RNA screening. FASEB J. 2009 Nov;23(11):3780-9. (IF2011 6,3)

27. Benedicto I, Molina-Jiménez F, Bartosch B, Cosset FL, Lavillette D, Prieto J, Moreno-Otero R, Valenzuela-Fernández A, Aldabe R, López-Cabrera M, Majano PL. The tight junction-associated protein occludin is required for a postbinding step in hepatitis C virus entry and infection. J Virol. 2009 Aug;83(16):8012-20. Epub 2009 Jun 10. (IF2011 5,4)

26. Dreux M, Dao Thi VL, Fresquet J, Guérin M, Julia Z, Verney G, Durantel D, Zoulim F, Lavillette D, Cosset FL, Bartosch B. Receptor complementation and mutagenesis reveal SR-BI as an essential HCV entry factor and functionally imply its intra- and extra-cellular domains. PLoS Pathog. 2009 Feb;5(2):e1000310. Epub 2009 Feb 20 (IF2011 9,1)

25. Fenouillet E., Lavillette D., Loureiro S., Krashias G., Maurin G., Cosset FL., Jones IM., Barbouche R.. Contribution of redox status to HCV E2 envelope protein function and antigenicity. J Biol Chem. 2008 Sep 26;283(39):26340-8. Epub 2008 Jul 30. (IF2011 5,11)

24. Meertens L, Bertaux C, Cukierman L, Cormier E, Lavillette D, Cosset FL, Dragic T. The tight junction proteins claudin-1, -6 and -9 are entry cofactors for the Hepatitis C virus. J Virol. 2008; 82:3555-3560. (IF2011 5,4)

23. Dreux, M., Boson, B., Ricard-Blum, S., Molle, J., Lavillette, D., Bartosch, B., Pécheur, E.-I. and Cosset., F.-L. The exchangeable apolipoprotein ApoC-I promotes membrane fusion of hepatitis C virus. J Biol Chem. 2007 Nov 2;282(44):32357-69. Epub 2007 Aug 30.

*22. Lavillette D, Pecheur EI, Donot P, Fresquet J, Molle J, Corbau R, Dreux M, Penin F, Cosset FL. Characterization of fusion determinants points to the involvement of three discrete regions of both E1 and E2 glycoproteins in the membrane fusion process of hepatitis C virus. J Virol. 2007 Aug;81(16):8752-65. (IF2011 5,4)

21. Pecheur EI, Lavillette D, Alcaras F, Molle J, Boriskin YS, Roberts M, Cosset FL, Polyak SJ. Biochemical Mechanism of Hepatitis C Virus Inhibition by the Broad-Spectrum Antiviral Arbidol. Biochemistry. 2007 May 22;46(20):6050-9.

20. Dreux M, Pietschmann T, Granier C, Voisset C, Ricard-Blum S, Mangeot PE, Keck Z, Foung S, Vu-Dac N, Dubuisson J, Bartenschlager R, Lavillette D, Cosset FL. High density lipoprotein inhibits hepatitis C virus-neutralizing antibodies by stimulating cell entry via activation of the scavenger receptor BI. J Biol Chem. 2006 Jul 7;281(27):18285-95.

*19. Lavillette D, Barbouche R, Yao Y, Boson B, Cosset FL, Jones IM, Fenouillet E. Significant redox insensitivity of the functions of the SARS-CoV Spike glycoprotein; comparison to HIV envelope. J Biol Chem. 2006 Apr 7;281(14):9200-4.2006.

*18. Lavillette D, Bartosch B, Nourrisson D, Verney G, Cosset FL, Penin F, Pecheur EI.  Hepatitis C virus glycoproteins mediate low pH-dependent membrane fusion with liposomes. J Biol Chem. 2006 Feb 17;281(7):3909-17.

17. Youn JW, Park SH, Lavillette D, Cosset FL, Yang SH, Lee CG, Jin HT, Kim CM, Shata MT, Lee DH, Pfahler W, Prince AM, Sung YC. Sustained E2 antibody response correlates with reduced peak viremia after hepatitis C virus infection in the chimpanzee. Hepatology. 2005 Dec;42(6):1429-36.

16. Owsianka A, Tarr AW, Juttla VS, Lavillette D, Bartosch B, Cosset FL, Ball JK, Patel AH.  Monoclonal antibody AP33 defines a broadly neutralizing epitope on the hepatitis C virus E2 envelope glycoprotein. J Virol. 2005 Sep;79(17):11095-104.

15. Bartosch B, Verney G, Dreux M, Donot P, Morice Y, Penin F, Pawlotsky JM, Lavillette D and Cosset FL. An interplay between hypervariable region 1 of the hepatitis C virus E2 glycoprotein, the scavenger receptor BI, and high-density lipoprotein promotes both enhancement of infection and protection against neutralizing antibodies. J Virol. 2005 Jul;79(13):8217-29.

*14. Lavillette D., Y. Morice, G. Germanidis, P. Donot, A. Soulier, E. Pagkalos, G. Sakellariou, L. Intrator, B. Bartosch, J.-M. Pawlotsky, and F.-L. Cosset. 2004. Human serum facilitates hepatitis C virus infection, and neutralizing responses inversely correlate with viral replication kinetics at the acute phase of hepatitis C virus infection. J Virol. 2005 May;79(10):6023-34. (IF2011 5,4)

*13. Lavillette D, Tarr AW, Voisset C, Donot P, Bartosch B, Bain C, Patel AH, Dubuisson J, Ball JK, Cosset FL. Characterization of host-range and cell entry properties of the major genotypes and subtypes of hepatitis C virus. Hepatology. 2005 Feb;41(2):265-74.

*12. Lavillette D and Kabat D. Porcine endogenous retroviruses infect cells lacking cognate receptors by an alternative pathway: implications for retrovirus evolution and xenotransplantation. J Virol. 2004 Aug;78(16):8868-77.

*11. Tailor CS*, Lavillette D*, Marin M*, Kabat D. Cell surface receptors for gammaretroviruses. Curr Top Microbiol Immunol. 2003;281:29-106. Review. (IF2011 4,9)

10. Marin M, Lavillette D, Kelly SM, Kabat. D. N-linked glycosylation and sequence changes in a critical negative control region of the ASCT1 and ASCT2 neutral amino acid transporters determine their retroviral receptor functions. J Virol. 2003 Mar;77(5):2936-45.

*9. Lavillette, D., Ruggieri, A., Boson, B., A. Maurice, M. and Cosset, F.-L. Structural inter-relations between subdomains of the SU that regulate receptor-mediated transition between the fusion-inhibited and fusion-active conformations of the MLV glycoprotein. J. Virol. 2002. 76:9673-9685.

*8. Lavillette, D., Marin, M., Ruggieri, A., Mallet, F., Cosset, F.L., and Kabat, D. The Envelope Glycoprotein of Human Endogenous Retrovirus Type -W Mediates Infections by Promiscuously Using a Divergent Family of Amino Acid Transporters/Cell Surface Receptors. J. Virol. 2002. 76:6442-6452.

*7. Lavillette, D., Russell, S. J., and Cosset, F. L. Retargeting gene delivery using surface-engineered retroviral vector particles. Curr Opin Biotechnol. 2001. Oct;12(5):461-6. (IF2011 7,7)

*6. Lavillette, D., Boson, B., Russell, S. J., and Cosset, F. L. Activation of membrane fusion by murine leukemia viruses is controlled in cis or in trans by interactions between the receptor-binding domain and a conserved disulfide loop of the carboxy-terminus of the surface glycoproteins. J Virol . 2001. 75,3685-95.

*5. Lavillette, D., Ruggieri, A., Russell, S. J., and Cosset, F. L. Activation of a cell entry pathway common to type C mammalian retroviruses by soluble envelope fragments. J Virol 2000. 74, 295-304.

4. Blond, J. L., Lavillette, D., Cheynet, V., Bouton, O., Oriol, G., Chapel-Fernandes, S., Mandrand, B., Mallet, F., and Cosset, F. L. An envelope glycoprotein of the human endogenous retrovirus HERV-W is expressed in the human placenta and fuses cells expressing the type D mammalian retrovirus receptor. 2000. J Virol  74, 3321-9.

3. Kim FJ, Seiliez I, Denesvre C, Lavillette D, Cosset FL, Sitbon M. Definition of an amino-terminal domain of the human T-cell leukemia virus type 1 envelope surface unit that extends the fusogenic range of an ecotropic murine leukemia virus. J Biol Chem. 2000 Aug 4;275(31):23417-20.

2. Bateman A, Bullough F, Murphy S, Emiliusen L, Lavillette D, Cosset FL, Cattaneo R, Russell SJ, Vile RG. Fusogenic membrane glycoproteins as a novel class of genes for the local and immune-mediated control of tumor growth. Cancer Res. 2000 Mar 15;60(6):1492-7.

*1. Lavillette, D., Maurice, M., Roche, C., Russell, S. J., Sitbon, M. and Cosset, F.-L. A proline-rich motif downstream of the receptor binding domain modulates conformation and fusogenicity of murine retroviral envelopes. J Virol 1998 Dec 72, 9955-9965.



Patents
Lavillette D, Levy C, Cosset FL, Boivin G. Chimeric pseudo-particles containing functional Human metapneumovirus (hMPV) proteins (Paramyxoviridae family, genus Metapneumovirus). (Patent application N° 12305283.9; applicant INSERM France - Institut Frapier Canada, 12 décembre 2012)

Verhoeyen E, Girard A., Lavillette D., Cosset FL. New Lentiviral vector pseudotyped with mutant BAeV glycoproteins allow efficient gene transfer of   hematopoietic cells (T cells, B cells and HSCs (Patent application N° 11306247; applicant INSERM, 29 september 2012 European patent; exclusive license).

Methods for enhancing the potency of HCV neutralizing antibodies. Cosset F.-L., Dreux M, Bartosch B. Lavillette D. Klatzmann D., Dalba C.  US provisional application, filed 23 Mars 2005 by Epixis (start-up), INSERM, ENS Lyon. B0342WO.

Improvements in or Relating to Treatment and Prevention of Viral Infections. A Patel, J Ball, A Tarr, FL Cosset, D Lavillette. C1695/M. filed 1/01/2005.

Modified receptor binding assays. M Chadwick, D Lavillette et F-L Cosset. (Application No. PCT 60/291,895) filed on May 18, 2001.

Detection procedure of the expression of a endogenous human retroviral envelope and use of one coding of this protein. Mallet F, Cosset FL, Blond JL, Lavillette D, Bouton O, Ruggieri A. FR99/11141 FR99/11793 PCT/FR00/02429 (FR2797889, EP1212359, WO0116171) déposée le 15 Septembre 1999

New polypeptides and their use for the rescue of fusion defective virus or retrovirus glycoproteins. Cosset F.-L. et D. Lavillette.1999. Demande de Brevet Européen (N°99 401 220.1) déposée le 20 Mai 1999. N° PCT/EP00/04534. WO 00/71578.

Use of a proline rich sequence to enhance the fusogenicity of retroviral envelope. Cosset F.-L. et D.Lavillette. 1998. FR98/00342. PCT/FR99/00016. WO 99/36561.

Research Interests

Microbiology

Virology

Conferences

   

Collaboration

   

Students

现指导学生

黄鹂  硕士研究生  085238-生物工程  

段博文  博士研究生  071005-微生物学