Membrane Domains and Viral Assembly

04 oct 2020 -  Delphine as a scientific advisor for this interesting animation of Influenza viral entry. Watch it here.

 

 



23 june 2020 - Click on the image to access the Youtube team webinar given in the webinar serie of the Réseau Technologique de Microscopie de Fluorescence Multidisciplinaire (MITI-CNRS).





15 may 2020 - The whole team is proud and happy to be part of the 2019 highlights of the "institut des Sciences Biologiques" of the CNRS.

https://pbs.twimg.com/media/EYdMYxYWoAAiGOx?format=png&name=small



30 Apr 2020 -
Congrats to Delphine guest Editor in Viruses
for the special issue

"RNA Viruses and Membranes"

https://www.mdpi.com/img/journals/viruses-logo.png?72c9debfea22cec2

20 Apr 2020 - Webinar AFM/Viruses - International symposium "An insight into viruses".

Congrats to Delphine Muriaux et Sébastien Lyonnais (CEMIPAI) for their outstanding talk during the Bruker webinar. Wonderful quantitative images at nm scale of numerous infectious viruses.





Dec 2019 -
Congrats Kaushik! Nice poster standing!
Kaushik has been awarded a travelling grant from the French Cell Biology Society (SBCF) to attend the ASCB-EMBO joint meeting in Washington and present his Ph.D. work



Nov 2019 -
We welcome 3 new Ph.D. in the
team!!


Rayane and Manon will work on HIV while Anita will focuss on designing new substrate to enhance TIRF microscopy contrast.

Nov 2019 - They're enlightening our last paper! (November 2019)

CNRS and ANRS (French national agengy for AIDS research) had release news on our on Science Advances paper.

                                       
Oct 2019 - HIV-1 makes its own lipid bed from the lymphocyte plasma membrane to promote virus assembly. (October 2019)

 
Jul 2019 - IYSN

Congrats to Kaushik selected to give a talk at the Imabio Young Scientist Network kickoff meeting (Institut Curie, Paris)

Jun 2019 - Post-Doc and Ph.D. available positions (june 2019)

 
We are hiring:
https://www.irim.cnrs.fr/images/stages-emplois/picto_closed.png
https://www.irim.cnrs.fr/images/stages-emplois/picto_closed.png

Apr 2019 - Exo-Endo Club

Delphine has been elected vice president of the Exo-Endo club.

Feb 2019 - On line lectures (in French...)

Delphine Muriaux : Biology for Physicists
Cyril Favard : Mesuring and analyzing molecules' dynamics in cells

Jan 2019 - Exo-Endo Congress 2019

Delphine is a member of the organizing comittee of the next Exo Endo and GEM joint meeting in Cannes 3-6 Apr 2019 : Membrane Biophysics of Exo-Endocytosis

Jan 2019 - Inserm School 2019
You still can register to the INSERM school we are organizing with H Berry (INRIA) et JB Masson (Inst. Pasteur) in Bordeaux Jun 24-26 2019 : “Dynamiques intracellulaires des molécules: analyse et modélisation”

Sep 2018 - MiFoBio 2018

Many people of the team will attend MiFoBio2018
Delphine and Cyril will give 2 different lectures.
Cyril is also organizing the Simulating and analyzing molecule's dynamics and interactions in living cells, with H Berry (INRIA), I. Izzedin (ESPCI) and A. Coulon (Inst. Curie).

Find the detailed program of this school here : MiFoBio2018 as well as a teaser video.

Jul 2018 - You can follow us on Twitter!!



Our team study the respective roles of virus capsid or matrix proteins and host cells lipids and lipid organisation in the assembly and budding of RNA envelopped viruses.


We adress 5 main questions:

  1. Lipid sorting during HIV-1 Gag self-assembly.
  2. Single Gag dynamics during HIV-1 Gag assembly in CD4+ T-Cells.
  3. Cortical actin dynamic and membrane curvature during virus assembly.
  4. Role of matrix M protein and cellular co-factors in influenza virus assembly.
  5. HIV-1 single viral particles assembly monitored by atomic force microscopy.

































1.Lipid sorting during HIV-1 Gag self-assembly.

We have previously shown that MLV assembly is induced by interaction of Gag matrix domain (MA) with PS-PIP2 lipids of the plasma membrane. (Hamard-Péron et al., 2010 ; Hamard-Péron & Muriaux, 2011). Instead of assembling in pre-existing plasma membrane domains, such as “rafts”, we proposed that the self assembly of HIV-1 Gag will induce the generation of acidic lipids enriched nanodomains at the plasma membrane of the host cells. (Kerviel et al., 2013, Yandapalli et al., 2014 and Mariani et al., 2014).

Using in silico coarse grained mecular dynamics, we proposed a new model of interaction of HIV-1 matrix domain (MA) of Gag with lipid membranes. In this new model, the sn-2 acyl chain of the PIP2 stays within the lipid membrane and the MA is surrounded by PIP2 and PS, as it is the case for MLV. (Charlier et al., 2014). This was experimentally confirmed later on by new NMR data. (Mercredi et al., 2016)

 

In vitro, using full length purified Gag and model lipid membrane with tuned compostions to mimic either « ratfs » containing plasma membrane or inner leaflet of plasma membrane, we showed that HIV-1 Gag self-assembly induced the formation of PIP2/Cholesterol enriched nanodomains. We also showed that sphingomyelin was excluded from these Gag self-assembly generated lipid nanodomains.  (Yandrapalli et al., 2016).   

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2. Single Gag dynamics during HIV-1 Gag assembly in CD4+ T-Cells.

We are monitoring the time-course of HIV-1 assembly in living CD4 T cells, by observing and quantifying hundreds of thousands of individual Gag molecules motions (Mariani et al., 2016, see cover on the right).

Using dedicated motion analysis and big data algorithms, we could build maps of densities, diffusion, trapping energies and we observe their temporal changes in and out the budding sites (Floderer et al., 2018)













(Collaboration with teams of JB Sibarita (IINS, Bordeaux), M. Dahan (Institut Curie, Paris) and J.B. Masson (Institut Pasteur)).

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3. Cortical actin dynamic and membrane curvature during virus assembly.

We have previously shown that the CD81 tetraspanin played a role in HIV-1 assembly in CD4 T cells (Grigorov et al., 2009) and that the clathrin mediated endocytosis played a role in CD4 cell to cell HIV-1 transmission (Bosch et al., 2008). We recently shown that one of the main regulator of cortical actin network and membrane curvature played a role in HIV-1 assembly and release in CD4 T cells (Thomas et al., 2015).


From Mariani et al., 2014.

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4. Role of matrix M protein and cellular co-factors in influenza virus assembly.

We are studying the role played by matrix proteins (M1 and M2) in the plasma membrane assembly of H1N1 influenza virus. M1 was shown to be necessary for viral assembly. We have recently shown that an arginine triplet (R76/77/78) of M1 was necessary for its plasma membrane localisation and for viral infectivity (Collaboration O.Moncorgé, IRIM and P. Roingeard, Tours University). Meanwhile, we also defined a minimal system for non infectious virus like particle (VLP) (Kerviel, Dash et al., 2016).




























5. HIV-1 single viral particles assembly monitored by atomic force microscopy.

under construction

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*Co-last and/or corresponding, # Co first
In bold type lab members.

2021

  1. K. Inamdar, F-C. Tsai, A. de Poret, R. Dibsy, J. Manzi, P. Merida, R. Muller, P. Lappalainen, P. Roingeard, J. Mak, P. Bassereau, C. Favard, D. Muriaux. Full assembly of HIV-1 particles requires assistance of the membrane curvature factor IRSp53.
2020
  1. A.L. Lereu, A. Mouttou, F. Le Marchand, T. Begou, A. Moreau, D. Muriaux, J. Lumeau, C. Favard, "Enhanced total internal reflection fluorescence imaging based on dielectric resonant multilayers for multimodal fluorescence microscopy," Proc. SPIE 11461, Active Photonic Platforms XII, 114610E
  2. Woringer M, Izeddin I, Favard C* and Berry H*. Anomalous Subdiffusion in Living Cells: Bridging the Gap Between Experiments and Realistic Models Through Collaborative Challenges . Front. Phys. 8:134.
  3. Serov AS, Laurent F, Floderer C, Perronet K, Favard C, Muriaux D, Westbrook N, Vestergaard CL, Masson JB. Statistical Tests for Force Inference in Heterogeneous Environments. Sci Rep. 10(1):3783
  4. F. Laurent, C. Floderer, C. Favard, D. Muriaux, J-B. Masson, C.L. Vestergaard Mapping spatio-temporal dynamics of single biomolecules in living cells Phys.Biol. 17(1):015003
  5. K. Hennig, I. Wang, P. Moreau, L. Valon, S De Beco, M Coppey, Y. Miroshnikova, C. Albiges Rizo, C. Favard, R. Voituriez, M.Balland, Stick-slip dynamics of cell adhesion triggers spontaneous symmetry breaking and directional migration.

 

2019

  1. C. Favard#, J Chojnacki#, P. Merida, N. Yandrapalli, J. Mak, C. Eggeling*, D. Muriaux*, HIV-1 Gag specifically restricts PI(4,5)P2 and cholesterol mobility in living cells creating a nanodomain platform for virus assembly. Science Adv., 5(10), eaaw8651
  2. K Inamdar , C Floderer , C Favard * and D Muriaux*, Monitoring HIV-1 Assembly in Living Cells: Insights from Dynamic and Single Molecule Microscopy Viruses, 11(1), 72
  3. J. Dufourt, M. Bellec, O. Messina, A. Trullo, C. Favard, O. Radulescu, M. Lagha. Zelda, le maestro du réveil du génome zygotique, Med Sci, 35 : 821–841.

2018

  1. Floderer C., Masson JB., Boiley E., Georgeault S., Merida P., El Beheiry M., Dahan M., Roingeard P., Sibarita JB., Favard C.,* Muriaux D*. Single molecule localisation microscopy reveals how HIV-1 Gag proteins sense membrane virus assembly sites in living host CD4 T cells. Sci Rep. 8(1):16283
  2. C. Favard, Numerical Simulation and FRAP Experiments Show that the Plasma Membrane Binding Protein PH-EFA6 does not Exhibit Anomalous Sub-Diffusion in Cells.  Biomolecules, 8, 90
  3. S.E. El Meshri, E. Boutant, A. Mouhand, A. Thomas, V. Larue, L. Richert, V. Vivet-Boudou, Y. Mély, C. Tisné*, D. Muriaux*, H. de Rocquigny*, The NC domain of HIV-1 Gag contributes to the interaction of Gag with TSG101.  Biochim Biophys Acta, 1862(6):1421-1431
  4. J. Dufourt, A. Trullo, J. Hunter, C. Fernandez, J. Lazaro, M. Dejean, L. Morales, K.N. Schulz, M. M. Harrison, C. Favard, O. Radulescu, M. Lagha, Temporal Control of Transcription by Zelda in living Drosophila embryos. Nat. Commun, 9(1),5194

2016

  1. Yandrapalli N, Lubart Q, Tanwar HS, Picart C, Mak J, Muriaux D*, Favard C*. Self assembly of HIV-1 Gag protein on lipid membranes generates PI(4,5)P2/Cholesterol nanoclusters. Sci Rep.;6:39332.
  2. Ahi YS, Zhang S, Thappeta Y, Denman A, Feizpour A, Gummuluru S, Reinhard B, Muriaux D, Fivash MJ, Rein A. Functional Interplay Between Murine Leukemia Virus Glycogag, Serinc5, and Surface Glycoprotein Governs Virus Entry, with Opposite Effects on Gammaretroviral and Ebolavirus Glycoproteins. mBio,7(6), pii : e01985-16
  3. Kerviel A, Dash S, Moncorgé O, Panthu B, Prchal J, Décimo D, Ohlmann T, Lina B, Favard C, Decroly E, Ottmann M, Roingeard P, Muriaux D. Involvement of an Arginine Triplet in M1 Matrix Protein Interaction with Membranes and in M1 Recruitment into Virus-Like Particles of the Influenza A(H1N1)pdm09 Virus. PLoS One.11(11):e0165421
  4. Balme S, Coulon PE, Lepoitevin M, Charlot B, Yandrapalli N, Favard C, Muriaux D, Bechelany M, Janot JM. Influence of Adsorption on Proteins and Amyloid Detection by Silicon Nitride Nanopore. Langmuir. 32(35):8916-25.
  5. Mariani-Floderer C, Sibarita JB, Favard C, Muriaux D. Hunting Down HIV-1 Gag Proteins at the Plasma Membrane of Human T Lymphocytes. AIDS Res Hum Retroviruses. 32(7):658-9. (cover page)
  6. Martinez E, Allombert J, Cantet F, Lakhani A, Yandrapalli N, Neyret A, Norville IH, Favard C, Muriaux D, Bonazzi M. Coxiella burnetii effector CvpB modulates phosphoinositide metabolism for optimal vacuole development. Proc Natl Acad Sci U S A. ;113(23):E3260-9.
  7. Mercredi PY, Bucca N, Loeliger B, Gaines CR, Mehta M, Bhargava P, Tedbury PR, Charlier L, Floquet N, Muriaux D, Favard C, Sanders CR, Freed EO, Marchant J, Summers MF. Structural and Molecular Determinants of Membrane Binding by the HIV-1 Matrix Protein. J Mol Biol. ;428(8):1637-55.

2015

  1. Rodríguez-Mora S, Mateos E, Moran M, Martín MÁ, López JA, Calvo E, Terrón MC, Luque D, Muriaux D, Alcamí J, Coiras M, López-Huertas MR. Intracellular expression of Tat alters mitochondrial functions in T cells : a potential mechanism to understand mitochondrial damage during HIV-1 replication. Retrovirology,12,78-102
  2. A. Thomas, C. Mariani-Floderer, M.-R. Lopez-Huertas, N. Gros, E. Hamard-Péron, C. Favard, T. Ohlmann, J. Alcami, and D. Muriaux. Involvement of the Rac1-IRSp53-Wave2-Arp2/3 signaling pathway in HIV-1 Gag particle release in CD4 T cells. J. Virol., 89(16), 8162-81
  3. Bernaud J, Castelnovo M, Muriaux D, Faivre-Moskalenko C. Atomic force microscopy : a tool to analyze the viral cycle. Med Sci., 31(5), 522-8.
  4. S Adjili, A Favier*, G Fargier, A. Thomas, J Massin, K Monier, C Favard, C Vanbelle, S Bruneau, N Peyriéras, C Andraud, D Muriaux*, M-T Charreyre*. *Corresponding authors. Biocompatible Photoresistant Far-Red Emitting Fluorescent Polymer Probes with Near-Infrared Two-Photon Absorption for Living Cell and Zebrafish Embryo Imaging. Biomaterials, 46, 70-81.

2014

  1. Mariani C, Desdouits M, Favard C, Benaroch P, Muriaux D. Role of Gag and lipids during HIV-1 assembly in CD4(+) T cells and macrophages. Front Microbiol, 5, 312-317.
  2. Yandrapalli N, Muriaux D, Favard C. Lipid domains in HIV-1 assembly. Front Microbiol, 5, 220-225.
  3. J.M. Escoffre, M. Hubert, J. Teissié, M.P. Rols, C. Favard. Evidence for electro-induced membrane defects assessed by lateral mobility measurement of a GPi anchored protein Eur. Biophys. J., 43(6-7), 277-86
  4. S Adjili, A Favier, J Massin, Y Bretonnière, W Lacour, Y-C Lin, E Chatre, C Place, C Favard, D Muriaux, C Andraud, M-T Charreyre. Synthesis of Multifunctional Lipid-Polymer Conjugates : Application to the Elaboration of Bright Far-Red Fluorescent Lipid Probes. RSC Adv., 4 (30), 15569-78.
  5. L. Charlier, M. Louet, L. Chaloin, P. Fuchs, J. Martinez, D. Muriaux, C. Favard* & N. Floquet*. Coarse Grained Simulations of the HIV-1 Matrix Protein Anchoring : revisiting its assembly on membrane domains. Biophys. J.,106(3):577-85.
  6. C. Faivre-Moskalenko, A. Thomas, K. Tartour, J. Bernaud, Y. Beck, M. Iazykov, J. Danial, M. Lourdin, D. Muriaux* & M. Castelnovo*. RNA control of HIV-1 particle size polydispersity. *co-last authors. PLOS one, 24 ;9(1):e83874.

2013

  1. M. Castelnovo, D. Muriaux & C. Faivre-Moskalenko. Entropic control of particle sizes during viral self-assembly. New J. Physics, 15:035028.
  2. Kerviel A, Thomas A, Chaloin L, Favard C, Muriaux D. Virus assembly and plasma membrane domains : Which came first ? Virus Res 171 : 332-340.
  3. Fargier G, Favard C, Parmeggiani A, Sahuquet A, Mérezègue F, Morel A, Denis M, Molinari N, Mangeat PH, Coopman PJ, Montcourrier P. Centrosomal targeting of Syk kinase is controlled by its catalytic activity and depends on microtubules and the dynein motor. FASEB J, 27(1):109–122.

2012

  1. Escoffre JM, Nikolova B, Mallet L, Henri J, Favard C, Golzio M, Teissie J, Tsoneva I, Rols MP. New insights in the gene electrotransfer process : evidence for the involvement of the plasmid DNA topology. Curr Gene Ther., 12(5):417-22.

2011

  1. Berger G, Durand S, Fargier G, Nguyen XN, Cordeil S, Bouaziz S, Muriaux D, Darlix JL, Cimarelli A. APOBEC3A is a specific inhibitor of the early phases of HIV-1 infection in myeloid cells. PLoS Pathog ;7(9):e1002221.
  2. Hamard-Peron E, Muriaux D. Retroviral matrix and lipids, the intimate interaction. Retrovirology ; 8:15-38.
  3. Favard C, Wenger J, Lenne PF, Rigneault H. FCS diffusion laws in two-phase lipid membranes : determination of domain mean size by experiments and Monte Carlo simulations. Biophys J ; 100(5):1242-51.
  4. Escoffre JM, Portet T, Favard C, Teissié J, Dean DS, Rols MP. Electromediated formation of DNA complexes with cell membranes and its consequences for gene delivery. Biochim Biophys Acta ; 1808(6):1538-43.

2010

  1. Muriaux D, Darlix JL. Properties and functions of the nucleocapsid protein in virus assembly. RNA Biol ; 7(6):744-53.
  2. Hamard-Peron E, Juillard F, Saad JS, Roy C, Roingeard P, Summers MF, Darlix JL, Picart C, Muriaux D. Targeting of murine leukemia virus gag to the plasma membrane is mediated by Pi(4,5)P2/P3 and a polybasic region in the matrix. J Virol ; 84(1):503-15.

2009

  1. Gasecka A, Han TJ, Favard C, Cho BR, Brasselet S. Quantitative imaging of molecular order in lipid membranes using two-photon fluorescence polarimetry. Biophys J. ; 97(10):2854-62.
  2. Grigorov B, Attuil-Audenis V, Perugi F, Nedelec M, Watson S, Pique C, Darlix JL, Conjeaud H and D.Muriaux A role for CD81 on the late steps of HIV-1 replication in a chronically infected T cell line. Retrovirology ; 6:28.
  3. F.Perugi, D.Muriaux, B.C.Ramirez, S.Chabani, E.Decroly, JL.Darlix, V.Blot & C.Pique Human Discs Large is a new negative regulator of HIV-1 infectivity. Mol.Cell.Biol. ; 20:498-508.
  4. Taulet N, Comunale F, Favard C, Charrasse S, Bodin S, Gauthier-Rouvière C. N-cadherin/p120 catenin association at cell-cell contacts occurs in cholesterol-rich membrane domains and is required for RhoA activation and myogenesis.J Biol Chem; 284(34):23137-45.
  5. Portet T, Camps i Febrer F, Escoffre JM, Favard C, Rols MP, Dean DS. Visualization of membrane loss during the shrinkage of giant vesicles under electropulsation. Biophys J ; 96(10):4109-21.

2008

  1. Macia E, Partisani M, Favard C, Mortier E, Zimmermann P, Carlier MF, Gounon P, Luton F, Franco M. The pleckstrin homology domain of the Arf6-specific exchange factor EFA6 localizes to the plasma membrane by interacting with phosphatidylinositol 4,5-bisphosphate and F-actin. J Biol Chem 283(28), 19836-44.
  2. Fritz JV, Didier P, Clamme JP, Schaub E, Muriaux D, Cabanne C, Morellet N, Bouaziz S, Darlix JL, Mély Y, de Rocquigny H. Direct Vpr-Vpr interaction in cells monitored by two photon fluorescence correlation spectroscopy and fluorescence lifetime imaging Retrovirology ; 22, 87.
  3. Bosch, B., Grigorov, B., JL. Darlix, D. Muriaux & J. Esté. A clathrin-dynamin-dependent endocytic pathway for the uptake of HIV-1 by direct T cell-T cell transmission. Antiviral Research ; 80:185-93.
  4. L. Houzet, Z. Morichaud, L. Didier, D. Muriaux, JL. Darlix & M.Mougel. Deletion in nucleocapsid turn HIV-1 into a DNA-containing virus. Nucleic Acids Res ; 36, 2311-9.
  5. Corbin, B. Grigorov, P. Roingeard, J.-L. Darlix et D. Muriaux. Une nouvelle vision de l’assemblage du HIV-1 / Revisiting HIV-1 assembly. Médecines & Sciences ; 24:49-55.

Current Team Members (2020)


  • Jittendriya Swain - Post-Doc, Biophysical Chemistry
  • Kaushik Inamdar - Ph.D Student CBS2 Montpellier, Virology
  • Aurore de Poret - Ph.D. Student CBS2 Montpelllier, Biotechnology
  • Rayane Dibsy - Ph.D. Student CBS2 Montpellier, Virology
  • Manon Gourdelier - Ph.D. Student CBS2 Montpellier, Biotechnology
  • Anita Mouttou - Ph.D. Student CBS2 Montpellier, Optics/Microscopy
  • Coline Arone - Master Student, ENS Lyon.
  • David Bracquemond - Master Student, ENS Chemistry Montpellier.
  • Aurélie Favarin (w/L. Picas) - Master Student, Montp. Univ., Virology.







Alumni

2019

 

 

2018
 
 
2017

  • Shantoshini Dash - Ph.D. CBS2 Montpellier, Now Post-Doc Pennsylvania University
  • Elise Boilley - Master EPHE Paris Sorbonne. Consultant for Efor Lyon
  • Salma Guerfallah - Master Infectious Disease, Univ. Montpellier
  • Aida Houhou - Master Biopysics Univ. Montpellier
  • Sarah Hadouch - B. Sc. Chemistry
  • Mélanie Amigues - Biotechnology Technician, CNRS



 

2016
  • Charlotte Mariani, Ph.D. "Quantifying the nano-dynamic of HIV-1 Gag protein on the plasma membrane of T-Cells during viral assembly." Now Bioprocess Validation Specialist @ Merck Inc.
  • Naresh Yandrapalli, Ph.D., "Role of HIV-1 Gag protein multimerization in the generation of nanodomains in lipid membranes", Now Post-Doc at Max Planck Institute Postdam.
  • Julien Noero, Master Biophysics NUM
  • Lisa Morichon, Biotechnology Technician Student
2015

 

  • Nathalie Gros, Lab Manager, Now CNRS Permanent position at CNRS at Cemipai.
  • Alexis Chesseron, Master Physics of the living systems, NUM
  • Jordan Tremolet, Biotechnology Technician Student
2014




  • Jan Prchal - Visiting Scientist - Sanofi Price - Institute of Chemical Technology - Prague (CZ)
  • Rony Midahuen - Master Biotechnology.
2013

 

  •  Audrey Thomas - Ph.D. Student.

  • Sophie Guillaume - B Sc Chemistry

  • Alexandre Pasquiou – Master Biological Imaging (Nice, Zeiss Fellowship) - Now @ Amplitech
  • Taoufik Lahdidioui - Master Software Engineering (Montpellier)
2012

 

  •  Charlotte Berliat –Engineer Chemistry/Physics/Electronics Lyon - Now @ Laboratoire Aguettant

  • Fatimata Diagne – Master EPHE.

  • Stéphane Pelletier - BSc Cell Biology

  • Elise Faye - BSc Chemistry


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Team Leader

Delphine Muriaux

Research Director CNRS,
Head of CEMIPAI facilities,
Virologist

Cyril Favard

Research Engineer CNRS,
Biophysicist

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At a Glance

We aim at characterizing the respective roles of viral proteins and host-cell lipids or sub-plasma membrane constituents during the assembly of enveloped viruses affecting human beings (such as HIV-1 and influenza viruses).

We are biologists and biophysicists using multi-disciplinary approaches.

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Financial Supports

                                        
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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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