RNA viruses and metabolism

Viruses have a limited number of genes and need to divert the metabolism of their hosts for their own replication. Identification of cellular factors allowing the host to control the viral replication cycle is therefore a major issue to fight these pathogens. Our lab is interested in RNA viruses responsible for worldwide epidemics including AIDS viruses and emerging Chikingunya and Zika viruses. We are using genetic screens as well as imaging and molecular virology technics in order to identify genes involved in the susceptibility or resistance of viral infections and to decipher the mechanisms governing these processes. These approaches will also allow us to define the physiologic functions of these factors and to evaluate the impact of their dysfunction induced by these viruses.

Our projects are :

1- Identification of cofactors involved in Chikungunya and Zika arbovirus replication

* Structure et biogenesis of replication complexes at the host plama membrane .

* Role of cellular RNA helicases in RNA arbovirus transcription translation.

2 - Understanding the antiviral mecanisms targetting retroviral capsids

* Deciphering  TRIM5alpha restiction using genetic screens.

* Identification of a novel antiviral protein in primate SIV transmission to humans.

3 - Study of viral interference to cellular metabolisme

* Epitranscriptomic et epigenetic modifications during neuroinfection ; consequences on viral replication and antiviral responses.

* Role the XPR1 retroviral receptor in phosphate homeostasis and calcification. Association of XPR1 to primary Familial Brain Calcification 
 
  
Key words :
 
Host-pathogen interaction, viral replication virale, restriction, arbovirus, lentivirus, genetic screens, phosphate metabolism, calcification, neuroinfection.

2017

  1. Mamede JI, Damond F, Bernardo A, Matheron S, Descamps D, Battini JL, Sitbon M, Courgnaud V. 2017. Cyclophilins and nucleoporins are required for infection mediated by capsids from circulating HIV-2 primary isolates. Sci Rep. 7:45214. PubMed

  2. Wichit S., Hamel R., Bernard E., Talignani L., Diop F., Ferraris P., Liegeois F., Ekchariyawat P., Luplertlop N., Surasombatpattana P., Thomas F., Merits A., Choumet V., Roques P., Yssel H., Briant L. and Missé D. Imipramine Inhibits Chikungunya Virus Replication in Human Skin Fibroblasts through Interference with Intracellular Cholesterol Trafficking. Scientific Reports 7(1):3145 (2017). PubMed

2016

  1. Anheim M, López-Sánchez U, Giovannini D, Richard AC, Touhami J, N'Guyen L, Rudolf G, Thibault-Stoll A, Frebourg T, Hannequin D, Campion D, Battini JL, Sitbon M, Nicolas G. 2016. XPR1 mutations are a rare cause of primary familial brain calcification. J Neurol. 263(8):1559-64. PubMed

  2. Simonin Y, Loustalot F, DESMETZ C., Foulongne V, CONSTANT O., Fournier-Wirth C, LEON F., Molès JP, GOUBAUD A., LEMAITRE J.M., MAQUART M., LEPARC-GOFFART I., Briant L, Nagot N, Van de Perre P and Salinas S,. Potential differential infection of human neural cells between Asian and African lineages of ZIKV. EBioMedicine Oct;12:161-169 (2016).
  3. Salinas S, Foulongne V, Loustalot F, Fournier-Wirth C, Molès JP, Briant L, Nagot N, Van de Perre P, Simonin Y. Zika virus an emerging threat. Med Sci (Paris). 2016 32(4):378-86. PubMed

  4. Thi Pham LIEN K.; Briant L.; TANG T.B.; TRANG B.M.; Gavotte L.; Cornillot E.; DUOC V.T.; DUONG T.N., FRUTOS R; NGA P.T. Surveillance of dengue and chikungunya infection in Dong Thap, Vietnam: A 13-month study. Asian Pacific Journal of Tropical Medicine 9(1):39-43 (2016). PubMed

2015

  1. Legati A., Giovannini D., …, Geschwind DH., Battini JL.*, Coppola G*. 2015. Mutations in XPR1 cause primary familial brain calcification associated with altered phosphate export. Nature Genetics 47: 579–581. PubMed
  2. Bernard E, Hamel R., Neyret A., Ekchariyawat P., Molès J.P., Simmons G., Chazal N., Desprès P., Missé D. and Briant L. Human keratinocytes restrict Chikungunya virus replication at a post-fusion step. Virology. 476:1-10 (2015). PubMed

     

  3. Nicolas G, Battini JL, Giovannini D, Sitbon M, Hannequin D. 2015. From the identification of the molecular bases of primary brain calcification to the disease mechanisms: New steps. Rev Neurol (Paris). 2015 Oct;171(10):685-7 PubMed

  4. Peric D, Barragan I, Giraud-Triboult K, Egesipe AL, Meyniel-Schicklin L, Cousin C, Lotteau V, Petit V, Touhami J, Battini JL, Sitbon M, Pinset C, Ingelman-Sundberg M, Laustriat D, Peschanski M. 2015. Cytostatic Effect of Repeated Exposure to Simvastatin: A Mechanism for Chronic Myotoxicity Revealed by the Use of Mesodermal Progenitors Derived from Human Pluripotent Stem Cells. Stem Cells. 33(10):2936-48. PubMed

  5. Ekchariyawat P., Hamel R., Bernard E., Wichit S., Surasombatpattana P. Talignani L., Thomas F., Choumet V., Yssel H., Desprès P., Briant L. and Missé D. Inflammasome signaling pathways exert antiviral effect against Chikungunya virus in human dermal fibroblasts. Infect. Genet. Evol. 32:401-408 (2015). PubMed

  6. Sébastien Besteiro a, Anne Blanc-Potard a, Matteo Bonazzi b, Laurence Briant b, Nathalie Chazal b *, Emmanuel Cornillot b, Gaëlle Lentini a, Roy Matkovic b, Armen Sanosyan c, Edouard Tuaillon c, Philippe Van de Perre c. Montpellier Infectious Diseases - Pôle Rabelais (MID) 3rd annual meeting (2015). Infect. Genet Evol. 32:161-164 (2015).

  7. Thi Kim Lien K., Duoc V.V., Gavotte L., CORNILLOT E., NGA P.T., Briant L., Frutos R., and Duong TN. Role of Aedes aegypti and Aedes albopictus during the 2011 dengue fever outbreaks in Hanoi, Vietnam. Asian Pacific Journal of Tropical Medicine 8:543-8 (2015).

  8. Hamel R., Dejarnac O., Wichit S., Ekchariyawat P., Neyret A., Natthanej L., Perera-Lecoin M., Talignani L., Thomas F., Cao-Lormeau V., Choumet V., Briant L., Desprès P., Amara A., Yssel H. and Missé M. Biology of Zika virus infection in human skin cells. J. Virol. 1;89(17):8880-96 (2015).

2014

  1. Eldin P., Chazal N., FENARD D., Bernard E., GUICHOU J.F., Briant L. Vpr expression abolishes the capacity of HIV-1 infected cells to repair uracilated DNA. Nucleic Acids Research. 1;42(3):1698-710.(2014).

  2. Oburoglu L., Tardito S., Fritz V., De Barros S.C., Merida P., Craveiro M., Mamede J., Cretenet G., Mongellaz C., An X., Klysz D., Touhami J., Battini JL., Dardalhon V., Zimmermann V.S., Mohandas N., Gottlieb E., Sitbon M., Kinet S., Taylor N. 2014. Glucose and glutamine metabolism regulate human hematopoietic stem cell lineage specification. Cell Stem Cell 15: 169-184.

  3. Joly J.P, Mata G., Eldin P., Briant L., Duca M. and Benhida R. Artificial nucleobase-amino acids conjugates: a new class of TAR RNA binding agents. Chemistry: a European Journal. 19, 1 – 10 (2014).

  4. Briant L. Desprès P., Choumet V. and Missé D. Role of skin immune cells on the host susceptibility to mosquito-borne viruses. Virology. Sep; 464-465C:26-32 (2014).

  5. Bahraoui E., Briant L. and Chazal N. E5564 inhibits immunosuppressive cytokine IL-10 induction promoted by HIV-1 Tat protein. Virology J. Dec 4;11(1):214 (2014).

2013

  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.

2012

  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.
  3. Muriaux, D. and J.L.Darlix. Properties and functions of the nucleocapsid protein in virus assembly. RNA Biol ;7(6).

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.

Locales

  • Sara SALINAS, INSERM U, Montpellier
  • Caroline GOUJON, IRIM UMR9004, Montpellier
  • Marc SITBON, IGMM UMR 5535, Montpellier
  • Patrick BRON, CBS, CNRS UMR 5048, INSERM U 1054, Montpellier
  • Jean-marie PELOPONESE, IRIM UMR9004, Montpellier

Nationales 

  • Bruno COUTARD, AFMB CNRS UMR7257, Marseille     
  • Nadia RABAH, AFMB CNRS UMR7257, Marseille
  • Gaël Nicolas, U1245 INSERM, CHU Rouen 

Internationales

  • Geir SLUPPHAUG, NTNU, Trondeihm, Norway
  • Andrès MERITS, University Tartu, Estonia
  • Giovanni COPPOLA, UCLA, Los Angeles, USA         

Membres de l’équipe

  • Laurence Briant– Research director-CNRS
  • Jean-Luc Battini– Research director-INSERM
  • Patrick Eldin- Staff scientist CNRS
  • Aymeric Neyret- Engineer-UM
  • Eric Bernard- Engineer-CNRS
  • William Bakhache- PhD student-infectiopole sud


 

 
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Responsables


Laurence BRIANT

Research director-CNRS
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Jean-Luc Battini

Research director-INSERM
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En bref

Model organisms

  • ARN virus
  • Arbovirus (Chikungunya, Zika)
  • Lentivirus ((VIH, VIS)

Biological process studied

  • Viral replication
  • Membrane remodeling
  • Cellular metabolism
  • Phosphate Homeostasis
Techiniques used
  • Genetic screenings
  • Confocal and electronic microscopies
  • Molecular virology

Medical applications

  • Therapeutic screening of viral infections
  • Genetic diseases and brain calcification
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IRIM
Institut de Recherche en Infectiologie de Montpellier
UMR 9004 - CNRS / UM
1919 route de Mende - 34293 Montpellier cedex 5
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