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.


2022

  1. Tury S, Giovannini D, Ivanova S, Touhami J, Courgnaud V, Battini JL. Identification of Copper Transporter 1 as a Receptor for Feline Endogenous Retrovirus ERV-DC14. J Virol. doi: 10.1128/jvi.00229-22. Pubmed
  2. Neyret A, Bernard E, Aïqui-Reboul-Paviet O, Bakhache W, Eldin P, Chaloin L, Briant L. Identification of a non-canonical G3BP-binding sequence in a Mayaro virus nsP3 hypervariable domain. Front Cell Infect Microbiol. doi: 10.3389/fcimb.2022.958176. Pubmed


2021

  1. Kril V, Aïqui-Reboul-Paviet O, Briant L, Amara A. New insights into Chikungunya Virus Infection and Pathogenesis. Annu Rev Virol. doi: 10.1146/annurev-virology-091919-102021. Pubmed



2020



  1. Bakhache W, Neyret A, Bernard E, Merits A, Briant L. Palmitoylated cysteines in Chikungunya virus nsP1 are critical for targeting to cholesterol-rich plasma membrane microdomains with functional consequences for viral genome replication. Journal of Virology. doi: 10.1128/JVI.02183-19. PubMed
  2. Cassinari K, Rovelet-Lecrux A, Tury S, Quenez O, Richard AC, Charbonnier C, Olaso R, Boland A, Deleuze JF, Besancenot JF, Delpont B, Pouliquen D, Lecoquierre F, Chambon P, Thauvin-Robinet C, Campion D, Frebourg T, Battini JL, Nicolas G. Haploinsufficiency of the Primary Familial Brain Calcification Gene SLC20A2 Mediated by Disruption of a Regulatory Element. Mov Disord. doi: 10.1002/mds.28090. Pubmed
  3. Clé M, Eldin P, Briant L, Lannuzel A, Simonin Y, Van de Perre P, Cabié A, Salinas S. Neurocognitive impacts of arbovirus infections. J Neuroinflammation. doi: 10.1186/s12974-020-01904-3. Pubmed
  4. Eldin P, Péron S, Galashevskaya A, Denis-Lagache N, Cogné M, Slupphaug G, Briant L. Impact of HIV-1 Vpr manipulation of the DNA repair enzyme UNG2 on B lymphocyte class switch recombination. J Transl Med.  doi: 10.1186/s12967-020-02478-7. Pubmed

     




2019

  1. Bakhache W, Neyret A, McKellar J, Clop C, Bernard E, Weger-Lucarelli J, Briant L. Fatty acid synthase and stearoyl-CoA desaturase-1 are conserved druggable cofactors of Old World Alphavirus genome replication. Antiviral Research. 172:104642. PubMed

  2. López-Sánchez U, Nicolas G, Richard AC, Maltête D, Charif M, Ayrignac X, Goizet C, Touhami J, Labesse G, Battini JL, Sitbon M. Characterization of XPR1/SLC53A1 variants located outside of the SPX domain in patients with primary familial brain calcification. Scientific Reports. 9(1):6776. PubMed

  3. Bakhache W, Couderc É, Neyret A, Briant L. Architecture and biogenesis of positive-stranded RNA virus replication organelles. Virologie 23(3):160-175. PubMed

  4. Neyret A, Gay B, Cransac A, Briant L, Coric P, Turcaud S, Laugâa P, Bouaziz S, Chazal N. Insight into the mechanism of action of EP-39, a bevirimat derivative that inhibits HIV-1 maturation. Antiviral Research. 164:162-175. PubMed

  5. Matkovic R, Bernard E, Fontanel S, Eldin P, Chazal N, Hassan Hersi D, Merits A, Péloponèse JM Jr, Briant L. The Host DHX9 DExH-Box Helicase Is Recruited to Chikungunya Virus Replication Complexes for Optimal Genomic RNA Translation. Journal of Virology. 2019 Feb 5;93(4). PubMed

 

2017

  1. Majdoul S, Cosette J, Seye AK, Bernard E, Frin S, Holic N, Chazal N, Briant L, Espert L, Galy A, Fenard D. Peptides derived from evolutionarily conserved domains in Beclin1 and Beclin2 enhance the entry of lentiviral vectors into human cells. J Biol Chem. 2017 Sep 19. PubMed
  2. 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

  3. 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

  4. Pham Thi KL, Briant L, Gavotte L, Labbe P, Perriat-Sanguinet M, Cornillot E, Vu TD, Nguyen TY, Tran VP, Nguyen VS, Devaux C, Afelt A, Tran CC, Phan TN, Tran ND, Frutos R. Incidence of dengue and chikungunya viruses in mosquitoes and human patients in border provinces of Vietnam. Parasites and Vectors. 2017 Nov 9;10(1):556. 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,. Zika Virus Strains Potentially Display Different Infectious Profiles in Human Neural Cells. EBioMedicine Oct;12:161-169 (2016). PubMed
  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). PubMed

  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). PubMed

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). PubMed

  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. PubMed

  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). PubMed

  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). PubMed

  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). PubMed

2013

  1. Giovannini D., Touhami J., Charnet P., Sitbon M., Battini JL. 2013. Inorganic phosphate export by the retrovirus receptor XPR1 in metazoans. 2013. Cell Reports 3: 1866-73. PubMed

  2. Giroud C., Chazal N., Gay B., Eldin P., Brun S. and Briant L. HIV-1-associated PKA acts as a cofactor for genome reverse transcription. Retrovirology. 17;10(1):157 (2013). PubMed

  3. Mamede JI., Sitbon M., Battini JL., Courgnaud V. 2013. Heterogeneous susceptibility of circulating SIV isolate capsids to HIV-interacting factors. Retrovirology 10: 77. PubMed

  4. Laval J, Touhami J, Herzenberg LA, Conrad C, Taylor N, Battini JL, Sitbon M, Tirouvanziam R. 2013. Metabolic adaptation of neutrophils in cystic fibrosis airways involves distinct shifts in nutrient transporter expression. J Immunol.190(12):6043-50. PubMed

  5. Patramool S., Bernard E., Hamel R., Natthanej. L, Chazal N., Surasombatpattana P., Ekchariyawat P., Daoust S., Thongrungkiat S., Thomas F., Briant L. and Missé D. Isolation of infectious Chikungunya virus and Dengue virus using anionic polymer-coated magnetic beads. Journal of Virological Methods. 193(1): 55-61 (2013). PubMed

  6. Petit V, Massonnet G, Maciorowski Z, Touhami J, Thuleau A, Némati F, Laval J, Château-Joubert S, Servely JL, Vallerand D, Fontaine JJ, Taylor N, Battini JL, Sitbon M, Decaudin D. 2013. Optimization of tumor xenograft dissociation for the profiling of cell surface markers and nutrient transporters. Lab Invest. 93(5):611-21. PubMed


2012

  1. Loisel-Meyer S, Swainson L, Craveiro M, Oburoglu L, Mongellaz C, Costa C, Martinez M, Cosset FL, Battini JL, Herzenberg LA, Herzenberg LA, Atkuri KR, Sitbon M, Kinet S, Verhoeyen E, Taylor N. 2012.  Glut1-mediated glucose transport regulates HIV infection. Proc Natl Acad Sci U S A. 109(7):2549-54. PubMed

  2. Vaughan AE, Mendoza R, Aranda R, Battini JL, Miller AD. 2012. Xpr1 is an atypical G-protein-coupled receptor that mediates xenotropic and polytropic murine retrovirus neurotoxicity. J Virol. 86(3):1661-9. PubMed

  3. B. Gay, E. Bernard, M. Solignat, N. Chazal, C. Devaux and L. Briant. pH-dependent entry of chikungunya virus into Aedes albopictus cells. Infection Genetics and Evolution. 12(6):1275-81 (2012). PubMed
  4. Coric P., Turcaud S., Souquet F., Briant L., Gay B., ROYER J., Chazal N. and Bouaziz S. Synthesis and biological evaluation of new derivatives of bevirimat with higher activity against HIV-1 maturation. European Journal or Medicinal Chemistry. 62:453-65 (2013). PubMed











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         

Team members

Laurence Briant– Research director-CNRS




Jean-Luc Battini– Research director-INSERM




Patrick Eldin- Staff scientist CNRS




Aymeric Neyret- Engineer-UM




Eric Bernard- Engineer-CNRS




Justine Girard - Doctorant




Olivier Aiqui - Doctorant




Arnaud Lecante - Doctorant




Lise Holsteyn - Contracted Engineer




Lise Chauveau - Post-doctorant





 

 They worked with us


  • Camille Clop (BTS then technician)
  • Yolande Provot (BTS)
  • Bernard Gay (maître de conférence)
  • Simon Fontanel (Contracted Engineer)
  • Elodie Couderc (Master 2)
  • Marie France Martin (Master 2)
  • Lina Castaño (Master 2)
  • Joe McKellar (Master 1)
  • Sona Allahverdiyeva (Master 1)
  • Roy Matkovic (doctorant)
  • Charline Giroud (doctorante)
  • Lou Etcheberry (Master 1)
  • William Bakhache (doctorant)
  • Sandrine Tury (post-doctorante)
  • Emilie Brouat (Master 1)
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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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Financements

               


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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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