Pathogenesis of viral infections of the developing and adult central nervous system

Coordinators: D. Dunia / C. Malnou

D. Dunia

AXIS 1 : Viral interference with neuronal homeostasis

 

 

C. Malnou

AXIS 2 : Role of extracellular placental vesicles during congenital viral infections

 

 

E. Suberbielle

AXIS 3 : Impact of pathogens on neuronal epigenetics and behavior

 

 

G. Ligat

AXIS 4 (emerging axis): Molecular biology of host-human cytomegalovirus interactions in brain tumors and therapeutic innovations

 

 
 
X:

https://twitter.com/ViNeDysLab

 

Scientific Objectives

To date, the mechanisms whereby pathogens can interfere with brain function are not well understood and the determinants responsible for the associated diseases are poorly defined. Our team has a strong interest in studying the mechanisms and consequences of pathogen infection of the central nervous system (CNS), from the developing to the adult brain.

For our different projects, we use several paradigms of CNS infections: infection by Borna Disease virus (BoDV), congenital infection by human Cytomegalovirus (hCMV) and Zika virus (ZIKV) and persistence of the parasite Toxoplasma gondii in the adult CNS.

In the context of the adult brain, we assess the pathophysiological and behavioral outcome of pathogen persistence in the CNS, either due to the pathogen itself or to the accompanying neuroinflammation. We also aim at identifying processes which could be highjacked by neurotropic pathogens and contribute to neuronal impairment or  the resulting neurodegenerative processes.

In the case of congenital infections during pregnancy, we study how viruses can disrupt the normal neurodevelopmental program and lead to severe sequelae in the newborn. In this setting, we examine the modalities of congenital infection and the resulting impact on neonatal brain development. These later aspects are facilitated by the integration in our team of several clinicians from the neonatology unit in Toulouse hospital, who help us to facilitate the clinical translation of our findings.

Our Projects


AXIS 1: Viral interference with neuronal homeostasis

In our laboratory, we study neuronal infection by Borna disease virus (BoDV-1), because we believe that this virus provides an ideal paradigm for studying the behavioral correlates of CNS viral infections. BoDV-1 is the perfect example of a neurotropic virus which achieves long-term persistence, while causing minimal damage to neurons. BoDV-1 infection, however, leads to brain dysfunction and disease, as a result of the selective interference with signaling pathways that are crucial for proper central nervous system (CNS) homeostasis. The ongoing project of our team are:

  • BoDV-1 as a neuroprotective tool? We recently showed that the BoDV-1 X protein, or a cell-permeable peptide derived from the X protein were able to prevent neurodegeneration in different in vitro and in vivo settings, by acting at the mitochondrial level.
Illustration-theme-Dunia

The BoDV-1 X protein is neuroprotective. Top: The X protein protects against rotenone-induced axonal fragmentation. Pictures of the axonal chambers of compartmentalized primary neuronal cultures subjected to rotenone treatment. Bottom: analysis of dopaminergic neurons (staining for tyrosine hydroxylase in the SNpc and the Striatum) in the brains of the MPTP mouse model for Parkinson’s disease.

 

We are now pursuing different aims : first, to gain further insight on the mechanisms underlying the neuroprotective properties of X, by deciphering its mitochondrial interactome and impact on mitochondrial physiology and dynamics; next, to further document the proof of concept of using X-derived peptides for neuroprotection, by testing its therapeutic potential in various models of chronic neurodegeneration, in the frame in collaborations in Toulouse, Bordeaux or Paris with experts in various neurodegenerative diseases.

 

  • Structure-function analysis of the BoDV replication machinery and impact on neuronal epigenetics. Considering the recent identification of BoDV-1 as a potential zoonotic agent, we have established collaborations with structural biologists and virus-host interaction experts. Our goals are to perform a comprehensive analysis of the BoDV replication machinery, a large-scale mapping of virus/host polypeptide interplays and of its consequences on viral fitness and on neuronal physiology. Together with Dr. E. Suberbielle in our team, we notably analyze the resulting consequences on neuronal epigenetics.

 

  • Development of a novel nanoelectronics platform to probe neuronal activity. In collaboration with physicists from the LAAS-CNRS laboratory in Toulouse, we have developed nanowire-based devices (Nano-electrode arrays, or NEA) interfaced with living neurons. We are now testing the relevance of such NEA to measure different parameters of neuronal activity (response to stimulation, plasticity, etc..) upon infection, expression of proteins of interest (BoDV-1 P and X proteins, notably), as well as after exposure to other neuronal insults, such as amyloid ß peptide or proinflammatory cytokines. This project is supported by the CNRS MITI (Mission for Transversal and Interdisciplinary Initiatives)

Nano-electrode array (NEA) setup to record neuronal activity. (A) Scanning electron micrograph of one NEA, with an enlarged view (B) of one electrode composed of 7 nanowires. Pictures taken at the LAAS CNRS. (C) NEA mounted on a printed circuit board, before neuronal seeding (D) and setting onto the recording setting (E). Copyright David Villa, Science Image, CNRS. (F) Staining of the neuronal network (using MAP2, shown in red). Copyright Frédérique Sueur, Infinity. (G) Examples of recordings made before and after stimulation of the neurons.

 
 
Head: D. Dunia
AXIS 2: Role of extracellular placental vesicles during congenital viral infections

Our research project explores the emerging concept that infection of the placenta with viruses such as human cytomegalovirus (hCMV) or Zika virus (ZIKV) could alter the amount and / or composition of placental extracellular vesicles (EVs) (Figure 1), which could then promote the dissemination of the virus towards the fetus and contribute to the alteration in brain development observed during congenital infections.

Figure 1: Analysis of small extracellular vesicles and their internalization in recipient cell. A) Placental small extracellular vesicles observed by electron microscopy, with gold bead immunostaining directed against CD63 surface molecule (collab. Institut Curie). B) Fluorescence microscopy image of a fibroblast cell after small extracellular vesicles internalization (Blue: DAPI, Red: actin, Green: membrane labeled-vesicles) extracellulaires (Bleu: DAPI, Rouge: actine, Vert: marquage membranaire des vésicules)

 

  • Impact of the infection of placental cells on the secretion and composition of EVs and consequences for the development of the fetal central nervous system.

Our results indicate that, upon infection with hCMV, there is a phenotypic modification of exosomes secreted from placental histocultures of early placentas or cultured trophoblast lines. The phenotypic characteristics of EVs isolated from infected cells suggest that they could act in a paracrine manner to facilitate the infection of surrounding or distant cells and that they thus participate in the pathophysiology of the disorders observed during pregnancy and in the fetus. Our work also suggests that EVs could play a role of biomarkers during infection in order to evaluate, via a simple blood test from the mother during pregnancy, the state of the placenta.

 

  • Role of the miRNA C19MC cluster carried by placental EVs.

EVs derived from the placenta are capable of conferring antiviral protection on target cells, via the action of the cluster of miRNA C19MC, contained in the EVs. Thanks to an original model of cells deleted for the entire cluster, we are studying the modalities of the antiviral action of these miRNAs. In addition, we are investigating whether placental EVs can also protect human neural stem cells from viral infection. Finally, we are evaluating their expression profile in EVs circulating in pregnant women during infections by hCMV, ZIKV or SARS-CoV2 in order to assess whether these infections modify their expression profile within EVs during pregnancy.

 

 

In conclusion, we hope to provide new pathophysiological elements to better understand the etiology of congenital viral infections, in order to improve the diagnosis and also offer new perspectives for therapeutic intervention.

 

Head: C. Malnou

AXIS 3: Impact of pathogens on neuronal epigenetics and behavior

The hypothesis at the center of our research interests:

Because of their lifelong persistence in the brain or the immune responses raised against them, pathogens in the central nervous system could contribute to neuronal dysfunction, cognitive senescence and neuropsychiatric diseases. From a mechanistic point of view, neuronal epigenetics, which is key to cognitive plasticity, may play a fundamental role in these disorders. In particular, we have shown that DNA double-strand breaks (DSB) represent a critical mode of regulation of neuronal epigenetics. We are interested in deciphering the mechanisms whereby DSB affect neuronal function and in understanding how perturbations in sensing, production and/or repair of DSB may underlie the behavioral impairment that is observed in many inflammatory, infectious, or age-related diseases affecting the CNS.

 

3 lines of research are currently being pursued:

 

  • Role of DSB in the pathophysiology of infection by Borna disease virus (BoDV).

Our recent data indicate that DSB contribute to the regulation of BoDV replication with consequences on the activity of the infected neuronal networks. Understanding how this structurally simple virus disrupts the DSB response will allow us to elucidate the mechanisms of DSB response in neurons.

  • Infection of the central nervous system by Toxoplasma gondii, a common human parasite.

Studying the impact of various strains of this parasite on behavior and the underlying mechanisms serves as a model for deciphering how a persistent infection in the brain could contribute to cognitive and immune senescence during healthy vs. pathological aging. In collaboration with Team 6 (link).

  • Epigenetic dysregulations of neuronal function in response to chronic inflammation. Due to aging or a lifelong response to environmental threats, chronic inflammation and in particular, the systemic increases in inflammatory mediators, are thought to have long-lasting impact on behavior. We study the how DSB response and epigenetic changes may be fundamental mechanisms underlying chronic inflammation-induced behavioral deficits.

 

Finally, the results of our research will allow us to elucidate the key mechanisms of DNA DSB response in neurons under pathophysiological circumstances, to maintain the physiological balance between DNA DSB generation and repair. In the long-term, our research may pave the way for new therapies against chronic neuroinflammation or Alzheimer’s disease.

Head: E. Suberbielle

AXIS 4 (emerging axis): Molecular biology of host-human cytomegalovirus interactions in brain tumors and therapeutic innovations

Our projects focus on the link between human cytomegalovirus (HCMV) infection and glioblastoma, an aggressive form of brain cancer.

Many of these projects have a translational aspect and include the discovery of new biomarkers and therapeutic targets. Through various collaborations, we are currently working on the vectorization of anti-HCMV therapeutic peptides into extracellular vesicles to improve their efficacy.

We hope to better understand the role of HCMV in the development and progression of brain tumors to identify new prognosis and therapeutic approaches.

Keywords: HCMV, Glioblastoma, Biotherapies

Head: G. Ligat (gaetan.ligat@inserm.fr)

Other information


Publications

2023

Malnou, Cécile E.; Ligat, Gaëtan

Editorial: Recent highlights in the development of therapeutic antiviral strategies Journal Article

In: Front. Microbiol., vol. 14, 2023, ISSN: 1664-302X.

Links | BibTeX

Martin, Charlène; Ligat, Gaëtan; Malnou, Cécile E.

The Yin and the Yang of extracellular vesicles during viral infections Journal Article

In: Biomedical Journal, 2023, ISSN: 2319-4170.

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Fourgeaud, Jacques; Magny, Jean-François; Couderc, Sophie; Garcia, Patricia; Maillotte, Anne-Marie; Benard, Melinda; Pinquier, Didier; Minodier, Philippe; Astruc, Dominique; Patural, Hugues; Ugolin, Melissa; Parat, Sophie; Guillois, Bernard; Garenne, Armelle; Guilleminot, Tiffany; Parodi, Marine; Bussières, Laurence; Ville, Yves; Leruez-Ville, Marianne

Clinical Value of Serial Quantitative Analysis of Cytomegalovirus DNA in Blood and Saliva Over the First 24 Months of Life in Congenital Infection: The French Cymepedia Cohort Journal Article

In: The Journal of Pediatrics, vol. 253, pp. 197–204.e5, 2023, ISSN: 0022-3476.

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2022

Martin, Charlène; Bergamelli, Mathilde; Malnou, Cécile E.; D'Angelo, Gisela

Placental extracellular vesicles in maternal-fetal communication during pregnancy Journal Article

In: Biochem Soc Trans, vol. 50, no. 6, pp. 1785–1795, 2022, ISSN: 1470-8752.

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Tarbouriech, Nicolas; Chenavier, Florian; Kawasaki, Junna; Bachiri, Kamel; Bourhis, Jean-Marie; Legrand, Pierre; Freslon, Lily L.; Laurent, Estelle M. N.; Suberbielle, Elsa; Ruigrok, Rob W. H.; Tomonaga, Keizo; Gonzalez-Dunia, Daniel; Horie, Masayuki; Coyaud, Etienne; Crépin, Thibaut

Borna Disease Virus 1 Phosphoprotein Forms a Tetramer and Interacts with Host Factors Involved in DNA Double-Strand Break Repair and mRNA Processing Journal Article

In: Viruses, vol. 14, no. 11, 2022, ISSN: 1999-4915.

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Bergamelli, Mathilde; Martin, Hélène; Aubert, Yann; Mansuy, Jean-Michel; Marcellin, Marlène; Burlet-Schiltz, Odile; Hurbain, Ilse; Raposo, Graça; Izopet, Jacques; Fournier, Thierry; Benchoua, Alexandra; Bénard, Mélinda; Groussolles, Marion; Cartron, Géraldine; Gac, Yann Tanguy Le; Moinard, Nathalie; D’Angelo, Gisela; Malnou, Cécile E.

Human Cytomegalovirus Modifies Placental Small Extracellular Vesicle Composition to Enhance Infection of Fetal Neural Cells In Vitro Journal Article

In: Viruses, vol. 14, no. 9, 2022, ISSN: 1999-4915.

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Martin, Hélène; Barthelemy, Jonathan; Chin, Yamileth; Bergamelli, Mathilde; Moinard, Nathalie; Cartron, Géraldine; Gac, Yann Tanguy Le; Malnou, Cécile E.; Simonin, Yannick

Usutu Virus Infects Human Placental Explants and Induces Congenital Defects in Mice Journal Article

In: Viruses, vol. 14, no. 8, 2022, ISSN: 1999-4915.

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Quelle est la réalité des infections humaines par les Bornavirus ? Journal Article

In: Virologie, vol. 26, no. 4, pp. 275–281, 2022, ISSN: 1267-8694.

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Marty, Florent Henri; Bettamin, Luca; Thouard, Anne; Bourgade, Karine; Allart, Sophie; Larrieu, Guilhem; Malnou, Cécile Evelyne; Gonzalez-Dunia, Daniel; Suberbielle, Elsa

Borna disease virus docks on neuronal DNA double-strand breaks to replicate and dampens neuronal activity Journal Article

In: iScience, vol. 25, no. 1, 2022, ISSN: 2589-0042.

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Ligat, Gaëtan; Ghelfenstein-Ferreira, Théo; Dellière, Sarah; Pichon, Maxime

Bringing clinical and fundamental young microbiologists together Journal Article

In: FEMS Microbes, vol. 3, 2022, ISSN: 2633-6685.

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2021

Ferré, Cécile A.; Thouard, Anne; Bétourné, Alexandre; Dorze, Anne-Louise Le; Belenguer, Pascale; Miquel, Marie-Christine; Peyrin, Jean-Michel; Gonzalez-Dunia, Daniel; Szelechowski, Marion

HSPA9/Mortalin mediates axo-protection and modulates mitochondrial dynamics in neurons Journal Article

In: Sci Rep, vol. 11, no. 1, 2021, ISSN: 2045-2322.

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Bourgade, Karine; Thouard, Anne; Abravanel, Florence; Hebral, Anne‐Laure; Bello, Arnaud Del; Viguier, Alain; Gonzalez‐Dunia, Daniel; Kamar, Nassim

Fatal encephalitis and Borna Disease Virus‐1 seropositivity in two kidney‐transplant patients living in the same nonendemic area Journal Article

In: Transplant Infectious Dis, vol. 23, no. 6, 2021, ISSN: 1399-3062.

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Bergamelli, Mathilde; Martin, Hélène; Bénard, Mélinda; Ausseil, Jérôme; Mansuy, Jean-Michel; Hurbain, Ilse; Mouysset, Maïlys; Groussolles, Marion; Cartron, Géraldine; le Gac, Yann Tanguy; Moinard, Nathalie; Suberbielle, Elsa; Izopet, Jacques; Tscherning, Charlotte; Raposo, Graça; Gonzalez-Dunia, Daniel; D’Angelo, Gisela; Malnou, Cécile E.

Human Cytomegalovirus Infection Changes the Pattern of Surface Markers of Small Extracellular Vesicles Isolated From First Trimester Placental Long-Term Histocultures Journal Article

In: Front. Cell Dev. Biol., vol. 9, 2021, ISSN: 2296-634X.

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Rolland, Maude; Martin, Hélène; Bergamelli, Mathilde; Sellier, Yann; Bessières, Bettina; Aziza, Jacqueline; Benchoua, Alexandra; Leruez‐Ville, Marianne; Gonzalez‐Dunia, Daniel; Chavanas, Stéphane

Human cytomegalovirus infection is associated with increased expression of the lissencephaly gene <scp> PAFAH1B1 </scp> encoding <scp>LIS1</scp> in neural stem cells and congenitally infected brains Journal Article

In: J. Pathol., 2021, ISSN: 1096-9896.

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2020

Portal, Benjamin; Delcourte, Sarah; Rovera, Renaud; Lejards, Camille; Bullich, Sebastien; Malnou, Cécile E.; Haddjeri, Nasser; Déglon, Nicole; Guiard, Bruno P.

Genetic and pharmacological inactivation of astroglial connexin 43 differentially influences the acute response of antidepressant and anxiolytic drugs Journal Article

In: Acta Physiologica, vol. 229, no. 1, 2020, ISSN: 1748-1716.

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2019

de Paz, Alexia Martínez; Khajavi, Leila; Martin, Hélène; Claveria-Gimeno, Rafael; Dieck, Susanne Tom; Cheema, Manjinder S.; Sanchez-Mut, Jose V.; Moksa, Malgorzata M.; Carles, Annaick; Brodie, Nick I.; Sheikh, Taimoor I.; Freeman, Melissa E.; Petrotchenko, Evgeniy V.; Borchers, Christoph H.; Schuman, Erin M.; Zytnicki, Matthias; Velazquez-Campoy, Adrian; Abian, Olga; Hirst, Martin; Esteller, Manel; Vincent, John B.; Malnou, Cécile E.; Ausió, Juan

MeCP2-E1 isoform is a dynamically expressed, weakly DNA-bound protein with different protein and DNA interactions compared to MeCP2-E2 Journal Article

In: Epigenetics & Chromatin, vol. 12, no. 1, 2019, ISSN: 1756-8935.

Abstract | Links | BibTeX

Malnou, E. Cécile; Umlauf, David; Mouysset, Maïlys; Cavaillé, Jérôme

Imprinted MicroRNA Gene Clusters in the Evolution, Development, and Functions of Mammalian Placenta Journal Article

In: Front. Genet., vol. 9, 2019, ISSN: 1664-8021.

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2018

Casanova, A; Bettamin, L; Blatche, M-C; Mathieu, F; Martin, H; Gonzalez-Dunia, D; Nicu, L; Larrieu, G

Nanowire based bioprobes for electrical monitoring of electrogenic cells Journal Article

In: J. Phys.: Condens. Matter, vol. 30, no. 46, 2018, ISSN: 1361-648X.

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Bétourné, Alexandre; Szelechowski, Marion; Thouard, Anne; Abrial, Erika; Jean, Arnaud; Zaidi, Falek; Foret, Charlotte; Bonnaud, Emilie M.; Charlier, Caroline M.; Suberbielle, Elsa; Malnou, Cécile E.; Granon, Sylvie; Rampon, Claire; Gonzalez-Dunia, Daniel

Hippocampal expression of a virus-derived protein impairs memory in mice Journal Article

In: Proc. Natl. Acad. Sci. U.S.A., vol. 115, no. 7, pp. 1611–1616, 2018, ISSN: 1091-6490.

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2017

Denadai-Souza, Alexandre; Ribeiro, Camilla Moreira; Rolland, Corinne; Thouard, Anne; Deraison, Céline; Scavone, Cristoforo; Gonzalez-Dunia, Daniel; Vergnolle, Nathalie; Avellar, Maria Christina Werneck

Effect of tryptase inhibition on joint inflammation: a pharmacological and lentivirus-mediated gene transfer study Journal Article

In: Arthritis Res Ther, vol. 19, no. 1, 2017, ISSN: 1478-6362.

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2016

Charlier, Caroline M.; Debaisieux, Solène; Foret, Charlotte; Thouard, Anne; Schiavo, Giampietro; Gonzalez-Dunia, Daniel; Malnou, Cécile E.

Neuronal retrograde transport of Borna disease virus occurs in signalling endosomes Journal Article

In: J Gen Virol, vol. 97, no. 12, pp. 3215–3224, 2016, ISSN: 1465-2099.

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Martin, Hélène; Laborel-Préneron, Emeline; Fraysse, Frédérique; Nguyen, Thien; Schmitt, Anne-Marie; Redoulès, Daniel; Davrinche, Christian

Aquaphilus dolomiaeextract counteracts the effects of cutaneousS. aureussecretome isolated from atopic children on CD4+T cell activation Journal Article

In: Pharmaceutical Biology, vol. 54, no. 11, pp. 2782–2785, 2016, ISSN: 1744-5116.

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Bonnaud, Emilie M.; Suberbielle, Elsa; Malnou, Cécile E.

Histone acetylation in neuronal (dys)function Journal Article

In: Biomolecular Concepts, vol. 7, no. 2, pp. 103–116, 2016, ISSN: 1868-503X.

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Rolland, Maude; Li, Xiaojun; Sellier, Yann; Martin, Hélène; Perez-Berezo, Teresa; Rauwel, Benjamin; Benchoua, Alexandra; Bessières, Bettina; Aziza, Jacqueline; Cenac, Nicolas; Luo, Minhua; Casper, Charlotte; Peschanski, Marc; Gonzalez-Dunia, Daniel; Leruez-Ville, Marianne; Davrinche, Christian; Chavanas, Stéphane

PPARγ Is Activated during Congenital Cytomegalovirus Infection and Inhibits Neuronogenesis from Human Neural Stem Cells Journal Article

In: PLoS Pathog, vol. 12, no. 4, 2016, ISSN: 1553-7374.

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Ferré, Cécile A.; Davezac, Noelie; Thouard, Anne; Peyrin, Jean‐Michel; Belenguer, Pascale; Miquel, Marie‐Christine; Gonzalez‐Dunia, Daniel; Szelechowski, Marion

Manipulation of the N‐terminal sequence of the Borna disease virus X protein improves its mitochondrial targeting and neuroprotective potential Journal Article

In: FASEB j., vol. 30, no. 4, pp. 1523–1533, 2016, ISSN: 1530-6860.

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Chavanas, Stéphane

Peroxisome proliferator-activated receptor γ (PPARγ) activation: A key determinant of neuropathogeny during congenital infection by cytomegalovirus Journal Article

In: Neurogenesis, vol. 3, no. 1, 2016, ISSN: 2326-2133.

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2015

Suberbielle, Elsa; Djukic, Biljana; Evans, Mark; Kim, Daniel H.; Taneja, Praveen; Wang, Xin; Finucane, Mariel; Knox, Joseph; Ho, Kaitlyn; Devidze, Nino; Masliah, Eliezer; Mucke, Lennart

DNA repair factor BRCA1 depletion occurs in Alzheimer brains and impairs cognitive function in mice Journal Article

In: Nat Commun, vol. 6, no. 1, 2015, ISSN: 2041-1723.

Abstract | Links | BibTeX

Leghmar, Kaoutar; Cenac, Nicolas; Rolland, Maude; Martin, Hélène; Rauwel, Benjamin; Bertrand-Michel, Justine; Faouder, Pauline Le; Bénard, Mélinda; Casper, Charlotte; Davrinche, Christian; Fournier, Thierry; Chavanas, Stéphane

Cytomegalovirus Infection Triggers the Secretion of the PPARγ Agonists 15-Hydroxyeicosatetraenoic Acid (15-HETE) and 13-Hydroxyoctadecadienoic Acid (13-HODE) in Human Cytotrophoblasts and Placental Cultures Journal Article

In: PLoS ONE, vol. 10, no. 7, 2015, ISSN: 1932-6203.

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Li, Xiao-Jun; Liu, Xi-Juan; Yang, Bo; Fu, Ya-Ru; Zhao, Fei; Shen, Zhang-Zhou; Miao, Ling-Feng; Rayner, Simon; Chavanas, Stéphane; Zhu, Hua; Britt, William J.; Tang, Qiyi; McVoy, Michael A.; Luo, Min-Hua

Human Cytomegalovirus Infection Dysregulates the Localization and Stability of NICD1 and Jag1 in Neural Progenitor Cells Journal Article

In: J Virol, vol. 89, no. 13, pp. 6792–6804, 2015, ISSN: 1098-5514.

Abstract | Links | BibTeX

Bonnaud, Emilie M.; Szelechowski, Marion; Bétourné, Alexandre; Foret, Charlotte; Thouard, Anne; Gonzalez-Dunia, Daniel; Malnou, Cécile E.

Borna Disease Virus Phosphoprotein Modulates Epigenetic Signaling in Neurons To Control Viral Replication Journal Article

In: J Virol, vol. 89, no. 11, pp. 5996–6008, 2015, ISSN: 1098-5514.

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Fu, Ya-Ru; Liu, Xi-Juan; Li, Xiao-Jun; Shen, Zhang-zhou; Yang, Bo; Wu, Cong-Cong; Li, Jia-Fu; Miao, Ling-Feng; Ye, Han-Qing; Qiao, Guan-Hua; Rayner, Simon; Chavanas, Stéphane; Davrinche, Christian; Britt, William J.; Tang, Qiyi; McVoy, Michael; Mocarski, Edward; Luo, Min-Hua

MicroRNA miR-21 Attenuates Human Cytomegalovirus Replication in Neural Cells by Targeting Cdc25a Journal Article

In: J Virol, vol. 89, no. 2, pp. 1070–1082, 2015, ISSN: 1098-5514.

Abstract | Links | BibTeX

2014

Szelechowski, Marion; Bétourné, Alexandre; Monnet, Yann; Ferré, Cécile A.; Thouard, Anne; Foret, Charlotte; Peyrin, Jean-Michel; Hunot, Stéphane; Gonzalez-Dunia, Daniel

A viral peptide that targets mitochondria protects against neuronal degeneration in models of Parkinson’s disease Journal Article

In: Nat Commun, vol. 5, no. 1, 2014, ISSN: 2041-1723.

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2013

Charlier, Caroline M.; Wu, Yuan-Ju; Allart, Sophie; Malnou, Cécile E.; Schwemmle, Martin; Gonzalez-Dunia, Daniel

Analysis of Borna Disease Virus Trafficking in Live Infected Cells by Using a Virus Encoding a Tetracysteine-Tagged P Protein Journal Article

In: J Virol, vol. 87, no. 22, pp. 12339–12348, 2013, ISSN: 1098-5514.

Abstract | Links | BibTeX

Liblau, Roland S.; Gonzalez-Dunia, Daniel; Wiendl, Heinz; Zipp, Frauke

Neurons as targets for T cells in the nervous system Journal Article

In: Trends in Neurosciences, vol. 36, no. 6, pp. 315–324, 2013, ISSN: 0166-2236.

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Suberbielle, Elsa; Sanchez, Pascal E; Kravitz, Alexxai V; Wang, Xin; Ho, Kaitlyn; Eilertson, Kirsten; Devidze, Nino; Kreitzer, Anatol C; Mucke, Lennart

Physiologic brain activity causes DNA double-strand breaks in neurons, with exacerbation by amyloid-β Journal Article

In: Nat Neurosci, vol. 16, no. 5, pp. 613–621, 2013, ISSN: 1546-1726.

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Szelechowski, Marion; Bergeron, Corinne; Gonzalez-Dunia, Daniel; Klonjkowski, Bernard

Production and Purification of Non Replicative Canine Adenovirus Type 2 Derived Vectors Journal Article

In: JoVE, no. 82, 2013, ISSN: 1940-087X.

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2011

Chevalier, Grégoire; Suberbielle, Elsa; Monnet, Céline; Duplan, Valérie; Martin-Blondel, Guillaume; Farrugia, Fanny; Masson, Gwendal Le; Liblau, Roland; Gonzalez-Dunia, Daniel

Neurons are MHC Class I-Dependent Targets for CD8 T Cells upon Neurotropic Viral Infection Journal Article

In: PLoS Pathog, vol. 7, no. 11, 2011, ISSN: 1553-7374.

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2010

Schmid, Sonja; Metz, Philippe; Prat, Christine M. A.; Gonzalez-Dunia, Daniel; Schwemmle, Martin

Protein kinase C-dependent phosphorylation of Borna disease virus P protein is required for efficient viral spread Journal Article

In: Arch Virol, vol. 155, no. 5, pp. 789–793, 2010, ISSN: 1432-8798.

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2009

Prat, Christine M. A.; Schmid, Sonja; Farrugia, Fanny; Cenac, Nicolas; Masson, Gwendal Le; Schwemmle, Martin; Gonzalez-Dunia, Daniel

Mutation of the Protein Kinase C Site in Borna Disease Virus Phosphoprotein Abrogates Viral Interference with Neuronal Signaling and Restores Normal Synaptic Activity Journal Article

In: PLoS Pathog, vol. 5, no. 5, 2009, ISSN: 1553-7374.

Links | BibTeX

Societal impact

Our research aims at a better understanding of the impact of viruses on the developing brain and on neuronal homeostasis and also of the pathophysiology of congenital viral infections. To this aim, we use two viral paradigms: the model system Bornavirus (BDV) and congenital infection by human cytomegalovirus (HCMV), which is a public health issue.

The remarkable features of BDV pathogenesis, notably its predominant tropism for limbic structures in the brain (cortex and hippocampus), constitute a fascinating model of viral interaction with the brain and make it a very valuable tool to gain insight on the pathogenesis of many human neurological diseases. A better understanding of the underlying mechanisms may provide new physiopathological clues for a better understanding of many human neurological diseases of unclear etiology.
The development of these projects is facilitated the gathering in the team of researchers, assistant professors and clinicians with leading and complementary expertise. Moreover, our connection with the neonatal department of the Children’s Hospital of Toulouse and the maternity ward offers opportunities for translational research, from basic to patient-oriented research.

Alumni

Post-docs

  • Raphael Boursereau
  • Karine Bourgade
  • Marion Szelechowski
  • Alexandre Bétourné
  • Amine Benarbia
  • Carine Duval
  • Valérie Duplan
  • Céline Monnet
  • Jeffrey Bajramovic

Students

  • Florent Marty
  • Luca Bettamin
  • Maude Rolland
  • Cécile Ferré
  • Leila Khajavi
  • Maïlys Mouysset
  • Joao Proença
  • Emilie Bonnaud
  • Caroline Charlier
  • Grégoire Chevalier
  • Christine Prat
  • Elsa Suberbielle
  • Romain Volmer
  • Aymeric Hans
  • Aline Taveira

Research Assistants

  • Morgane Duvivier
  • Marine Fraisse
  • Charlotte Foret
Collaborations

INFINITY

  • Jacques Izopet/Bernard Lagane
  • Jérôme Ausseil/Rémy Poupot
  • Nicolas Blanchard
  • Sylvie Guerder/Nicolas Fazilleau
  • Roland Liblau/Abdel Saoudi

 

National

  • Team RADOPT, CRCT, Toulouse (E. Moyal)
  • CNR Herpesvirus, INSERM UMR 1092, Limoges (S. Alain, S. Hantz)
  • Institut Charles Gerhardt Montpellier, CNRS UMR 5253, Montpellier (M. Morille)
  • Institut Broca, Bordeaux  (A. Favereaux)
  • Inserm UMR 1058, Pathogenesis and control of chronic infections, Montpellier (S. Salinas)
  • Team MINDING, CRCA, CNRS UMR 5169, Toulouse (P. Belenguer, M-C. Miquel)
  • Laboratoire d’analyse et d’architecture des systèmes, LAAS-CNRS, Toulouse (G. Larrieu)
  • Centre de Recherche ICM INSERM/UPMC UMR 975 – CNRS UMR 7225, Paris (S. Hunot)
  • Centre de Biologie Paris Seine (IBPS), CNRS UNMR 8256, Paris (J-M. Peyrin)
  • Team METAMAL, CRCT, Toulouse (J.E. Sarry)
  • Institut des cellules souches pour le traitement et l’étude des maladies monogéniques, Unité UMR861-ISTEM, Evry (M. Peschanski, A.Benchoua)
  • IPBS, Toulouse (O. Schiltz)
  • Institut Curie, CNRS UMR144, Paris (G. Raposo et G. D’Angelo)
  • MCD, CBI, Toulouse (J. Cavaillé)
  • IBS, Genoble (T. Crépin)
  • PRISM, Lille (E. Coyaud)
  • Inserm UMR 1058, Montpellier (Y. Simonin)
  • CHU Toulouse, services gynéco-obstétrique et néonatologie

 

International

  • Kyoto University, Japan (K. Tomonaga)
  • The Gorgas Memorial Institute for Health and Diseases, Panama city, Panama (S. Lopez-Verges)
  • The Gladstones Institute, USCF, USA (L. Mucke)

Partenaires Equipe 7

France Parkinson

France Parkinson

AFM

AFM

Union Nationale des Aveugles et Déficients Visuels

Union Nationale des Aveugles et Déficients Visuels

CNRS

CNRS

Université Toulouse Paul Sabatier

Université Toulouse Paul Sabatier

Région Occitanie

Région Occitanie

Agence nationale de la recherche

Agence nationale de la recherche

INSERM

INSERM

France Alzheimer

France Alzheimer

Marie Curie actions

Marie Curie actions

NARSAD

NARSAD

FRM

FRM

Agence de la biomédecine

Agence de la biomédecine

Fondation Vaincre Alzheimer

Fondation Vaincre Alzheimer

Inspire

Inspire

Fondation Villa M

Fondation Villa M

Défi Clé Biothérapies

Défi Clé Biothérapies