Autophagy and Infections

Projects

The projects of the team focus on the role of autophagy during infections, mainly HIV-1 infection.

1. Autophagy and AIDS
In HIV-1-infected patients, CD4 T lymphocyte depletion is mainly due to apoptosis in bystander, uninfected CD4 T lymphocytes, since the degree of cell loss largely exceeds the number of infected cells. We demonstrated that autophagy is triggered during HIV-1 entry by the fusion of the viral and target cell membranes and that this mechanism is responsible for apoptosis of the bystander CD4 T cells. Autophagy is thus directly involved in HIV-1-induced immunodeficiency. The aim is now to study the pathways that are activated by the membrane fusion and that lead to autophagy. We also want to decipher the link between autophagy and apoptosis, a highly debated subject among the scientific community, which, during HIV-1 infection, plays an essential physiopathological role.

2. Autophagy: an antiviral mechanism counteracted by HIV-1 to favour its own replication
Autophagy can be a selective degradative mechanism by specifically targeting proteins or organelles through adaptor proteins. The team has shown very recently that autophagy is an anti-HIV-1 process by specifically degrading Tat, a viral protein essential for HIV-1 replication. To counteract this very powerful defence mechanism, several viral proteins, including Vif, can block autophagy. Results from a yeast two-hybrid screen indicate that all the HIV-1 proteins interact with several autophagy proteins (ATGs). We are now studying the role of Vpr in the regulation of autophagy.
  
              
Summary diagram of the projects


 

2017

Majdoul Sahila, Cosette Jérémie, Seye Ababacar Khalil, Bernard Eric, Frin Sophie, Holic Nathalie, Chazal Nathalie, Briant Laurence, Espert Lucile, Galy Anne, Fenard David. Peptides derived from evolutionarily conserved domains in Beclin-1 and Beclin-2 enhance the entry of lentiviral vectors into human cells. J Biol Chem., 2017 292(45):18672-18681.

Vergne I, Lafont F, Espert L, Esclatine A, Biard-Piechaczyk M. Autophagy, ATG proteins and infectious diseases. Med Sci (Paris). 2017 Mar;33(3):312-318.

Gómez-Mora E, Robert-Hebmann V, García E, Massanella M, Clotet B, Cabrera C, Blanco J, Biard-Piechaczyk M. Brief Report: Impaired CD4 T-Cell Response to Autophagy in Treated HIV-1-Infected Individuals. J Acquir Immune Defic Syndr. 2017 Feb 1;74(2):201-205

 

2016

Klionsky DJ, Abdelmohsen, … Biard- Piechaczyk  M, … Espert L et al. Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition). Autophagy. 2016 Apr;8(4):445-544.

 

2015

Borel S., Robert-Hebmann V., Alfaisal J., Jain A., Faure M., Espert L., Chaloin L., Paillart J. C., Johansen T., Biard-Piechaczyk M. HIV-1 Vif interacts with LC3 and inhibits autophagy. AIDS. 29:275–286.

Sagnier S., Daussy C.F., Beaumelle B., Borel S., Robert-Hebmann V., Faure M., Blanchet F.P., Biard-Piechaczyk M., Espert L.. Autophagy restricts HIV-1 infection by selectively degrading Tat in CD4 T lymphocytes. Journal of Virology. 89(1):615-25. Article online in Global Medical Discovery (https://globalmedicaldiscovery.com/)

Papin L., Daussy CF., Alfaisal J., Espert L., Blanchet FP., Blanco J., Biard-Piechaczyk M. Autophagy and HIV infection. Encyclopedia of AIDS.

María-Soledad V., de Armas-Rillo L., Barroso-González J., Ziglio S., Batisse J., Dubois N., Marrero-Hernández S., Borel S., García-Expósito L., Biard-Piechaczyk M., Paillart JC., Valenzuela-Fernández A. The HDAC6/APOBEC3G complex regulates HIV-1 infectiveness by inducing Vif autophagic degradation. Retrovirology. 12 :53.

Espert L., Beaumelle B., Vergne I. Autophagy in Mycobacterium tuberculosis and HIV infections. Microbiology. Front Cell Infect Microbiol. 2;5:49.

Daussy CF, Beaumelle B, Espert L. Autophagy restricts HIV-1 infection. Oncotarget. 2015 Aug 28;6(25):20752-3.

 

2014

Loukil A., Zonca M., Rebouissou C., Baldin V., Coux O., Biard-Piechaczyk M., Blanchard JM., Peter M. High resolution live cell imaging reveals novel cyclin A2 degradation foci involving autophagy. J Cell Sci. 127:2145-2150.

Alfaisal J., Daussy C.F., Blanchet F.P., Espert L., Salinas S., Biard-Piechaczyk M. To eat or not to eat: the intricate relationship between autophagy and HIV-1. Current Topics in Virology. 12:23-51.

 

2013

Espert L. and Biard-Piechaczyk M. Induction of Autophagy in HIV-1-Uninfected Cells: Role of Fusogenic Activity of gp41. Book chapter, Elsevier Publishing Company. Autophagy: Cancer, Other Pathologies, Inflammation, Immunity, and Infection. Volume 2 - Role in General Diseases. Editor : M Hayat.

 

2012

Klionsky DJ., … Biard-Piechaczyk M…. Espert L…(alphabetical order). Guidelines for the Use and Interpretation of Assays for Monitoring Autophagy. Autophagy 8:4, 1–100.

Eekels J.M., Sagnier S., Geerts D., Jeeninga R .E., Biard-Piechaczyk M., Berkhout B. Inhibition of HIV-1 replication with stable RNAi-mediated knockdown of autophagy factors. Virol. J. 9:69. “Highly accessed”

Biard-Piechaczyk M., Espert L., Borel S., De Bettignies G., Coux O. HIV-1, Ubiquitin and Ubiquitin-like proteins: the dialectic interactions of a virus with a sophisticated network of post-translational modifications. Biol. Cell. 104, 1–24

Borel S., Espert L., Biard-Piechaczyk M.. Macroautophagy regulation during HIV-1 infection of CD4+ T cells and macrophages. Front. Immunol. 3:97.

 

2011

Sagnier S., Biard-Piechaczyk M., Espert L. Autophagie. Chapitre de livre : Ubiquitine/Ubiquitine-like/protéasome publié aux éditions Lavoisier.

Sitbon M., Biard-Piechaczyk M., Robert V., Briant L., Köhler S., Labesse G., Devaux C.. Montpellier Infectious Diseases (MID): 1st Annual Meeting. Infect Genet Evol. 11(7):1493-8.

Pombo-Grégoire I., Borel S., Richetta C., Meyniel L., Pradezynski F., Diaz O., Deloire A., Le Breton M., Azocar O., Mangeot P.E., Navratil V., Joubert P.E., Flacher M., Vidalain P.O., André P., Lotteau V., Biard-Piechaczyk M., Rabourdin-Combe C., Faure M. IRGM is a common target of RNA viruses that subvert the autophagy network. PLoS Pathog. 7(12): e1002422


2010

 

Local :

National :

  • CODOGNO, INEM, Paris
  • FAURE, CIRI, Lyon
  • N. MAZURE, Unice, Nice
  • I. VERGNE, IPBS, Toulouse

International :

  • J. BLANCO, IrsiCaixa Foundation, Barcelona, Spain
  • A. FERNANDEZ-VALENZUELA, University of La Laguna, Tenerife, Spain
  • T. JOHANSEN, UiT, Tromso, Norway
  • S. TOOZE, The Francis Crick Institute, Londres, UK

Membres de l’équipe

Martine Biard – Team Leader - DR2 CNRS - HDR

Lucile Espert – CR CNRS - HDR

Véronique Robert-Hebmann
- IR - CNRS

Mathilde Galais
– PhD Student - LABEX EpiGenMed

Baptiste Pradel - M2R Student

 

 

 

Alumni

PhD Students:

2014-20147


Laure PAPIN –
Sidaction

Characterization of the early steps of HIV-1 entry in Dendritic Cells

 

2013-2016


Jamal ALFAISAL
– ERASMUS MUNDUS

Autophagy inhibition in HIV-1-infected CD4 T Lymphocytes. The role of Vif and Vpr accessory proteins.



Coralie DAUSSY
– MRT Scholarship

Role of selective autophagy during HIV-1 infection of CD4 T Lymphocytes

 

2012-2015


Sophie BOREL
MRT Scholarship

Role of autophagy in HIV-1-infected CD4 T lymphocytes

 

2011-2015


Sophie SAGNIER – ANRS/Sidaction

Autophagy, une mechanism involved in HIV-1 physiopathology

 

Stagiaires :

2017

Justine LAGISQUET – M2 (Parcours) – Montpellier

Alice MACHADO – M2 (Parcours) - Montpellier

 

2016

Mathilde GALAIS – M2 Université Libre de Bruxelles – Belgique

Sixtine FAURE – M2 (parcours) - Montpellier

 

2015

Andrea WERKEYN - L2 Biologie parcours Ingénierie de la Santé Université de Montpellier

Lucille PENALVA-MOUSSET – L3 Physiologie animale et neurosciences, Université de Montpellier

 

2014

Brieux CHARDES – 1ère année du Diplôme de Formation Approfondie en Sciences Pharmaceutiques (DFASP-1), Faculté de Pharmacie, Université de Montpellier

Sophie BRANKA – L3 Biologie Cellulaire et physiologie, Université de Toulouse

 

2013

Laure PAPIN, M2 Interactions micro-organismes, hôtes et environnement (IMHE), Université de Montpellier

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Team Leader


Martine Biard

DR2 CNRS, HDR

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In Brief

Autophagy is a lysosomal degradation process involved in cellular homeostasis and in innate and adaptative immunities against pathogens.
Our team studies the role of autophagy during viral infections, in particular HIV-1.EnregistrerEnregistrer

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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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