Chronicité des Infections Virales [CVI]
Presentation
The Chronicity of Viral Infections [CVI] is an Emerging Team investigating the molecular and cellular mechanisms driving pathogen persistence in myeloid cells. Our goals are: I) to think about strategies to neutralize pathogens before they reach safe intracellular niches (such as the macrophage and other myeloid cells, including their hematopoietic progenitors) and also to think about how to block the pathogen spreading from these cellular niches to different cells and tissues; II) to unveil the mechanisms of latency of intracellular pathogens, responsible for disease persistence; and III) to contribute to the development of efficient therapeutic approaches for chronic, potentially lethal, diseases. Currently we are tackling long-term immune dysfunctions caused by HIV-1 and SARS-CoV-2 hosted by macrophages, megakaryocytes and their precursors, in order to understand these myeloid viral hideouts and ultimately devise improved therapeutic strategies against HIV/AIDS and COVID-19. The human immunodeficiency virus (HIV), the causative agent of AIDS, has been a major public health issue for over 40 years. HIV causes host immunosuppression through infection, multiplication and persistence in myeloid and lymphoid immune cells, which can be transformed into viral reservoirs. Dr Fernando Real’s team aims to detect and better characterise these cells, in particular the cells of myeloid lineage such as the macrophage and the megakaryocyte, and to understand the cellular and molecular mechanisms underlying their maintenance and their deleterious action on the immune system. The team is investigating whether viral reservoirs are inflammatory cells that support the production of viruses and viral components that compromise the function and generation of new immune cells. These investigations could open up new therapeutic avenues for treating persistent viral infections and their long-term sequelae.
Research Activity
- The research program of the Chronicity of Viral Infections [CVI] Emerging Team is currently divided in two research axes:
- Macrophages are durable hosts for viral pathogens via infection of common myeloid progenitors
Chronic inflammation is commonly observed in HIV-infected patients despite antiretroviral treatment and in individuals with post-acute sequelae of COVID-19. We are investigating: i) whether macrophages precursors (common myeloid progenitors) are primed early at the bone marrow stage by a first inflammatory stimulus (e.g. viral primo-infection), displaying thereafter an enhanced inflammatory response upon a second stimulus (e.g. re-infection or superinfection) once they are terminally differentiated into tissue-like macrophages; and ii) whether this trained response is directly implicated in persistent viral replication in tissular macrophages, sustaining infection and chronic inflammation deleterious for the homeostasis.
- Megakaryocytes targeted by viruses participate in infectious disease progression
Megakaryocytes, precursor of platelets, are gaining momentum in immunology field as inflammatory/immune system actors – a poorly understood but exciting topic in immunology. We will investigate the detrimental consequences of megakaryocyte infection for the immune system and the cellular/molecular mechanisms controlling viral persistent in this myeloid cell. We aim at deciphering the megakaryocyte factors expressed upon viral infections that will be inherited by their daughter platelets and that thereafter will immunomodulate immune cells upon platelet-cell contact. Virus-induced, platelet druggable targets will be functionally assessed by blockage/inhibition using antibodies and CRISPR/Cas9 strategies, in in vitro and in vivo models, opening avenues for novel therapeutical strategies.
Funding: CNRS, Région Hauts-de-France, SIDACTION
Informations : https://www.ciil.fr/teams/chronicity-of-viral-infections-cvi
Team Members
Fernando REAL
CNRS CRCN, head of the team
Numéro ORCID : 0000-0002-5060-4334
Post-doc (CNRS)
Cyrine BENTALEB
Post-doc (University of Lille)
Souad ADROUCHE
Master 2 student (University of Poitiers)
Selected publications
Real F, Zhu A, Belmellat A, Sennepin A, (…), Bomsel M.
S100A8-mediated metabolic adaptation controls HIV-1 persistence in macrophages in vivo.
Nature Communications, 2022 doi: 10.1038/s41467-022-33401-x
Real F, Ganor Y, Bomsel M
Experimental Models to Study HIV Latency Reversal from Male Genital Myeloid Cells
Methods in Molecular Biology. HIV reservoirs 2022. doi: 10.1007/978-1-0716-1871-4_14
Real F, Capron C, Sennepin A, Arrigucci R, Zhu A, (…) Bomsel M.
Platelets from cART-suppressed HIV-infected patients with poor CD4+ T cell recovery carry infectious HIV
Science Translational Medicine. 2020 doi: 10.1126/scitranslmed.aat6263
Pessoa CC, Reis LC, (…) Real F
ATP6V0d2 controls Leishmania parasitophorous vacuole biogenesis via cholesterol homeostasis
PLoS Pathogens. 2019 Jun 14;15(6):e1007834.doi: 10.1371/journal.ppat.1007834
Real F, Sennepin A, Ganor Y, Schmitt A, Bomsel M.
Live Imaging of HIV-1 Transfer across T Cell Virological Synapse to Epithelial Cells that Promotes Stromal Macrophage Infection
Cell Reports. 2018 May 8;23(6):1794-1805. doi: 10.1016/j.celrep.2018.04.028
Keywords
Contact
Head of the Emerging team « Chronicity of Viral Infections »
fernando.real@cnrs.fr
03 20 87 12 01