A5074708473- HIV Research and Treatment
- Immune cells in cancer
- HIV/AIDS drug development and treatment
- Immune Cell Function and Interaction
- Phagocytosis and Immune Regulation
- Epigenetics and DNA Methylation
- HIV-related health complications and treatments
- Adenosine and Purinergic Signaling
- RNA modifications and cancer
- Cytomegalovirus and herpesvirus research
- CRISPR and Genetic Engineering
- COVID-19 Impact on Reproduction
- Cancer Immunotherapy and Biomarkers
- Autophagy in Disease and Therapy
- DNA Repair Mechanisms
- PARP inhibition in cancer therapy
- COVID-19 Clinical Research Studies
- Erythrocyte Function and Pathophysiology
- Macrophage Migration Inhibitory Factor
- Gene expression and cancer classification
- Plant and Fungal Interactions Research
- Cancer-related Molecular Pathways
- Plant Virus Research Studies
- Cell death mechanisms and regulation
- interferon and immune responses
Inserm
2014-2024
Université Paris-Saclay
2017-2024
Institut Gustave Roussy
2014-2024
Université Paris-Sud
2017-2019
Institut Pasteur
2013-2017
Scuola Normale Superiore
2009-2011
Significance Macrophages, with CD4 + T lymphocytes, are a major cell target for HIV-1 infection. We have previously reported that the induction of cellular protein, cyclin-dependent kinase p21, inhibits replication in macrophages. now show p21 impairs reverse transcription and other primate lentiviruses, including simian immunodeficiency virus (SIV)mac, by blocking synthesis deoxynucleotides (dNTP) used retroviral transcriptase viral DNA synthesis. represses expression key enzyme dNTP...
Abstract Background An essential event during the replication cycle of HIV-1 is integration reverse transcribed viral DNA into host cellular genome. Our former report revealed that integrase (IN), enzyme catalyzes reaction, positively regulated by acetylation mediated histone acetyltransferase (HAT) p300. Results In this study we demonstrate another HAT, GCN5, acetylates IN leading to enhanced 3'-end processing and strand transfer activities. GCN5 participates in step as demonstrated reduced...
Recent advances in fluorescence microscopy provided tools for the investigation and analysis of viral replication steps cellular context. In HIV field, current visualization systems successfully achieve fluorescent labeling envelope proteins, but not genome. Here, we developed a system able to visualize proviral DNA HIV-1 through immunofluorescence detection repair foci double-strand breaks specifically induced genome by heterologous expression I-SceI endonuclease. The Single-Cell Imaging...
Purinergic receptors and nucleotide-binding domain leucine-rich repeat containing (NLR) proteins have been shown to control viral infection. Here, we show that the NLR family member NLRP3 purinergic receptor P2Y2 constitutively interact regulate susceptibility HIV-1 We found acts as an inhibitory factor of entry represses F-actin remodeling. The binding envelope its host cell (CD4, CXCR4, and/or CCR5) overcomes this restriction by stimulating P2Y2. Once activated, enhances interaction with...
Abstract Even though cell death modalities elicited by anticancer chemotherapy and radiotherapy have been extensively studied, the ability of treatments to induce non-cell-autonomous has never investigated. By means multispectral imaging flow-cytometry-based technology, we analyzed lethal fate cancer cells that were treated with conventional agents co-cultured untreated cells, observing can simultaneously trigger cell-autonomous in cells. After ionizing radiation, oxaliplatin, or cisplatin...
Canine vector-borne diseases (CVBDs) are of major concern in veterinary medicine worldwide. Amongst the arthropods transmitting CVBD-causing pathogens, brown dog tick (Rhipicephalus sanguineus sensu lato) is an important vector agents, such as Babesia vogeli, Cercopithifilaria spp., Ehrlichia canis, Hepatozoon and Anaplasma platys. While data on CVBDs transmitted by Rh. s.l. limited Morocco, Leishmania phlebotomine sand flies, known to be endemic several regions country. In this study, we...
Purinergic receptors and NOD-like receptor protein 3 (NLRP3) inflammasome regulate inflammation viral infection, but their effects on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection remain poorly understood. Here, we report that the purinergic P2X7 NLRP3 are cellular host factors required for SARS-CoV-2 infection. Lung autopsies from patients with disease 2019 (COVID-19) reveal expression is increased in targets of including alveolar macrophages, type II pneumocytes...
ABSTRACT HIV-1 infection of noncycling cells, such as dendritic cells (DCs), is impaired due to limited availability deoxynucleoside triphosphates (dNTPs), which are needed for reverse transcription. The levels dNTPs tightly regulated during the cell cycle and depend on balance between dNTP biosynthesis degradation. SAMHD1 potently blocks replication in DCs, although underlying mechanism still unclear. has been reported be able degrade viral nucleic acids, may both hamper relative...
Abstract Targeting the reprogramming and phagocytic capacities of tumor-associated macrophages (TAMs) has emerged as a therapeutic opportunity for cancer treatment. Here, we demonstrate that tumor cell phagocytosis drives pro-inflammatory activation TAMs identify key role cyclin-dependent kinase inhibitor CDKN1A (p21). Through transcriptional repression Signal-Regularity Protein α ( SIRPα ), p21 promotes leukemia and, subsequently, extends to surrounding through Interferon γ. In mouse models...
Homologous recombination (HR) is a prominent DNA repair pathway maintaining genome integrity. Mutations in many HR genes lead to cancer predisposition. Paradoxically, the implication of pivotal factor RAD51 on development remains puzzling. Particularly, no mouse models are available address role aging and carcinogenesis vivo. We engineered model with an inducible dominant-negative form (SMRad51) that suppresses RAD51-mediated without stimulating alternative mutagenic pathways. found vivo...
Abstract Background Tumor-associated macrophages (TAMs) are essential components of the inflammatory microenvironment tumors and associated with poor clinical outcomes in majority cancers. TAMs mainly exhibit anti-inflammatory functions that promote support tissue remodeling, immune suppression tumor growth. Regarding their plasticity, functional reprogramming into proinflammatory phenotype recently emerged as a therapeutic opportunity to improve effectiveness anticancer treatments such...
During AD pathology, Tau protein levels progressively increase from early pathological stages. altered expression causes an unbalance of subcellular localization in the cytosol and nuclear compartment leading to synaptic dysfunction, neuronal cell death neurodegeneration as a consequence. Due relevant role epigenetic remodellers activity physiology neurodegeneration, particular TRIM28 HDAC1, we investigated relationship between these factors. By molecular, imaging biochemical approaches,...
Post-translational modifications, such as acetylation, dynamically modulate the chemical and structural properties of proteins generating new protein-protein interfaces. HIV-1 integrase is acetylated by p300 at three specific lysines located in carboxy terminal domain. In attempt to understand how acetylation modifies integration event, we have searched for cellular cofactors that may specifically require bind integrase. To this aim a tethered catalysis system has been exploited perform...
Abstract The reprogramming of tumor-associated macrophages (TAMs) by radiotherapy is associated with cancer patient’s response and sensitization to immune checkpoint blockade, but the molecular mechanisms involved remain largely unknown. Here, we show that following ionizing radiation (IR), accumulate single double strand-DNA breaks fragmented mitochondria in their cytosol, stabilize DNA sensor cyclic GMP-AMP synthase (cGAS). We demonstrate mitochondrial fragmentation induced activation...
Background Macrophages play crucial roles in HIV/AIDS pathogenesis as they are important targets for HIV-1 replication and contribute to viral spread reservoir formation. We have previously reported that p21 inhibits HIV-1, HIV-2 SIV macrophages by a major block at the level of reverse transcription [1]. This study aimed understanding molecular mechanisms involved p21-mediated restriction.