A5018932260- interferon and immune responses
- HIV Research and Treatment
- Viral Infections and Vectors
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- Herpesvirus Infections and Treatments
- RNA and protein synthesis mechanisms
- RNA regulation and disease
- Cytomegalovirus and herpesvirus research
- SARS-CoV-2 and COVID-19 Research
- T-cell and B-cell Immunology
- Trace Elements in Health
- HIV/AIDS drug development and treatment
- Viral Infections and Immunology Research
- Zoonotic diseases and public health
- Immune Response and Inflammation
- vaccines and immunoinformatics approaches
- Heavy Metal Exposure and Toxicity
- Bacteriophages and microbial interactions
- Hepatitis B Virus Studies
- Polyomavirus and related diseases
- Advanced biosensing and bioanalysis techniques
- Influenza Virus Research Studies
- Virus-based gene therapy research
- Iron Metabolism and Disorders
Centre National de la Recherche Scientifique
2015-2024
Medical Research Council
2020-2024
University of Oxford
2020-2024
Institut de Recherche en Infectiologie de Montpellier
2021-2024
Université de Montpellier
2021-2024
Institut Pasteur
2015-2022
Department of Virology
2015-2022
Université Paris Cité
2022
MRC Human Immunology Unit
2020-2022
MRC Weatherall Institute of Molecular Medicine
2020-2022
Increased IFN-α production contributes to the pathogenesis of infectious and autoimmune diseases. Plasmacytoid dendritic cells (pDCs) from females produce more upon TLR7 stimulation than pDCs males, yet mechanisms underlying this difference remain unclear. In article, we show that basal levels IFN regulatory factor (IRF) 5 in were significantly higher compared with males positively correlated percentage IFN-α-secreting pDCs. Delivery recombinant IRF5 protein into human primary increased...
Abstract Human cells respond to infection by SARS-CoV-2, the virus that causes COVID-19, producing cytokines including type I and III interferons (IFNs) proinflammatory factors such as IL6 TNF. IFNs can limit SARS-CoV-2 replication but cytokine imbalance contributes severe COVID-19. We studied how detect infection. report cytosolic RNA sensor MDA5 was required for IFN induction in lung cancer cell line Calu-3 upon Type further MAVS IRF3. In contrast, of TNF independent MDA5-MAVS-IRF3 axis...
Significance Human immunodeficiency viruses (HIV) have developed strategies to interfere with DNA repair in host cells. Some pathways represent restriction mechanisms that counteract the virus as soon it penetrates into cell, before establishment of an interferon response. Here we identify helicase-like transcription factor (HLTF) a new protein degraded by viral R (Vpr) from HIV-1. HLTF mediates stalled replication forks bypass lesions and ensure genome integrity. is early after Vpr delivery...
Varicella-Zoster virus (VZV) causes chickenpox and shingles. Although the infection is associated with severe morbidity in some individuals, molecular mechanisms that determine innate immune responses remain poorly defined. We found cGAS/STING DNA sensing pathway was required for type I interferon (IFN) induction during VZV recognition of by cGAS restricted its replication. Screening a ORF expression library identified essential tegument protein ORF9 as antagonist. Ectopically or virally...
Pattern recognition receptors (PRRs) protect against microbial invasion by detecting specific molecular patterns found in pathogens and initiating an immune response. Although microbial-derived PRR ligands have been extensively characterized, the contribution relevance of endogenous to activation remains overlooked. Here, we characterize landscape that engage RIG-I-like (RLRs) upon infection different RNA viruses. In each infection, several RNAs transcribed polymerase III (Pol3) specifically...
DNA sensing is important for antiviral immunity. The sensor cGAS synthesizes 2'3'-cyclic GMP-AMP (cGAMP), a second messenger that activates STING, which induces innate cGAMP not only STING in the cell where it produced but also transfers to other cells. Transporters, channels, and pores (including SLC19A1, SLC46A2, P2X7, ABCC1, volume-regulated anion channels (VRACs)) release into extracellular space and/or import cGAMP. We report infection with multiple human viruses depletes some of these...
Although plasmacytoid dendritic cells (pDCs) represent a rare immune cell type, they are the most important source of type I interferons (IFNs) upon viral infection. Phagocytosed RNA viruses and virus-infected detected by pDCs with endosomal pattern recognition receptor (PRR) toll-like 7 (TLR7). We showed that replication yellow fever live vaccine YF-17D in human pDC-like lines stimulated IFN production through RIG-I (retinoic acid-inducible gene I), member RIG-I-like (RLR) family cytosolic...
APOBEC3A (A3A), one of the seven-member APOBEC3 family cytidine deaminases, lacks strong antiviral activity against lentiviruses but is a potent inhibitor adeno-associated virus and endogenous retroelements. In this report, we characterize biochemical properties mammalian cell-produced catalytically active E. coli-produced A3A. The enzyme binds to single-stranded DNA with Kd 150 nM forms dimeric monomeric fractions. A3A, unlike APOBEC3G (A3G), deaminates substrates nonprocessively. Using...
Cyclic GMP-AMP (cGAMP) is an immunostimulatory molecule produced by cGAS that activates STING. cGAMP adjuvant when administered alongside antigens. also incorporated into enveloped virus particles during budding. Here, we investigate whether inclusion of within viral vaccine vectors enhances their immunogenicity. We immunise mice with virus-like (VLPs) containing HIV-1 Gag and the vesicular stomatitis envelope glycoprotein G (VSV-G). loading VLPs augments CD4 CD8 T-cell responses. It...
Abstract Plasmacytoid dendritic cells (pDC) are specialized in secretion of type I interferon response to pathogens. Here we show that natural monoamines and synthetic amines inhibit pDC activation by RNA viruses. Furthermore, a analogue histamine reduces production mouse model influenza infection. We identify CXC chemokine receptor 4 (CXCR4) as used pDC. Our study establishes functional link between the innate immune system identifies CXCR4 potential ‘on-off’ switch activity with...
Copper is a critical element for eukaryotic life involved in numerous cellular functions, including redox balance, but toxic excess. Therefore, tight regulation of copper acquisition and homeostasis essential cell physiology survival. Here, we identify different regulatory mechanism that requires the presence an endogenous retroviral envelope glycoprotein called Refrex1. We show cells respond to elevated extracellular by increasing expression Refrex1, which regulates through interaction with...
Human Immunodeficiency Virus-type 2 (HIV-2) encodes Vpx that degrades SAMHD1, a cellular restriction factor active in non-dividing cells. HIV-2 replicates lymphocytes but the susceptibility of monocyte-derived dendritic cells (MDDCs) to vitro infection remains partly characterized.Here, we investigated replication primary CD4+ T lymphocytes, both activated and non-activated, as well MDDCs. We focused on requirement for productive infection, using reference ROD strain, proviral clone GL-AN,...
ABSTRACT HIV-1 poorly infects monocyte-derived dendritic cells (MDDCs). This is in large part due to SAMHD1, which restricts viral reverse transcription. Pseudotyping with vesicular stomatitis virus G protein (VSV-G) strongly enhances infection, suggesting that earlier steps of replication, including fusion, are also inefficient MDDCs. The site fusion remains controversial and may depend on the cell type, reports indicating it occurs at plasma membrane or, conversely, an endocytic...
ABSTRACT Human immunodeficiency virus (HIV) in humans and simian (SIV) macaques (MAC) lead to chronic inflammation AIDS. Natural hosts, such as African green monkeys (AGM) sooty mangabeys (SM), are protected against SIV-induced Here, we report that AGM plasmacytoid dendritic cells (pDC) express extremely low levels of CD4, unlike MAC human pDC. Despite this, pDC efficiently sensed SIVagm, but not heterologous HIV/SIV isolates, indicating a virus-host adaptation. Moreover, both SM were found...
Abstract Human cells respond to infection by SARS-CoV-2, the virus that causes COVID-19, producing cytokines including type I and III interferons (IFNs) proinflammatory factors such as IL6 TNF. IFNs can limit SARS-CoV-2 replication but cytokine imbalance contributes severe COVID-19. We studied how detect infection. report cytosolic RNA sensor MDA5 was required for IFN induction in lung cancer cell line Calu-3 upon Type further MAVS IRF3. In contrast, of TNF independent MDA5-MAVS-IRF3 axis...
Abstract Pattern recognition receptors (PRRs) protect against host invasion by detecting specific molecular patterns found in pathogens and initiating an immune response. While microbial-derived PRR ligands have been extensively characterized, the contribution relevance of endogenous to activation during viral infection remain overlooked. In this work, we characterize landscape that engage RIG-I-like (RLRs) upon a positive-sense RNA virus, negative-sense virus or retrovirus. We several RNAs...
SUMMARY Varicella-Zoster virus (VZV) causes chickenpox and shingles. Although infection is associated with severe morbidity in some individuals, molecular mechanisms that determine innate immune responses remain poorly defined. We found the cGAS/STING DNA sensing pathway was required for type I interferon (IFN) induction during VZV recognition of by cGAS restricted its replication. Viral gene overexpression screening identified essential tegument protein ORF9 as a antagonist. Ectopically...
Over 1 million patients are infected with HIV-2, which is often described as an attenuated retroviral infection. Patients frequently have undetectable viremia and evolve at more slowly toward AIDS than HIV-1-infected patients. Several studies reported a smaller viral reservoir in peripheral blood mononuclear cells HIV-2-infected patients, while others found similar sizes of reservoirs but reduced amount cell-associated RNA, suggesting block HIV-2 transcription. Recent associations between...
Cellular metabolism provides all molecules essential for the cell's functions including nucleic acids, amino acids and fatty but also energy via glycolysis mitochondrial respiration (also known as OXPHOS). Viruses hijack these pathways to support different steps of their replication, making metabolic state infected cell a key factor influencing viral replication. In particular, Human Immunodeficiency virus (HIV) remains latent in resting, metabolically inactive CD4 T lymphocytes actively...
Abstract Cyclic GMP-AMP (cGAMP) is an immunostimulatory second messenger produced by cGAS that activates STING. Soluble cGAMP acts as adjuvant when administered with antigens. also incorporated into enveloped virus particles during budding. We hypothesised inclusion of the within viral vaccine vectors would promote adaptive immunity against vector immunised mice virus-like (VLPs) containing HIV-1 Gag protein and VSV-G. Inclusion these VLPs augmented splenic VLP-specific CD4 CD8 T cell...