A5056285356- HIV Research and Treatment
- Ubiquitin and proteasome pathways
- HIV/AIDS drug development and treatment
- Mosquito-borne diseases and control
- CRISPR and Genetic Engineering
- Biochemical and Molecular Research
- Virus-based gene therapy research
- T-cell and Retrovirus Studies
- interferon and immune responses
- Reproductive System and Pregnancy
- HIV/AIDS Research and Interventions
- Virology and Viral Diseases
- Immunotherapy and Immune Responses
- Chromosomal and Genetic Variations
- Viral Infections and Vectors
- Immune Cell Function and Interaction
- Cytomegalovirus and herpesvirus research
- SARS-CoV-2 and COVID-19 Research
- Bacteriophages and microbial interactions
- Viral-associated cancers and disorders
- Cellular transport and secretion
- Phagocytosis and Immune Regulation
- RNA Interference and Gene Delivery
- Cancer Research and Treatments
- Glycosylation and Glycoproteins Research
Inserm
2011-2025
CEA Paris-Saclay
2020-2025
Commissariat à l'Énergie Atomique et aux Énergies Alternatives
2011-2025
Université Paris-Saclay
2020-2025
Infectious Disease Models and Innovative Therapies
2022-2025
Hôpital Saint-Louis
2007-2021
Institut de Biologie Intégrative de la Cellule
2021
CEA Paris-Saclay - Etablissement de Saclay
2021
Université Paris Cité
2010-2020
Centre National de la Recherche Scientifique
2009-2020
An unprecedented epidemic of chikungunya virus (CHIKV) infection recently started in countries the Indian Ocean area, causing an acute and painful syndrome with strong fever, asthenia, skin rash, polyarthritis, lethal cases encephalitis. The basis for disease tropism CHIKV remain unknown. Here, we describe replication characteristics recent clinical strains. Human epithelial endothelial cells, primary fibroblasts and, to a lesser extent, monocyte-derived macrophages, were susceptible allowed...
ZIKA virus (ZIKV) is an emerging pathogen responsible for neurological disorders and congenital microcephaly. However, the molecular basis ZIKV neurotropism remains poorly understood. Here, we show that Axl expressed in human microglia astrocytes developing brain it mediates infection of glial cells. Axl-mediated entry requires ligand Gas6, which bridges particles to Following binding, internalized through clathrin-mediated endocytosis traffics Rab5+ endosomes establish productive infection....
The endosomal sorting complex ESCRT-III, which is formed by the structurally related CHMP proteins, engaged HIV-1 to promote viral budding. Here we show that progressive truncations into C-terminal acidic domains of proteins trigger an increasingly robust anti-HIV budding activity. Together with biochemical evidence for specific intramolecular interactions between basic and halves CHMP3 CHMP4B, these results suggest are autoinhibitory. half also interacts endosome-associated ubiquitin...
Abstract Motivation: Post-translational modification by the Small Ubiquitin-like Modifier (SUMO) proteins, a process termed SUMOylation, is involved in many fundamental cellular processes. SUMO proteins are conjugated to protein substrate, creating an interface for recruitment of cofactors harboring SUMO-interacting motifs (SIMs). Mapping both SUMO-conjugation sites and SIMs required study functional consequence SUMOylation. To define best candidate experimental validation we designed JASSA,...
LEDGF/p75 (LEDGF) is the main cellular cofactor of HIV-1 integrase (IN). It acts as a tethering factor for IN, and targets integration HIV in actively transcribed gene regions chromatin. A recently developed class IN allosteric inhibitors can inhibit LEDGF-IN interaction.
Nef is a virulence factor of HIV-1 and other primate lentiviruses that crucial for rapid progression to AIDS. In cell culture, increases the infectivity progeny virions by an unknown mechanism. We now show dynamin 2 (Dyn2), key regulator vesicular trafficking, binding partner required its ability increase viral infectivity. Dominant-negative Dyn2 or depletion small interfering RNA potently inhibited effect on Furthermore, in Dyn2-depleted cells, this function could be rescued ectopically...
Abstract The rate of HIV-1 gene expression is a key step that determines the kinetics virus spread and AIDS progression. Viral entry were described to be determinants for cell permissiveness HIV. Recent reports highlighted involvement miRNA in regulating replication post-transcriptionally. In this study we explored role cellular factors required miRNA-mediated mRNA translational inhibition expression. Here show mRNAs associate co-localize with components RNA Induced Silencing Complex (RISC),...
ABSTRACT The live attenuated yellow fever virus (YFV) vaccine 17D stands as a “gold standard” for successful vaccine. was developed empirically by passaging the wild-type Asibi strain in mouse and chicken embryo tissues. Despite its immense success, molecular determinants virulence attenuation immunogenicity of are poorly understood. evolved several mutations genome, most which lie within envelope (E) protein. Given major role played YFV E protein during entry, it has been hypothesized that...
Dengue virus (DENV) is a mosquito-borne flavivirus responsible for dengue disease, major human health concern which no specific therapies are available. Like other viruses, DENV relies heavily on the host cellular machinery productive infection. In this study, we performed genome-wide CRISPR-Cas9 screen using haploid HAP1 cells to identify genes important We identified DPM1 and -3, two subunits of endoplasmic reticulum (ER) resident dolichol-phosphate mannose synthase (DPMS) complex, as...
The human acute monocytic leukemia (AML) THP-1 cell line is widely used as a model to study the functions of monocyte-derived macrophages, including their interplay with significant pathogens such immunodeficiency virus (HIV). Compared other immortalized lines myeloid origin, cells retain many intact inflammatory signaling pathways and display phenotypic characteristics that more closely resemble those primary monocytes, ability differentiate into macrophages when treated...
HIV-1 integrase (IN) orchestrates the integration of reverse transcribed viral cDNA into host cell genome and participates also in other steps replication. Cellular factors assist IN performing its multiple functions, post-translational modifications contribute to modulate activities. Here, we show that is modified by SUMO proteins phylogenetically conserved SUMOylation consensus motifs represent major acceptor sites. Viruses harboring site mutants displayed a replication defect was mapped...
The human T-lymphotropic virus type I oncoprotein Tax is critical for T-cell transformation, acting mainly through nuclear factor kappa B essential modulator (NEMO) binding and subsequent factor-κB activation. localizes to bodies the centrosome subjected ubiquitylation small ubiquitin-like modifier (SUMO)ylation, which are both necessary complete transcriptional Using photoconvertible fluorophore Dendra-2 coupled with live video confocal microscopy, we show first time that same molecule...
ABSTRACT Nef is a human immunodeficiency virus type 1 (HIV-1) auxiliary protein that plays an important role in replication and the onset of acquired immunodeficiency. Although known functions might explain its contribution to HIV-1-associated pathogenesis, how increases infectivity still open question. In vitro , Nef-deleted viruses have defect prevents efficient completion early steps replication. We previously shown this restriction not due absence viral particles. Rather, loss function...
Genomic integration, an obligate step in the HIV-1 replication cycle, is blocked by integrase inhibitor raltegravir. A consequence excess of unintegrated viral DNA genomes, which undergo intramolecular ligation and accumulate as 2-LTR circles. These circularized genomes are also reliably observed vivo absence antiviral therapy they persist non-dividing cells. However, have long been considered dead-end products that not precursors to integration further propagation.Here, we show raltegravir...
Abstract SAMHD1 is a cellular triphosphohydrolase (dNTPase) proposed to inhibit HIV-1 reverse transcription in non-cycling immune cells by limiting the supply of dNTP substrates. Yet, phosphorylation T592 downregulates antiviral activity, but not its dNTPase function, implying that additional mechanisms contribute viral restriction. Here, we show SUMOylated on residue K595, modification relies presence proximal SUMO-interacting motif (SIM). Loss K595 SUMOylation suppresses restriction...
Abstract Human immunodeficiency virus type 1 (HIV-1) efficiently replicates in dividing and non-dividing cells. However, HIV-1 infection is blocked at an early post-entry step quiescent CD4+ T cells vitro . The molecular basis of this restriction still poorly understood. Here, we show that cells, incoming sub-viral complexes concentrate stably reside the centrosome for several weeks. Upon cell activation, viral replication resumes leading to gene expression. Thus, can persist as a stable,...
Background Although viral RNA constitutes the majority of nucleic acids packaged in virions, a late occurring step reverse transcription leads to presence infectious cDNA foamy virus particles. This peculiarity distinguishes them from rest retroviral family. Principal Findings To evaluate respective contribution these replication viruses, their fate was studied by real-time PCR and RT-PCR early after infection, or absence AZT. We found that an step, which occurs during first hours...