A5009783412- Virus-based gene therapy research
- Chemokine receptors and signaling
- Cancer Mechanisms and Therapy
- RNA Research and Splicing
- RNA Interference and Gene Delivery
- Nuclear Structure and Function
- Immunotherapy and Immune Responses
- Autophagy in Disease and Therapy
- Viral Infectious Diseases and Gene Expression in Insects
- Cytomegalovirus and herpesvirus research
- SARS-CoV-2 and COVID-19 Research
- CAR-T cell therapy research
- Animal Virus Infections Studies
- HIV Research and Treatment
- RNA regulation and disease
- CRISPR and Genetic Engineering
- Viral gastroenteritis research and epidemiology
- Herpesvirus Infections and Treatments
- Cellular transport and secretion
- Retinoids in leukemia and cellular processes
- Viral-associated cancers and disorders
- Protein Degradation and Inhibitors
- COVID-19 Clinical Research Studies
- Genomics and Chromatin Dynamics
- Virology and Viral Diseases
Centre National de la Recherche Scientifique
2016-2025
Université de Bordeaux
2016-2025
Institut Polytechnique de Bordeaux
2015-2025
Laboratoire de Microbiologie Fondamentale et Pathogénicité
2012-2024
Centre Hospitalier Universitaire de Bordeaux
2022
Leibniz Institute of Virology (LIV)
2000-2013
Institut de Génétique Moléculaire de Montpellier
2005-2010
Université de Montpellier
2007-2010
Scripps Research Institute
2001-2006
Universität Hamburg
2000-2004
In contrast to enveloped viruses, the mechanisms involved in membrane penetration by nonenveloped viruses are not as well understood. these studies, we determined relationship between adenovirus (Ad) capsid disassembly and development of lytic activity. Exposure low pH or heating induced conformational changes wild-type Ad but temperature-sensitive (ts1) particles that fail escape early endosome. Wild-type ts1 permeabilized model membranes (liposomes) facilitated cytosolic delivery a...
<h3>Background</h3> <i>Escherichia coli</i> strains harbouring the <i>pks</i> island (<i>pks</i>+ <i>E. coli</i>) are often seen in human colorectal tumours and have a carcinogenic effect independent of inflammation an AOM/IL-10<sup>−/−</sup> (azoxymethane/interleukin) mouse model. <h3>Objective</h3> To investigate mechanism sustaining <i>pks</i>+ coli</i>-induced carcinogenesis. <h3>Method</h3> Underlying cell processes were investigated <i>in vitro</i> vivo</i> (xenograft model) using...
We present a systematic comparison of three modules that enhance expression from retroviral gene transfer vectors at posttranscriptional level: (i) splice signals (SS) create an intron in the 5' untranslated region; (ii) constitutive RNA transport elements (CTE), originally discovered D-type retroviruses; and (iii) regulatory element woodchuck hepatitis virus (WPRE). Here we show enhancement depends not only on specific element, but also interest, implying context-dependent activity...
Correlative light and electron microscopy (CLEM) is an emerging technique which combines functional information provided by fluorescence (FM) with the high-resolution structural of (EM). So far, correlative cryo frozen-hydrated samples has not reached better than micrometre range accuracy. Here, a method presented that enables correlation between fluorescently tagged proteins tomography (cryoET) data nanometre precision. Specifically, thin areas vitrified whole cells are examined (cryoFM)...
Although it has been known for 50 years that adenoviruses (Ads) interact with erythrocytes ex vivo, the molecular and structural basis this interaction, which serendipitously exploited diagnostic tests, is unknown. In study, we characterized interaction between unrelated Ad serotypes, human 5 (HAd5) 37 (HAd37), canine 2 (CAV-2). While these serotypes agglutinate erythrocytes, they use different receptors, have tropisms and/or infect species. Using molecular, biochemical, transgenic...
Viruses use cellular machinery to enter and infect cells. In this study we address the cell entry mechanisms of nonenveloped adenoviruses (Ads). We show that protein VI, an internal capsid protein, is rapidly exposed after surface attachment internalization remains partially associated with during intracellular transport. found a PPxY motif within VI recruits Nedd4 E3 ubiquitin ligases bind ubiquitylate VI. further involved in rapid, microtubule-dependent movement Ads mutated can efficiently...
A key step in adenovirus cell entry is viral penetration of cellular membranes to gain access the cytoplasm and deliver genome nucleus. Yet little known about this important event adenoviral life cycle. Using cytosolic protein galectin-3 (gal3) as a marker membrane rupture with both live- fixed-cell imaging, we demonstrate that majority instances, exposure pVI recruitment gal3 ruptured occur early at or near surface minimally EEA-1-positive (EEA-1(+)) endosomes LAMP-1(+) late...
In vertebrates the microtubule-associated proteins MAP6 and MAP6d1 stabilize cold-resistant microtubules. Cilia flagella have cold-stable microtubules but not been identified in these organelles. Here, we describe TbSAXO as first MAP6-related protein to be a protozoan, Trypanosoma brucei. Using heterologous expression system, show that is microtubule stabilizing protein. Furthermore identify domains of responsible for binding they share homologies with microtubule-stabilizing Mn proteins. We...
Cells employ active measures to restrict infection by pathogens, even prior responses from the innate and humoral immune defenses. In this context selective autophagy is activated upon pathogen induced membrane rupture sequester deliver fragments their contents for lysosomal degradation. Adenoviruses, which breach endosome entry, escape fate penetrating into cytosol autophagosome sequestration of ruptured endosome. We show that virus damage recognized through Galectin-8 sequesters receptors...
ABSTRACT Adenoviruses are nonenveloped viruses with an ∼36-kb double-stranded DNA genome that replicate in the nucleus. Protein VII, abundant structural component of adenovirus core is strongly associated DNA, imported into nucleus contemporaneously shortly after virus infection and may promote import. In this study, we evaluated whether protein VII uses specific receptor-mediated mechanisms for import We found it contains potent nuclear localization signal (NLS) activity by transfection...
Gene expression of DNA viruses requires nuclear import the viral genome. Human Adenoviruses (Ads), like most viruses, encode factors within early transcription units promoting their own gene and counteracting cellular antiviral defense mechanisms. The transcriptional repressor Daxx prevents through assembly repressive chromatin remodeling complexes targeting incoming genomes. However, it has remained unclear how initial activation adenoviral genome is achieved. Here we show that mediated...
In this study, we characterized the molecular basis for binding of adenovirus (AdV) to cytoplasmic face nuclear pore complex (NPC), a key step during delivery viral genome into nucleus. We used RNA interference (RNAi) deplete cells either Nup214 or Nup358, two major Phe-Gly (FG) repeat nucleoporins localized on side NPC, and evaluated impact hexon AdV infection. The accumulation purified trimers partially disassembled at envelope (NE) was observed in digitonin-permeabilized absence cytosolic...
Disassembly of the nuclear lamina is essential in mitosis and apoptosis requiring multiple coordinated enzymatic activities nucleus cytoplasm. Activation coordination different poorly understood moreover complicated as some factors translocate between cytoplasm preparatory phases. Here we used ability parvoviruses to induce membrane breakdown understand triggers key mitotic enzymes. Nuclear envelope disintegration was shown upon infection, microinjection but also their application...
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections initiate in the bronchi of upper tract and are able to disseminate lower tract, where can cause an distress with a high degree mortality elderly patients. We used reconstituted primary bronchial epithelia from adult child donors follow SARS-CoV-2 infection dynamics. show that, donors, multiciliated cells spread within 24 48 h throughout whole epithelia. Syncytia formed ciliated basal appeared at apical side 3 4 d were...
Previous work has shown that the transport of some small protein cargoes through nuclear pore complex (NPC) can occur in vitro absence nucleoside triphosphate hydrolysis. We now demonstrate importin alpha/beta and transportin import pathways, efficient large proteins, contrast to smaller requires hydrolyzable GTP GTPase Ran. Morphological biochemical analysis indicates presence Ran allows cargo efficiently cross central regions NPC. further this function RanGTP at least partly involves its...
Viruses must deliver their genomes to host cells ensure replication and propagation. Characterizing the fate of viral is crucial understand life cycle virus-derived vector tools. Here, we integrated ANCHOR3 system, an in vivo DNA-tagging technology, into adenoviral genome for real-time detection. tagging permitted visualization incoming at onset infection replicated late phases infection. Using this show attachment condensed chromosomes during mitosis, identifying mechanism as a mode...
Intracellular pathogens cause membrane distortion and damage as they enter host cells. Cells perceive these alterations danger signals respond by activating autophagy. This response has primarily been studied during bacterial invasion, only rarely in viral infections. Here, we investigate the cellular to adenoviral entry. Adenoviruses their vector derivatives, that are an important vaccine platform against SARS-CoV-2, cell endocytosis followed lysis of endosomal membrane. We previously...
Retroviral gene expression requires nuclear export and translation of incompletely spliced RNA. In the case human immunodeficiency virus (HIV), this is facilitated by viral Rev protein binding to its cognate RNA response element (RRE), while other retroviruses contain constitutive transport elements (CTE) cellular factors. These CTE can substitute for HIV-1 Rev/RRE system, albeit with reduced efficiency. Here, we show that multimeric copies restore levels comparable or higher than in various...