A5030498342- Virus-based gene therapy research
- Cytomegalovirus and herpesvirus research
- Crystallization and Solubility Studies
- X-ray Diffraction in Crystallography
- CRISPR and Genetic Engineering
- Telomeres, Telomerase, and Senescence
- RNA Research and Splicing
- RNA and protein synthesis mechanisms
- Viral Infectious Diseases and Gene Expression in Insects
- Herpesvirus Infections and Treatments
- Chromosomal and Genetic Variations
- DNA Repair Mechanisms
- Advanced biosensing and bioanalysis techniques
- Porphyrin and Phthalocyanine Chemistry
- Genetics, Aging, and Longevity in Model Organisms
- Biochemical and Molecular Research
- RNA regulation and disease
- HIV/AIDS drug development and treatment
- Viral Infections and Immunology Research
- Infectious Diseases and Mycology
- Animal Genetics and Reproduction
- Cancer Research and Treatments
- Genomics and Chromatin Dynamics
- Virology and Viral Diseases
- Bacteriophages and microbial interactions
Institut des Technologies Avancées en sciences du Vivant
2014-2020
Advanced Life Science Institute
2018-2020
Université de Toulouse
2010-2018
Université Toulouse III - Paul Sabatier
2012-2018
Centre National de la Recherche Scientifique
2010-2018
Université de Montréal
2008-2017
Laboratoire de Biologie Moléculaire des Eucaryotes
2010-2017
Institut Municipal d'Assistència Sanitària
2008
Genome dynamics are intimately linked to the regulation of gene expression, most fundamental mechanism in biology, yet we still do not know whether very process transcription drives spatial organization at specific loci. Here, have optimized ANCHOR/ParB DNA-labeling system for real-time imaging a single-copy, estrogen-inducible transgene human cells. Motion an ANCHOR3-tagged DNA locus was recorded same cell before and during appearance nascent MS2-labeled mRNA. We found that initiation by...
Chromosome breakage is a major threat to genome integrity. The most accurate way repair DNA double strand breaks (DSB) homologous recombination (HR) with an intact copy of the broken locus. Mobility has been seen increase during search for donor copy. Observing chromosome dynamics earlier steps HR, mainly resection from DSB ends that generates recombinogenic single strands, requires visualization system does not interfere process, and small relative few kilobases undergo processing. Current...
Transcripts containing expanded CNG repeats, which are found in several neuromuscular diseases, not exported from the nucleus and aggregate as ribonuclear inclusions by an unknown mechanism. Using MS2–GFP system, tethers fluorescent proteins to a specific mRNA, we followed dynamics of single CUG-repeat transcripts RNA aggregation living cells. Single with 145 CUG repeats dystrophia myotonica-protein kinase (DMPK) gene had reduced diffusion kinetics compared only five repeats. Fluorescence...
Human cytomegalovirus (HCMV) induces latent lifelong infections in all human populations. Between 30% and nearly 100% of individuals are affected depending on the geographic area socioeconomic conditions. The biology virus is difficult to explore due its extreme sophistication lack a pertinent animal model. Here, we present first application ANCHOR DNA labeling system herpesvirus, enabling real-time imaging direct monitoring HCMV infection replication living cells. composed protein (OR) that...
Human herpesviruses are latent opportunistic large dsDNA viruses that can have deleterious effect in immunocompromised patients by triggering life-threatening infections. Over the past years, different antivirals been developed against a variety of herpesviruses, including Acyclovir for herpes simplex (HSV1 and 2) ganciclovir letermovir human cytomegalovirus (hCMV). However, broad-spectrum inhibitors herpesvirus infections still missing. Here we report efficacy LAVR-289, new acyclic...
Adenoviruses are responsible for a range of pathologies, including respiratory infections in children, accounting 5-10% such cases. Although most adenovirus self-resolving, they can cause serious illness, particularly immunocompromised individuals. There is currently no approved treatment infections, although various therapeutic approaches under investigation, nucleoside analog inhibitors replication. However, these treatments have shown limited efficacy. In this study, we report on the...
Poxviruses are double-stranded DNA viruses including relevant zoonotic pathogens with high morbidity. Although African Swine Fever Virus (ASFV) belongs to the Asfarviridae family and is not strictly classified as a member of Poxviridae, both fall within same class Pokkesviricetes, which replicate in cytoplasm, some poxviruses pose potential biological warfare threats. Among compounds targeting these viruses, acyclic nucleoside phosphonate prodrugs, analogues inhibitors viral polymerases,...
Human papillomavirus (HPV) genomes replicate and partition as minichromosomes alongside host chromatin during persistent infection. However, it is difficult to monitor genome dynamics in living cells because the small compact will not easily tolerate expression cassettes. Here, we use ANCHOR™ technology detect HPV18 cells. We incorporated cis element from into late region of expressed ParB-GFP protein an HPV18-dependent replicon. The replicon contains replication origin viral transcriptional...
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...
Purpose: The Epstein–Barr virus (EBV)-associated cancer nasopharyngeal carcinoma (NPC) is rare in Europe and North America but a real public health problem some regions of the world, such as southern Asia, Africa, for Inuit populations. Due to anatomy location nasopharynx, surgery rarely used treat primary NPC cancers. Treatment by radiotherapy, combined or not with chemotherapy, are efficient tumors often do protect against fatal relapses metastases. Methods: Search new therapeutic...
The guanabenz derivative Sephin1 has recently been proposed to increase the levels of translation initiation factor 2 (eIF2α) phosphorylation by inhibiting dephosphorylation protein phosphatase 1 - GADD34 (PPP1R15A) complex. As eIF2α kinase R (PKR) is a prominent cellular antiviral pathway, we evaluated consequences treatment on virus replication. Our results provide evidence that downregulates replication human respiratory syncytial virus, measles adenovirus 5 enterovirus D68,...
New acyclic pyrimidine nucleoside phosphonate prodrugs with a 4-(2,4-diaminopyrimidin-6-yl)oxy-but-2-enyl]phosphonic acid skeleton (O-DAPy nucleobase) were prepared through convergent synthesis by olefin cross-metathesis as the key step. Several prodrug exhibited in vitro antiviral activity submicromolar or nanomolar range against varicella zoster virus (VZV), human cytomegalovirus (HCMV), herpes type 1 (HSV-1) and 2 (HSV-2), vaccinia (VV), good selective index (SI). Among them, analogue 9c...
Emerging and reemerging viruses pose significant public health threats, underscoring the urgent need for new antiviral drugs. Recently, a novel family of acyclic nucleoside phosphonates (ANP) composed 4-(2,4-diaminopyrimidin-6-yl)oxy-but-2-enyl phosphonic acid skeleton (O-DAPy nucleobase) has shown promise. Among these, LAVR-289 stands out its potent inhibitory effects against various DNA viruses. Despite efficacy, LAVR-289s poor water solubility hampers effective drug delivery. To address...
Telomerase can generate a novel telomere at DNA double-strand breaks (DSBs), an event called de novo addition. How this activity is suppressed remains unclear. Combining single-molecule imaging and deep sequencing, we show that the budding yeast telomerase RNA (TLC1 RNA) spatially segregated to nucleolus excluded from sites of repair in cell cycle-dependent manner. Although TLC1 accumulates nucleoplasm G1/S, Pif1 promotes localization G2/M. In presence DSBs, nucleolar most G2/M cells but...
Different nitroporphyrinoid derivatives were synthesized and studied as potential agents against human Cytomegalovirus. Interestingly, two nitrocorroles display strong activity Cytomegalovirus with IC50 < 0.5 μM. These compounds also possess antiproliferative activities without detected in vivo toxicity. Therefore, appear for the first time active that can be applied health.
Many steps in the baculovirus life cycle, from initial ingestion to subsequent infection of all larval cells, remain largely unknown; primarily because it has hitherto not been possible follow individual genomes and their lineages. Use ANCHORTM technology allows a high intensity fluorescent labelling DNA. When applied virus genome, is particles, overall course infection. This adapted enable Autographa californica Multiple NucleoPolyhedroVirus as first step its application other...
As a live biologic agent, oncolytic vaccinia virus has the ability to target and selectively amplify at tumor sites. We have previously reported that deletion of thymidine kinase ribonucleotide reductase genes in can increase safety efficacy virus. Here, allow direct visualization viral genome living cells, we incorporated ANCH sequence OR3-Santaka gene double-deleted Infection human cells with ANCHOR3-tagged enables quantification dynamics cells. The results show ANCHOR technology permits...
New generation of anti hCMV molecules: 29 fluorinated corroles were studied for their antiviral activity evaluation against human cytomegalovirus infection and maximum is achieved A<sub>2</sub>B-corroles with SI above 400.
We report the 2nd generation of seventeen A<sub>2</sub>B- and A<sub>3</sub>-substituted fluoronitrocorroles discovery optimized compounds with a selectivity index >200 against hCMV.
A series of 43 antiviral corrole-based molecules have been tested on myxoma virus (Lausanne-like T1MYXV strain). An autofluorescent MYXV, with an ANCHOR cassette, has used for the studies. A2B-fluorocorroles display various toxicities, from 40 being very toxic (CC50 = 1.7 μM) to nontoxic 38 > 50 μM), whereas A3-fluorocorroles, one three fluorine atoms, are not (with exception corroles 9, 10, and 22). In vitro, these compounds show a good selectivity index when alone. Corrole 35 seems be most...