A5022567237- Viral Infections and Outbreaks Research
- Viral Infections and Vectors
- Viral gastroenteritis research and epidemiology
- Hepatitis B Virus Studies
- Virology and Viral Diseases
- Mosquito-borne diseases and control
- Animal Virus Infections Studies
- HIV Research and Treatment
- Disaster Response and Management
- DNA and Nucleic Acid Chemistry
- Virus-based gene therapy research
- Respiratory viral infections research
- Bacteriophages and microbial interactions
- Herpesvirus Infections and Treatments
- DNA Repair Mechanisms
- Chemical Reactions and Isotopes
- Rabies epidemiology and control
- Animal Disease Management and Epidemiology
- RNA and protein synthesis mechanisms
- T-cell and Retrovirus Studies
- Genomics, phytochemicals, and oxidative stress
- Cancer-related molecular mechanisms research
- Resilience and Mental Health
- Hepatitis Viruses Studies and Epidemiology
- vaccines and immunoinformatics approaches
École Normale Supérieure de Lyon
2011-2023
Inserm
2011-2023
Université Claude Bernard Lyon 1
2011-2023
Centre National de la Recherche Scientifique
2011-2023
Centre International de Recherche en Infectiologie
2011-2023
Université de Lyon
2008-2014
Structure Fédérative de Recherche Biosciences
2005-2006
Philipps University of Marburg
1997-2001
State Research Center of Virology and Biotechnology VECTOR
1995-2000
Institute of Bioorganic Chemistry
1989
In the present study, we have investigated processing and maturation of envelope glycoprotein (GP) Ebola virus. When GP expressed from vaccinia virus vectors was analyzed by pulse-chase experiments, mature form two different precursors were identified. First, endoplasmic reticulum preGPer, full-length with oligomannosidic N-glycans, detected. preGPer (110 kDa) replaced Golgi-specific preGP (160 kDa), containing carbohydrates. finally converted proteolysis into GP1,2, which consisted...
To study the mechanisms underlying high pathogenicity of Ebola virus, we have established a system that allows recovery infectious virus from cloned cDNA and thus permits genetic manipulation. We created mutant in which editing site gene encoding envelope glycoprotein (GP) was eliminated. This no longer expressed nonstructural sGP. Synthesis GP increased, but most it accumulated endoplasmic reticulum as immature precursor. The significantly more cytotoxic than wild-type indicating...
During Ebola virus (EBOV) infection a significant amount of surface glycoprotein GP is shed from infected cells in soluble form due to cleavage by cellular metalloprotease TACE. Shed and non-structural secreted sGP, both expressed the same gene, have been detected blood human patients experimentally animals. In this study we demonstrate that could play particular role during EBOV infection. effect it binds activates non-infected dendritic macrophages inducing secretion pro- anti-inflammatory...
ABSTRACT Ebola virus (EBOV) protein VP35 is a double-stranded RNA (dsRNA) binding inhibitor of host interferon (IFN)-α/β responses that also functions as viral polymerase cofactor. Recent structural studies identified key features, including central basic patch, required for dsRNA activity. To address the functional significance these features EBOV replication and pathogenesis, two point mutations, K319A/R322A, abrogate activity severely impair its suppression IFN-α/β production were...
ABSTRACT The Nipah virus (NiV) phosphoprotein (P) gene encodes the C, P, V, and W proteins. W, have in common an amino-terminal domain sufficient to bind STAT1, inhibiting its interferon (IFN)-induced tyrosine phosphorylation. P is also essential for RNA-dependent RNA polymerase function. C encoded by alternate open reading frame (ORF) within domain. Mutations residues 81 113 of impaired cofactor function, as assessed a minireplicon assay, but these mutants retained STAT1 inhibitory residue...
Synthesis of the structural, surface glycoprotein (GP) Ebola virus (EBOV) is dependent on transcriptional RNA editing phenomenon. Editing results in insertion an extra adenosine by viral polymerase at site (7 consecutive template uridines) during transcription GP gene wild-type (EBOV/7U). In this study, we demonstrate that passage EBOV/7U Vero E6 cells appearance and rapid accumulation a variant (EBOV/8U) containing additional uridine genome. EBOV/8U outgrows eventually replaces EBOV 4-5...
Marburg virus (MARV) has a high fatality rate in humans, causing hemorrhagic fever characterized by massive viral replication and dysregulated inflammation. Here, we demonstrate that VP24 of MARV binds Kelch-like ECH-associated protein 1 (Keap1), negative regulator nuclear transcription factor erythroid-derived 2 (Nrf2). Binding to Keap1 Kelch domain releases Nrf2 from Keap1-mediated inhibition promoting persistent activation panoply cytoprotective genes implicated cellular responses...
In sharp contrast to human and nonhuman primates, guinea pigs some other mammals resist Ebola virus (EBOV) replication do not develop illness upon inoculation. However, serial passaging of EBOV in results a selection variants with high pathogenicity. this report, using reverse genetics approach, we demonstrate that dramatic increase pathogenicity is associated amino acid substitutions the structural protein VP24. We show although recombinant carrying wild-type VP24 impaired primary...
The nucleotide sequences of the L gene and 5′ trailer region Ebola virus strain Mayinga (subtype Zaire) have been determined, thus completing sequence genome. putative transcription start signal was identical to determined terminus mRNA (5′ GAGGAAGAUUAA) showed a high degree similarity corresponding regions other genes. 3′ end terminated with AUUAUAAAAAA, which is distinct from proposed termination signals genomic RNA consisted 676 nt revealed self-complementary at extreme may play an...
Nipah virus (NiV) is predicted to encode four proteins from its P gene (P, V, W, and C) via mRNA editing an alternate open reading frame. By use of specific antibodies, the expression C in NiV-infected cells has now been confirmed. Analysis P-gene transcripts shows a ratio P:V:W 1:1:1, but this differs over time, with greater proportions V W observed as infection progresses. Eighty-two percent are edited, up 11 G insertions observed. This exceptionally high frequency ensures proteins.
Ebolavirus (EBOV) is the etiological agent of a severe hemorrhagic fever with high mortality rate. The spike glycoprotein (GP) believed to be one major determinants virus pathogenicity. In this study, we demonstrated molecular mechanism responsible for downregulation surface markers caused by EBOV GP expression. We showed that expression mature on plasma membrane results in masking cellular proteins, including histocompatibility complex class I. Overexpression also certain antigenic epitopes...
VP30 is a phosphoprotein essential for the initiation of Ebola virus transcription. In this work, we have studied effect mutations in phosphorylation sites on ebolavirus replication cycle by using reverse genetics system. We demonstrate that involved reinitiation gene transcription and activity affected at sites.
The structural protein VP24 of Ebola virus (EBOV) is a determinant virulence in rodent models and possesses an interferon antagonist function. In this study, we investigate the role EBOV replication using RNA interference by small interfering to knock down expression virus-infected cells. We reveal that required for assembly viral nucleocapsids silencing prevents release EBOV.
Nipah virus (NiV) is a highly pathogenic, negative-strand RNA paramyxovirus that has recently emerged from flying foxes to cause serious human disease. We have analyzed the role of nonstructural NiV C protein in viral immunopathogenesis using recombinant lacking expression (NiVΔC). While wild-type was pathogenic hamster animal model, NiVΔC strongly attenuated. Replication followed by production NiV-specific antibodies and associated with higher recruitment inflammatory cells less intensive...
Ebola virus (EBOV) transcription is dependent on the phosphoprotein VP30, a component of viral nucleocapsid. VP30 phosphorylated at 2 serine residue clusters located N-terminal part protein. In this report, we have investigated role phosphorylation in EBOV replication using reverse genetics approach. effect, recombinant EBOVs with substituted either by nonphosphorylatable alanines or phosphorylation-mimicking aspartates were generated and characterized. We show that comparison to wild-type...