- Rabies epidemiology and control
- Viral Infections and Vectors
- Viral Infections and Outbreaks Research
- Virology and Viral Diseases
- Microbial infections and disease research
- Streptococcal Infections and Treatments
- SARS-CoV-2 and COVID-19 Research
- Long-Term Effects of COVID-19
- Poxvirus research and outbreaks
- Venomous Animal Envenomation and Studies
- Olfactory and Sensory Function Studies
- Bacteriophages and microbial interactions
- Immune responses and vaccinations
- Toxoplasma gondii Research Studies
- Neuroinflammation and Neurodegeneration Mechanisms
- Mosquito-borne diseases and control
- Immune Response and Inflammation
- Viral gastroenteritis research and epidemiology
- Respiratory viral infections research
- Viral Infectious Diseases and Gene Expression in Insects
- Plant Virus Research Studies
- Cystic Fibrosis Research Advances
- Infectious Encephalopathies and Encephalitis
- interferon and immune responses
- Advanced Biosensing Techniques and Applications
Université Paris Cité
2012-2024
Institut Pasteur
2014-2024
The University of Melbourne
2019
Inserm
2018
Institut Cochin
2018
Centre National de la Recherche Scientifique
2018
Centre de Coopération Internationale en Recherche Agronomique pour le Développement
2018
Université de Reims Champagne-Ardenne
2018
Délégation Paris 7
2012-2013
Sorbonne Paris Cité
2012-2013
Whereas recent investigations have revealed viral, inflammatory, and vascular factors involved in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lung pathogenesis, the pathophysiology of neurological disorders disease 2019 (COVID-19) remains poorly understood. Olfactory taste dysfunction are common COVID-19, especially mildly symptomatic patients. Here, we conducted a virologic, molecular, cellular study olfactory neuroepithelium seven patients with COVID-19 presenting loss...
Understanding how SARS-CoV-2 spreads within the respiratory tract is important to define parameters controlling severity of COVID-19. Here we examine functional and structural consequences infection in a reconstructed human bronchial epithelium model. replication causes transient decrease epithelial barrier function disruption tight junctions, though viral particle crossing remains limited. Rather, leads rapid loss ciliary layer, characterized at ultrastructural level by axoneme...
Abstract Currently circulating SARS-CoV-2 variants have acquired convergent mutations at hot spots in the receptor-binding domain 1 (RBD) of spike protein. The effects these on viral infection and transmission efficacy vaccines therapies remains poorly understood. Here we demonstrate that recently emerged BQ.1.1 XBB.1.5 bind host ACE2 with high affinity promote membrane fusion more efficiently than earlier Omicron variants. Structures BQ.1.1, XBB.1 BN.1 RBDs bound to fragment antigen-binding...
Rabies is a progressively fatal and incurable viral encephalitis caused by lyssavirus infection. Almost all of the 55 000 annual rabies deaths in humans result from infection with dog viruses (RABV). Despite importance for human health, little known about spread RABV populations, patterns biodiversity have only been studied limited geographical space. To address these questions on global scale, we sequenced 62 new isolates performed an extensive comparative analysis gene sequence data,...
Lyssaviruses are RNA viruses with single-strand, negative-sense genomes responsible for rabies-like diseases in mammals. To date, genomic and evolutionary studies have most often utilized partial genome sequences, particularly of the nucleoprotein glycoprotein genes, little consideration genome-scale evolution. Herein, we report first analysis using complete sequences all recognised lyssavirus genotypes, including 14 new field isolates from 6 genotypes one genotype that is completely...
Abstract Anosmia was identified as a hallmark of COVID-19 early in the pandemic, however, with emergence variants concern, clinical profile induced by SARS-CoV-2 infection has changed, anosmia being less frequent. Here, we assessed clinical, olfactory and neuroinflammatory conditions golden hamsters infected original Wuhan strain, its isogenic ORF7-deletion mutant three variants: Gamma, Delta, Omicron/BA.1. We show that animals develop variant-dependent disease including anosmia, ORF7...
RNA viruses of the family Rhabdoviridae include arthropod-borne agents that infect plants, fish and mammals, also a variety non-vector-borne mammalian viruses. Herein is presented molecular phylogenetic analysis, largest undertaken to date, 56 rhabdoviruses, including 20 which are currently unassigned or assigned as tentative species within Rhabdoviridae. Degenerate primers targeting region block III L polymerase gene were defined used for RT-PCR amplification sequencing. A...
European bat lyssaviruses types 1 and 2 (EBLV-1 EBLV-2) are widespread in Europe, although little is known of their evolutionary history. We undertook a comprehensive sequence analysis to infer the selection pressures, rates nucleotide substitution, age genetic diversity, geographical origin, population growth EBLV-1. Our study encompassed data from 12 countries collected over time span 35 years focused on glycoprotein (G) nucleoprotein (N) genes. show that two subtypes EBLV-1--EBLV-1a...
Abstract We identified 2 cases of European bat lyssavirus subtype 1 transmission to domestic carnivores (cats) in France. Bat-to-cat is suspected. Low amounts virus antigen cat brain made diagnosis difficult.
Background. Rabies virus (RABV) causes rabies disease resulting in >55 000 human deaths/year. The multifunctional RABV P-protein has essential roles genome replication, and forms interactions with cellular STAT proteins that are thought to underlie viral antagonism of interferon-dependent immunity. However, the molecular details P-protein-STAT interaction, its importance unresolved.
Article12 July 2021Open Access Source DataTransparent process Attenuation of clinical and immunological outcomes during SARS-CoV-2 infection by ivermectin Guilherme Dias de Melo orcid.org/0000-0003-0747-7760 Lyssavirus Epidemiology Neuropathology Unit, Institut Pasteur, Paris, France Search for more papers this author Françoise Lazarini orcid.org/0000-0001-5572-6982 Perception Memory CNRS UMR 3571, Florence Larrous orcid.org/0000-0003-0881-4263 Lena Feige Etienne Kornobis Biomics...
Rabies infection is nearly 100% lethal if untreated and kills more than 50,000 people annually, many of them children. Existing rabies vaccines target the virus glycoprotein (RABV-G) but generate short-lived immune responses, likely because protein heterogeneous under physiological conditions. Here, we report 3.39 Å cryo–electron microscopy structure trimeric, prefusion RABV-G complexed with RVA122, a potently neutralizing human antibody. RVA122 binds to quaternary epitope at top RABV-G,...
ABSTRACT The rabies virus (RABV) phosphoprotein P is a multifunctional protein: it plays an essential role in viral transcription and replication, addition, RABV has been identified as interferon antagonist. Here, yeast two-hybrid screen revealed that interacts with the focal adhesion kinase (FAK). binding involved 106-to-131 domain, corresponding to dimerization domain of C-terminal FAK containing proline-rich domains PRR2 PRR3. P-FAK interaction was confirmed infected cells by...
ABSTRACT The evasion of host innate immunity by Rabies virus , the prototype genus Lyssavirus depends on a unique mechanism selective targeting interferon-activated STAT proteins viral phosphoprotein (P-protein). However, immune strategies other lyssaviruses, including several lethal human pathogens, are unresolved. Here, we show that this is conserved between most distantly related members genus, providing important insights into pathogenesis and potential therapeutic lyssaviruses.
In addition to the commonly accepted importance of vampire bat in maintenance and transmission rabies virus (RABV) South America, RABV infection other species is widely evidenced, challenging their role viral cycle.To identify bioecological drivers circulation neotropical communities, we conducted a molecular serological survey on almost 1,000 bats from 30 species, 4-year longitudinal two colonies French Guiana. was molecularly detected common frugivorous bat. The sequences corresponded...
ABSTRACT Lyssaviruses, which are members of the Rhabdoviridae family, induce apoptosis, plays an important role in neuropathogenesis rabies. However, mechanisms by these viruses mediate neuronal apoptosis have not been elucidated. Here we demonstrate that early induction a model lyssavirus-infected neuroblastoma cells involves TRAIL-dependent pathway requiring activation caspase-8 but caspase-9 or caspase-10. The results caspase-3 and caspase-6, as shown increase cleavage specific caspase...
Abstract The matrix (M) protein of wild isolates rabies virus such as Tha (M-Tha) was previously shown to be able interact with RelAp43, a the NF-κB family, and efficiently suppress NF-κB-dependent reporter gene expression, in contrast vaccine strain SAD. Here, we analyze mechanisms involved RelAp43-M interaction. We demonstrate that central part M-Tha, specific C-terminal region RelAp43 are required for this Four differences corresponding amino acid sequences M-Tha M-SAD crucial interaction...
Rabies is a zoonotic disease that endemic in many parts of the developing world, especially Africa and Asia. However its epidemiology remains largely unappreciated much these regions, such as Nepal, where limited information available about spatiotemporal dynamics main etiological agent, rabies virus (RABV). In this study, we describe for first time phylogenetic diversity evolution RABV circulating well their geographical relationships within broader region. A total 24 new isolates obtained...
The definitive diagnosis of lyssavirus infection (including rabies) in animals and humans is based on laboratory confirmation. reference techniques for post-mortem rabies are still direct immunofluorescence virus isolation, but molecular techniques, such as polymerase chain reaction (PCR) methods, increasingly being used now constitute the principal tools diagnosing epidemiological analyses. However, it remains a key challenge to obtain relevant specificity sensitivity with these while...
At the crossroad between NF-κB and MAPK pathways, ternary complex composed of p105, ABIN2 TPL2 is essential for host cell response to pathogens. The matrix protein (M) field isolates rabies virus was previously shown disturb signaling induced by RelAp43, a close RelA/p65. Here, we investigated how M disturbs pathway in RelAp43-dependant manner potential involvement this mechanism. Using tandem affinity purification coupled with mass spectrometry approach, show that RelAp43 interacts...
Abstract Rabies virus (RABV) causes fatal encephalitis in more than 59,000 people yearly. Upon the bite of an infected animal, development clinical disease can be prevented with post-exposure prophylaxis (PEP), which includes administration immunoglobulin (RIG). However, high cost and limited availability serum-derived RIG severely hamper its wide use resource-limited countries. A safe low-cost alternative is provided by using broadly neutralizing monoclonal antibodies (bnAbs). Here we...
Article18 September 2020Open Access Transparent process A combination of two human monoclonal antibodies cures symptomatic rabies Guilherme Dias de Melo orcid.org/0000-0003-0747-7760 Lyssavirus Epidemiology and Neuropathology Unit, Institut Pasteur, Paris, France Search for more papers by this author Florian Sonthonnax orcid.org/0000-0003-4777-7274 Sorbonne-Paris Cité, Cellule Université Paris-Diderot, Gabriel Lepousez Perception Memory Grégory Jouvion Experimental INSERM, Pathophysiology...
ABSTRACT The rapid and accurate identification of pathogens is critical in the control infectious disease. To this end, we analyzed capacity for viral detection a newly described high-density resequencing microarray (RMA), termed PathogenID, which was designed multiple pathogen using database similarity searching. We focused on one largest most diverse families to date, family Rhabdoviridae . demonstrate that approach has potential identify both known related viruses precise sequence...
To evade immunity, many viruses express interferon antagonists that target STAT transcription factors as a major component of pathogenesis. Because lack direct structural data, these interfaces are poorly understood. We report the analysis full-length STAT1 binding to an antagonist human pathogenic virus. The interface revealed by transferred cross-saturation NMR is complex, involving multiple regions in both viral and cellular proteins. Molecular mapping analysis, combined with biophysical...
The devastating coronavirus disease 2019 (COVID-19) pandemic, due to SARS-CoV-2, has caused more than 47 million confirmed cases and 1.2 human deaths around the globe 1 , most of severe COVID-19 in humans are associated with neurological symptoms such as anosmia ageusia, uncontrolled inflammatory immune response 2–5 . Among therapeutic options 6–8 use anti-parasitic drug ivermectin (IVM), been proposed, given its possible anti-SARS-CoV-2 activity 9 Ivermectin is a positive allosteric...