International Center for Infectiology Research

Sainte-Foy-lès-Lyon, France

International Center for Infectiology Research

Sainte-Foy-lès-Lyon, France
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Mathieu C.,Cornell University | Mathieu C.,International Center for Infectiology Research | Mathieu C.,French Institute of Health and Medical Research | Mathieu C.,French National Center for Scientific Research | And 19 more authors.
Journal of Virology | Year: 2015

Measles virus (MV) infection is undergoing resurgence and remains one of the leading causes of death among young children worldwide despite the availability of an effective measles vaccine. MV infects its target cells by coordinated action of the MV H and the fusion (F) envelope glycoprotein; upon receptor engagement by H, the prefusion F undergoes a structural transition, extending and inserting into the target cell membrane and then refolding into a postfusion structure that fuses the viral and cell membranes. By interfering with this structural transition of F, peptides derived from the heptad-repeat (HR) regions of F can potently inhibit MV infection at the entry stage. We show here that specific features of H's interaction with its receptors modulate the susceptibility of MV F to peptide fusion inhibitors. A higher concentration of inhibitory peptides is required to inhibit F-mediated fusion when H is engaged to its nectin-4 receptor than when H is engaged to its CD150 receptor. Peptide inhibition of F may be subverted by continued engagement of receptor by H, a finding that highlights the ongoing role of H-receptor interaction after F has been activated and that helps guide the design of more potent inhibitory peptides. Intranasal administration of these peptides results in peptide accumulation in the airway epithelium with minimal systemic levels of peptide and efficiently prevents MV infection in vivo in animal models. The results suggest an antiviral strategy for prophylaxis in vulnerable and/or immunocompromised hosts. © 2015, American Society for Microbiology.

Ramage T.,9 Quartier de la Glaciere | Martins-Simoes P.,University Claude Bernard Lyon 1 | Martins-Simoes P.,International Center for Infectiology Research | Mialdea G.,University Claude Bernard Lyon 1 | And 7 more authors.
European Journal of Taxonomy | Year: 2017

We report here on the taxonomic and molecular diversity of 10 929 terrestrial arthropod specimens, collected on four islands of the Society Archipelago, French Polynesia. The survey was part of the ‘SymbioCode Project’ that aims to establish the Society Islands as a natural laboratory in which to investigate the flux of bacterial symbionts (e.g., Wolbachia) and other genetic material among branches of the arthropod tree. The sample includes an estimated 1127 species, of which 1098 included at least one DNA-barcoded specimen and 29 were identified to species level using morphological traits only. Species counts based on molecular data emphasize that some groups have been understudied in this region and deserve more focused taxonomic effort, notably Diptera, Lepidoptera and Hymenoptera. Some taxa that were also subjected to morphological scrutiny reveal a consistent match between DNA and morphology-based species boundaries in 90% of the cases, with a larger than expected genetic diversity in the remaining 10%. Many species from this sample are new to this region or are undescribed. Some are under description, but many await inspection by motivated experts, who can use the online images or request access to ethanol-stored specimens. © Museum National d'Histoire Naturelle. All rights reserved.

Reynaud J.M.,International Center for Infectiology Research | Reynaud J.M.,French Institute of Health and Medical Research | Reynaud J.M.,French National Center for Scientific Research | Reynaud J.M.,University of Lyon | And 17 more authors.
Journal of Virology | Year: 2014

Human herpesvirus 6 (HHV-6) is widely spread in the human population and has been associated with several neuroinflammatory diseases, including multiple sclerosis. To develop a small-animal model of HHV-6 infection, we analyzed the susceptibility of several lines of transgenic mice expressing human CD46, identified as a receptor for HHV-6. We showed that HHV-6A (GS) infection results in the expression of viral transcripts in primary brain glial cultures from CD46-expressing mice, while HHV-6B (Z29) infection was inefficient. HHV-6A DNA persisted for up to 9 months in the brain of CD46-expressing mice but not in the nontransgenic littermates, whereas HHV-6B DNA levels decreased rapidly after infection in all mice. Persistence in the brain was observed with infectious but not heat-inactivated HHV-6A. Immunohistological studies revealed the presence of infiltrating lymphocytes in periventricular areas of the brain of HHV-6A-infected mice. Furthermore, HHV-6A stimulated the production of a panel of proinflammatory chemokines in primary brain glial cultures, including CCL2, CCL5, and CXCL10, and induced the expression of CCL5 in the brains of HHV-6A-infected mice. HHV-6A-induced production of chemokines in the primary glial cultures was dependent on the stimulation of toll-like receptor 9 (TLR9). Finally, HHV-6A induced signaling through human TLR9 as well, extending observations from the murine model to human infection. Altogether, this study presents a first murine model for HHV-6A-induced brain infection and suggests a role for TLR9 in the HHV-6A-initiated production of proinflammatory chemokines in the brain, opening novel perspectives for the study of virus-associated neuropathology. © 2014, American Society for Microbiology.

Horvat B.,International Center for Infectiology Research | Horvat B.,French Institute of Health and Medical Research | Horvat B.,French National Center for Scientific Research | Horvat B.,University of Lyon | And 3 more authors.
Current Opinion in Virology | Year: 2014

Progress in the identification of suitable animal models for human herpesvirus (HHV)-6A and HHV-6B infections has been slow. Recently, new models have been established, mainly for HHV-6A, which reproduce some pathological features seen in humans. Neuroinflammatory signs were observed in infected marmosets and CD46-transgenic mice; although viral replication was not prominent, persistence of viral DNA and specific immunologic responses were detected, suggesting an immune-mediated pathogenic mechanism. Pig-tailed macaques showed robust viral replication concomitant with acute-phase symptoms, and provided a model to study the effects of HHV-6A on AIDS progression. In humanized mice, viral replication was less evident, but infection led to T-cell alterations. Altogether, these recent developments have opened new perspectives for studying the pathogenic role of HHV-6A in humans. © 2014, Elsevier B.V. All rights reserved.

Baumert T.F.,University of Strasbourg | Baumert T.F.,Institut Universitaire de France | Schuster C.,University of Strasbourg | Cosset F.-L.,International Center for Infectiology Research | And 8 more authors.
Journal of Hepatology | Year: 2016

Following the discovery of the hepatitis C virus (HCV) more than 25 years ago the field has succeeded to develop methods that have changed the safety of blood products, understand the molecular virology, epidemiology and clinical disease of HCV, and identify specific targets for the development of direct-acting antivirals for HCV cure. Nevertheless, major clinical and scientific challenges remain: therapy is still only available to a fraction of infected patients worldwide and many patients remain undiagnosed and/or live in countries where therapy is unattainable. An urgently needed HCV vaccine to eradicate infection remains still elusive. Scientifically, major questions remain regarding the life cycle, pathogenesis and mechanisms of viral clearance and persistence. Addressing these challenges, this meeting report reviews key findings of the 22nd International Symposium on Hepatitis C Virus and Related Viruses in Strasbourg, France from October 9 to 13, 2015. © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Mathieu C.,International Center for Infectiology Research | Mathieu C.,French Institute of Health and Medical Research | Mathieu C.,French National Center for Scientific Research | Mathieu C.,University of Lyon | And 8 more authors.
Expert Review of Anti-Infective Therapy | Year: 2015

Hendra virus and Nipah virus are closely related, recently emerged zoonotic paramyxoviruses, belonging to the Henipavirus genus. Both viruses induce generalized vasculitis affecting particularly the respiratory tract and CNS. The exceptionally broad species tropism of Henipavirus, the high case fatality rate and person-to-person transmission associated with Nipah virus outbreaks emphasize the necessity of effective antiviral strategies for these intriguing threatening pathogens. Current therapeutic approaches, validated in animal models, target early steps in viral infection; they include the use of neutralizing virus-specific antibodies and blocking membrane fusion with peptides that bind the viral fusion protein. A better understanding of Henipavirus pathogenesis is critical for the further advancement of antiviral treatment, and we summarize here the recent progress in the field. © 2015 Informa UK, Ltd

Hammann P.,University of Strasbourg | Parmentier D.,University of Strasbourg | Cerciat M.,University of Strasbourg | Reimegard J.,Uppsala University | And 7 more authors.
Biochimie | Year: 2014

We have adapted a method to map cell surface proteins and to monitor the effect of specific regulatory RNAs on the surface composition of the bacteria. This method involves direct labeling of surface proteins of living bacteria using fluorescent dyes and a subsequent separation of the crude extract by 2D gel electrophoresis. The strategy yields a substantial enrichment in surface proteins over cytoplasmic proteins. We validated this method by monitoring the effect of the regulatory RNA MicA in Escherichia coli, which regulates the synthesis of several outer membrane proteins, and highlighted the role of Staphylococcus aureus RNAIII for the maintenance of cell wall integrity. © 2014 The Authors.

Nitzan M.,Hebrew University of Jerusalem | Fechter P.,University of Strasbourg | Peer A.,Hebrew University of Jerusalem | Altuvia Y.,Hebrew University of Jerusalem | And 9 more authors.
Nucleic Acids Research | Year: 2015

Cells adapt to environmental changes by efficiently adjusting gene expression programs. Staphylococcus aureus, an opportunistic pathogenic bacterium, switches between defensive and offensive modes in response to quorum sensing signal. We identified and studied the structural characteristics and dynamic properties of the core regulatory circuit governing this switch by deterministic and stochastic computational methods, as well as experimentally. This module, termed here Double Selector Switch (DSS), comprises the RNA regulator RNAIII and the transcription factor Rot, defining a double-layered switch involving both transcriptional and post-transcriptional regulations. It coordinates the inverse expression of two sets of target genes, immuno-modulators and exotoxins, expressed during the defensive and offensive modes, respectively. Our computational and experimental analyses show that the DSS guarantees fine-tuned coordination of the inverse expression of its two gene sets, tight regulation, and filtering of noisy signals. We also identified variants of this circuit in other bacterial systems, suggesting it is used as a molecular switch in various cellular contexts and offering its use as a template for an effective switching device in synthetic biology studies. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

PubMed | Center dInfectiologie Charles Merieux, Edouard Herriot Hospital, International Center for Infectiology Research and Gabriel Toure Hospital
Type: Journal Article | Journal: PloS one | Year: 2015

There are very limited data on children with pneumonia in Mali. The objective was to assess the etiology and factors associated with community-acquired pneumonia in hospitalized children <5 years of age in Mali.A prospective hospital-based case-control study was implemented in the Pediatric department of Gabriel Tour University Hospital at Bamako, Mali, between July 2011-December 2012. Cases were children with radiologically-confirmed pneumonia; Controls were hospitalized children without respiratory features, matched for age and period. Respiratory specimens, were collected to identify 19 viruses and 5 bacteria. Whole blood was collected from cases only. Factors associated with pneumonia were assessed by multivariate logistic regression.Overall, 118 cases and 98 controls were analyzed; 44.1% were female, median age was 11 months. Among pneumonia cases, 30.5% were hypoxemic at admission, mortality was 4.2%. Pneumonia cases differed from the controls regarding clinical signs and symptoms but not in terms of past medical history. Multivariate analysis of nasal swab findings disclosed that S. pneumoniae (adjusted odds ratio [aOR] = 3.4, 95% confidence interval [95% CI]: 1.6-7.0), human metapneumovirus (aOR = 17.2, 95% CI: 2.0-151.4), respiratory syncytial virus [RSV] (aOR = 7.4, 95% CI: 2.3-23.3), and influenza A virus (aOR = 10.7, 95% CI: 1.0-112.2) were associated with pneumonia, independently of patient age, gender, period, and other pathogens. Distribution of S. pneumoniae and RSV differed by season with higher rates of S. pneumoniae in January-June and of RSV in July-September. Pneumococcal serotypes 1 and 5 were more frequent in pneumonia cases than in the controls (P = 0.009, and P = 0.04, respectively).In this non-PCV population from Mali, pneumonia in children was mainly attributed to S. pneumoniae, RSV, human metapneumovirus, and influenza A virus. Increased pneumococcal conjugate vaccine coverage in children could significantly reduce the burden of pneumonia in sub-Saharan African countries.

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