Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Sexually transmitted viruses infect the genital and colorectal mucosa of the partner exposed to contaminated genital secretions through a wide range of mechanisms, dictated in part by the organization of the mucosa. Because understanding the modes of entry into the organism of viruses transmitted through sexual intercourse is a necessary prerequisite to the design of treatments to block those infections, in vitro modeling of the transmission is essential. The aim of this review is to present the models and methodologies available for the in vitro study of the interactions between viruses and mucosal tissue and for the preclinical evaluation of antiviral compounds, and to point out their advantages and limitations according to the question being studied.
ISSN: 0042-6822

Droits : http://creativecommons.org/licenses/by/
hal-01663650
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01663650
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01663650/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01663650/file/Frouard%20-%20In%20vitro%20models%20for%20deciphering.pdf
DOI : 10.1016/j.virol.2017.11.023

Éditeur(s) : HAL CCSD American Society for Microbiology
Résumé : International audience
Under physiological conditions, the liver sinusoidal endothelial cells (LSECs) mediate hepatic immune tolerance toward self or foreign antigens through constitutive expression of anti-inflammatory mediators. However, upon viral infection or Toll-like receptor 2 (TLR2) activation, LSECs can achieve proinflammatory functions, but their role in hepatic inflammation during acute viral hepatitis is unknown. Using the highly virulent mouse hepatitis virus type 3 (MHV3) and the attenuated variants 51.6-MHV3 and YAC-MHV3, exhibiting lower tropism for LSECs, we investigated in vivo and in vitro the consequence of LSEC infection on their proinflammatory profiles and the aggravation of acute hepatitis process. In vivo infection with virulent MHV3, in comparison to attenuated strains, resulted in fulminant hepatitis associated with higher hepatic viral load, tissue necrosis, and levels of inflammatory mediators and earlier recruitment of inflammatory cells. Such hepatic inflammatory disorders correlated with disturbed production of interleukin-10 (IL-10) and vascular factors by LSECs. We next showed in vitro that infection of LSECs by the virulent MHV3 strain altered their production of anti-inflammatory cytokines and promoted higher release of proinflammatory and procoagulant factors and earlier cell damage than infection by attenuated strains. This higher replication and proinflammatory activation in LSECs by the virulent MHV3 strain was associated with a specific activation of TLR2 signaling by the virus. We provide evidence that TLR2 activation of LSCEs by MHV3 is an aggravating factor of hepatic inflammation and correlates with the severity of hepatitis. Taken together, these results indicate that preservation of the immunotolerant properties of LSECs during acute viral hepatitis is imperative in order to limit hepatic inflammation and damage. IMPORTANCE Viral hepatitis B and C infections are serious health problems affecting over 350 million and 170 million people worldwide, respectively. It has been suggested that a balance between protection and liver damage mediated by the host's immune response during the acute phase of infection would be determinant in hepatitis outcome. Thus, it appears crucial to identify the factors that predispose in exacerbating liver inflammation to limit hepatocyte injury. Liver sinusoidal endothelial cells (LSECs) can express both anti- and proinflammatory functions, but their role in acute viral hepatitis has never been investigated. Using mouse hepatitis virus (MHV) infections as animal models of viral hepatitis, we report for the first time that in vitro and in vivo infection of LSECs by the pathogenic MHV3 serotype leads to a reversion of their intrinsic anti-inflammatory phenotype toward a proinflammatory profile as well to as disorders in vascular factors, correlating with the severity of hepatitis. These results highlight a new virus-promoted mechanism of exacerbation of liver inflammatory response during acute hepatitis.
ISSN: 0022-538X

hal-01390974
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01390974
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01390974/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01390974/file/Mouse%20Hepatitis%20Virus%20Infection_accepted.pdf
DOI : 10.1128/JVI.01069-16

Éditeur(s) : HAL CCSD Springer Verlag
Résumé : International audience
The purpose of this investigation was to characterize the management and prognosis of severe Pneumocystis jirovecii pneumonia (PJP) in human immunodeficiency virus (HIV)-negative patients. An observational cohort study of HIV-negative adults with PJP documented by bronchoalveolar lavage (BAL) through Gomori-Grocott staining or immunofluorescence, admitted to one intensive care unit (ICU) for acute respiratory failure, was undertaken. From 1990 to 2010, 70 patients (24 females, 46 males) were included, with a mean age of 58.6 ± 18.3 years. The mean Simplified Acute Physiology Score (SAPS)-II was 36.9 ± 20.4. Underlying conditions included hematologic malignancies (n = 21), vasculitis (n = 13), and solid tumors (n = 13). Most patients were receiving systemic corticosteroids (n = 63) and cytotoxic drugs (n = 51). Not a single patient received trimethoprim-sulfamethoxazole as PJP prophylaxis. Endotracheal intubation (ETI) was required in 42 patients (60.0 %), including 38 with acute respiratory distress syndrome (ARDS). In-ICU mortality was 52.9 % overall, reaching 80.9 % and 86.8 %, respectively, for patients who required ETI and for patients with ARDS. In the univariate analysis, in-ICU mortality was associated with SAPS-II (p = 0.0131), ARDS (p < 0.0001), shock (p < 0.0001), and herpes simplex virus (HSV) or cytomegalovirus (CMV) on BAL (p = 0.0031). In the multivariate analysis, only ARDS was associated with in-ICU mortality (odds ratio [OR] 23.4 [4.5-121.9], p < 0.0001). PJP in non-HIV patients remains a serious disease with high in-hospital mortality. Pulmonary co-infection with HSV or CMV may contribute to fatal outcome.
ISSN: 0934-9723

inserm-00872789
http://www.hal.inserm.fr/inserm-00872789
DOI : 10.1007/s10096-012-1730-7
PUBMED : 22930407

Éditeur(s) : HAL CCSD
Résumé : National audience
Introduction-objectifsBien que la prise en charge de personnes vivant avec le VIH (PVVIH) s’améliore globalement en Guyane, les disparités régionales et communautaires restent importantes. L’objectif est ici de décrire pour la première fois les caractéristiques épidémiologiques, spatiales et cliniques des PVVIH suivies en zones isolées. Matériels et MéthodesLes données présentées sont issues du suivi clinique réalisé en Centres Délocalisés de Prévention et de Soins (CDPS) de janvier 2014 à novembre 2015. Ces données ont été analysées et comparées aux données des PVVIH suivis dans les 3 centres hospitaliers de Guyane issues du logiciel Nadis®.Résultats 174 PVVIH ont étés pris en charge en CDPS et comparés à 2143 patients suivis sur le littoral. L’évolution du taux annuel de découvertes de séropositivité VIH montre une arrivée plus tardive mais particulièrement active en zones isolées par rapport au littoral, notamment chez les patients d’origine brésilienne (p<0,005). L’âge médian est de 43,8 ans, le sex ratio homme/femme est de 0,98. En zone isolées comme sur le littoral 1/3 des PVVIH sont dépistés tardivement (<200 CD4/mm3). Le succès virologiques après 6 mois de traitement est de 80% vs 88% sur le littoral (p=0,135), la moyenne des derniers CD4 (424 vs 569/mm3) est plus basse que sur le littoral (p<0,005) enfin la charge virale moyenne est plus élevée que sur le littoral (8960 vs 5317 copies /mL) (p<0,005). L’histoplasmose est la première cause d’infection opportuniste retrouvée. La répartition spatiale des patients suivis montre une incidence et prévalence de cas particulièrement élevée dans les villes frontalières charnières que constituent Maripasoula et Saint Georges de l’Oyapock. ConclusionLe caractère particulièrement actif et original de l’épidémie et les indicateurs de suivi moins bons que sur le littoral rappellent l’importance de compléter les moyens de la prise en charge des PVVIH en zones isolées en Guyane.
SFLS 2016 - XVIIème Congrès de la Société française de lutte contre le sida
Montpellier, France

inserm-01475954
http://www.hal.inserm.fr/inserm-01475954
http://www.hal.inserm.fr/inserm-01475954/document
http://www.hal.inserm.fr/inserm-01475954/file/2016%2C%20Mosnier%20-%20Les%20p%C3%A9riph%C3%A9ries%20de%20l%27%C3%A9pid%C3%A9mie%20de%20VIH%20en%20Guyane.pdf

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
IntroductionLeishmania RNA virus type 1 (LRV1) is an endosymbiont of some Leishmania (Vianna) species in South America. Presence of LRV1 in parasites exacerbates disease severity in animal models and humans, related to a disproportioned innate immune response, and is correlated with drug treatment failures in humans. Although the virus was identified decades ago, its genomic diversity has been overlooked until now.Methodology/Principles findingsWe subjected LRV1 strains from 19 L. (V.) guyanensis and one L. (V.) braziliensis isolates obtained from cutaneous leishmaniasis samples identified throughout French Guiana with next-generation sequencing and de novo sequence assembly. We generated and analyzed 24 unique LRV1 sequences over their full-length coding regions. Multiple alignment of these new sequences revealed variability (0.5%±23.5%) across the entire sequence except for highly conserved motifs within the 5' untranslated region. Phylogenetic analyses showed that viral genomes of L. (V.) guyanensis grouped into five distinct clusters. They further showed a species-dependent clustering between viral genomes of L. (V.) guyanensis and L. (V.) braziliensis, confirming a long-term co-evolutionary history. Noteworthy, we identified cases of multiple LRV1 infections in three of the 20 Leishmania isolates.Conclusions/SignificanceHere, we present the first-ever estimate of LRV1 genomic diversity that exists in Leishmania (V.) guyanensis parasites. Genetic characterization and phylogenetic analyses of these viruses has shed light on their evolutionary relationships. To our knowledge, this study is also the first to report cases of multiple LRV1 infections in some parasites. Finally, this work has made it possible to develop molecular tools for adequate identification and genotyping of LRV1 strains for diagnostic purposes. Given the suspected worsening role of LRV1 infection in the pathogenesis of human leishmaniasis, these data have a major impact from a clinical viewpoint and for the management of Leishmania-infected patients.
ISSN: 1935-2727

pasteur-01583523
https://hal-riip.archives-ouvertes.fr/pasteur-01583523
DOI : 10.1371/journal.pntd.0005764
PUBMED : 28715422

Éditeur(s) : HAL CCSD American Society of Tropical Medicine and Hygiene
Résumé : International audience
Histoplasmosis is the first cause of acquired immunodeficiency syndrome (AIDS) and AIDS-related deaths in French Guiana. Cohort data were used to determine whether primary prophylaxis with 100 mg itraconazole for patients with CD4 counts < 150/mm(3) was cost-effective with different scenarios. For a scenario where 12% of patients died, 60% were aware of their human immunodeficiency virus (HIV) infection and adherence was only 50%, primary prophylaxis would prevent 1 death and 9 cases of histoplasmosis for a cost of 36,792 Euros per averted death, 1,533 per life-year saved, 4,415 Euros per averted case, when only counting the costs of itraconazole prophylaxis. Taking into account the total costs of hospitalization showed that primary prophylaxis would allow a savings of 185,178 Euros per year. Even in a scenario of low adherence, primary prophylaxis would be cost-effective in French Guiana, and presumably in the rest of the Guianas and the Amazon.
ISSN: 0002-9637

inserm-00913886
http://www.hal.inserm.fr/inserm-00913886
http://www.hal.inserm.fr/inserm-00913886/document
http://www.hal.inserm.fr/inserm-00913886/file/2013_Nacher_-_Primary_prophylaxissur disseminated_histoplasmosis_in_HIV_patients_in_French_Guiana_a_cost_effectiveness_study.pdf
DOI : 10.4269/ajtmh.13-0082

Éditeur(s) : HAL CCSD Taylor & Francis
Résumé : International audience
The retroviral genome consists of an intron-containing transcript that has essential cytoplasmic functions in the infected cell. This viral transcript can escape splicing, circumvent the nuclear checkpoint mechanisms and be transported to the cytoplasm by hijacking the host machinery. Once in the cytoplasm, viral unspliced RNA acts as mRNA to be translated and as genomic RNA to be packaged into nascent viruses. The murine leukemia virus (MLV) is among the first retroviruses discovered and is classified as simple Retroviridae due to its minimal encoding capacity. The oncogenic and transduction abilities of MLV are extensively studied, whereas surprisingly the crucial step of its nuclear export has remained unsolved until 2014. Recent work has revealed the recruitment by MLV of the cellular NXF1/Tap-dependent pathway for export. Unconventionally, MLV uses of Tap to export both spliced and unspliced viral RNAs. Unlike other retroviruses, MLV does not harbor a unique RNA signal for export. Indeed, multiple sequences throughout the MLV genome appear to promote export of the unspliced MLV RNA. We review here the current understanding of the export mechanism and highlight the determinants that influence MLV export. As the molecular mechanism of MLV export is elucidated, we will gain insight into the contribution of the export pathway to the cytoplasmic fate of the viral RNA
ISSN: 1547-6286

hal-01217990
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01217990
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01217990/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01217990/file/Insights%20into%20the%20nuclear%20export%20of%20murine%20leukemia%20virus%20intron-containing%20RNA.pdf
DOI : 10.1080/15476286.2015.1065375

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
A retrospective cohort study was conducted on 1541 HIV-infected patients to determine variables associated with the incidence of herpes zoster. A single failure Cox model showed that herpes zoster incidence increased following the first 6 months of antiretroviral treatment adjusted hazard ratio (AHR)=5 (95%CI=2.6-9.2), P<0.001; in the >60 years age group AHR=2 (95%CI=1-4), P=0.04; in patients in the top CD8 quartile AHR=2.1 (95%CI=1.3-3.6), P<0.001; and in patients previously reported to use crack cocaine AHR=5.9, (95%CI=1.4-25), P=0.02. Herpes zoster incidence increased in patients with CD4 counts<500 per mm(3) and gradually declined since 1992-1996, with AHR=0.3 (95%CI=0.2-0.5), P<0.001 for the 1997-2002 period and AHR=0.24 (95%CI=0.14-0.4), P<0.001 for the 2002-2008 period. Contrary to what has been described elsewhere, there was no specific effect of protease inhibitors on herpes zoster incidence. The present study is the first to suggest that crack cocaine is associated with an increased incidence of herpes zoster. The neurological or immunological effects of crack are discussed.
ISSN: 1932-6203

inserm-00921158
http://www.hal.inserm.fr/inserm-00921158
http://www.hal.inserm.fr/inserm-00921158/document
http://www.hal.inserm.fr/inserm-00921158/file/2013_Nacher_-_Predictive_factorssur herpes_zoster.pdf
DOI : 10.1371/journal.pone.0080187

Éditeur(s) : HAL CCSD Oxford University Press (OUP)
Résumé : International audience
OBJECTIVES: The aims of the study were to assess in patients with advanced HIV disease receiving antiretroviral therapy (ART) intensification with enfuvirtide (i) resistance at virological failure (VF), (ii) impact of baseline tropism on immunovirological response, and (iii) HIV-1 DNA tropism evolution during ART. METHODS: The ANRS 130 APOLLO randomized trial evaluated in naive patients the immunovirological impact of standard ART without (control arm) or with enfuvirtide. Tropism was determined on RNA and DNA by V3-loop sequencing interpreted using the Geno2Pheno algorithm. RESULTS: At baseline the median CD4 cell count was 30 cells/mm(3). Among the 170 patients assessable in this virological substudy, HIV-1 RNA tropism was as follows: 60% of viruses were R5 and 40% were R5X4/X4. HIV-1 DNA tropism was as follows: 54% were R5 and 46% were R5X4/X4. At week 24, 39% and 49% of patients experienced VF in the enfuvirtide and control arms, respectively. In the enfuvirtide arm, only resistance-associated mutations to enfuvirtide were detected. In the control arm, two patients displayed drug-resistant viruses at the time of VF. No impact of baseline tropism was observed on immunovirological response, regardless of the study arm. Among the 25 patients experiencing DNA tropism switch between baseline and week 24, 16 (64%) switched from R5 to R5X4/X4. These latter were mostly successfully suppressed patients receiving enfuvirtide and exhibiting poorer immunological response. CONCLUSIONS: Baseline RNA tropism had no impact on the immunovirological response. Drug resistance mutations were only detected for the fusion inhibitor. Finally, the mechanism of replenishment of the viral cellular reservoir with X4 viruses observed needs to be further analysed.
ISSN: 0305-7453

hal-00875130
https://hal.archives-ouvertes.fr/hal-00875130
DOI : 10.1093/jac/dks455
PUBMED : 23152480

Résumé : Les variétés modernes de canne à sucre sont d'origine bispécifique et possèdent une structure génétique complexe, aneuploïde et hautement polyploïde rendant difficile les études de résistance génétique. La feuille jaune de la canne a sucre est une maladie dont l'agent causal est le sugarcane yellow leaf virus (scylv). Ce virus a une large diversité. Seuls trois génotypes viraux, différenciables par rtpcr, ont été trouves en Guadeloupe. Les objectifs de l'étude sont d'évaluer: l/la possibilité de marquer la résistance de la plante au scylv grâce a une étude d'association pan-génomique 2/l'impact de la diversité de l'agent pathogène sur la résistance de la canne a sucre au scylv. Les études d'association ont été menées avec plus de 4000 marqueurs aflp et d'art sur quatre types de données phénotypiques (intensité et densité virale dans les feuilles et les tiges). Les phénotypes ont été mesures sur 189 variétés de cannes à sucre dans deux essais successifs dans un dispositif en trois blocs randomises. De ces variétés, 40 ont été sélectionnées et ont permis d'obtenir 10 croisements biparentaux. Les descendances obtenues ont été suivies sur deux essais. L'incidence et la diversité du scylv ont été évaluées pour les 40 variétés et les descendances. L'héritabilité au sens strict de la résistance aux scylv a été déterminée. Six marqueurs de résistance au scylv ont été identifies ainsi que deux gènes ayant potentiellement un rôle dans la résistance au virus. L'étude montre également que la résistance de la plante est variable en fonction du génotype du scylv et que cette résistance est en partie transmise aux descendances. Créer des variétés résistantes au scylv est donc possible.
Modern varieties of sugarcane have a bispecific origin and a complex genetic structure, aneuploid and highly polyploid, maklng genetic resistance study uneasy to perform. Yellow leaf of sugarcane is a viral disease whose causal agent is the sugarcane yellow leaf virus (scylv). This virus has a wide range of diversity. Only three viral genotypes, distinguishable by rt-pcr, were found in guadeloupe. The objectives of this srudy are to assess: l/the possibility to find markers associated with plant resistance to scylv through a genome wide association study 2 1 the impact of the pathogen diversity on the resistance of sugarcane to scylv. Association studies have been conducted with more than 4000 aflp and dart markers on four types of phenotypic data (virus intensity and density in leaves and canes). Phenotypes were measured on 189 varieties of sugarcane in two successive trials in a three randomized complete block design. From these varieties, 40 were selected and allowed to obtain 10 biparental crosses. The offspring were followed during two trials. The incidence and the diversity of scylv were evaluated in the 40 varieties and the offspring. The narrow sense heritability of the resistance to the scylvs was determined. Six markers of the resistance to the scylv and two genes, with potential contribution in virus resistance, have been identified. The study also shows that the resistance of the plant is variable depending on the scylv genotype and that this resistance is partly transmitted to the offspring. Breeding for scylv resistance is practicable.

http://www.theses.fr/2012AGUY0554/document

Éditeur(s) : HAL CCSD Society for Molecular Biology and Evolution
Résumé : International audience
Complex nongradual evolutionary processes such as gene remodeling are difficult to model, to visualize, and to investigate systematically. Despite these challenges, the creation of composite (or mosaic) genes by combination of genetic segments from unrelated gene families was established as an important adaptive phenomena in eukaryotic genomes. In contrast, almost no general studies have been conducted to quantify composite genes in viruses. Although viral genome mosaicism has been well-described, the extent of gene mosaicism and its rules of emergence remain largely unexplored. Applying methods from graph theory to inclusive similarity networks, and using data from more than 3,000 complete viral genomes, we provide the first demonstration that composite genes in viruses are 1) functionally biased, 2) involved in key aspects of the arm race between cells and viruses, and 3) can be classified into two distinct types of composite genes in all viral classes. Beyond the quantification of the widespread recombination of genes among different viruses of the same class, we also report a striking sharing of genetic information between viruses of different classes and with different nucleic acid types. This latter discovery provides novel evidence for the existence of a large and complex mobilome network, which appears partly bound by the sharing of genetic information and by the formation of composite genes between mobile entities with different genetic material. Considering that there are around 10E31 viruses on the planet, gene remodeling appears as a hugely significant way of generating and moving novel sequences between different kinds of organisms on Earth.
ISSN: 1759-6653

Droits : http://creativecommons.org/licenses/by/
hal-01324848
http://hal.upmc.fr/hal-01324848
http://hal.upmc.fr/hal-01324848/document
http://hal.upmc.fr/hal-01324848/file/Genome%20Biol%20Evol-2014-Jachiet-2195-205.pdf
DOI : 10.1093/gbe/evu168

Éditeur(s) : HAL CCSD
Résumé : Hepatitis C virus (HCV) is one of the leading causes of hepatocellular carcinoma. Therapeutic treatment against the virus has been recently improved by a tritherapy including pegylated interferon, ribavirin and antiviral protease. Nevertheless, the importance of side effects and the emergence of resistant mutants require the development of new antivirals. In this context, our team has recently discovered that Type III phosphatidylinositol 4-kinases (PI4KIIIα and PI4KIIIβ) are essential for the propagation of the virus in a human hepatic cell line at the entry and replication steps. To further characterize these potential therapeutic targets, we investigate the implication of these kinases during the HCV entry, using primary human hepatocytes, a model closer to the in vivo conditions. Two lines of research were developed: Verification of the importance of the kinase activity of PI4KIIIs during HCV entry in primary human hepatocytes, through a chemical approach; Validation of the involvement of these kinases and their enzymatic activity during viral entry through a genetic approach based on RNA interference and phenotype rescue. In parallel, we studied the expression of PI4KIIIα in liver diseases. Our results suggest the involvement of PI4KIIIα in HCV entry; the involvement of PI4KIIIIβ needs to be confirmed. The analysis of PI4KIIIα expression in hepatocellular carcinoma led us to propose this kinase as a new molecular marker, which could improve the already established prognosis models and could lead to the development of new therapeutic approaches.
Le virus de l’hépatite C (VHC) est l’un des principaux facteurs étiologiques du carcinome hépatocellulaire. Le traitement des hépatites virales C a été récemment amélioré grâce à une trithérapie (interféron, ribavirine et anti-protéase virale). Néanmoins l’importance des effets secondaires et l’émergence de mutants résistants nécessitent de découvrir de nouveaux antiviraux. Dans ce contexte, notre équipe a récemment découvert que les phosphatidylinositol 4-kinases de type III (PI4KIIIα et PI4KIIIβ) étaient indispensables à la propagation du virus dans une lignée hépatique humaine, et ce, à 2 étapes de son cycle biologique : l’entrée et la réplication. L’objectif du présent travail était de poursuivre la validation de ces nouvelles cibles thérapeutiques potentielles, en approfondissant nos connaissances sur la dépendance du virus à l’égard de ces kinases au cours de son entrée. Pour cela, nous avons utilisé le modèle des hépatocytes humains primaires, système in vitro plus proche du contexte physiologique que les modèles utilisés jusqu’à présent et qui étaient basés sur l’exploitation de lignées. Deux axes ont été développés : Vérification de l’importance de l’activité kinase des PI4KIIIs au cours de l’entrée du VHC dans les hépatocytes humains primaires, à travers une approche chimique ; Validation de l’implication de ces kinases et de leur activité enzymatique au cours de l’entrée virale grâce à une approche génétique basée sur l’ARN interférence et la restauration de phénotype. En parallèle, nous avons étudié l’expression de PI4KIIIα au cours de pathologies hépatiques. Nos résultats suggèrent une implication de PI4KIIIα au cours de l’entrée du VHC dans les hépatocytes humains primaires, mais restent à confirmer quant à l’implication de PI4KIIIβ. Par ailleurs, l’analyse de l’expression de PI4KIIIα dans le carcinome hépatocellulaire (CHC) conduit à proposer cette kinase comme un nouveau marqueur moléculaire, qui pourrait améliorer les modèles de pronostic déjà établis et pourrait conduire au développement de nouvelles approches thérapeutiques pour les patients atteints d’un CHC, quelque soit l’étiologie.
https://tel.archives-ouvertes.fr/tel-00950335

Droits : info:eu-repo/semantics/OpenAccess
NNT : 2013REN1B006
tel-00950335
https://tel.archives-ouvertes.fr/tel-00950335
https://tel.archives-ouvertes.fr/tel-00950335/document
https://tel.archives-ouvertes.fr/tel-00950335/file/ILBOUDOAdeodat.pdf

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Background: Influenza is an important cause of serious illness and death, particularly in elderly and high-risk groups. Objectives Aim of this study was to identify factors associated with poor outcomes among adults hospitalized in France for laboratory-confirmed seasonal influenza. Study design Patients hospitalized for influenza were identified in a prospective, multicenter study carried out in French hospitals during three consecutive influenza seasons (2012–2015). Influenza virus infection was confirmed by reverse transcription polymerase chain reaction. Sociodemographic and clinical variables were compared according to the virus type and subtype. Risk factors for complications, intensive care unit (ICU) admission and death were analyzed by backward stepwise logistic regression. Results The study population consisted of 566 patients, of whom 56% were older than 65 years and 82% had underlying chronic illnesses. Type A influenza viruses infected 422 patients (75%), including subtype H3N2 in 239 patients (57%). The prior vaccine coverage rate was 38%. Complications occurred in 255 patients (45%), consisting mainly of pneumonia (n = 143, 30%) and respiratory failure (n = 116, 20%). Eighty-three patients (15%) were admitted to an ICU, and the in-hospital mortality rate was 4% (n = 21). Sixty-six patients (12%) received oseltamivir. Age over 65 years was the only identified risk factor for complications. Risk factors for ICU admission were an absence of vaccination, no oseltamivir administration before admission, pre-existing chronic respiratory disease, and current smoking. Age over 65 years and ICU admission were risk factors for death. Conclusions Older individuals and patients with underlying conditions are most at risk of influenza complications. Vaccination and early oseltamivir administration, both of which are recommended for these patients, appear to reduce ICU admissions
ISSN: 1386-6532

hal-01302409
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01302409
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01302409/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01302409/file/Factors%20associated%20with%20poor%20outcomes.pdf
DOI : 10.1016/j.jcv.2016.04.005

Résumé : By looking at the common thread between 4 programs* in which the IFREMER Palavas (34, Languedoc-Roussillon region in France) station took part, this report show the evolution over 20 years in the perception of the pathology of farmed fish, and of the sea bass in particular (Dicentrarchus labrax). During the 1990’s farming techniques became sufficiently reliable to enable to distinguish between problems of a zootechnical nature and those with a pathological origin. In anticipation of future illnesses, the necessary tools and monitoring were implemented in order to study the immune system of the sea bass. These methods arose from the recent creation of anti-immunoglobin monoclonal probes in the sea bass. These techniques, together with others, served to search for a solution to the nodavirus epidemic which struck in1996. In the absence of a cure for this virus, the research focused on knowledge of the virus, its epidemiology and vaccine development. Despite interesting scientific results, the solution withheld to curb the Nodavirus epidemic was zootechnical. This pragmatic outcome catalysed reflections on the role of pathology, leading to notions of health, animal well-being and image. Management choices in the health of farmed fish stocks became a parameter, amongst others, included in a global commercial and farming policy. * Définition des critères d’évaluation de l’immunocompétente chez le loup et le turbot. UMR1 Université Montpellier II IFREMER ; Nodavirus disease of cultured marine fish in Europe. FAIR PL98 4036 EU; Recherche de moyens de dépistage et prévention de la nodavirose du bar. ANVAR 9804041J ; Welfare and Health in Sustainable Aquaculture WEALTH. E.U N°501984.
En prenant comme fil conducteur les travaux de 4 programmes* auxquels a participé la station IFREMER de Palavas (34), ce rapport montre l’évolution sur 20 ans de la perception de la pathologie des poissons d’élevages et du loup en particulier (Dicentrarchus labrax). Dans les années 1990 les techniques d’élevages devinrent suffisamment fiables pour permettre de distinguer les problèmes d’origines zootechniques de ceux d’origines pathologiques. En prévision des futures maladies potentielles, les outils d’étude et de suivi du système immunitaire spécifique du loup furent mis en place. Ils découlaient de la création récente de sondes monoclonales anti-immunoglobulines de loup. Ces techniques, couplées à d’autres, servirent à chercher une solution à l’épidémie de nodavirose des années 1996. En l’absence de traitement pour un virus l’accent fut mis sur la connaissance du virus, de son épidémiologie et de la vaccination. Bien que les résultats scientifiques furent très satisfaisants la solution trouvée pour juguler l’épidémie de Nodavirose fut zootechnique. Cette issue pragmatique catalysa une réflexion sur le rôle de la pathologie qui maturait depuis plusieurs années et qui déboucha sur la notion de santé, de bien être des animaux et d’image. Les choix de gestion de la santé des cheptels devinrent un paramètre, parmi d’autres, s’incluant dans d’une politique globale d’élevage et commerciale * Définition des critères d’évaluation de l’immunocompétente chez le loup et le turbot. UMR1 Université Montpellier II IFREMER ; Nodavirus disease of cultured marine fish in Europe. FAIR PL98 4036 EU; Recherche de moyens de dépistage et prévention de la nodavirose du bar. ANVAR 9804041J ; Welfare and Health in Sustainable Aquaculture WEALTH. E.U N°501984.

Droits : 2013 Ifremer
http://archimer.ifremer.fr/doc/00167/27866/26103.pdf
http://archimer.ifremer.fr/doc/00167/27866/26105.pdf
http://archimer.ifremer.fr/doc/00167/27866/26106.pdf
http://archimer.ifremer.fr/doc/00167/27866/

Éditeur(s) : HAL CCSD
Résumé : International audience
This paper investigates the narrative challenges and opportunities that contemporary virology offers to popular science and to fiction. The study of viruses reveals extremely complex relations, playing out over different physical and temporal scales. Viruses constitute a heterogeneous population whose interactions with living organisms occur on multiple levels, and whose numbers are vastly superior to human and even bacterial populations on earth. The resulting challenges for narration can be grouped into three main formal questions. The first is the problem of scale, since the numbers and sizes of virus and host populations are vastly different, as are the temporalities over which they transform and survive. The second is the complexity of actants, since viruses are involved in relations where destruction and mutual benefit can overlap, and genetic transformations are played out over many generations. The third is the choice of images through which to convey their behaviours: many existing metaphors in microbiology, such as “chimeras”, “parasites” or “kill-the-winner dynamics”, carry the narrative potential of a mythological and/or theatrical imagination.These questions will first be examined as challenges encountered in the narration of biology for vulgarization purposes, and effects on narrative forms will be outlined: shifts in focalization in order to create multiscalar perspectives; unstable actantial models as expressions of complex relations; and the use or resistance to narrative structures implied by several key metaphors in virological discourse. These formal characteristics will then be presented through two case studies drawn from contemporary fiction. In his “scientific fable” Conflits Intérieurs (2015), microbiologist Eric Bapteste creates a multiscalar narrative by using humans and viruses as both protagonists and narrators in a battle of ideas. In the graphic novel aâma (2011-2014), Frederik Peeters explores the ambiguous potential, both symbiotic and threatening, of a meta-organism uniting humans with microscopic agents. Both these novels play with scale, metaphor and actants so as to question the fundaments of human identity. They posit the act of narration as a defining human attribute, and consequently use the narrative voice as an arena in which we observe the weakening of the notion of the subject by microbiology.
“Narrative, Cognition & Science” Symposium
Erlangen, Germany

hal-01434744
https://hal.archives-ouvertes.fr/hal-01434744

Éditeur(s) : HAL CCSD American Society of Tropical Medicine and Hygiene
Résumé : International audience
In disease-endemic areas, histoplasmosis is the main differential diagnosis for tuberculosis among human immunodeficiency virus (HIV)-infected patients. However, no study has compared the two diseases. Thus, the objective of this study was to compare tuberculosis and histoplasmosis in HIV-infected patients. A population of 205 HIV-infected patients (99 with tuberculosis and 106 with histoplasmosis) hospitalized in Cayenne, French Guiana during January 1, 1997-December 31, 2008 were selected retrospectively from the French Hospital Database on HIV. Multivariate analysis showed that tuberculosis was associated with cough (adjusted odds ratio [AOR] = 0.20, 95% confidence interval [CI] = 0.05-0.73) and a C-reactive protein level > 70 mg/L (AOR = 0.98, 95% CI = 0.97-0.99). Variables associated with disseminated histoplasmosis were a γ-glutamyl transferase level > 72 IU/L (AOR = 4.99, 95% CI = 1.31-18.99), origin from French Guiana (AOR = 5.20, 95% CI = 1.30-20.73), disseminated localization (AOR = 6.40, 95% CI = 1.44-28.45), a concomitant opportunistic infection (AOR = 6.71, 95% CI = 1.50-29.96), a neutrophil count < 2,750 cells/mm(3) (AOR = 10.54, 95% CI = 2.83-39.24), a CD4 cell count < 60 cells/mm(3) (AOR = 11.62, 95% CI = 2.30-58.63), and a platelet count < 150,000/mm(3) (AOR = 19.20, 95% CI = 3.35-110.14). Tuberculosis and histoplasmosis have similarities, but some factors show a greater association with one of these diseases. Thus, adapted therapeutic choices can be made by using simple clinical and paraclinical criteria.
ISSN: 0002-9637

inserm-01065027
http://www.hal.inserm.fr/inserm-01065027
http://www.hal.inserm.fr/inserm-01065027/document
http://www.hal.inserm.fr/inserm-01065027/file/2014_Adenis_-_Tuberculosis_and_Histoplasmosis_among_HIV.pdf
DOI : 10.4269/ajtmh.13-0084

Éditeur(s) : HAL CCSD MDPI
Résumé : International audience
Tetherin (BST2/CD317) has been recently recognized as a potent interferon-induced antiviral molecule that inhibits the release of diverse mammalian enveloped virus particles from infected cells. By targeting an immutable structure common to all these viruses, the virion membrane, evasion of this antiviral mechanism has necessitated the development of specific countermeasures that directly inhibit tetherin activity. Here we review our current understanding of the molecular basis of tetherin's mode of action, the viral countermeasures that antagonize it, and how virus/tetherin interactions may affect viral transmission and pathogenicity.
ISSN: 1999-4915

hal-01121799
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01121799
PUBMED : 21994744
DOI : 10.3390/v3050520
PUBMEDCENTRAL : PMC3185764

Résumé : Le but de ce programme pathologie est de rechercher et d'étudier les agents pathogènes connus et inconnus chez les mollusques bivalves marins, plus particulièrement chez l'huître creuse, Crassostrea gigas, afin d'identifier d'éventuels agents causant des mortalités, de proposer des mesures prophylactiques et de définir des conditions zootechniques permettant aux professionnels de limiter l'impact des maladies sur leur cheptel. La présence de maladies, chez les mollusques bivalves marins dont l'impact socio économique peut être catastrophique pour les productions conchylicoles, et l'accroissement des échanges de produits d'aquaculture entre les pays de la CEE et avec les pays tiers nécessitent le renforcement des recherches dans les domaines de la pathologie. En particulier, du fait du mono élevage de l'huître japonaise, Crassostrea gigas, en France, il semble aujourd'hui indispensable d'effectuer des contrôles zoosanitaires réguliers chez cette espèce. Ces travaux ont d'autant plus d'importance qu'aujourd'hui, devant les pathologies rencontrées, les professionnels restent extrêmement démunis (traitements inapplicables ou inexistants). Dans ce cadre, la promptitude du diagnostic ainsi que l'acquisition de données épidémiologiques et biologiques concernant les agents pathogènes impliqués sont les meilleurs moyens d'éviter leur dissémination chez les mollusques bivalves marins. Les travaux entrepris dans ce cadre par l'URPIG, semblent d'autant plus indispensables qu'il n'existait pas jusqu'à ces dernières années de pathologies identifiées chez l'huître creuse, Crassostrea gigas, sur le littoral français. Cependant depuis 1991, sont apparus dans certaines écloseries françaises des épisodes de mortalité sur des larves de cette espèce. Il a été possible de détecter un virus apparenté à la famille des Herpesviridae par ses caractères morphologiques (NICOLAS et al., 1992) et de démontrer sa pathogénicité pour les larves (LE DEUFF et al., 1994). Par ailleurs, en 1993, 1994 et 1995, un virus de même type, a été observé en association à de fortes mortalités sur différents lots de naissain de la même espèce, originaires d'écloseries et de captage naturel. Par ailleurs, en 1993, suite à l'observation d'anomalies au niveau des branchies chez des huîtres creuses provenant de Charente Maritime et du bassin d'Arcachon associées à de médiocres performances de croissance, il a été entrepris des analyses de divers échantillons, en histologie classique et en microscopie électronique à transmission. Ces examens ont permis de révéler la présence au niveau des branchies, chez un nombre non négligeable d'animaux, d'un microorganisme de type chlamydien (RENAULT and COCHENNEC, 1995). Il a également été possible, chez cette même espèce, de détecter la présence d'un organisme de type rickettsien au niveau des branchies (RENAULT, COCHENNEC and CHOLLET, 1995).

Droits : 1995 Ifremer
http://archimer.ifremer.fr/doc/00043/15453/12828.pdf
http://archimer.ifremer.fr/doc/00043/15453/

Éditeur(s) : HAL CCSD
Résumé : International audience
Yellow leaf disease is a recent, important and widely spread disease of sugarcane (6), causing severe yield losses on susceptible cultivars. The disease is caused by Sugarcane Yellow Leaf Virus (SCLRV) of the genus Polerovirus in the family Luteoviridae. This virus is transmitted from plant to plant only by aphids in a persistent, circulative and non replicative manner. The epidemic of the SCYLV was little studied and there is a need for information on the spatial spread of the disease and on the role of the aphid in the disease spread. SCYLV was first identified in Guadeloupe in 1996 and Melanaphis sacchari has been the only SCYLV vector found in sugarcane fields. Even if the infection rate is relatively low (0% to 21%), disease may increase and cause damage to sugarcane in Guadeloupe. Even though disease free tissue cultured plants are used for sanitary control in Guadeloupe, understanding SCYLV spread by its vector may help determine additional management strategies against the virus.
IEW
New York, United States

hal-00684226
https://hal.archives-ouvertes.fr/hal-00684226

Éditeur(s) : Inter-Research
Résumé : Macrobrachium rosenbergii nodavirus (MrNV) and extra small virus (XSV) were purified from diseased freshwater prawns M rosenbergii and used to infect healthy post-larvae (PL) by an immersion method. Three groups of prawns were challenged with various combined doses of MrNV and XSV. Signs of white-tail disease (WTD) were observed in Groups 1 and 2, which had been challenged with combinations containing relatively high proportions of MrNV and low proportions of XSV. By contrast there was little sign of WTD in Group 3, which had been challenged with a higher proportion of XSV than MrNV. A 2-step Taqman real-time RT-PCR was developed and applied to quantify viral copy numbers in each challenged PL. Results showed that genomic copies of both viruses were much higher in Groups 1 and 2 than they were in Group 3, indicating that MrNV plays a key role in WTD of M rosenbergii. The linear correlation between MrNV and XSV genome copies in infected prawns demonstrated that XSV is a satellite virus, dependent on MrNV, but its role in pathogenicity of WTD remains unclear.
Diseases of aquatic organisms (0177-5103) (Inter-Research), 2006-07 , Vol. 71 , N. 1 , P. 11-17

Droits : Inter-Research 2006
http://archimer.ifremer.fr/doc/2006/publication-3568.pdf
DOI:10.3354/dao071011
http://archimer.ifremer.fr/doc/00000/3568/