Suivi immuno-virologique et thérapeutique de l'infection à VIH chez des enfants suivis au CHU pédiatrique de Ouagadougou (collaboration ESTHER)

L accès au TAR pour tous, demeure un défi majeur et un enjeu stratégique de la lutte contre le VIH. Défi majeur car le prix des traitements reste inabordable pour la grande majorité de ceux qui en ont besoin. Enjeu stratégique car traiter permet de réduire la mortalité des personnes infectées, mais permet aussi d agir sur l incidence de la maladie en diminuant le nombre de nouvelles contaminations, notamment par la réduction du risque de transmission mère-enfant. Dans le cadre du programme ESTHER, les laboratoires du CHU pédiatrique Charles De Gaulle de Ouagadougou et celui du CHU Charles Nicolle travaillent dans le but d'améliorer la prise en charge des enfants infectés par le VIH. L objectif de notre travail a été de décrire les caractéristiques immuno-virologiques et thérapeutiques et de l infection à VIH chez les enfants suivis au CHU pédiatrique de Ouagadougou, et de préciser les aspects génotypiques des virus infectant ces malades Nos résultats montrent que les patients traités ont un taux de suppression virologique de près de 70%, et ce quelle que soit la ligne considérée. Comme attendu, l'état immunologique des patients traités était meilleur que celui des patients non traités. Chez les patients traités en situation d'échec virologique, les mutations de résistance aux INTI montrent une forte prévalence de la M184V et des TAM's. Les mutations de résistance aux INNTI sont nombreuses et confèrent une résistance aux INNTI de première génération très importante. La grande majorité des mutations de résistance aux IP sont des mutations mineures ou polymorphiques.ROUEN-BU Médecine-Pharmacie (765402102) / SudocSudocFranceF

Misidentification of a Hepatitis C Virus (HCV) recombinant form leading to treatment failure with new direct acting antivirals

International audienc

Polyomaviruses KI and WU in Immunocompromised Patients with Respiratory Disease

Polyomaviruses KI (KIPyV) and WU (WUPyV) were recently identified, mainly in respiratory specimens from children. Among 200 patients with respiratory disorders admitted to Saint Louis Hospital, Paris, France, KIPyV was detected in 8% and WUPyV in 1%. KIPyV was significantly more frequent among human stem cell transplant patients (17.8% vs. 5.1%; p = 0.01)

HIV-1/M+O INTERGROUP DUAL INFECTIONS AND ASSOCIATED HIV-MO RECOMBINANTS IN FRANCE FROM 2004 TO 2014

International audienc

A FRET-Based High Throughput Screening Assay to Identify Inhibitors of Anthrax Protective Antigen Binding to Capillary Morphogenesis Gene 2 Protein

Anti-angiogenic therapies are effective for the treatment of cancer, a variety of ocular diseases, and have potential benefits in cardiovascular disease, arthritis, and psoriasis. We have previously shown that anthrax protective antigen (PA), a non-pathogenic component of anthrax toxin, is an inhibitor of angiogenesis, apparently as a result of interaction with the cell surface receptors capillary morphogenesis gene 2 (CMG2) protein and tumor endothelial marker 8 (TEM8). Hence, molecules that bind the anthrax toxin receptors may be effective to slow or halt pathological vascular growth. Here we describe development and testing of an effective homogeneous steady-state fluorescence resonance energy transfer (FRET) high throughput screening assay designed to identify molecules that inhibit binding of PA to CMG2. Molecules identified in the screen can serve as potential lead compounds for the development of anti-angiogenic and anti-anthrax therapies. The assay to screen for inhibitors of this protein–protein interaction is sensitive and robust, with observed Z' values as high as 0.92. Preliminary screens conducted with a library of known bioactive compounds identified tannic acid and cisplatin as inhibitors of the PA-CMG2 interaction. We have confirmed that tannic acid both binds CMG2 and has anti-endothelial properties. In contrast, cisplatin appears to inhibit PA-CMG2 interaction by binding both PA and CMG2, and observed cisplatin anti-angiogenic effects are not mediated by interaction with CMG2. This work represents the first reported high throughput screening assay targeting CMG2 to identify possible inhibitors of both angiogenesis and anthrax intoxication

A comprehensive analysis of filamentous phage display vectors for cytoplasmic proteins: an analysis with different fluorescent proteins

Filamentous phage display has been extensively used to select proteins with binding properties of specific interest. Although many different display platforms using filamentous phage have been described, no comprehensive comparison of their abilities to display similar proteins has been conducted. This is particularly important for the display of cytoplasmic proteins, which are often poorly displayed with standard filamentous phage vectors. In this article, we have analyzed the ability of filamentous phage to display a stable form of green fluorescent protein and modified variants in nine different display vectors, a number of which have been previously proposed as being suitable for cytoplasmic protein display. Correct folding and display were assessed by phagemid particle fluorescence, and with anti-GFP antibodies. The poor correlation between phagemid particle fluorescence and recognition of GFP by antibodies, indicates that proteins may fold correctly without being accessible for display. The best vector used a twin arginine transporter leader to transport the displayed protein to the periplasm, and a coil-coil arrangement to link the displayed protein to g3p. This vector was able to display less robust forms of GFP, including ones with inserted epitopes, as well as fluorescent proteins of the Azami green series. It was also functional in mock selection experiments

Infection respiratoire à coronavirus (étude d'une épidémie)

CAEN-BU Médecine pharmacie (141182102) / SudocLYON1-BU Santé (693882101) / SudocSudocFranceF

Comparison of the bioMérieux NucliSENS EasyQ HIV-1 v2.0–HIV-1 RNA quantification assay versus Abbott RealTime HIV-1 and Roche Cobas TaqMan HIV-1 v2.0 on current epidemic HIV-1 variants

International audienc

Misidentification of a Hepatitis C Virus (HCV) recombinant form leading to treatment failure with new direct acting antivirals

International audienc

Impact of natural polymorphisms of HIV-1 non-group M on genotypic susceptibility to the attachment inhibitor fostemsavir

International audienceBackground:Fostemsavir belongs to the new class of attachment inhibitors (AIs); it inhibits the entry of HIV into CD4+ T-lymphocytes by blocking conformational changes in gp120. This is a promising AI, but previous phenotypic data showed that genetically divergent HIV-1 group O could present natural resistance to this drug. These data were obtained from only two strains, which are not representative of the high intra-group genetic diversity. Moreover, no data are available concerning the other divergent HIV-1 groups (N and P).Objectives:To further investigate the natural genotypic susceptibility of HIV-1 groups O, N and P (HIV-1 non-M) to fostemsavir, using a large set of sequences.Methods:The frequency of eight substitutions associated with decreased susceptibility to fostemsavir (L116P, A204D, S375M/H, M426L, M434I, M475I and V506M), was investigated in 111 gp120 sequences from groups O (n = 100), N (n = 9) and P (n = 2).Results:All HIV-1 group N sequences harboured the three substitutions S375M, M426L and M434I, whereas only 1% and 10% of HIV-1 group O sequences harboured the S375H + M426L and S375H + M434I patterns, respectively. The main genetic profile of HIV-1 groups P and O combined S375H with two atypical substitutions (M426S and M434L). Five group O sequences did not display any of the eight substitutions, but had atypical residues with unknown impact.Conclusions:The genetic polymorphisms in the gp120 of HIV-1 non-M viruses support the hypothesis that these viruses could largely be resistant to inhibition by fostemsavir. Only 5% of group O strains could display full genetic susceptibility. Extensive phenotypic studies are now required