Differential activity of candidate microbicides against early steps of HIV-1 infection upon complement virus opsonization

ABSTRACT: BACKGROUND: HIV-1 in genital secretions may be opsonized by several molecules including complement components. Opsonized HIV-1 by complement enhances the infection of various mucosal target cells, such as dendritic cells (DC) and epithelial cells. RESULTS: We herein evaluated the effect of HIV-1 complement opsonization on microbicide candidates activity, by using three in vitro mucosal models: CCR5-tropic HIV-1JR-CSF transcytosis through epithelial cells, HIV-1JR-CSF attachment on immature monocyte-derived dendritic cells (iMDDC), and infectivity of iMDDC by CCR5-tropic HIV-1BaL and CXCR4-tropic HIV-1NDK. A panel of 10 microbicide candidates [T20, CADA, lectines HHA & GNA, PVAS, human lactoferrin, and monoclonal antibodies IgG1B12, 12G5, 2G12 and 2F5], were investigated using cell-free unopsonized or opsonized HIV-1 by complements. Only HHA and PVAS were able to inhibit HIV trancytosis. Upon opsonization, transcytosis was affected only by HHA, HIV-1 adsorption on iMDDC by four molecules (lactoferrin, IgG1B12, IgG2G5, IgG2G12), and replication in iMDDC of HIV-1BaL by five molecules (lactoferrin, CADA, T20, IgG1B12, IgG2F5) and of HIV-1NDK by two molecules (lactoferrin, IgG12G5). CONCLUSION: These observations demonstrate that HIV-1 opsonization by complements may modulate in vitro the efficiency of candidate microbicides to inhibit HIV-1 infection of mucosal target cells, as well as its crossing through mucos

Antibody evasion by the N terminus of murid herpesvirus-4 glycoprotein B

Herpesviruses characteristically transmit infection from immune hosts. Although their success in escaping neutralization by pre-formed antibody is indisputable, the underlying molecular mechanisms remain largely unknown. Glycoprotein B (gB) is the most conserved component of the herpesvirus entry machinery and its N terminus (gB-NT) is a common neutralization target. We used murid herpesvirus-4 to determine how gB-NT contributes to the virus–antibody interaction. Deleting gB-NT had no obvious impact on virus replication, but paradoxically increased virion neutralization by immune sera. This reflected greater antibody access to neutralization epitopes on gH/gL, with which gB was associated. gB-NT itself was variably protected against antibody by O-linked glycans; on virions from epithelial cells it was protected almost completely. gB-NT therefore provides a protective and largely protected cover for a vulnerable part of gH/gL. The conservation of predicted glycosylation sites in other mammalian herpesvirus gB-NTs suggests that this evasion mechanism is widespread. Interestingly, the gB-NT glycans that blocked antibody binding could be targeted for neutralization instead by a lectin, suggesting a means of therapeutic counterattack

Photometric calibration of an in situ broadband optical thickness monitoring of thin films in a large vacuum chamber

International audienceTo improve the in situ monitoring of thin films at the Laboratoire des Matériaux Avancés, a broadband optical monitoring of the coated thin films was developed and installed in the biggest ion-beam sputtering machine in the world. Due to the configuration of the coating machine and the chamber strain under vacuum, a standard calibration procedure is impossible and a double-beam optical system is not suitable. A novel theoretical and practical solution to calibrate the measurements was found and is described in this paper. Some relevant results achieved thanks to this technique are discussed as well

Direct measurement of the two principal refractive indexes of a nematic liquid crystal slab

A new technique to measure the principal refractive indexes of a nematic liquid crystal is presented. The method is based on an indirect measurement of the refraction angle by determining the direction of a magnetic field which minimizes the light scattering. With this technique one can perform different light scattering experiments, which require a knowledge of the refractive indexes, on the same crystal slab. The accuracy is better than ±0.15%. A discussion about the systematic error due to the distortion of the director profile near the holder edges and the relative correction is give

High precision metrology for large bandpass filters

International audienceHigh precision measurements of the filters bandpass used on wide-field imagers mounted on large telescopes is critical for type Ia supernovae studies. A dedicated spectrophotometric bench is used to re-measure the now decommissioned ugriz filters used for the SNLS on CFHT-MegaCam. A full characterization of the optical response with respect to the location on the surface and the angle of incidence was performed for each filter. Strong variation over the filter surface is observed. The impact of the actual response on the observation is evaluated and we demonstrate an improvement with respect to the previous published results (SNLS1 and 2). © (2018) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE). Downloading of the abstract is permitted for personal use only

Synthesis and in vitro cytostatic activity of new beta-D-arabino furan[1',2':4,5]oxazolo- and arabino-pyrimidinone derivatives

A series of nucleoside derivatives was obtained via heteroatom annulation of the amino oxazoline of D-(-)-arabinose. Unequivocal proofs for the stereostructure of some new arabinosyl pyrimidinone derivatives were obtained by X-ray structure analysis. These newly synthesized compounds were then evaluated for their cytostatic activity against murine leukemia (L1210), and human T-lymphocytes (Molt 4/C8 and CEM). Of all the compounds in the series, the protected silylated tricyclic fused pyrimidinone 10 showed the most significant antitumor activity against murine leukemia L1210 (IC(50)=6 microM), and human T-lymphocytes cells Molt 4/C8 (IC(50)=7.9 microM) and CEM/0 cell lines (IC(50)=7.5 microM). None of the compounds exhibited significant antiviral inhibitory activities.status: publishe

Differential in vitro inhibitory activity against HIV-1 of alpha-(1-3)- and alpha-(1-6)-D-mannose specific plant lectins : Implication for microbicide development

<p>Abstract</p> <p>Background</p> <p>Plant lectins such as <it>Galanthus nivalis </it>agglutinin (GNA) and <it>Hippeastrum hybrid </it>agglutinin (HHA) are natural proteins able to link mannose residues, and therefore inhibit HIV-target cell interactions. Plant lectins are candidate for microbicide development.</p> <p>Objective</p> <p>To evaluate the activity against HIV of the mannose-specific plant lectins HHA and GNA at the cellular membrane level of epithelial cells and monocyte-derived dendritic cells (MDDC), two potential target cells of HIV at the genital mucosal level.</p> <p>Methods</p> <p>The inhibitory effects of HHA and GNA were evaluated on HIV adsorption to genital epithelial HEC-1A cell line, on HIV transcytosis throughout a monolayer of polarized epithelial HEC-1A cells, on HIV adsorption to MDDC and on transfer of HIV from MDDC to autologous T lymphocytes.</p> <p>Results</p> <p>HHA faintly inhibited attachment to HEC-1A cells of the R5-tropic HIV-1_Ba-Lstrain, in a dose-dependent manner, whereas GNA moderately inhibited HIV adsorption in the same context, but only at high drug doses. Only HHA, but not GNA, inhibited HIV-1_JR-CSFtranscytosis in a dose-dependent manner. By confocal microscopy, HHA, but not GNA, was adsorbed at the epithelial cell surface, suggesting that HHA interacts specifically with receptors mediating HIV-1 transcytosis. Both plant lectins partially inhibited HIV attachment to MDDC. HHA inhibited more efficiently the transfer of HIV from MDDC to T cell, than GNA. Both HHA and GNA lacked toxicity below 200 μg/ml irrespective the cellular system used and do not disturb the monolayer integrity of epithelial cells.</p> <p>Conclusion</p> <p>These observations demonstrate higher inhibitory activities of the lectin plant HHA by comparison to GNA, on HIV adsorption to HEC-1A cell line, HIV transcytosis through HEC-1A cell line monolayer, HIV adsorption to MDDC and HIV transfer from MDDC to T cells, highlighting the potential interest of HHA as effective microbicide against HIV.</p

Large and extremely low loss: the unique challenges of gravitational wave mirrors

International audienceThis paper describes the making of large mirrors for laser interferometer gravitational wave detectors. These optics, working in the near infrared, are among the best optics ever created and played a crucial role in the first direct detection of gravitational waves from black holes or neutron star fusions