Inhibition of HIV-1 replication by balsamin, a ribosome inactivating protein of Momordica balsamina

Ribosome-inactivating proteins (RIPs) are endowed with several medicinal properties, including antiviral activity. We demonstrate here that the recently identified type I RIP from Momordica balsamina also possesses antiviral activity, as determined by viral growth curve assays and single-round infection experiments. Importantly, this activity is at play even as doses where the RIP has no cytotoxic effect. In addition, balsamin inhibits HIV-1 replication not only in T cell lines but also in human primary CD4(+) T cells. This antiviral compound exerts its activity at a viral replicative step occurring later than reverse-transcription, most likely on viral protein translation, prior to viral budding and release. Finally, we demonstrate that balsamin antiviral activity is broad since it also impedes influenza virus replication. Altogether our results demonstrate that type I RIP can exert a potent anti-HIV-1 activity which paves the way for new therapeutic avenues for the treatment of viral infections

Spatial and temporal variations of aridity shape dung beetle assemblages towards the Sahara desert

Assemblage responses to environmental gradients are key to understand the general principles behind the assembly and functioning of communities. The spatially and temporally uneven distribution of water availability in drylands creates strong aridity gradients. While the effects of spatial variations of aridity are relatively well known, the influence of the highly-unpredictable seasonal and inter-annual precipitations on dryland communities has been seldom addressed. Aims: Here, we study the seasonal and inter-annual responses of dung beetle. Dung beetle abundance and species richness showed large seasonal variations, but remained relatively similar between years. Indeed, aridity and its interaction with season and year were the strongest correlates of variations in species richness and composition. Increasing aridity resulted in decreasing species richness and an ordered replacement of species, namely the substitution of the Mediterranean fauna by desert assemblages dominated by saprophagous and generalist species both in space towards the Sahara and in the dry season.Indradatta deCastro-Arrazola was funded by an FPI grant from the Spanish Ministry of Science and Innovation (BES-2012-054353). This work was supported by the Spanish Ministry of Science and Innovation project SCARPO (grant CGL2011-29317)

Quantitative Multicolor Super-Resolution Microscopy Reveals Tetherin HIV-1 Interaction

Virus assembly and interaction with host-cell proteins occur at length scales below the diffraction limit of visible light. Novel super-resolution microscopy techniques achieve nanometer resolution of fluorescently labeled molecules. The cellular restriction factor tetherin (also known as CD317, BST-2 or HM1.24) inhibits the release of human immunodeficiency virus 1 (HIV-1) through direct incorporation into viral membranes and is counteracted by the HIV-1 protein Vpu. For super-resolution analysis of HIV-1 and tetherin interactions, we established fluorescence labeling of HIV-1 proteins and tetherin that preserved HIV-1 particle formation and Vpu-dependent restriction, respectively. Multicolor super-resolution microscopy revealed important structural features of individual HIV-1 virions, virus assembly sites and their interaction with tetherin at the plasma membrane. Tetherin localization to micro-domains was dependent on both tetherin membrane anchors. Tetherin clusters containing on average 4 to 7 tetherin dimers were visualized at HIV-1 assembly sites. Combined biochemical and super-resolution analysis revealed that extended tetherin dimers incorporate both N-termini into assembling virus particles and restrict HIV-1 release. Neither tetherin domains nor HIV-1 assembly sites showed enrichment of the raft marker GM1. Together, our super-resolution microscopy analysis of HIV-1 interactions with tetherin provides new insights into the mechanism of tetherin-mediated HIV-1 restriction and paves the way for future studies of virus-host interactions

Arsenic modulates APOBEC3G-mediated restriction to HIV-1 infection in myeloid dendritic cells

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TLR-4 engagement of dendritic cells confers a BST-2/tetherin-mediated restriction of HIV-1 infection to CD4+ T cells across the virological synapse

International audienceBackground : Dendritic cells and their subsets, located at mucosal surfaces, are among the first immune cells toencounter disseminating pathogens. The cellular restriction factor BST-2/tetherin (also known as CD317 or HM1.24)potently restricts HIV-1 release by retaining viral particles at the cell surface in many cell types, including primarycells such as macrophages. However, BST-2/tetherin does not efficiently restrict HIV-1 infection in immaturedendritic cells.Results : We now report that BST-2/tetherin expression in myeloid (myDC) and monocyte-derived dendritic cells (DC)can be significantly up-regulated by IFN-αtreatment and TLR-4 engagement with LPS. In contrast to HeLa or 293Tcells, infectious HIV-1 release in immature DC and IFN-α–matured DC was only modestly affected in the absence ofVpu compared to wild-type viruses. Strikingly, immunofluorescence analysis revealed that BST-2/tetherin was excludedfrom HIV containing tetraspanin-enriched microdomains (TEMs) in both immature DC and IFN-α–matured DC. Incontrast, in LPS-mediated mature DC, BST-2/tetherin exerted a significant restriction in transfer of HIV-1 infection toCD4+T cells. Additionally, LPS, but not IFN-αstimulation of immature DC, leads to a dramatic redistribution of cellularrestriction factors to the TEM as well as at the virological synapse between DC and CD4+Tcells. Conclusions : In conclusion, we demonstrate that TLR-4 engagement in immature DC significantly up-regulates theintrinsic antiviral activity of BST-2/tetherin, during cis-infection of CD4+T cells across the DC/T cell virological synapse.Manipulating the function and potency of cellular restriction factors such as BST-2/tetherin to HIV-1 infection, hasimplications in the design of antiviral therapeutic strategies

Comparaisons des caractéristiques sociales des patients au début des épidémies de Chikungunya 2014 versus dengue 2013 à Cayenne (EMERG-03).

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Comparaisons des caractéristiques sociales des patients au début des épidémies de Chikungunya 2014 versus dengue 2013 à Cayenne (EMERG-03).

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