Hybrid spreading mechanisms and T cell activation shape the dynamics of HIV-1 infection

HIV-1 can disseminate between susceptible cells by two mechanisms: cell-free infection following fluid-phase diffusion of virions and by highly-efficient direct cell-to-cell transmission at immune cell contacts. The contribution of this hybrid spreading mechanism, which is also a characteristic of some important computer worm outbreaks, to HIV-1 progression in vivo remains unknown. Here we present a new mathematical model that explicitly incorporates the ability of HIV-1 to use hybrid spreading mechanisms and evaluate the consequences for HIV-1 pathogenenesis. The model captures the major phases of the HIV-1 infection course of a cohort of treatment naive patients and also accurately predicts the results of the Short Pulse Anti-Retroviral Therapy at Seroconversion (SPARTAC) trial. Using this model we find that hybrid spreading is critical to seed and establish infection, and that cell-to-cell spread and increased CD4+ T cell activation are important for HIV-1 progression. Notably, the model predicts that cell-to-cell spread becomes increasingly effective as infection progresses and thus may present a considerable treatment barrier. Deriving predictions of various treatments' influence on HIV-1 progression highlights the importance of earlier intervention and suggests that treatments effectively targeting cell-to-cell HIV-1 spread can delay progression to AIDS. This study suggests that hybrid spreading is a fundamental feature of HIV infection, and provides the mathematical framework incorporating this feature with which to evaluate future therapeutic strategies

SYSTÈME D'INFORMATION DOCUMENTAIRE GÉORÉFÉRENCÉ<br />SUR LE PATRIMOINE ARCHÉOLOGIQUE<br />ET HISTORIQUE DES ALPES-MARITIMES

accessible en ligne : http://www.archimuse.com/publishing/ichim05/boutros-ichim05-s01-v3.pdfThe creation of the « base de données archéologiques et patrimoniales du département des<br />Alpes-Maritimes » (Archeological and patrimonial database of the department of the Alpes-<br />Maritimes) is a joint project of the general council of the Alpes Maritimes, UMR 6130 of the<br />CEPAM (Centre of studies, Prehistory, Antiquity, Middle age) of CNRS (French National<br />Center for Research) and UNSA (University of Sofia-Antipolis). This project lies within the<br />scope of Partnership for the Alpes-Maritimes heritage and knowledge.<br />The goal is to build a single application that allow to browse and to locate scientific<br />documentation relating to the archeological sites and the heritage monuments of the<br />department.<br />Each site or monument is described and located by the integration of geographical references.<br />These geo coordinates make it possible to visualise the sites in their spacial, environmental<br />and chronological context thanks to a documentary and geographical information system<br />associating descriptive data base and thematic maps.La constitution de la base de données archéologiques et patrimoniales du département des<br />Alpes-Maritimes est une entreprise conjointe du Conseil Général des Alpes-Maritimes, de<br />l'UMR 6130 du CEPAM (Centre d'études, Préhistoire, Antiquité, Moyen Âge) du CNRS et<br />de l'UNSA (Université de Nice Sophia Antipolis). Elle s'inscrit dans le cadre de l'action de<br />Partenariat pour la connaissance du Patrimoine des Alpes Maritimes.<br />L'objectif est de construire un outil de travail unique permettant de connaître et de localiser la<br />documentation scientifique concernant les sites archéologiques et les monuments<br />patrimoniaux du département.<br />Chaque site ou monument patrimonial est décrit et localisé grâce à l'intégration de références<br />géographiques. Ces dernières permettent de replacer et visualiser les sites dans leur contexte<br />spatial, environnemental et chronologique grâce à un système à la fois documentaire<br />relationnel et d'information géographique associant en ligne une base de données descriptives<br />et des cartes thématiques

Chapitre 6. L’époque contemporaine

1. Interprétation (P. E.) Cette dernière phase, qui va de la fin du XVIIe siècle à nos jours, n’a été que partiellement abordée. Le secteur est toujours resté une zone agricole jusqu’à la construction actuelle. La fruiticulture est restée prépondérante durant le XXe siècle, où ce sont des pruniers qui ont succédé aux vignes, après l’inondation du terrain causé par la rupture du barrage du Malpasset. La ferme n’apparaît qu’en 1825, sur une carte anonyme, puis sur le cadastre napoléonien de 182..

Extensive complement-dependent enhancement of HIV-1 by autologous non-neutralising antibodies at early stages of infection

Background: Non-neutralising antibodies to the envelope glycoprotein are elicited during acute HIV-1 infection and are abundant throughout the course of disease progression. Although these antibodies appear to have negligible effects on HIV-1 infection when assayed in standard neutralisation assays, they have the potential to exert either inhibitory or enhancing effects through interactions with complement and/or Fc receptors. Here we report that non-neutralising antibodies produced early in response to HIV-1 infection can enhance viral infectivity.Results: We investigated this complement-mediated antibody-dependent enhancement (C'-ADE) of early HIV infection by carrying out longitudinal studies with primary viruses and autologous sera derived sequentially from recently infected individuals, using a T cell line naturally expressing the complement receptor 2 (CR2; CD21). The C'-ADE was consistently observed and in some cases achieved infection-enhancing levels of greater than 350-fold, converting a low-level infection to a highly destructive one. C'-ADE activity declined as a neutralising response to the early virus emerged, but later virus isolates that had escaped the neutralising response demonstrated an increased capacity for enhanced infection by autologous antibodies. Moreover, sera with autologous enhancing activity were capable of C'ADE of heterologous viral isolates, suggesting the targeting of conserved epitopes on the envelope glycoprotein. Ectopic expression of CR2 on cell lines expressing HIV-1 receptors was sufficient to render them sensitive to C'ADE.Conclusions: Taken together, these results suggest that non-neutralising antibodies to the HIV-1 envelope that arise during acute infection are not 'passive', but in concert with complement and complement receptors may have consequences for HIV-1 dissemination and pathogenesis