Cell-Cell Transmission Enables HIV-1 to Evade Inhibition by Potent CD4bs Directed Antibodies

HIV is known to spread efficiently both in a cell-free state and from cell to cell, however the relative importance of the cell-cell transmission mode in natural infection has not yet been resolved. Likewise to what extent cell-cell transmission is vulnerable to inhibition by neutralizing antibodies and entry inhibitors remains to be determined. Here we report on neutralizing antibody activity during cell-cell transmission using specifically tailored experimental strategies which enable unambiguous discrimination between the two transmission routes. We demonstrate that the activity of neutralizing monoclonal antibodies (mAbs) and entry inhibitors during cell-cell transmission varies depending on their mode of action. While gp41 directed agents remain active, CD4 binding site (CD4bs) directed inhibitors, including the potent neutralizing mAb VRC01, dramatically lose potency during cell-cell transmission. This implies that CD4bs mAbs act preferentially through blocking free virus transmission, while still allowing HIV to spread through cell-cell contacts. Thus providing a plausible explanation for how HIV maintains infectivity and rapidly escapes potent and broadly active CD4bs directed antibody responses in vivo

Effective Treatment of SIVcpz-Induced Immunodeficiency in a Captive Western Chimpanzee

Abstract Background Simian immunodeficiency virus of chimpanzees (SIVcpz), the progenitor of human immunodeficiency virus type 1 (HIV-1), is associated with increased mortality and AIDS-like immunopathology in wild-living chimpanzees (Pan troglodytes). Surprisingly, however, similar findings have not been reported for chimpanzees experimentally infected with SIVcpz in captivity, raising questions about the intrinsic pathogenicity of this lentivirus. Findings Here, we report progressive immunodeficiency and clinical disease in a captive western chimpanzee (P. t. verus) infected twenty years ago by intrarectal inoculation with an SIVcpz strain (ANT) from a wild-caught eastern chimpanzee (P. t. schweinfurthii). With sustained plasma viral loads of 105 to 106 RNA copies/ml for the past 15 years, this chimpanzee developed CD4+ T cell depletion (220 cells/μl), thrombocytopenia (90,000 platelets/μl), and persistent soft tissue infections refractory to antibacterial therapy. Combination antiretroviral therapy consisting of emtricitabine (FTC), tenofovir disoproxil fumarate (TDF), and dolutegravir (DTG) decreased plasma viremia to undetectable levels (<200 copies/ml), improved CD4+ T cell counts (509 cell/μl), and resulted in the rapid resolution of all soft tissue infections. However, initial lack of adherence and/or differences in pharmacokinetics led to low plasma drug concentrations, which resulted in transient rebound viremia and the emergence of FTC resistance mutations (M184V/I) identical to those observed in HIV-1 infected humans. Conclusions These data demonstrate that SIVcpz can cause immunodeficiency and other hallmarks of AIDS in captive chimpanzees, including P. t. verus apes that are not naturally infected with this virus. Moreover, SIVcpz-associated immunodeficiency can be effectively treated with antiretroviral therapy, although sufficiently high plasma concentrations must be maintained to prevent the emergence of drug resistance. These findings extend a growing body of evidence documenting the immunopathogenicity of SIVcpz and suggest that experimentally infected chimpanzees may benefit from clinical monitoring and therapeutic intervention

Méthodes d’identification des aliments ionisés

Après avoir dressé un tableau des différentes méthodes utilisables, l’accent est particulièrement mis sur celles qui débouchent actuellement: résonance paramagnétique électronique, thermoluminescence et méthode des lipides. Ces méthodes sont également discutées quant à leur spécificité (preuve ou présomption); de plus, elles sont restituées dans le cadre du programme d’identification des aliments ionisés récemment lancé par le Bureau Communautaire de Référence de la CCE, sous la direction de l’auteur

Détection par RPE d'aliments ionisés

Après avoir défini dans quelles conditions la Résonance paramagnétique électronique (RPE) peut être utilisée pour démontrer qu'un aliment a été ou non ionisé, on détaille les résultats obtenus lors de l'intercomparaison organisée pour le Bureau Communautaire de Référence avec 22 laboratoires européens. L’identification des viandes, raisins secs et papayes ionisés ne pose aucun problème; des études cinétiques, espèce par espèce, sont nécessaires dans le cas des poissons; celui de la pistache, plus compliqué, nécessite des travaux complémentaires. Si tous les laboratoires ont été capables de faire la distinction entre les deux zones de doses (1-3 et 7-10 kGy), il faut noter un certain recouvrement des divers résultats

Application of ESR to identification of irradiated foodstuffs

The conditions required to use Electron Spin Resonance (ESR) in identification of irradiated foods is firs t described. Then we present the results of an intercomparison sponsored by the Community Bureau of Reference involving 22 european laboratories on meat and fish bones and fruits. Then the ESR protocols given to the BCR are described

Asymmetric topologies on statistical manifolds

Asymmetric information distances are used to define asymmetric norms and quasimetrics on the statistical manifold and its dual space of random variables. Quasimetric topology, generated by the Kullback-Leibler (KL) divergence, is considered as the main example, and some of its topological properties are investigated