Induction and modulation of type I interferon synthesis upon BTV infection

Bluetongue virus (BTV) is an arthropod-borne virus belonging to the Reoviridae family. It causes an haemorrhagic disease in ruminants that induces important economic losses. BTV infection triggers type I interferon (IFN-α/β) synthesis in vivo and in vitro, which is crucial to mount an efficient cellular antiviral response. This event requires viral replication since a UV inactivate virus is unable to induce IFN-β synthesis. We also showed that RNA helicases RIG-I and MDA5 are both involved in IFN-α/β production upon BTV infection. As this response is deleterious for viral replication, most of viruses have developed strategies to circumvent IFN action. We found that the non structural NS3 protein of BTV is a potent IFN-α/β inhibitorLe virus de la fièvre catarrhale ovine (FCO ; Bluetongue virus, BTV) est un arbovirus appartenant à la famille des Reoviridae. Il est responsable d’une maladie hémorragique chez les ruminants qui provoque d’importantes pertes économiques. L’infection par le BTV induit la production des interférons de type I (IFN-α/β) in vivo et in vitro, événement essentiel pour l’établissement d’une réponse cellulaire antivirale. Cette production requiert la réplication virale puisqu’un virus inactivé aux UV a perdu la capacité d’induire la synthèse d’IFN-β. Nous avons aussi pu démontrer que les ARN hélicases RIGI et MDA5 étaient impliquées dans la production d’IFN-α/β en réponse au BTV. Cette réponse étant délétère pour la multiplication virale, la plupart des virus ont développé des stratégies pour limiter l’action de l’interféron. Nous avons ainsi pu montrer que la protéine non structurale NS3 de BTV était un puissant antagoniste de la voie des IFN-α/

Improved functional expression of recombinant human ether-a-go-go (hERG) K+ channels by cultivation at reduced temperature

<p>Abstract</p> <p>Background</p> <p>HERG potassium channel blockade is the major cause for drug-induced long QT syndrome, which sometimes cause cardiac disrhythmias and sudden death. There is a strong interest in the pharmaceutical industry to develop high quality medium to high-throughput assays for detecting compounds with potential cardiac liability at the earliest stages of drug development. Cultivation of cells at lower temperature has been used to improve the folding and membrane localization of trafficking defective hERG mutant proteins. The objective of this study was to investigate the effect of lower temperature maintenance on wild type hERG expression and assay performance.</p> <p>Results</p> <p>Wild type hERG was stably expressed in CHO-K1 cells, with the majority of channel protein being located in the cytoplasm, but relatively little on the cell surface. Expression at both locations was increased several-fold by cultivation at lower growth temperatures. Intracellular hERG protein levels were highest at 27°C and this correlated with maximal ³H-dofetilide binding activity. In contrast, the expression of functionally active cell surface-associated hERG measured by patch clamp electrophysiology was optimal at 30°C. The majority of the cytoplasmic hERG protein was associated with the membranes of cytoplasmic vesicles, which markedly increased in quantity and size at lower temperatures or in the presence of the Ca²⁺-ATPase inhibitor, thapsigargin. Incubation with the endocytic trafficking blocker, nocodazole, led to an increase in hERG activity at 37°C, but not at 30°C.</p> <p>Conclusion</p> <p>Our results are consistent with the concept that maintenance of cells at reduced temperature can be used to boost the functional expression of difficult-to-express membrane proteins and improve the quality of assays for medium to high-throughput compound screening. In addition, these results shed some light on the trafficking of hERG protein under these growth conditions.</p

Impact of Schmallenberg virus on British farms

Erratum in : Vet Rec. 2014 Aug 30;175(8):200International audienc

Repulsion of superinfecting virions: a mechanism for rapid virus spread

National audienc

Zoonotic Hepatitis E Virus: Classification, Animal Reservoirs and Transmission Routes

During the past ten years, several new hepatitis E viruses (HEVs) have been identified in various animal species. In parallel, the number of reports of autochthonous hepatitis E in Western countries has increased as well, raising the question of what role these possible animal reservoirs play in human infections. The aim of this review is to present the recent discoveries of animal HEVs and their classification within the Hepeviridae family, their zoonotic and species barrier crossing potential, and possible use as models to study hepatitis E pathogenesis. Lastly, this review describes the transmission pathways identified from animal sources

Hépatite E, zoonose alimentaire

National audienceLa santé est une préoccupation primordiale qui irrigue une part déterminante des travaux de l’Inra d’une manière transversale. À l’occasion du Salon international de l’agriculture 2017, l'Institut a ainsi choisi de consacrer son colloque scientifique au thème Homme, animal, environnement : la santé en partage

Hépatite E, zoonose alimentaire

National audienceLa santé est une préoccupation primordiale qui irrigue une part déterminante des travaux de l’Inra d’une manière transversale. À l’occasion du Salon international de l’agriculture 2017, l'Institut a ainsi choisi de consacrer son colloque scientifique au thème Homme, animal, environnement : la santé en partage