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Blanchet M.,INRS - Institute National de la Recherche Scientifique | Sureau C.,Sanguine | Labonte P.,INRS - Institute National de la Recherche Scientifique
Antiviral Research | Year: 2014

Worldwide there are approximately 240 million individuals chronically infected with the hepatitis B virus (HBV), including 15-20 million coinfected with the hepatitis delta virus (HDV). Treatments available today are not fully efficient and often associated to important side effects and development of drug resistance. Targeting the HBV/HDV entry step using preS1-specific lipopeptides appears as a promising strategy to block viral entry for both HBV and HDV (Gripon et al., 2005; Petersen et al., 2008). Recently, the human Sodium Taurocholate Cotransporting Polypeptide (hNTCP) has been identified as a functional, preS1-specific receptor for HBV and HDV. This groundbreaking discovery has opened a very promising avenue for the treatment of chronic HBV and HDV infections. Here we investigated the ability of FDA approved therapeutics with documented inhibitory effect on hNTCP cellular function to impair viral entry using a HDV in vitro infection model based on a hNTCP-expressing Huh7 cell line. We demonstrate the potential of three FDA approved molecules, irbesartan, ezetimibe, and ritonavir, to alter HDV infection in vitro. © 2014 Elsevier Ltd. All rights reserved.

Sureau C.,Sanguine
Methods in molecular biology (Clifton, N.J.) | Year: 2010

Worldwide, it is estimated that more than 350 million people are chronically infected with hepatitis B virus (HBV), approximately 15 million of whom are coinfected with hepatitis D virus (HDV), a satellite of HBV that uses the envelope proteins of the latter to assemble its infectious particles. For a long time after HBV discovery, research on the viral life cycle, viral entry in particular, has been hampered by the lack of practical tissue culture systems. To date, in vitro isolation and serial propagation of HBV are still problematic, but the examination of the entire HBV life cycle is possible using two separate systems: (i) permissive human hepatoma cell lines to study HBV DNA replication, viral transcription, translation, assembly, and release of viral particles and (ii) primary cultures of human or chimpanzee hepatocytes or the susceptible HepaRG cell line for viral entry examination. The experimental model described here for analyzing the function of HBV envelope proteins at viral entry is based on this dual tissue culture system, in which HDV is substituted to HBV for practical reasons.

Garraud O.,Sanguine | Garraud O.,Jean Monnet University | Cognasse F.,Jean Monnet University
Frontiers in Immunology | Year: 2015

Small fragments circulating in the blood were formally identified by the end of the nineteenth century, and it was suggested that they assisted coagulation via interactions with vessel endothelia. Wright, at the beginning of the twentieth century, identified their bone-marrow origin. For long, platelets have been considered sticky assistants of hemostasis and pollutants of blood or tissue samples; they were just cell fragments. As such, however, they were acknowledged as immunizing (to specific HPA and HLA markers): the platelet's dark face. The enlightened face showed that besides hemostasis, platelets contained factors involved in healing. As early as 1930s, platelets entered the arsenal of medicines were transfused, and were soon manipulated to become a kind of glue to repair damaged tissues. Some gladly categorized platelets as cells but they were certainly not fully licensed as such for cell physiologists. Actually, platelets possess almost every characteristic of cells, apart from being capable of organizing their genes: they have neither a nucleus nor genes. This view prevailed until it became evident that platelets play a role in homeostasis and interact with cells other than with vascular endothelial cells; then began the era of physiological and also pathological inflammation. Platelets have now entered the field of immunity as inflammatory cells. Does assistance to immune cells itself suffice to license a cell as an "immune cell"? Platelets prove capable of sensing different types of signals and organizing an appropriate response. Many cells can do that. However, platelets can use a complete signalosome (apart from the last transcription step, though it is likely that this step can be circumvented by retrotranscribing RNA messages). The question has also arisen as to whether platelets can present antigen via their abundantly expressed MHC class I molecules. In combination, these properties argue in favor of allowing platelets the title of immune cells. © 2015 Garraud and Cognasse.

Musso D.,Institute Louis Malarde | Richard V.,Institute Louis Malarde | Broult J.,Sanguine | Cao-Lormeau V.-M.,Institute Louis Malarde
Transfusion | Year: 2014

Background Dengue virus (DENV) is the most prevalent arbovirus in tropical and subtropical regions. Transfusion-transmitted DENV infections have already been reported and the risk for blood products to be contaminated by DENV needs to be considered in dengue-endemic areas, especially during outbreaks. Blood product inactivation processes, including amotosalen and ultraviolet A (UVA) illumination, have been developed to reduce transfusion-transmitted infections. In this study we demonstrate the efficiency of using amotosalen and UVA illumination for DENV inactivation in human plasma.Study Design and Methods Plasma units from volunteer blood donors were spiked with DENV. Viral titers and viral RNA loads were measured in plasma before and after amotosalen and UVA photochemical treatment.Results The mean DENV titer in plasma before inactivation was 5.61 log 50% tissue culture infectious dose (TCID50)/mL and the mean viral RNA load was 10.21 log copies/mL. In inactivated plasma, the mean DENV RNA load was 9.37 log copies/mL, but cell cultures inoculated with inactivated plasma did not result in infected cells and did not produce any replicative virus nor detectable viral RNA.Conclusion We report here that amotosalen combined with UVA light inactivated DENV in fresh-frozen plasma (5.61 log inactivation of viral titer). This inactivation process is an efficient method to prevent plasma transfusion-transmitted DENV infections. © 2014 AABB.

Aubry M.,Institute Louis Malarde | Richard V.,Institute Louis Malarde | Green J.,Cerus Corporation | Broult J.,Sanguine | Musso D.,Institute Louis Malarde
Transfusion | Year: 2016

BACKGROUND Zika virus (ZIKV) is an arthropod-borne virus (arbovirus) transmitted by mosquitoes. The potential for ZIKV transmission through blood transfusion was demonstrated during the ZIKV outbreak that occurred in French Polynesia from October 2013 to April 2014. Pathogen inactivation of blood products is a proactive strategy that provides the potential to reduce transfusion-transmitted diseases. Inactivation of arboviruses by amotosalen and ultraviolet A (UVA) illumination was previously demonstrated for chikungunya, West Nile, and dengue viruses. We report here the efficiency of this process for ZIKV inactivation of human plasma. STUDY DESIGN AND METHODS Plasma units were spiked with ZIKV. Viral titers and RNA loads were measured in plasma before and after amotosalen and UVA photochemical treatment. RESULTS The mean ZIKV titers and RNA loads in plasma before inactivation were respectively 6.57 log TCID50/mL and 10.25 log copies/mL. After inactivation, the mean ZIKV RNA loads was 9.51 log copies/mL, but cell cultures inoculated with inactivated plasma did not result in infected cells and did not produce any replicative virus after one passage, nor detectable viral RNA from the second passage. CONCLUSION In this study we demonstrate that amotosalen combined with UVA light inactivates ZIKV in fresh-frozen plasma. This inactivation process is of particular interest to prevent plasma transfusion-transmitted ZIKV infections in areas such as French Polynesia, where several arboviruses are cocirculating. © 2015 The Authors Transfusion published by Wiley Periodicals, Inc. on behalf of AABB.

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