BACKGROUND: Better treatments are urgently needed for the management of Ebola virus epidemics in Equatorial Africa. METHODS: We conducted a systematic review of the literature on the use of passive immunotherapy for the treatment or prevention of Ebola virus disease. We placed findings from this review into the context of passive immunotherapy currently used for venom-induced disease, and recent improvements in manufacturing of polyvalent antivenom products. RESULTS: Passive immunotherapy appears to be one of the most promising specific treatments for Ebola. However, its potential has been incompletely evaluated, considering the overall experience and recent improvement of immunotherapy. Development and use of heterologous serum derivatives could protect people exposed to Ebola viruses with reasonable cost and logistics. CONCLUSION: Hyperimmune equine IgG fragments and purified polyclonal whole IgG deserve further consideration as treatment for exposure to the Ebola virus.

Human immunodeficiency virus (HIV) causes acquired immunodeficiency syndrome by targeting and destroying CD4+ T cells via its Envelope protein (Env), while Ebola virus (EBOV) causes a lethal hemorrhagic fever and targets antigen presenting cells (APCs) via its glycoprotein (GP). There are no licensed vaccines for either virus, posing a problem particularly in Africa, where succumbing to EBOV or HIV is a grim reality. We hypothesized that a replication-competent HIV expressing GP as a replacement for Env will redirect the virus from CD4+ T cells toward antigen presenting cells and act as a live, bivalent vaccine to induce cellular and humoral immune responses against both pathogens, and confer protection against a lethal EBOV challenge in mice. Recombinant HIV-1 molecular clones containing different truncations of the GP gene to replace HIV gp120 were generated and used to rescue three GP-expressing vaccines, HIV-EBOV, HIV-EBOVΔ1, and HIV-EBOVΔ2. These demonstrated tropism for the monocyte cell line, THP-1, and decreased tropism for the CD4+ T cell line, SupT1. While all vaccines induced HIV p24- and GP-specific IFN-γ-secreting T cell responses, HIV-EBOVΔ1 and HIV-EBOVΔ2 induced the most robust responses at 21 days post-vaccination (dpv), respectively. While all vaccines induced total anti-p24 and anti-GP IgG responses, HIV-EBOVΔ1 induced the most robust responses at 42 dpv. HIV-EBOVΔ1 demonstrated the highest protective efficacy against lethal EBOV challenge, followed by HIV-EBOVΔ2 and HIV-EBOV, providing 83%, 67%, and 50% survival in mice, respectively. HIV-EBOVΔ1 shows promise as a protective vaccine against EBOV, but may require further optimization and characterization regarding its mechanism of action and ability to protect against HIV. / October 2016

Ebolavirus (EBOV) is a negative sense, single stranded RNA virus that causes Ebola hemorrhagic fever. This disease causes substantial morbidity and mortality in humans, with death occurring in 50-90% of cases. Despite years of intensive research, much of the molecular mechanism underlying the entry of EBOV remains unknown. We performed a bioinformatics screen to identify novel entry cofactors by correlating mRNA expression in a panel of human cancer cell lines with permissivity to the EBOV entry glycoprotein. This assay identified several known EBOV entry cofactors such as actin and the tyrosine kinase Axl. In addition, several genes involved in macropinocytosis and endosomal maturation were also correlated with EBOV permissivity. Subsequent evaluation of plasma membrane proteins correlated by this screen showed T-cell immunoglobulin and mucin domain-1 (TIM-1) mRNA expression correlated extremely well with EBOV pseudovirion transduction. Depletion of TIM-1 from highly-permissive cells inhibits EBOV pseudovirion transduction. Conversely, expression of TIM-1 in poorly-permissive cells significantly and specifically enhances EBOV pseudovirion transduction and infection. TIM-1 binds to EBOV GP and this binding is important in the initial interaction between the virus and the host cell. ARD5, a TIM-1 mAb, significantly inhibits EBOV GP-mediated entry into several cell lines and primary human airway epithelia in a dose and time-dependent manner. Therefore, TIM-1 is the first receptor identified for EBOV. Additionally, AMP-activated protein kinase (AMPK) mRNA correlated strongly with EBOV pseudovirion transduction. Compound C, a specific AMPK inhibitor, inhibited EBOV pseudovirion transduction and infection in a time and dose-dependent manner into several cell lines and primary human monocyte derived macrophages. Mouse embryonic fibroblasts (MEFs) lacking functional AMPK were significantly less permissive to EBOV GP-mediated infection that WT MEFs. Visualization of virus entry into these cells revealed that EBOV causes actin polymerization independently of AMPK, but AMPK-/- cells do not form lamellipodia in the presence of EBOV and, consequently, cannot internalize virus into cells by macropinocytosis.

Thèse de doctorat : Mathématiques : Mathématiques appliquées : Metz : 2006. / Thèse soutenue sur ensemble de travaux. Bibliogr. p. 133-139.

Thèse de doctorat : Biologie Moléculaire : Nancy 1 : 2007. / Titre provenant de l'écran-titre. Bibliogr.

SAMMANFATTNING Bakgrund Ebolasmitta orsakas av ett virus som sprids via kroppsvätskor och har orsakat utbrott vid flera tillfällen i världen. Utbrottet som startade år 2013 i Västafrika räknas som det största utbrottet hittills. I och med att människor reser allt mer blir också risken att epidemier som denna ska kunna drabba även Sverige större. Detta kräver en beredskap hos sjuksköterskor och de verksamheter där de arbetar. Ansvaret för att denna beredskap upprätthålls finns enligt lag hos både arbetsgivare och arbetstagare. Akutmottagningen är troligen den verksamhet som först möter patienter med akuta besvär och därmed krävs där adekvata rutiner och riktlinjer för att kunna hantera ett fall av misstänkt ebolasmitta. Syfte Studiens syfte var att beskriva de förberedelser sjuksköterskor på akutmottagningen vidtagit inför ett eventuellt vårdande av en patient som misstänkts ha smittats av ebolavirus. Metod Studien har genomförts med kvalitativa intervjuer för att belysa sjuksköterskornas egen upplevelse. Totalt har åtta sjuksköterskor intervjuats på tre akutmottagningar. Intervjuerna har transkriberats ordagrant och analyserats med manifest kvalitativ innehållsanalys. Resultat Ur resultatet framkom att sjuksköterskorna tagit ett eget ansvar för att tillskansa sig vetskap gällande ebolasmittan. Vidare beskrivs att sjuksköterskorna anser att ansvaret för kompetensutveckling bör delas mellan dem själva och deras arbetsgivare. Sjuksköterskorna upplevde själva att de överlag var nöjda med de förberedelser som gjorts och att det lett till en ökad vetskap samt minskad oro och rädsla för att ebolasmittan skulle drabba dem själva. Dock upplevde de att möjligheterna till praktiska övningar borde ha varit bättre. Slutsats Sjuksköterskorna anses visa god följsamhet till kraven ställda på dem genom bland annat Socialstyrelsens kompetensbeskrivning för legitimerade sjuksköterskor. Förbättringspotential anses finnas gällande formerna för kompetensutveckling. Beredskapen har blivit något bättre jämfört med vad tidigare studie visade på, men ett fortsatt arbete krävs.

Thesis supervisor: Wendy J. Maury. Includes bibliographic references (p. 56-66).

Thèse (M.Sc.)--Université Laval, 2003. / Bibliogr.: f. [87]-101. Publié aussi en version électronique.

Recent studies have shown that Ebola virus can persist in wastewater, and the potential for the virus to be aerosolized and pose a risk of inhalation exposure has not been evaluated. We considered this risk for three wastewater systems: toilets, a lab-scale model of an aeration basin, and a lab-scale model of converging sewer pipes. We measured the aerosol size distribution generated by each system, spiked Ebola virus surrogates into each system, and determined the emission rate of viruses into the air. While the number of aerosols released ranged from 105 to 107 per flush from the toilets or per minute from the lab-scale models, the total volume of aerosols generated by these systems was ~10-8 to 10-7 mL per flush or per minute in all cases. The Ebola virus surrogates MS2 and Phi6, spiked into toilets at an initial concentration of 107 PFU mL-1, were not detected in air after flushing. Airborne concentrations of MS2 and Phi6 were ~20 PFU L-1 and ~0.1 PFU L-1, respectively, associated with the aeration basin and sewer models. This corresponds to emission rates of 547 PFU min-1 and 3.8 PFU min-1 of MS2 and Phi6, respectively, for the aeration basin and 79 PFU min-1 and 0.3 PFU min-1 for the sewer model. Since information on the aerosolization of Ebola virus is quite limited, these emission rates can greatly help inform risk assessment of inhalation exposure to Ebola virus. / Master of Science

This thesis explores representations of Africans in the American media coverage of the 2014 Ebola outbreak and the differing policy solutions they sometimes elicit. I hypothesize that there is a connection between identity construction and policy solutions that can be explored along two major trajectories. First, I find sources that prefer "othering" stereotypes of Africans in their coverage often produce "securitized" solutions. I explore this trend through literature that links identity, geography, and infectious diseases constructing an image of an "infectious other". From the "French" disease to the "Spanish" flu, the association of disease and geography is a longstanding one that again is manifested with the Ebola virus (Harrison 2014). "Othered" from "civilized" and healthy populations, the people that inhabited these "dangerous" and "infected" areas became similarly stereotyped. In comparison to the first category, I find sources in the second trajectory that undertake a societal and structural analysis of the outbreak often favor approaches aimed at improving access to healthcare for the affected populations. Doctor Paul Farmer's work informs this section of examination. I conclude the thesis by briefly posing a few questions for future research as well as examining the Ebola virus in relation to the Zika virus. / Master of Arts