Les virus Ebola (EBOV) et Marburg (MARV) causent des fièvres hémorragiques chez les primates, y compris l'homme. Le taux de létalité peut atteindre 90% et il n'existe ni vaccin ni traitement contre ces virus. En raison de leurs caractéristiques moléculaires communes, EBOV et MARV sont regroupés au sein de la famille des Filoviridae. Le virion est composé de 7 protéines, dont la VP24, qui joue un rôle important dans l'assemblage et la condensation des nucléocapsides, et pour EBOV, elle est également responsable de l'inhibition de la réponse à l'IFN. Des mutations dans la séquence protéique de VP24 sont impliquées dans le processus d'adaptation chez un nouvel hôte. La protéine VP24 d'EBOV est donc multifonctionnelle. Pour MARV, cette protéine ne semble pas porter les fonctions décrites pour la VP24 d'EBOV. Afin de comprendre le rôle de la VP24 de MARV, nous avons identifié ses partenaires cellulaires par un crible double-hybride en levures. Nous avons mis en évidence l'interaction entre Keap1 et la VP24 de MARV, et confirmé ce résultat en cellules mammifères. Keap1 est une protéine impliquée dans le contrôle de la réponse au stress oxydatif, car elle inhibe le facteur de transcription Nrf2, qui régule l'expression d'enzymes impliquées dans la réduction des ERO. Nos résultats montrent que le domaine de Keap1 liant la VP24 est le même que celui liant Nrf2, et que la VP24 de MARV active Nrf2 pour la synthèse de molécules anti-oxydantes. Nous avons enfin évalué l'impact de la VP24 de MARV sur ERR, une autre cible de Keap1, et mesuré l'activité Nrf2 au cours de l'infection par EBOV. Nos résultats montrent des effets opposés des VP24 d' EBOV et de MARV sur l'activité de Nrf2.

Ebola, a type of filovirus that causes hemorrhagic fevers, dominated global headlines in 2014 when the largest Ebola epidemic in history took place in West Africa. Healthcare practitioners were at particular risk of contracting Ebola while taking care of patients with the disease because they were easily exposed to bodily fluids such as blood, urine, saliva, and feces, quite often in the intensive care unit (ICU). While personal protective equipment (PPE) protects the healthcare practitioner by providing an effective barrier against the virus, users were also at risk for heat stress because of the type of protective clothing. In this study, coveralls made of monolithic barriers, which prevent water vapor from escaping the suit, were compared to coveralls made of micro- porous material, which allows evaporated sweat to escape the suit. The Microgard® 2000 TS Plus, made of micro-porous barrier material and the monolithic barrier Microgard® 2300 Plus were compared against a control ensemble of work clothes consisting of a long-sleeve shirt and trouser. A progressive heat stress protocol was used to determine the critical environment at the upper limit of compensable heat stress. The critical condition was the point at which the heat gain caused by wearing the protective ensemble as well as dry heat exchange was balanced by the maximum heat loss due to evaporative cooling. Wet bulb globe temperature at the critical condition (WBGTcrit ) ,total evaporative resistance (Re,T,a), and clothing adjustable factor (CAF) were calculated for each ensemble based on data at the critical point. Also at the critical condition, participant rectal temperature vi (Tre) , heart rate (HR), skin temperature (Tsk), and physiological strain index (PSI) were noted and compared for each ensemble. A two-way ANOVA (ensemble x participant) for WBGTcrit and Re,T,a as dependent variables was used to determine whether or not there were differences among ensembles. Tukey’s honest significance test was used to determine where significant differences occurred. WBGTcrit was 33.8, 26.3, and 22.9 °C-WBGT for Work Clothes, M2000, and M2300 respectively. Re,T,a was 0.012, 0.031, and 0.054 kPa m2 W-1 for WC, M2000, and M2300 respectively. The higher the WBGTcrit for an ensemble, the more it can support evaporative cooling and hence the better it is at ameliorating heat stress. Based on this trial, the micro-porous ensemble Microgard® 2000 TS Plus has better heat stress performance than vapor-barrier Microgard® 2300 Plus. As expected, there were no differences for any of the physiological metrics at the critical conditions.