Search

Members of the genus Ebolavirus cause lethal disease in humans, with Zaire ebolavirus (EBOV) being the most pathogenic (up to 90% morality) and Bundibugyo ebolavirus (BDBV) the least pathogenic (~37% mortality). Historically, there has been a lack of research on BDBV, and there is no means to study BDBV outside of a high-containment laboratory. Here, we describe a minigenome replication system to study BDBV transcription and compare the efficacy of small-molecule inhibitors between EBOV and BDBV. Using this system, we examined the ability of the polymerase complex proteins from EBOV and BDBV to interact and form a functional unit as well as the impact of the genomic untranslated ends, known to contain important signals for transcription (39-untranslated region) and replication (59-untranslated region). Various levels of compatibility were observed between proteins of the polymerase complex from each ebolavirus, resulting in differences in genome transcription efficiency. Most pronounced was the effect of the nucleoprotein and the 39-untranslated region. These data suggest that there are intrinsic specificities in the polymerase complex and untranslated signaling regions that could offer insight regarding observed pathogenic differences. Further adding to the differences in the polymerase complexes, posttransfection/infection treatment with the compound remdesivir (GS-5734) showed a greater inhibitory effect against BDBV than EBOV. The delayed growth kinetics of BDBV and the greater susceptibility to polymerase inhibitors indicate that disruption of the polymerase complex is a viable target for therapeutics. [ABSTRACT FROM AUTHOR]

Highlights • Sensitive and specific pan-filo RT-qPCR assay. • Optimized for both lyophilized and liquid based reagents. • Tested using ebola virus disease patient samples from epidemic in 2014. • Detected Bombalivirus. Abstract Background During the five decades since their discovery, filoviruses of four species have caused human hemorrhagic fever outbreaks: Marburg (MARV) marburgvirus, and Zaire (EBOV), Sudan (SUDV) and Bundybugyo (BDBV) ebolaviruses. The largest, devastating EBOV epidemic in West Africa in 2014-16, has been followed by outbreaks of MARV in Uganda, 2017, and EBOV in Democratic Republic of Congo, 2018, emphasizing the need to develop preparedness to diagnose all filoviruses. Objectives The aim of this study was to optimize a new filovirus RT-qPCR to detect all filoviruses, define its limits of detection (LOD) and perform a field evaluation with outbreak samples. Study design A pan-filovirus RT-qPCR targeting the L gene was developed and evaluated within the EbolaMoDRAD (Ebola virus: modern approaches for developing bedside rapid diagnostics) project. Specificity and sensitivity were determined and the effect of inactivation and PCR reagents (liquid and lyophilized format) were tested. Results The LODs for the lyophilized pan-filovirus L-RT-qPCR assay were 9.4 copies per PCR reaction for EBOV, 9.9 for MARV, 1151 for SUDV, 65 for BDBV and 289 for Taï Forest virus. The test was set at the Pasteur Institute, Dakar, Senegal, and 83 Ebola patient samples, with viral load ranging from 5 to 5 million copies of EBOV per reaction, were screened. The results for the patient samples were in 100% concordance with the reference EBOV-specific assay. Discussion Overall, the assay showed good sensitivity and specificity, covered all filoviruses known to be human pathogens, performed well both in lyophilized and liquid-phase formats and with EBOV outbreak clinical samples. [ABSTRACT FROM AUTHOR]

Ebola is examined as a Critical Event which shaped the communities in Bundibugyo district. The local framing of ebola epidemic 2007-8 as a curse to the particular ethnic groups affected the social networks and individual identities within communities. Ethnographic interviews and observations among victims of ebola were used as data, and a phenomenological approach was used to guide the research process. The paper recovers the lost moments and experiences of ebola survivors. The epidemic altered the socio-cultural set-up of the community and its impact have lasted for a long time; including stigma, discrimination, trauma, poverty and the orphan problem. [ABSTRACT FROM AUTHOR]

Viral preparations are essential components in diagnostic research and development. The production of large quantities of virus traditionally is done by infecting numerous tissue culture flasks or roller bottles, which require large incubators and/or roller bottle racks. The Corning HYPER Flask ® is a multilayer flask that uses a gas permeable film to provide gas exchange between the cells and culture medium and the atmospheric environment. This study evaluated the suitability of the HYPER Flask for production of Lassa, Ebola, Bundibugyo, Reston, and Marburg viruses and compared it to more traditional methods using tissue culture flasks and roller bottles. The HYPER Flask produced cultures were equivalent in virus titer and indistinguishable in immunodiagnostic assays. The use of the Corning HYPER Flask for viral production is a viable alternative to traditional tissue culture flasks and roller bottles. HYPER Flasks allow for large volumes of virus to be produced in a small space without specialized equipment. [ABSTRACT FROM AUTHOR]

The first known Ebola hemorrhagic fever (EHF) outbreak caused by Bundibugyo Ebola virus occurred in Bundibugyo District, Uganda, in 2007. Fifty-six cases of EHF were laboratory confirmed. Although signs and symptoms were largely nonspecific and similar to those of EHF outbreaks caused by Zaire and Sudan Ebola viruses, proportion of deaths among those infected was lower (≈40%).

The glycoprotein (GP) of ebolaviruses participates in a critical membrane fusion process to establish infection of a cell and therefore, represents an important target of both vaccines and antivirals. The latest reports on pan-ebolavirus monoclonal antibodies in small animal models may offer promising outcomes and insight into how best to target the GP in vaccine and antiviral discovery. [ABSTRACT FROM AUTHOR]

Ethnobotanical studies of the Rwenzori Mountain forest area in Bundibugyo District in Uganda were carried out between May and December 1991, and covered the northern part of the Rwenzori Mountain slopes occupied by the Bakonjo people. The presence of a major footpath through the forest with numerous utility trails radiating from it showed that some forest resources are being sought by the local population. Plant biodiversity is high, as is indicated by the fact that in a study plot of only 4 250 m , a total of 115 plant species, 101 genera and 57 families were identified from a collection of 300 plant specimens. Seventy-seven plant species were found to be of some importance to the local communities. Out of the 77 useful plant species recorded: 22 species were used for medicinal purposes; 16 for firewood; 13 for construction, joinery and furniture; 12 for craftwork; 10 provided edible fruits and vegetables; and 27 were used for a variety of other purposes. These other purposes include construction of shrines, covering of granary floors, use as toilet paper, carry ing luggage, and fodder for goats, sheep and cattle. Arundinaria alpina K. Schum. (bamboo) is the species that is most extensively harvested from the forest.

Recent and ongoing outbreaks of Ebola virus disease (EVD) underscore the unpredictable nature of ebolavirus reemergence and the urgent need for antiviral treatments. Unfortunately, available experimental vaccines and immunotherapeutics are specific for a single member of the Ebolavirus genus, Ebola virus (EBOV), and ineffective against other ebolaviruses associated with EVD, including Sudan virus (SUDV) and Bundibugyo virus (BDBV). Here we show that MBP134 AF , a pan-ebolavirus therapeutic comprising two broadly neutralizing human antibodies (bNAbs), affords unprecedented effectiveness and potency as a therapeutic countermeasure to antigenically diverse ebolaviruses. MBP134 AF could fully protect ferrets against lethal EBOV, SUDV, and BDBV infection, and a single 25-mg/kg dose was sufficient to protect NHPs against all three viruses. The development of MBP134 AF provides a successful model for the rapid discovery and translational advancement of immunotherapeutics targeting emerging infectious diseases., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Several ebolavirus species, with varying lethality rates, have caused sporadic outbreaks in Africa resulting in human disease. Ebolaviruses also have the potential for use as biological weapons. Currently, there are no licensed vaccines or therapeutics to respond to outbreaks or deliberate misuse of ebolaviruses. Vaccine or therapeutic efficacy testing of medical countermeasures against ebolaviruses requires an animal model of disease; in vitro testing in cell culture cannot reproduce the complicated balance between host-pathogen interactions required for the ultimate licensure of a countermeasure. Depending on the target of the countermeasure, demonstration of efficacy in the nonhuman primate ebolavirus disease models will most likely be required before licensure. Here, we describe the selection and use of nonhuman primates for vaccine and therapeutic studies against ebolaviruses.