Project description:Bundibugyo virus (BDBV) is the most recently discovered pathogenic species of ebolavirus, with mortality rates of 25% and 51% reported in two identified. BDBV infection is non-uniformly lethal in macaques. The lack of uniform lethality offers the opportunity for identification of biomarkers that correlate with positive and negative outcomes following infection that can help define mechanisms of pathogenesis and potentially serve as guides for clinical care. In both the treatment and control groups, ~58% survived infection, an increase over lethality seen in historical controls. There was no differential advantage of the BDBV GP expressing vaccine, suggesting a general effect of rVSV. Our transcriptomic analysis identified strong initial responses to infection and treatment in all animals. This response returned to baseline in animals with mild disease by day 7. In animals with severe disease, fatal cases could be predicted beginning at day 5 post infection based on the expression of 5 circulating mRNAs. This study suggested a nonspecific effect of treating NHPs with VSV-based vectors as a postexposure therapy following BDBV infection and identified potential biomarkers of outcome.
Project description:Bundibugyo virus: Genome sequencing by Pathogen Genomic Lab, Institut National de Recherche Biomédicale, Kinshasa, Democratic Republic of the Congo
Project description:<p>Tick-borne encephalitis virus is an enveloped, pathogenic, RNA virus in the family Flaviviridae, genus Flavivirus. Viral particles are formed when the nucleocapsid, consisting of an RNA genome and multiple copies of the capsid protein, buds through the endoplasmic reticulum membrane and acquires the viral envelope and the associated proteins. The coordination of the nucleocapsid components to the sites of assembly and budding are poorly understood. Here, we investigate nucleocapsid assembly by characterizing the interactions of the wild-type and truncated capsid proteins with membranes by using biophysical methods and model membrane systems. We show that capsid protein initially binds membranes via electrostatic interactions with negatively-charged lipids which is followed by membrane insertion. Additionally, we show that membrane-bound capsid protein can recruit viral genomic RNA. We confirm the biological relevance of the biophysical findings by using mass spectrometry to show that purified virions contain negatively-charged lipids. Our results suggest that nucleocapsid assembly is coordinated by negatively-charged membrane patches on the endoplasmic reticulum and that the capsid protein mediates direct contacts between the nucleocapsid and the membrane.</p>
