human fatal zaire ebola virus infection is associated with an aberrant innate immunity and with massive lymphocyte apoptosis.ebolavirus species zaire (zebov) causes highly lethal hemorrhagic fever, resulting in the death of 90% of patients within days. most information on immune responses to zebov comes from in vitro studies and animal models. the paucity of data on human immune responses to this virus is mainly due to the fact that most outbreaks occur in remote areas. published studies in this setting, based on small numbers of samples and limited panels of immunological markers, have given somewhat different result ...201020957152
ebola virus glycoprotein fc fusion protein confers protection against lethal challenge in vaccinated mice.ebola virus is a filoviridae that causes hemorrhagic fever in humans and induces high morbidity and mortality rates. filoviruses are classified as "category a bioterrorism agents", and currently there are no licensed therapeutics or vaccines to treat and prevent infection. the filovirus glycoprotein (gp) is sufficient to protect individuals against infection, and several vaccines based on gp are under development including recombinant adenovirus, parainfluenza virus, venezuelan equine encephalit ...201121329775
the tyro3 receptor kinase axl enhances macropinocytosis of zaire ebolavirus.axl, a plasma membrane-associated tyro3/axl/mer (tam) family member, is necessary for optimal zaire ebolavirus (zebov) glycoprotein (gp)-dependent entry into some permissive cells but not others. to date, the role of axl in virion entry is unknown. the focus of this study was to characterize entry pathways that are used for zebov uptake in cells that require axl for optimal transduction and to define the role of axl in this process. through the use of biochemical inhibitors, interfering rna (rna ...201021047970
postexposure protection of non-human primates against a lethal ebola virus challenge with rna interference: a proof-of-concept study.we previously showed that small interfering rnas (sirnas) targeting the zaire ebola virus (zebov) rna polymerase l protein formulated in stable nucleic acid-lipid particles (snalps) completely protected guineapigs when administered shortly after a lethal zebov challenge. although rodent models of zebov infection are useful for screening prospective countermeasures, they are frequently not useful for prediction of efficacy in the more stringent non-human primate models. we therefore assessed the ...201020511019
vesicular stomatitis virus-based ebola vaccine is well-tolerated and protects immunocompromised nonhuman primates.ebola virus (ebov) is a significant human pathogen that presents a public health concern as an emerging/re-emerging virus and as a potential biological weapon. substantial progress has been made over the last decade in developing candidate preventive vaccines that can protect nonhuman primates against ebov. among these prospects, a vaccine based on recombinant vesicular stomatitis virus (vsv) is particularly robust, as it can also confer protection when administered as a postexposure treatment. ...200819043556
global suppression of the host antiviral response by ebola- and marburgviruses: increased antagonism of the type i interferon response is associated with enhanced virulence.we studied the effect of filovirus infection on host cell gene expression by characterizing the regulation of gene expression responses in human liver cells infected with zaire ebolavirus (zebov), reston ebolavirus (rebov), and marburgvirus (marv), using transcriptional profiling and bioinformatics. expression microarray analysis demonstrated that filovirus infection resulted in the up-regulation of immune-related genes and the down-regulation of many coagulation and acute-phase proteins. these ...200616501110
protection of nonhuman primates against two species of ebola virus infection with a single complex adenovirus vector.ebola viruses are highly pathogenic viruses that cause outbreaks of hemorrhagic fever in humans and other primates. to meet the need for a vaccine against the several types of ebola viruses that cause human diseases, we developed a multivalent vaccine candidate (ebo7) that expresses the glycoproteins of zaire ebolavirus (zebov) and sudan ebolavirus (sebov) in a single complex adenovirus-based vector (cadvax). we evaluated our vaccine in nonhuman primates against the parenteral and aerosol routes ...201020181765
large serological survey showing cocirculation of ebola and marburg viruses in gabonese bat populations, and a high seroprevalence of both viruses in rousettus aegyptiacus.ebola and marburg viruses cause highly lethal hemorrhagic fevers in humans. recently, bats of multiple species have been identified as possible natural hosts of zaire ebolavirus (zebov) in gabon and republic of congo, and also of marburgvirus (marv) in gabon and democratic republic of congo.200919785757
single-injection vaccine protects nonhuman primates against infection with marburg virus and three species of ebola virus.the filoviruses marburg virus and ebola virus cause severe hemorrhagic fever with high mortality in humans and nonhuman primates. among the most promising filovirus vaccines under development is a system based on recombinant vesicular stomatitis virus (vsv) that expresses a single filovirus glycoprotein (gp) in place of the vsv glycoprotein (g). here, we performed a proof-of-concept study in order to determine the potential of having one single-injection vaccine capable of protecting nonhuman pr ...200919386702
ebola virus vp24 proteins inhibit the interaction of npi-1 subfamily karyopherin alpha proteins with activated stat1.the zaire ebolavirus protein vp24 was previously demonstrated to inhibit alpha/beta interferon (ifn-alpha/beta)- and ifn-gamma-induced nuclear accumulation of tyrosine-phosphorylated stat1 (py-stat1) and to inhibit ifn-alpha/beta- and ifn-gamma-induced gene expression. these properties correlated with the ability of vp24 to interact with the nuclear localization signal receptor for py-stat1, karyopherin alpha1. here, vp24 is demonstrated to interact not only with overexpressed but also with endo ...200717928350
pathogenesis of filoviral haemorrhagic fevers.the filoviruses, marburgvirus and ebolavirus, cause epidemics of haemorrhagic fever with high case-fatality rates. the severe illness results from a complex of pathogenetic mechanisms that enable the virus to suppress innate and adaptive immune responses, infect and kill a broad variety of cell types, and elicit strong inflammatory responses and disseminated intravascular coagulation, producing a syndrome resembling septic shock. most experimental data have been obtained on zaire ebolavirus, whi ...200415288821
isolation and characterisation of ebolavirus-specific recombinant antibody fragments from murine and shark immune libraries.members of the genus ebolavirus cause fulminating outbreaks of disease in human and non-human primate populations with a mortality rate up to 90%. to facilitate rapid detection of these pathogens in clinical and environmental samples, robust reagents capable of providing sensitive and specific detection are required. in this work recombinant antibody libraries were generated from murine (single chain variable domain fragment; scfv) and nurse shark, ginglymostoma cirratum (ignar v) hosts immunise ...201121752470
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