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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
rna polymerase i-driven minigenome system for ebola viruses.in general, ebola viruses are well known for their ability to cause severe hemorrhagic fever in both human and nonhuman primates. however, despite substantial sequence homology to other members of the family filoviridae, reston ebolavirus displays reduced pathogenicity for nonhuman primates and has never been demonstrated to cause clinical disease in humans, despite its ability to cause infection. in order to develop a tool to explore potential roles for transcription and replication in the redu ...200515767442
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
assessment of a vesicular stomatitis virus-based vaccine by use of the mouse model of ebola virus hemorrhagic fever.in humans and nonhuman primates, ebola virus causes a virulent viral hemorrhagic fever for which no licensed vaccines or therapeutic drugs exist. in the present study, we used the mouse model for ebola hemorrhagic fever to assess the safety and efficacy of a vaccine based on a live attenuated vesicular stomatitis virus expressing the zaire ebolavirus (zebov) glycoprotein.200717940977
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
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
enhanced protection against ebola virus mediated by an improved adenovirus-based vaccine.the ebola virus is transmitted by direct contact with bodily fluids of infected individuals, eliciting death rates as high as 90% among infected humans. currently, replication defective adenovirus-based ebola vaccine is being studied in a phase i clinical trial. another ebola vaccine, based on an attenuated vesicular stomatitis virus has shown efficacy in post-exposure treatment of nonhuman primates to ebola infection. in this report, we modified the common recombinant adenovirus serotype 5-base ...200919390586
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
high prevalence of both humoral and cellular immunity to zaire ebolavirus among rural populations in gabon.to better understand zaire ebolavirus (zebov) circulation and transmission to humans, we conducted a large serological survey of rural populations in gabon, a country characterized by both epidemic and non epidemic regions. the survey lasted three years and covered 4,349 individuals from 220 randomly selected villages, representing 10.7% of all villages in gabon. using a sensitive and specific elisa method, we found a zebov-specific igg seroprevalence of 15.3% overall, the highest ever reported. ...201020161740
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
the survival of filoviruses in liquids, on solid substrates and in a dynamic aerosol.filoviruses are associated with high morbidity and lethality rates in humans, are capable of human-to-human transmission, via infected material such as blood, and are believed to have low infectious doses for humans. filoviruses are able to infect via the respiratory route and are lethal at very low doses in experimental animal models, but there is minimal information on how well the filoviruses survive within aerosol particles. there is also little known about how well filoviruses survive in li ...201020553340
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
management of accidental exposure to ebola virus in the biosafety level 4 laboratory, hamburg, germany.a needlestick injury occurred during an animal experiment in the biosafety level 4 laboratory in hamburg, germany, in march 2009. the syringe contained zaire ebolavirus (zebov) mixed with freund's adjuvant. neither an approved treatment nor a postexposure prophylaxis (pep) exists for ebola hemorrhagic fever. following a risk-benefit assessment, it was recommended the exposed person take an experimental vaccine that had shown pep efficacy in zebov-infected nonhuman primates (nhps) [12]. the vacci ...201121987751
A replicating cytomegalovirus-based vaccine encoding a single Ebola virus nucleoprotein CTL epitope confers protection against Ebola virus.Human outbreaks of Ebola virus (EBOV) are a serious human health concern in Central Africa. Great apes (gorillas/chimpanzees) are an important source of EBOV transmission to humans due to increased hunting of wildlife including the 'bush-meat' trade. Cytomegalovirus (CMV) is an highly immunogenic virus that has shown recent utility as a vaccine platform. CMV-based vaccines also have the unique potential to re-infect and disseminate through target populations regardless of prior CMV immunity, whi ...201121858240
ebola virus vaccines - reality or fiction?for 40 years ebolaviruses have been responsible for sporadic outbreaks of severe and often fatal hemorrhagic fever in humans and nonhuman primates. in december 2013 an unprecedented zaire ebolavirus epidemic began in west africa. although "patient zero" has finally been reached after 2 years, the virus is again causing disease in the region. currently there are no licensed vaccines or therapeutic countermeasures against ebolaviruses; however, the epidemic in west africa has focused attention on ...201627078187
ebola virus disease: from epidemiology to prophylaxis.the outbreak of ebola virus disease (evd) continues to spread through west africa. since the first report of evd in march 2014, the number of cases has increased rapidly, with the fatality rate of >50%. the most prevalent ebola virus belongs to the species of zaire ebolavirus, with a fatality rate as high as 90%. although there were cases introduced into other continents, africa is the endemic area where fruit bats and apes are suspected to be ebola virus carriers. the virus might be transmitted ...201526000173
a single-vector, single-injection trivalent filovirus vaccine: proof of concept study in outbred guinea pigs.the filoviruses, marburg marburgvirus (marv), zaire ebolavirus (zebov), and sudan ebolavirus (sebov), cause severe and often fatal hemorrhagic fever in humans and nonhuman primates (nhps). monovalent recombinant vesicular stomatitis virus (rvsv)-based vaccine vectors, which encode a filovirus glycoprotein (gp) in place of the vsv glycoprotein, have shown 100% efficacy against homologous filovirus challenge in rodent and nhp studies. here, we examined the utility of a single-vector, single-inject ...201525957964
single-dose attenuated vesiculovax vaccines protect primates against ebola makona virus.the family filoviridae contains three genera, ebolavirus (ebov), marburg virus, and cuevavirus. some members of the ebov genus, including zaire ebolavirus (zebov), can cause lethal haemorrhagic fever in humans. during 2014 an unprecedented zebov outbreak occurred in west africa and is still ongoing, resulting in over 10,000 deaths, and causing global concern of uncontrolled disease. to meet this challenge a rapid-acting vaccine is needed. many vaccine approaches have shown promise in being able ...201525853476
modeling the disease course of zaire ebolavirus infection in the outbred guinea pig.rodent models that accurately reflect human filovirus infection are needed as early screens for medical countermeasures. prior work in rodents with the zaire species of ebola virus (zebov) primarily used inbred mice and guinea pigs to model disease. however, these inbred species do not show some of the important features of primate zebov infection, most notably, coagulation abnormalities.201526038397
geographic potential of disease caused by ebola and marburg viruses in africa.filoviruses represent a significant public health threat worldwide. west africa recently experienced the largest-scale and most complex filovirus outbreak yet known, which underlines the need for a predictive understanding of the geographic distribution and potential for transmission to humans of these viruses. here, we used ecological niche modeling techniques to understand the relationship between known filovirus occurrences and environmental characteristics. our study derived a picture of the ...201627311387
comparison of the aerosol stability of 2 strains of zaire ebolavirus from the 1976 and 2013 outbreaks.the largest outbreak of ebola virus disease began in guéckédou, guinea, west africa, in december 2013 and rapidly spread to major population centers in 3 west african countries. early reports in some scientific and public media speculated that the virus had evolved to more effectively transmit between humans. one route of transmission postulated was aerosol transmission, although there was little epidemiological evidence to support this claim. this study investigates the viability of 2 zaire ebo ...201627503365
phylogenetic analysis of guinea 2014 ebov ebolavirus outbreak.members of the genus ebolavirus have caused outbreaks of haemorrhagic fever in humans in africa. the most recent outbreak in guinea, which began in february of 2014, is still ongoing. recently published analyses of sequences from this outbreak suggest that the outbreak in guinea is caused by a divergent lineage of zaire ebolavirus. we report evidence that points to the same zaire ebolavirus lineage that has previously caused outbreaks in the democratic republic of congo, the republic of congo an ...201424860690
vesicular stomatitis virus-based vaccines protect nonhuman primates against bundibugyo ebolavirus.ebola virus (ebov) causes severe and often fatal hemorrhagic fever in humans and nonhuman primates (nhps). currently, there are no licensed vaccines or therapeutics for human use. recombinant vesicular stomatitis virus (rvsv)-based vaccine vectors, which encode an ebov glycoprotein in place of the vsv glycoprotein, have shown 100% efficacy against homologous sudan ebolavirus (sebov) or zaire ebolavirus (zebov) challenge in nhps. in addition, a single injection of a blend of three rvsv vectors co ...201324367715
survey and visual detection of zaire ebolavirus in clinical samples targeting the nucleoprotein gene in sierra leone.ebola virus (ebov) can lead to severe hemorrhagic fever with a high risk of death in humans and other primates. to guide treatment and prevent spread of the viral infection, a rapid and sensitive detection method is required for clinical samples. here, we described and evaluated a reverse transcription loop-mediated isothermal amplification (rt-lamp) method to detect zaire ebolavirus using the nucleoprotein gene (np) as a target sequence. two different techniques were used, a calcein/mn(2+) comp ...201526648918
Ebola virion attachment and entry into human macrophages profoundly effects early cellular gene expression.Zaire ebolavirus (ZEBOV) infections are associated with high lethality in primates. ZEBOV primarily targets mononuclear phagocytes, which are activated upon infection and secrete mediators believed to trigger initial stages of pathogenesis. The characterization of the responses of target cells to ZEBOV infection may therefore not only further understanding of pathogenesis but also suggest possible points of therapeutic intervention. Gene expression profiles of primary human macrophages exposed t ...201122028943
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
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
mucosal immunization of cynomolgus macaques with the vsvdeltag/zebovgp vaccine stimulates strong ebola gp-specific immune responses.zaire ebolavirus (zebov) produces a lethal viral hemorrhagic fever in humans and non-human primates.200919440245
isolates of zaire ebolavirus from wild apes reveal genetic lineage and recombinants.over the last 30 years, zaire ebolavirus (zebov), a virus highly pathogenic for humans and wild apes, has emerged repeatedly in central africa. thus far, only a few virus isolates have been characterized genetically, all belonging to a single genetic lineage and originating exclusively from infected human patients. here, we describe the first zebov sequences isolated from great ape carcasses in the gabon/congo region that belong to a previously unrecognized genetic lineage. according to our esti ...200717942693
recombinant vesicular stomatitis virus vaccine vectors expressing filovirus glycoproteins lack neurovirulence in nonhuman primates.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 (rvsv) that expresses an individual filovirus glycoprotein (gp) in place of the vsv glycoprotein (g). the main concern with all replication-competent vaccines, including the rvsv filovirus gp vectors, is their safety. to address this concern, we ...201222448291
antibodies are necessary for rvsv/zebov-gp-mediated protection against lethal ebola virus challenge in nonhuman primates.ebola viruses cause hemorrhagic disease in humans and nonhuman primates with high fatality rates. these viruses pose a significant health concern worldwide due to the lack of approved therapeutics and vaccines as well as their potential misuse as bioterrorism agents. although not licensed for human use, recombinant vesicular stomatitis virus (rvsv) expressing the filovirus glycoprotein (gp) has been shown to protect macaques from ebola virus and marburg virus infections, both prophylactically an ...201323319647
chinese hamster ovary cell lines selected for resistance to ebolavirus glycoprotein mediated infection are defective for npc1 expression.ebolavirus causes severe hemorrhagic fever in humans and non-human primates. entry of ebolavirus is mediated by the viral glycoprotein, gp; however, the required host factors have not been fully elucidated. a screen utilizing a recombinant vesicular stomatitis virus (vsv) encoding zaire ebolavirus gp identified four chinese hamster ovary (cho) cell lines resistant to gp-mediated viral entry. susceptibility to vectors carrying sars coronavirus s or vsv-g glycoproteins suggests that endocytic and ...201222726751
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
current knowledge on lower virulence of reston ebola virus (in french: connaissances actuelles sur la moindre virulence du virus ebola reston).ebola viruses (ebov) and marburg virus belong to the family filoviridae, order mononegavirales. the genus ebolavirus consists of four species: zaire ebolavirus (zebov), sudan ebolavirus (sebov), ivory coast ebolavirus (icebov) and reston ebolavirus (rebov). three species of ebolaviruses, zebov, sebov, icebov, and marburg virus are known to be extremely pathogenic in primates and humans and cause severe hemorrhagic fever leading up to case fatality rate of some 90%, while rebov is thought to be p ...200717610952
human immunodeficiency viral vector pseudotyped with the spike envelope of severe acute respiratory syndrome coronavirus transduces human airway epithelial cells and dendritic cells.the human severe acute respiratory syndrome coronavirus (sars-cov) is a highly infectious virus that causes severe respiratory infections in humans. the spike envelope glycoprotein of sars-cov, the main determinant of sars-cov tropism, was isolated and used to pseudotype a human immunodeficiency virus (hiv)-based vector. spike-pseudotyped hiv vector was generated and evaluated in vitro on well-differentiated human airway epithelial cells and bronchial explants and in vivo in murine airways. the ...200717518614
rapid and simple detection of ebola virus by reverse transcription-loop-mediated isothermal amplification.ebola virus (ebov) causes severe hemorrhagic fever in humans and nonhuman primates with high mortality rates. rapid identification of the virus is required to prevent spread of the infection. in this study, we developed and evaluated a one-step simple reverse transcription-loop mediated isothermal amplification (rt-lamp) assay for the rapid detection of zaire ebolavirus (zebov), the most virulent species of ebov, targeting the trailer region of the viral genome. the assay could detect 20 copies ...200717194485
assessing the safety and immunogenicity of recombinant vesicular stomatitis virus ebola vaccine in healthy adults: a randomized clinical trial.the 2013-2016 ebola virus outbreak in west africa was the most widespread in history. in response, alive attenuated recombinant vesicular stomatitis virus (rvsv) vaccine expressing zaire ebolavirus glycoprotein (rvsvδg-zebov-gp) was evaluated in humans.201728630358
novel cross-reactive monoclonal antibodies against ebolavirus glycoproteins show protection in a murine challenge model.out of an estimated 31,100 cases since their discovery in 1976, ebolaviruses have caused approximately 13,000 deaths. the vast majority (∼11,000) of these occurred during the 2013-2016 west african epidemic. three out of five species in the genus are known to cause ebola virus disease in humans. several monoclonal antibodies against the ebolavirus glycoprotein are currently in development as therapeutics. however, there is still a paucity of monoclonal antibodies that can cross-react between the ...201728592526
molecular determinants of ebola virus virulence in mice.zaire ebolavirus (zebov) causes severe hemorrhagic fever in humans and nonhuman primates, with fatality rates in humans of up to 90%. the molecular basis for the extreme virulence of zebov remains elusive. while adult mice resist zebov infection, the mayinga strain of the virus has been adapted to cause lethal infection in these animals. to understand the pathogenesis underlying the extreme virulence of ebola virus (ebov), here we identified the mutations responsible for the acquisition of the h ...200616848640
generation of egfp expressing recombinant zaire ebolavirus for analysis of early pathogenesis events and high-throughput antiviral drug screening.zaire ebolavirus causes large outbreaks of severe and usually fatal hemorrhagic disease in humans for which there is no effective treatment or cure. to facilitate examination of early critical events in viral pathogenesis and to identify antiviral compounds, a recombinant zaire ebolavirus was engineered to express a foreign protein, egfp, to provide a rapid and sensitive means to monitor virus replication in infected cells. this genetically engineered virus represents the first insertion of a fo ...200515661137
vsvδg/ebov gp-induced innate protection enhances natural killer cell activity to increase survival in a lethal mouse adapted ebola virus infection.members of the species zaire ebolavirus cause severe hemorrhagic fever with up to a 90% mortality rate in humans. the vsvδg/ebov gp vaccine has provided 100% protection in the mouse, guinea pig, and nonhuman primate (nhp) models, and has also been utilized as a post-exposure therapeutic to protect mice, guinea pigs, and nhps from a lethal challenge of ebola virus (ebov). ebov infection causes rapid mortality in human and animal models, with death occurring as early as 6 days after infection, sug ...201525494457
chimpanzee adenovirus vaccine generates acute and durable protective immunity against ebolavirus challenge.ebolavirus disease causes high mortality, and the current outbreak has spread unabated through west africa. human adenovirus type 5 vectors (rad5) encoding ebolavirus glycoprotein (gp) generate protective immunity against acute lethal zaire ebolavirus (ebov) challenge in macaques, but fail to protect animals immune to ad5, suggesting natural ad5 exposure may limit vaccine efficacy in humans. here we show that a chimpanzee-derived replication-defective adenovirus (chad) vaccine also rapidly induc ...201425194571
quantification of viral and host biomarkers in the liver of rhesus macaques: a longitudinal study of zaire ebolavirus strain kikwit (ebov/kik).zaire ebolavirus (ebov) causes ebola virus disease (evd), which carries a fatality rate between 25% and 90% in humans. liver pathology is a hallmark of terminal evd; however, little is known about temporal disease progression. we used multiplexed fluorescent immunohistochemistry and in situ hybridization in combination with whole slide imaging and image analysis (ia) to quantitatively characterize temporospatial signatures of viral and host factors as related to ebov pathogenesis. eighteen rhesu ...202032275904
the challenge of using experimental infectivity data in risk assessment for ebola virus: why ecology may be important.analysis of published data shows that experimental passaging of zaire ebolavirus (ebov) in guinea pigs changes the risk of infection per plaque-forming unit (pfu), increasing infectivity to some species while decreasing infectivity to others. thus, a pfu of monkey-adapted ebov is 10(7) -fold more lethal to mice than a pfu adapted to guinea pigs. the first conclusion is that the infectivity of ebov to humans may depend on the identity of the donor species itself and, on the basis of limited epide ...201626480954
visual detection of ebola virus using reverse transcription loop-mediated isothermal amplification combined with nucleic acid strip detection.ebola virus (species zaire ebolavirus) (ebov) is highly virulent in humans. the largest recorded outbreak of ebola hemorrhagic fever in west africa to date was caused by ebov. therefore, it is necessary to develop a detection method for this virus that can be easily distributed and implemented. in the current study, we developed a visual assay that can detect ebov-associated nucleic acids. this assay combines reverse transcription loop-mediated isothermal amplification and nucleic acid strip det ...201626831931
vaccines against 'the other' ebolavirus species.the ebolavirus genus includes five member species, all of which pose a threat to global public health. these viruses cause fatal hemorrhagic fever in humans and nonhuman primates, and are considered category a pathogens due to the risk of their use as a bioweapon. the potential for an outbreak, either as a result of a natural emergence, deliberate release, or imported case underscores the need for protective vaccines. recent progress in advancing vaccines for use against the strain of zaire ebol ...201627010528
ebola virus modulates transforming growth factor β signaling and cellular markers of mesenchyme-like transition in hepatocytes.ebola virus (ebov) causes a severe hemorrhagic disease in humans and nonhuman primates, with a median case fatality rate of 78.4%. although ebov is considered a public health concern, there is a relative paucity of information regarding the modulation of the functional host response during infection. we employed temporal kinome analysis to investigate the relative early, intermediate, and late host kinome responses to ebov infection in human hepatocytes. pathway overrepresentation analysis and f ...201424942569
mapping of conserved and species-specific antibody epitopes on the ebola virus nucleoprotein.filoviruses (viruses in the genus ebolavirus and marburgvirus in the family filoviridae) cause severe haemorrhagic fever in humans and nonhuman primates. rapid, highly sensitive, and reliable filovirus-specific assays are required for diagnostics and outbreak control. characterisation of antigenic sites in viral proteins can aid in the development of viral antigen detection assays such immunochromatography-based rapid diagnosis. we generated a panel of mouse monoclonal antibodies (mabs) to the n ...201323702199
functional mutations in spike glycoprotein of zaire ebolavirus associated with an increase in infection efficiency.ebola virus (ebov) is extremely virulent, and its glycoprotein is necessary for viral entry. ebov may adapt to its new host humans during outbreaks by acquiring mutations especially in glycoprotein, which allows ebov to spread more efficiently. to identify these evolutionary selected mutations and examine their effects on viral infectivity, we used experimental-phylogenetic-structural interdisciplinary approaches. in evolutionary analysis of all available zaire ebolavirus glycoprotein sequences, ...201728084671
expanding the watch list for potential ebola virus antibody escape mutations.the 2014 outbreak of ebola virus disease (evd) in western africa is the largest recorded filovirus disease outbreak and led to the death of over 11,000 people. the recent evd outbreaks (since may 2018) in the democratic republic of the congo has already claimed the lives of over 250 people. tackling ebola virus (ebov) outbreaks remains a challenge. over the years, significant efforts have been put into developing vaccines or antibody therapies which rely on an envelope glycoprotein (gp) of zaire ...201930897171
recombinant proteins of zaire ebolavirus induce potent humoral and cellular immune responses and protect against live virus infection in mice.infections with filoviruses in humans are highly virulent, causing hemorrhagic fevers which result in up to 90% mortality. in addition to natural infections, the ability to use these viruses as bioterrorist weapons is of significant concern. currently, there are no licensed vaccines or therapeutics available to combat these infections. the pathogenesis of disease involves the dysregulation of the host's immune system, which results in impairment of the innate and adaptive immune responses, with ...201728216187
detection of zaire ebolavirus in swine: assay development and optimization.ebolaviruses (family filoviridae, order mononegavirales) cause often fatal, haemorrhagic fever in primates including humans. pigs have been identified as a species susceptible to reston ebolavirus (restv) infection, with indicated transmission to humans in the philippines; however, their role during ebola outbreaks in africa needs to be clarified. to perform surveillance studies, detection of ebolavirus requires a prerequisite validation of viral rna and antibody detection methods in swine sampl ...201728345293
immunopathogenesis of severe acute respiratory disease in zaire ebolavirus-infected pigs.ebola viruses (ebov) are filamentous single-stranded rna viruses of the family filoviridae. zaire ebolavirus (zebov) causes severe haemorrhagic fever in humans, great apes and non-human primates (nhps) with high fatality rates. in contrast, reston ebolavirus (rebov), the only species found outside africa, is lethal to some nhps but has never been linked to clinical disease in humans despite documented exposure. rebov was isolated from pigs in the philippines and subsequent experiments confirmed ...201323626748
ebola virus outbreaks in africa: past and present.ebola haemorrhagic fever (ehf) is a zoonosis affecting both human and non-human primates (nhp). outbreaks in africa occur mainly in the congo and nile basins. the first outbreaks of ehf occurred nearly simultaneously in 1976 in the democratic republic of the congo (drc, former zaire) and sudan with very high case fatality rates of 88% and 53%, respectively. the two outbreaks were caused by two distinct species of ebola virus named zaire ebolavirus (zebov) and sudan ebolavirus (sebov). the source ...201223327370
cathepsin b & l are not required for ebola virus replication.ebola virus (ebov), family filoviridae, emerged in 1976 on the african continent. since then it caused several outbreaks of viral hemorrhagic fever in humans with case fatality rates up to 90% and remains a serious public health concern and biothreat pathogen. the most pathogenic and best-studied species is zaire ebolavirus (zebov). ebov encodes one viral surface glycoprotein (gp), which is essential for replication, a determinant of pathogenicity and an important immunogen. gp mediates viral en ...201223236527
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
rapid detection of filoviruses by real-time taqman polymerase chain reaction assays.ebola virus (ebov) and marburg virus (marv) are causative agents of severe hemorrhagic fever with high mortality rates in humans and non-human primates and there is currently no licensed vaccine or therapeutics. to date, there is no specific laboratory diagnostic test in china, while there is a national need to provide differential diagnosis during outbreaks and for instituting acceptable quarantine procedures. in this study, the taqman rt-pcr assays targeting the nucleoprotein genes of the zair ...201223001480
the ebola virus glycoprotein contributes to but is not sufficient for virulence in vivo.among the ebola viruses most species cause severe hemorrhagic fever in humans; however, reston ebolavirus (rebov) has not been associated with human disease despite numerous documented infections. while the molecular basis for this difference remains unclear, in vitro evidence has suggested a role for the glycoprotein (gp) as a major filovirus pathogenicity factor, but direct evidence for such a role in the context of virus infection has been notably lacking. in order to assess the role of gp in ...201222876185
ebolavirus replication and tetherin/bst-2.ebolavirus (ebov) is an enveloped, non-segmented, negative-stranded rna virus, which consists of five species: zaire ebolavirus, sudan ebolavirus, tai forest ebolavirus, bundibugyo ebolavirus, and reston ebolavirus. ebov causes a lethal hemorrhagic fever in both humans and non-human primates. the ebov rna genome encodes seven viral proteins: np, vp35, vp40, gp, vp30, vp24, and l. vp40 is a matrix protein and is essential for virus assembly and release from host cells. expression of vp40 in mamma ...201222485110
circulating follicular t helper cells and cytokine profile in humans following vaccination with the rvsv-zebov ebola vaccine.the most recent zaire ebolavirus (zebov) outbreak was the largest and most widespread in recorded history, emphasizing the need for an effective vaccine. here, we analyzed human cellular immune responses induced by a single dose of the rvsv-zebov vaccine candidate, which showed significant protective efficacy in endemic populations in guinea. this is the first in-depth characterization of zebov-gp specific, circulating follicular t cells (ctfh). since antibody titers correlated with protection i ...201627323685
the face of ebola: changing frequency of haemorrhage in the west african compared with eastern-central african outbreaks.the west-african (wa) zaire ebolavirus disease (evd) outbreak was characterized by an exceptionally high number of cases and deaths as compared with the eastern-central african (eca) outbreaks. despite the zaire ebolavirus being the most lethal for humans, case-fatality rate, close to 80 % in eca outbreaks, almost halved to 47 % in guinea-liberia-sierra leone (wa). such an improvement was due to the remarkable implementation of international humanitarian aids. some studies also suggested that th ...201526653293
animal models for ebolavirus countermeasures discovery: what defines a useful model?ebolaviruses are highly pathogenic filoviruses, which cause disease in humans and nonhuman primates (nhp) in africa. the zaire ebolavirus outbreak in 2014, which continues to greatly affect western africa and other countries to which the hemorrhagic fever was exported due to travel of unsymptomatic yet infected individuals, was complicated by the lack of available licensed vaccines or therapeutics to combat infection. after almost a year of research at an increased pace to find and test vaccines ...201526004783
experimental aerosolized guinea pig-adapted zaire ebolavirus (variant: mayinga) causes lethal pneumonia in guinea pigs.eight guinea pigs were aerosolized with guinea pig-adapted zaire ebolavirus (variant: mayinga) and developed lethal interstitial pneumonia that was distinct from lesions described in guinea pigs challenged subcutaneously, nonhuman primates challenged by the aerosol route, and natural infection in humans. guinea pigs succumbed with significant pathologic changes primarily restricted to the lungs. intracytoplasmic inclusion bodies were observed in many alveolar macrophages. perivasculitis was note ...201524829285
distinct immunogenicity and efficacy of poxvirus-based vaccine candidates against ebola virus expressing gp and vp40 proteins.zaireandsudan ebolavirusspecies cause a severe disease in humans and non-human primates (nhps) characterized by high mortality rate. there are no licensed therapies or vaccines against ebola virus disease (evd), and the recent 2013-2016 outbreak in west africa highlighted the need of evd-specific medical countermeasures. here, we have generated and characterized head-to-head the immunogenicity and efficacy of five vaccine candidates against zaire ebolavirus (ebov) and sudan ebolavirus (sudv) bas ...201829514907
bats as putative zaire ebolavirus reservoir hosts and their habitat suitability in africa.the genus ebolavirus comprises some of the deadliest viruses for primates and humans and associated disease outbreaks are increasing in africa. different evidence suggests that bats are putative reservoir hosts and play a major role in the transmission cycle of these filoviruses. thus, detailed knowledge about their distribution might improve risk estimations of where future disease outbreaks might occur. a maxent niche modelling approach based on climatic variables and land cover was used to in ...202032868789
epitopes of naturally acquired and vaccine-induced anti-ebola virus glycoprotein antibodies in single amino acid resolution.the ebola virus (ebov) can cause severe infections in humans, leading to a fatal outcome in a high percentage of cases. neutralizing antibodies against the ebov surface glycoprotein (gp) can prevent infections, demonstrating a straightforward way for an efficient vaccination strategy. meanwhile, many different anti-ebov antibodies have been identified, whereas the exact binding epitopes are often unknown. here, the analysis of serum samples from an ebov vaccine trial with the recombinant vesicul ...202032463974
structure-based design of prefusion-stabilized filovirus glycoprotein trimers.ebola virus causes severe hemorrhagic fever, often leading to death in humans. the trimeric fusion glycoprotein (gp) is the sole target for neutralizing antibodies and is the major focus of vaccine development. soluble gp ectodomains are unstable and mostly monomeric when not fused to a heterologous trimerization domain. here, we report structure-based designs of ebola and marburg gp trimers based on a stabilizing mutation in the hinge loop in refolding region 1 and substitution of a partially b ...202032234486
recombinant subunit vaccines protect guinea pigs from lethal ebola virus challenge.ebola virus (ebov) is among the deadliest pathogens known to man causing infrequent outbreaks of hemorrhagic disease. in humans, the case fatality rates in the outbreaks can reach 90%. during the west african epidemic almost 30,000 people were infected and of these over 11,000 fatalities were reported. currently, we are facing an uncontained larger outbreak in the democratic republic of the congo. even though ebov was discovered in 1976, extensive efforts to develop countermeasures, particularly ...201931324500
exploring the human-animal interface of ebola virus disease outbreaks.whereas the prevention and treatment of ebola virus disease (evd) have been well studied after the 2013-16 outbreak in west africa, the emergence of human outbreaks and their mechanisms have yet to be explored in detail. in particular, it has yet to be clarified whether the emergence records offer any theoretical insight into the changing interface between humans and animal reservoirs. here we explore the epidemiological record of emergence, investigating predominant causes of the introduction t ...201931137254
the roles of ebolavirus glycoproteins in viral pathogenesis.ebolaviruses are highly dangerous pathogens exhibiting extreme virulence in humans and nonhuman primates. the majority of ebolavirus species, most notably zaire ebolavirus, can cause ebola virus disease (evd), formerly known as ebola hemorrhagic fever, in humans. evd is associated with case-fatality rates as high as 90%, and there is currently no specific treatment or licensed vaccine available against evd. understanding the molecular biology and pathogenesis of ebolaviruses is important for the ...201727853993
serological detection of ebola virus exposures in native non-human primates of southern nigeria.ebola viruses (family: filoviridae) are the cause of ebola virus disease (evd), a highly fatal illness characterised by haemorrhagic fever syndrome in both humans and non-human primates (nhps). west africa was the epicentre of the 2013-2015 evd epidemic which caused the death of over 11,000 people, including eight casualties in southern nigeria. antibodies to filoviruses have been detected among nhps in some countries, but there is no documented evidence of exposures to filoviruses among nhps in ...201830864758
comparative transcriptomics in ebola makona-infected ferrets, nonhuman primates, and humans.the domestic ferret is a uniformly lethal model of infection for 3 species of ebolavirus known to be pathogenic in humans. reagents to systematically analyze the ferret host response to infection are lacking; however, the recent publication of a draft ferret genome has opened the potential for transcriptional analysis of ferret models of disease. in this work, we present comparative analysis of longitudinally sampled blood taken from ferrets and nonhuman primates infected with lethal doses of th ...201830476250
tip your cap for ebola virus neutralization.outbreaks of ebola virus disease are caused by multiple virus species although current therapeutic monoclonal antibodies (mab) are essentially limited to treating one species, zaire ebolavirus. in this issue of immunity, gilchuk et al. (2018) identify new mabs with potent cross-neutralizing activity against three ebolavirus species pathogenic to humans.201830134198
systematic detection of positive selection in the human-pathogen interactome and lasting effects on infectious disease susceptibility.infectious disease has shaped the natural genetic diversity of humans throughout the world. a new approach to capture positive selection driven by pathogens would provide information regarding pathogen exposure in distinct human populations and the constantly evolving arms race between host and disease-causing agents. we created a human pathogen interaction database and used the integrated haplotype score (ihs) to detect recent positive selection in genes that interact with proteins from 26 diff ...201829799843
assessment of the ability of v920 recombinant vesicular stomatitis-zaire ebolavirus vaccine to replicate in relevant arthropod cell cultures and vector species.v920, rvsvδg-zebov-gp, is a recombinant vesicular stomatitis-zaire ebolavirus vaccine which has shown an acceptable safety profile and provides a protective immune response against ebola virus disease (evd) induced by zaire ebolavirus in humans. the purpose of this study was to determine whether the v920 vaccine is capable of replicating in arthropod cell cultures of relevant vector species and of replicating in live mosquitoes. while the v920 vaccine replicated well in vero cells, no replicatio ...201729206076
sending the right message: wild game and the west africa ebola outbreak.the unprecedented scale of the ebola epidemic in west africa in 2014-15 caught the world by surprise. zaire ebolavirus had not previously been documented in guinea, sierra leone, or liberia. however, since this strain of filovirus was first identified in 1976, scientists have been studying the disease and its origins. they have identified forest-dwelling animals that carry the virus, and some that die from it, but have yet to isolate how it is transmitted from animals to humans. during the heigh ...201829451827
towards a thermodynamic mechanistic model for the effect of temperature on arthropod vector competence for transmission of arboviruses.arboviruses such as west nile virus (wnv), bluetongue virus (btv), dengue virus (denv) and chikungunya virus (chikv) infect their arthropod vectors over a range of average temperatures depending on the ambient temperature. how the transmission efficiency of an arbovirus (i.e. vector competence) varies with temperature influences not only the short term risk of arbovirus outbreaks in humans and livestock but also the long term impact of climate change on the geographical range of the virus. the s ...201932289057
cooperation of the ebola virus proteins vp40 and gp1,2with bst2 to activate nf-κb independently of virus-like particle trapping.bst2 is a host protein with dual functions in response to viral infections: it traps newly assembled enveloped virions at the plasma membrane in infected cells, and it induces nf-κb activity, especially in the context of retroviral assembly. in this study, we examined whether ebola virus proteins affect bst2-mediated induction of nf-κb. we found that the ebola virus matrix protein, vp40, and envelope glycoprotein, gp, each cooperate with bst2 to induce nf-κb activity, with maximal activity when ...201728878074
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