| pathogenic potential of filoviruses: role of geographic origin of primate host and virus strain. | african filoviruses have caused outbreaks of fulminating hemorrhagic fever among humans. in 1989, related filoviruses were isolated from cynomolgus monkeys imported into the united states from the philippines. the pathogenic potential of these new filoviruses was compared in 16 asian monkeys (macaca fascicularis-cynomolgus) and 16 african monkeys (cercopithecus aethiops-african green) using african filoviruses from zaire (ebola virus) and sudan or asian filoviruses (reston and pennsylvania). afr ... | 1992 | 1527410 |
| emergence of subtype zaire ebola virus in gabon. | gabon has recently been struck three times by ebola hemorrhagic fever. the first isolate originating from the 1994 outbreak has been subjected to molecular characterization of its gp and vp24 genes. sequence analysis demonstrates that the agent, gabon-94 virus, belongs to subtype zaire of ebola virus. the isolate is closely related to the kikwit-95 isolate, and both viruses seem to have evolved from a progenitor virus different from that of the zaire-76 isolates. the relatively close relationshi ... | 1997 | 9185597 |
| immunoglobulin g enzyme-linked immunosorbent assay using truncated nucleoproteins of reston ebola virus. | we developed an immunoglobulin g (igg) enzyme-linked immunosorbent assay (elisa), using partial recombinant nucleoproteins (rnp) of reston ebola virus (ebo-r) and zaire ebola virus (ebo-z). we examined the reaction of 10 sera from cynomolgus macaques naturally infected with ebo-r to each of the partial rnp in the igg elisa. all the sera reacted to the c-terminal halves of the rnp of both ebo-r and ebo-z. most of the sera reacted to the rdeltac (amino acid (aa) 360-739), and rdelta6 (aa 451-551) ... | 2003 | 12825739 |
| antigen capture enzyme-linked immunosorbent assay for specific detection of reston ebola virus nucleoprotein. | antigen capture enzyme-linked immunosorbent assay (elisa) is one of the most useful methods to detect ebola virus rapidly. we previously developed an antigen capture elisa using a monoclonal antibody (mab), 3-3d, which reacted not only to the nucleoprotein (np) of zaire ebola virus (ebo-z) but also to the nps of sudan (ebo-s) and reston ebola (ebo-r) viruses. in this study, we developed antigen capture elisas using two novel mabs, res2-6c8 and res2-1d8, specific to the np of ebo-r. res2-6c8 and ... | 2003 | 12853385 |
| properties of replication-competent vesicular stomatitis virus vectors expressing glycoproteins of filoviruses and arenaviruses. | replication-competent recombinant vesicular stomatitis viruses (rvsvs) expressing the type i transmembrane glycoproteins and selected soluble glycoproteins of several viral hemorrhagic fever agents (marburg virus, ebola virus, and lassa virus) were generated and characterized. all recombinant viruses exhibited rhabdovirus morphology and replicated cytolytically in tissue culture. unlike the rvsvs with an additional transcription unit expressing the soluble glycoproteins, the viruses carrying the ... | 2004 | 15113924 |
| 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 ... | 2004 | 15288821 |
| a c-terminal basic amino acid motif of zaire ebolavirus vp35 is essential for type i interferon antagonism and displays high identity with the rna-binding domain of another interferon antagonist, the ns1 protein of influenza a virus. | the ebolavirus vp35 protein antagonizes the cellular type i interferon response by blocking phosphorylation of irf-3, a transcription factor that turns on the expression of a large number of antiviral genes. to identify the domain of vp35 responsible for interferon antagonism, we generated mutations within the vp35 gene and found that a c-terminal basic amino acid motif is required for inhibition of isg56 reporter gene expression as well as ifn-beta production. remarkably, this basic amino acid ... | 2004 | 15464838 |
| rescue of ebola virus from cdna using heterologous support proteins. | using the infectious clone for zaire ebolavirus, the functional specificity of viral proteins of the ribonucleoprotein complex in transcription/replication was investigated by substituting them with heterologous proteins derived from closely (reston ebolavirus) and distantly related filoviruses (marburgvirus). the data clearly demonstrated that transcription/replication are neither strictly species-specific nor genus-specific. protein interactions between the nucleoprotein np and the virion prot ... | 2004 | 15522446 |
| 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 ... | 2005 | 15661137 |
| 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 ... | 2005 | 15767442 |
| wave-like spread of ebola zaire. | in the past decade the zaire strain of ebola virus (zebov) has emerged repeatedly into human populations in central africa and caused massive die-offs of gorillas and chimpanzees. we tested the view that emergence events are independent and caused by zebov variants that have been long resident at each locality. phylogenetic analyses place the earliest known outbreak at yambuku, democratic republic of congo, very near to the root of the zebov tree, suggesting that viruses causing all other known ... | 2005 | 16231972 |
| the role of reverse genetics systems in determining filovirus pathogenicity. | the family filoviridae is comprised of two genera: marburgvirus and ebolavirus. to date minigenome systems have been developed for two ebola viruses (reston ebolavirus and zaire ebolavirus [zebov]) as well as for lake victoria marburgvirus, the sole member of the marburgvirus genus. the use of these minigenome systems has helped characterize functions for many viral proteins in both genera and have provided valuable insight towards the development of an infectious clone system in the case of zeb ... | 2005 | 16355872 |
| chimpanzee adenovirus vaccine protects against zaire ebola virus. | this study evaluated the use of a chimpanzee-based adenovirus vaccine in mouse and guinea pigs models of zaire ebola virus (zebov) infection. vaccine vector expressing the envelope glycoprotein of zebov was created from the molecular clone of chimpanzee adenovirus pan7 (adc7). adc7 vaccine stimulated robust t and b cell responses to zebov in naïve mice inducing complete protection to an otherwise lethal challenge of zebov. complete protection to zaire ebola virus was also observed in guinea pigs ... | 2006 | 16356525 |
| development of a cadvax-based bivalent ebola virus vaccine that induces immune responses against both the sudan and zaire species of ebola virus. | ebola virus (ebov) causes a severe hemorrhagic fever for which there are currently no vaccines or effective treatments. while lethal human outbreaks have so far been restricted to sub-saharan africa, the potential exploitation of ebov as a biological weapon cannot be ignored. two species of ebov, sudan ebolavirus (sebov) and zaire ebolavirus (zebov), have been responsible for all of the deadly human outbreaks resulting from this virus. therefore, it is important to develop a vaccine that can pre ... | 2006 | 16501083 |
| 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 ... | 2006 | 16501110 |
| conserved receptor-binding domains of lake victoria marburgvirus and zaire ebolavirus bind a common receptor. | the gp(1,2) envelope glycoproteins (gp) of filoviruses (marburg- and ebolaviruses) mediate cell-surface attachment, membrane fusion, and entry into permissive cells. here we show that a 151-amino acid fragment of the lake victoria marburgvirus gp1 subunit bound filovirus-permissive cell lines more efficiently than full-length gp1. an homologous 148-amino acid fragment of the zaire ebolavirus gp1 subunit similarly bound the same cell lines more efficiently than a series of longer gp1 truncation v ... | 2006 | 16595665 |
| postexposure protection of guinea pigs against a lethal ebola virus challenge is conferred by rna interference. | ebola virus (ebov) infection causes a frequently fatal hemorrhagic fever (hf) that is refractory to treatment with currently available antiviral therapeutics. rna interference represents a powerful, naturally occurring biological strategy for the inhibition of gene expression and has demonstrated utility in the inhibition of viral replication. here, we describe the development of a potential therapy for ebov infection that is based on small interfering rnas (sirnas). | 2006 | 16703508 |
| the signal peptide of the ebolavirus glycoprotein influences interaction with the cellular lectins dc-sign and dc-signr. | the c-type lectins dc-sign and dc-signr (collectively referred to as dc-sign/r) bind to the ebolavirus glycoprotein (ebov-gp) and augment viral infectivity. dc-sign/r strongly enhance infection driven by the gp of ebov subspecies. zaire (zebov) but have a much less pronounced effect on infection mediated by the gp of ebov subspecies. sudan (sebov). for this study, we analyzed the determinants of the differential dc-sign/r interactions with zebov- and sebov-gp. the efficiency of dc-sign engagemen ... | 2006 | 16775318 |
| reverse genetic generation of recombinant zaire ebola viruses containing disrupted irf-3 inhibitory domains results in attenuated virus growth in vitro and higher levels of irf-3 activation without inhibiting viral transcription or replication. | the vp35 protein of zaire ebola virus is an essential component of the viral rna polymerase complex and also functions to antagonize the cellular type i interferon (ifn) response by blocking activation of the transcription factor irf-3. we previously mapped the irf-3 inhibitory domain within the c terminus of vp35. in the present study, we show that mutations that disrupt the irf-3 inhibitory function of vp35 do not disrupt viral transcription/replication, suggesting that the two functions of vp ... | 2006 | 16775331 |
| infection of naive target cells with virus-like particles: implications for the function of ebola virus vp24. | infectious virus-like particle (ivlp) systems have recently been established for several negative-strand rna viruses, including the highly pathogenic zaire ebolavirus (zebov), and allow study of the viral life cycle under biosafety level 2 conditions. however, current systems depend on the expression of viral helper nucleocapsid proteins in target cells, thus making it impossible to determine whether ribonucleoprotein complexes transferred by ivlps are able to facilitate initial transcription, a ... | 2006 | 16809331 |
| identification of two amino acid residues on ebola virus glycoprotein 1 critical for cell entry. | using site-directed mutagenesis and retroviral vector pseudotyping of the wild type or mutated glycoprotein of zaire ebolavirus (zebov), we analyzed 15 conserved residues in the n-terminus of the filovirus glycoprotein 1 (gp1) in order to identify residues critical for cell entry. results from infectivity assays and western blot analyses identified two phenylalanine residues at positions 88 and 159 that appear to be critical for zebov entry in vitro. we extended this observation by introduction ... | 2006 | 16839637 |
| 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 ... | 2006 | 16848640 |
| ebola outbreak killed 5000 gorillas. | over the past decade, the zaire strain of ebola virus (zebov) has repeatedly emerged in gabon and congo. each human outbreak has been accompanied by reports of gorilla and chimpanzee carcasses in neighboring forests, but both the extent of ape mortality and the causal role of zebov have been hotly debated. here, we present data suggesting that in 2002 and 2003 zebov killed about 5000 gorillas in our study area. the lag between neighboring gorilla groups in mortality onset was close to the zebov ... | 2006 | 17158318 |
| 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 ... | 2007 | 17194485 |
| 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 ... | 2007 | 17518614 |
| 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 ... | 2007 | 17610952 |
| 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 ... | 2007 | 17928350 |
| spatial and temporal patterns of zaire ebolavirus antibody prevalence in the possible reservoir bat species. | to characterize the distribution of zaire ebolavirus (zebov) infection within the 3 bat species (epomops franqueti, hypsignathus monstrosus, and myonycteris torquata) that are possible reservoirs, we collected 1390 bats during 2003-2006 in gabon and the republic of the congo. detection of zebov immunoglobulin g (igg) in 40 specimens supports the role of these bat species as the zebov reservoirs. zebov igg prevalence rates (5%) were homogeneous across epidemic and nonepidemic regions during outbr ... | 2007 | 17940947 |
| diagnostic reverse-transcription polymerase chain reaction kit for filoviruses based on the strain collections of all european biosafety level 4 laboratories. | a network of european biosafety level 4 laboratories has designed the first industry-standard molecular assay for all filoviruses species, based on the strain collections of all participants. it uses 5 optimized l gene primers and 3 probes, as well as an internal control with a separate detection probe. detection limits (probit analysis, 95% detection chance) were as follows: zaire ebolavirus, 487 copies/ml of plasma; sudan ebolavirus maleo, 586 copies/ml; sudan ebolavirus gulu, 1128 copies/ml; ... | 2007 | 17940950 |
| high-throughput molecular detection of hemorrhagic fever virus threats with applications for outbreak settings. | within the past dozen years, outbreaks of filoviral hemorrhagic fever within the human population have been occurring with increasing frequency, with an average of 1 epidemic now occurring every 1-2 years. many of the outbreaks have been large (involving >150 cases), necessitating rapid responses from the international community to help implement infection control and surveillance. this increased activity, combined with today's climate of bioterrorism threats, has heightened the need for high-th ... | 2007 | 17940951 |
| secreted glycoprotein from live zaire ebolavirus-infected cultures: preparation, structural and biophysical characterization, and thermodynamic stability. | milligram quantities of zaire ebolavirus nonstructural, secreted glycoprotein (sgp) were purified to homogeneity, and this preparation was characterized by an array of biophysical and biochemical experiments. mass-spectrometry analysis revealed sgp posttranslational modifications and regions susceptible to limited proteolysis. in solution, sgp has an absolute molar mass of 103 kda, is monodisperse, and folds into a predominantly beta -sheet conformation with a distinct tertiary structure. sgp ap ... | 2007 | 17940953 |
| ebola virus inactivation with preservation of antigenic and structural integrity by a photoinducible alkylating agent. | current methods for inactivating filoviruses are limited to high doses of irradiation or formalin treatment, which may cause structural perturbations that are reflected by poor immunogenicity. in this report, we describe a novel inactivation technique for zaire ebola virus (zebov) that uses the photoinduced alkylating probe 1,5-iodonaphthylazide (ina). ina is incorporated into lipid bilayers and, when activated by ultraviolet irradiation, alkylates the proteins therein. ina treatment of zebov re ... | 2007 | 17940961 |
| lymphocyte death in a mouse model of ebola virus infection. | a striking feature of zaire ebola virus (zebov) infection in nonhuman primates is the rapid depletion of t and nk lymphocytes by apoptosis. in a mouse model of zebov infection, lymphocyte death is a prominent finding; however, the mechanism of death and the lymphocyte subsets that are targeted remain unknown. | 2007 | 17940964 |
| in vitro and in vivo characterization of recombinant ebola viruses expressing enhanced green fluorescent protein. | to facilitate an understanding of the molecular aspects of the pathogenesis of zaire ebolavirus (zebov) infection, we generated 2 different recombinant viruses expressing enhanced green fluorescent protein (egfp) from additional transcription units inserted at different positions in the virus genome. these viruses showed in vitro phenotypes similar to that of wild-type zebov (wt-zebov) and were stable over multiple passages. infection with one of the viruses expressing egfp produced only mild di ... | 2007 | 17940966 |
| pathologic findings associated with delayed death in nonhuman primates experimentally infected with zaire ebola virus. | zaire ebola virus infection in macaques causes a fatal disease with a pathogenesis similar to that in humans. during several independent therapy studies, we noted altered tissue tropism in 6 rhesus macaques that survived longer than those with a typical disease course. the mean time to death for these 6 macaques was 21.7 days, which is significantly longer than the average mean time to death of 8.3 days for 20 untreated historical control animals. in addition to living significantly longer, thes ... | 2007 | 17940967 |
| epitopes required for antibody-dependent enhancement of ebola virus infection. | we have shown that antibody-dependent enhancement (ade) of infection with zaire ebola virus (zebov) is mediated by interaction of virus-specific antibodies with fc receptors or complement component c1q and its receptors in vitro. ade activities of the antisera to the viral glycoprotein (gp) were virus species specific and were primarily correlated with immunoglobulin (ig) g2a and igm levels but not with igg1 levels. interestingly, compared with zebov, reston ebola virus (rebov) had substantially ... | 2007 | 17940970 |
| cytokine and chemokine expression in humans infected with sudan ebola virus. | the size and duration of the 2000 outbreak of sudan ebola virus (sebov) infection in uganda made it possible to collect serial serum samples from 87 patients (53 survivors and 34 nonsurvivors). surprisingly, the levels of tumor necrosis factor- alpha and interferon (ifn)- gamma , which had been found to be increased in patients with fatal zaire ebola virus infection, were not increased in any of the patients with sebov infection. the levels of interleukin (il)-1 beta , ifn- gamma -inducible prot ... | 2007 | 17940971 |
| in vitro evaluation of antisense rna efficacy against filovirus infection, by use of reverse genetics. | recent reports indicate the possibility of using small interfering rnas (sirnas) to treat filovirus infections; however, they also show that the effectiveness of this approach is highly dependent on target site selection. therefore, we explored the application of minigenomes as screening tools to identify functional sirna targets under biosafety level 2 conditions. | 2007 | 17940974 |
| recombinant human activated protein c for the postexposure treatment of ebola hemorrhagic fever. | infection of primates with zaire ebolavirus (zebov) leads to hypotension, coagulation disorders, and an impaired immune response and, in many ways, resembles severe sepsis. rapid decreases in plasma levels of protein c are a prominent feature of severe sepsis and zebov hemorrhagic fever (zhf). currently, recombinant human activated protein c (rhapc [xigris; eli lilly]) is licensed for treating human patients with severe sepsis who are at high risk of death. the aim of this study was to test the ... | 2007 | 17940975 |
| 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. | 2007 | 17940977 |
| mucosal delivery of adenovirus-based vaccine protects against ebola virus infection in mice. | mucosal vaccination can offer several advantages over conventional intramuscular immunization to protect against ebola virus (ebov) infection, such as immune protection at sites of viral entry into susceptible individuals, and can be administered using needle-free devices. | 2007 | 17940978 |
| 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 ... | 2007 | 17942693 |
| inhibition of irf-3 activation by vp35 is critical for the high level of virulence of ebola virus. | zaire ebolavirus causes a rapidly progressing hemorrhagic disease with high mortality. identification of the viral virulence factors that contribute to the severity of disease induced by ebola virus is critical for the design of therapeutics and vaccines against the disease. given the rapidity of disease progression, virus interaction with the innate immune system early in the course of infection likely plays an important role in determining the outcome of the disease. the ebola virus vp35 prote ... | 2008 | 18199658 |
| recombinant vesicular stomatitis virus vector mediates postexposure protection against sudan ebola hemorrhagic fever in nonhuman primates. | recombinant vesicular stomatitis virus (vsv) vectors expressing homologous filoviral glycoproteins can completely protect rhesus monkeys against marburg virus when administered after exposure and can partially protect macaques after challenge with zaire ebolavirus. here, we administered a vsv vector expressing the sudan ebolavirus (sebov) glycoprotein to four rhesus macaques shortly after exposure to sebov. all four animals survived sebov challenge, while a control animal that received a nonspec ... | 2008 | 18385248 |
| phosphoinositide-3 kinase-akt pathway controls cellular entry of ebola virus. | the phosphoinositide-3 kinase (pi3k) pathway regulates diverse cellular activities related to cell growth, migration, survival, and vesicular trafficking. it is known that ebola virus requires endocytosis to establish an infection. however, the cellular signals that mediate this uptake were unknown for ebola virus as well as many other viruses. here, the involvement of pi3k in ebola virus entry was studied. a novel and critical role of the pi3k signaling pathway was demonstrated in cell entry of ... | 2008 | 18769720 |
| vesicular stomatitis virus-based vaccines protect nonhuman primates against aerosol challenge with ebola and marburg viruses. | considerable progress has been made over the last decade in developing candidate preventive vaccines that can protect nonhuman primates against ebola and marburg viruses. a vaccine based on recombinant vesicular stomatitis virus (vsv) seems to be particularly robust as it can also confer protection when administered as a postexposure treatment. while filoviruses are not thought to be transmitted by aerosol in nature the inhalation route is among the most likely portals of entry in the setting of ... | 2008 | 18930776 |
| 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. ... | 2008 | 19043556 |
| the marburg virus 3' noncoding region structurally and functionally differs from that of ebola virus. | we have previously shown that the first transcription start signal (tss) of zaire ebola virus (zebov) is involved in formation of an rna secondary structure regulating vp30-dependent transcription activation. interestingly, transcription of marburg virus (marv) minigenomes occurs independently of vp30. in this study, we analyzed the structure of the marv 3' noncoding region and its influence on vp30 necessity. secondary structure formation of the tss of the first gene was experimentally determin ... | 2009 | 19225002 |
| 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 ... | 2009 | 19386702 |
| 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 ... | 2009 | 19390586 |
| 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. | 2009 | 19440245 |
| zaire ebola virus entry into human dendritic cells is insensitive to cathepsin l inhibition. | cathepsins b and l contribute to ebola virus (ebov) entry into vero cells and mouse embryonic fibroblasts. however, the role of cathepsins in ebov-infection of human dendritic cells (dcs), important targets of infection in vivo, remains undefined. here, ebov-like particles containing a beta-lactamase-vp40 fusion reporter and ebola virus were used to demonstrate the cathepsin dependence of ebov entry into human monocyte-derived dcs. however, while dc infection is blocked by cathepsin b inhibitor, ... | 2010 | 19775255 |
| 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. | 2009 | 19785757 |
| biochemical and structural characterization of cathepsin l-processed ebola virus glycoprotein: implications for viral entry and immunogenicity. | ebola virus (ebov) cellular attachment and entry is initiated by the envelope glycoprotein (gp) on the virion surface. entry of this virus is ph dependent and associated with the cleavage of gp by proteases, including cathepsin l (catl) and/or catb, in the endosome or cell membrane. here, we characterize the product of catl cleavage of zaire ebov gp (zebov-gp) and evaluate its relevance to entry. a stabilized recombinant form of the ebov gp trimer was generated using a trimerization domain linke ... | 2010 | 20053739 |
| 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. ... | 2010 | 20161740 |
| 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 ... | 2010 | 20181765 |
| ebolavirus glycoprotein structure and mechanism of entry. | ebolavirus (ebov) is a highly virulent pathogen capable of causing a severe hemorrhagic fever with 50-90% lethality. the ebov glycoprotein (gp) is the only virally expressed protein on the virion surface and is critical for attachment to host cells and catalysis of membrane fusion. hence, the ebov gp is a critical component of vaccines as well as a target of neutralizing antibodies and inhibitors of attachment and fusion. the crystal structure of the zaire ebolavirus gp in its trimeric, prefusio ... | 2009 | 20198110 |
| antiviral activity of a small-molecule inhibitor of filovirus infection. | there exists an urgent need to develop licensed drugs and vaccines for the treatment or prevention of filovirus infections. fgi-103 is a low-molecular-weight compound that was discovered through an in vitro screening assay utilizing a variant of zaire ebolavirus (zebov) that expresses green fluorescent protein. in vitro analyses demonstrated that fgi-103 also exhibits antiviral activity against wild-type zebov and sudan ebolavirus, as well as marburgvirus (marv) strains ci67 and ravn. in vivo ad ... | 2010 | 20211898 |
| reduced virus replication, proinflammatory cytokine production, and delayed macrophage cell death in human pbmcs infected with the newly discovered bundibugyo ebolavirus relative to zaire ebolavirus. | bundibugyo ebolavirus is a newly identified ebolavirus species. the virus was responsible for a recent hemorrhagic fever outbreak in uganda with an approximate 30% case fatality rate. in this study, we compared the pathogenesis of bundibugyo with highly lethal zaire ebolavirus by using in vitro human pbmcs. we found that pbmcs infected with bundibugyo ebolaviruses resulted in 1 to 2 log lower virus yields compared to zaire ebolavirus and produced 2- to 10-fold lower levels of tnf-alpha, mcp-1, i ... | 2010 | 20394957 |
| structural and functional characterization of reston ebola virus vp35 interferon inhibitory domain. | ebolaviruses are causative agents of lethal hemorrhagic fever in humans and nonhuman primates. among the filoviruses characterized thus far, reston ebola virus (rebov) is the only ebola virus that is nonpathogenic to humans despite the fact that rebov can cause lethal disease in nonhuman primates. previous studies also suggest that rebov is less effective at inhibiting host innate immune responses than zaire ebola virus (zebov) or marburg virus. virally encoded vp35 protein is critical for immun ... | 2010 | 20399790 |
| 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 ... | 2010 | 20511019 |
| 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 ... | 2010 | 20553340 |
| genetic factors of ebola virus virulence in guinea pigs. | zaire ebolavirus (zebov) causes severe hemorrhagic fever in primates, whereas in guinea pigs it induces a nonlethal infection with a mild fever and subsequent recovery. we performed 7 selective passages in guinea pigs resulted in obtaining of guinea pig-adapted strain (gpa-p7) strain. by the 7th passage, the infection with ebov induced a lethal disease in animals accompanied by the characteristic hematological changes: leukocytosis (primarily due to neutrophilia) as well as pronounced deficienci ... | 2010 | 20654661 |
| infectious lassa virus, but not filoviruses, is restricted by bst-2/tetherin. | bone marrow stromal antigen 2 (bst-2/tetherin) is a cellular membrane protein that inhibits the release of hiv-1. we show for the first time, using infectious viruses, that bst-2 also inhibits egress of arenaviruses but has no effect on filovirus replication and spread. specifically, infectious lassa virus (lasv) release significantly decreased or increased in human cells in which bst-2 was either stably expressed or knocked down, respectively. in contrast, replication and spread of infectious z ... | 2010 | 20686043 |
| advanced antisense therapies for postexposure protection against lethal filovirus infections. | currently, no vaccines or therapeutics are licensed to counter ebola or marburg viruses, highly pathogenic filoviruses that are causative agents of viral hemorrhagic fever. here we show that administration of positively charged phosphorodiamidate morpholino oligomers (pmoplus), delivered by various dosing strategies initiated 30-60 min after infection, protects>60% of rhesus monkeys against lethal zaire ebola virus (zebov) and 100% of cynomolgus monkeys against lake victoria marburg virus (marv) ... | 2010 | 20729866 |
| cellular entry of ebola virus involves uptake by a macropinocytosis-like mechanism and subsequent trafficking through early and late endosomes. | zaire ebolavirus (zebov), a highly pathogenic zoonotic virus, poses serious public health, ecological and potential bioterrorism threats. currently no specific therapy or vaccine is available. virus entry is an attractive target for therapeutic intervention. however, current knowledge of the zebov entry mechanism is limited. while it is known that zebov enters cells through endocytosis, which of the cellular endocytic mechanisms used remains unclear. previous studies have produced differing outc ... | 2010 | 20862315 |
| association of kir2ds1 and kir2ds3 with fatal outcome in ebola virus infection. | zaïre ebolavirus (zebov) infection rapidly outruns the host's immunity and leads to death within a week. fatal cases have been associated with an aberrant innate, proinflammatory immune response followed by a suppressed adaptive response leading to the rapid depletion of peripheral nk cells and lymphocytes. a critical role for nk cells has been suggested but not elucidated. in this genetic study, we investigated the association of kir genotype with disease outcome by comparing genotypes of a gab ... | 2010 | 20878400 |
| identification of novel cellular targets for therapeutic intervention against ebola virus infection by sirna screening. | while much progress has been made in developing drugs against a few prominent viruses such as hiv, few examples exist for emerging infectious agents. in some cases broad spectrum anti-viral drugs, such as ribavirin, are effective, but for some groups of viruses, these show little efficacy in animal models. traditional methods focus on screening small molecule libraries to identify drugs that target virus factors, with the intention that side-effects to the host can be minimized. however, this gr ... | 2009 | 20930947 |
| 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 ... | 2010 | 20957152 |
| proposal for a revised taxonomy of the family filoviridae: classification, names of taxa and viruses, and virus abbreviations. | the taxonomy of the family filoviridae (marburgviruses and ebolaviruses) has changed several times since the discovery of its members, resulting in a plethora of species and virus names and abbreviations. the current taxonomy has only been partially accepted by most laboratory virologists. confusion likely arose for several reasons: species names that consist of several words or which (should) contain diacritical marks, the current orthographic identity of species and virus names, and the simila ... | 2010 | 21046175 |
| 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 ... | 2010 | 21047970 |
| 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 ... | 2011 | 21329775 |
| involvement of viral envelope gp2 in ebola virus entry into cells expressing the macrophage galactose-type c-type lectin. | ebola virus (ebov) infection is initiated by the interaction of the viral surface envelope glycoprotein (gp) with the binding sites on target cells. differences in the mortality among different species of the ebola viruses, i.e., zaire ebolavirus (zebov) and reston ebolavirus (rebov), correspond to the in vitro infectivity of the pseudo-typed virus constructed with the gps in cells expressing macrophage galactose-type calcium-type lectin (mgl/cd301). through mutagenesis of gp2, the transmembrane ... | 2011 | 21362405 |
| tyrosine kinase receptor axl enhances entry of zaire ebolavirus without direct interactions with the viral glycoprotein. | in a bioinformatics-based screen for cellular genes that enhance zaire ebolavirus (zebov) transduction, axl mrna expression strongly correlated with zebov infection. a series of cell lines and primary cells were identified that require axl for optimal zebov entry. using one of these cell lines, we identified zebov entry events that are axl-dependent. interactions between zebov-gp and the axl ectodomain were not detected in immunoprecipitations and reduction of surface-expressed axl by rnai did n ... | 2011 | 21529875 |
| from the cover: t-cell immunoglobulin and mucin domain 1 (tim-1) is a receptor for zaire ebolavirus and lake victoria marburgvirus. | the glycoproteins (gp) of enveloped viruses facilitate entry into the host cell by interacting with specific cellular receptors. despite extensive study, a cellular receptor for the deadly filoviruses ebolavirus and marburgvirus has yet to be identified and characterized. here, we show that t-cell ig and mucin domain 1 (tim-1) binds to the receptor binding domain of the zaire ebola virus (ebov) glycoprotein, and ectopic tim-1 expression in poorly permissive cells enhances ebov infection by 10- t ... | 2011 | 21536871 |
| replication, pathogenicity, shedding, and transmission of zaire ebolavirus in pigs. | background. reston ebolavirus was recently detected in pigs in the philippines. specific antibodies were found in pig farmers, indicating exposure to the virus. this important observation raises the possibility that pigs may be susceptible to ebola virus infection, including from other species, such as zaire ebolavirus (zebov), and can transmit to other susceptible hosts. methods. this study investigated whether zebov, a species commonly reemerging in central africa, can replicate and induce dis ... | 2011 | 21571728 |
| depletion of gtp pool is not the predominant mechanism by which ribavirin exerts its antiviral effect on lassa virus. | ribavirin (1-β-d-ribofuranosyl-1,2,4-triazole-3-carboxamide) is the standard treatment for lassa fever, though its mode of action is unknown. one possibility is depletion of the intracellular gtp pool via inhibition of the cellular enzyme inosine monophosphate dehydrogenase (impdh). this study compared the anti-arenaviral effect of ribavirin with that of two other impdh inhibitors, mycophenolic acid (mpa) and 5-ethynyl-1-β-d-ribofuranosylimidazole-4-carboxamide (eicar). all three compounds were ... | 2011 | 21616094 |
| aerosol exposure to zaire ebolavirus in three nonhuman primate species: differences in disease course and clinical pathology. | there is little known concerning the disease caused by zaire ebolavirus (zebov) when inhaled, the likely route of exposure in a biological attack. cynomolgus macaques, rhesus macaques, and african green monkeys were exposed to aerosolized zebov to determine which species might be the most relevant model of the human disease. a petechial rash was noted on cynomolgus and rhesus macaques after fever onset but not on african green monkeys. fever duration was shortest in rhesus macaques (62.7±16.3 h) ... | 2011 | 21651988 |
| reston ebolavirus antibodies in bats, the philippines. | to the editor: filoviruses cause highly lethal hemorrhagic fever in humans and nonhuman primates, except for reston ebolavirus (rebov), which causes severe hemorrhagic fever in macaques (1,2). rebov epizootics among cynomolgus macaques occurred in 1989, 1990, 1992, and 1996 (2) and among swine in 2008 (3). african fruit bats have been suggested to be natural reservoirs for zaire ebolavirus and marburg virus (4-6). however, the natural reservoir of rebov in the philippines is unknown. thus, we de ... | 2011 | 21801651 |
| an alternative method of measuring aerosol survival using spiders' webs and its use for the filoviruses. | understanding the ability to survive in an aerosol leads to better understanding of the hazard posed by pathogenic organisms and can inform decisions related to the control and management of disease outbreaks. this basic survival information is sometimes lacking for high priority select agents such as the filoviruses which cause severe disease with high case fatality rates and can be acquired through the aerosol route. microthreads in the form of spiders' webs were used to capture aerosolised fi ... | 2011 | 21762730 |
| 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 ... | 2011 | 21752470 |
| functional genomics reveals the induction of inflammatory response and metalloproteinase gene expression during lethal ebola virus infection. | ebola virus is the etiologic agent of a lethal hemorrhagic fever in humans and nonhuman primates with mortality rates of up to 90%. previous studies with zaire ebola virus (zebov), mouse-adapted virus (ma-zebov), and mutant viruses (zebov-np(ma), zebov-vp24(ma), and zebov-np/vp24(ma)) allowed us to identify the mutations in viral protein 24 (vp24) and nucleoprotein (np) responsible for acquisition of high virulence in mice. to elucidate specific molecular signatures associated with lethality, we ... | 2011 | 21734050 |
| inactivated or live-attenuated bivalent vaccines that confer protection against rabies and ebola viruses. | the search for a safe and efficacious vaccine for ebola virus continues, as no current vaccine candidate is nearing licensure. we have developed (i) replication-competent, (ii) replication-deficient, and (iii) chemically inactivated rabies virus (rabv) vaccines expressing zaire ebola virus (zebov) glycoprotein (gp) by a reverse genetics system based on the sad b19 rabv wildlife vaccine. zebov gp is efficiently expressed by these vaccine candidates and is incorporated into virions. the vaccine ca ... | 2011 | 21849459 |
| Emergence of divergent Zaire ebola virus strains in Democratic Republic of the Congo in 2007 and 2008. | Zaire ebolavirus was responsible for 2 outbreaks in Democratic Republic of the Congo (DRC), in 1976 and 1995. The virus reemerged in DRC 12 years later, causing 2 successive outbreaks in the Luebo region, Kasai Occidental province, in 2007 and 2008. | 2011 | 21987750 |
| real-time monitoring of cardiovascular function in rhesus macaques infected with zaire ebolavirus. | nine rhesus macaques were implanted with multisensor telemetry devices and internal jugular vein catheters before being infected with zaire ebolavirus. all animals developed viremia, fever, a hemorrhagic rash, and typical changes of ebola hemorrhagic fever in clinical laboratory tests. three macaques unexpectedly survived this usually lethal disease, making it possible to compare physiological parameters in lethally challenged animals and survivors. after the onset of fever, lethal illness was c ... | 2011 | 21987736 |
| impact of systemic or mucosal immunity to adenovirus on ad-based ebola virus vaccine efficacy in guinea pigs. | approximately 35% of the north american population and an estimated 90% of the sub-saharan african population have antibodies against adenovirus serotype 5 (adhu5) that are capable of neutralizing adhu5-based vaccines. in mice, intranasal delivery of adhu5 expressing the zaire ebolavirus glycoprotein human adenovirus serotype 5 (ad) containing the genes for the zaire ebolavirus glycoprotein (zgp) under the expressional control of a cytomegalovirus immediate early promoter (cmv)) can bypass syste ... | 2011 | 21987739 |
| single immunization with a monovalent vesicular stomatitis virus-based vaccine protects nonhuman primates against heterologous challenge with bundibugyo ebolavirus. | the recombinant vesicular stomatitis virus (rvsv) vector-based monovalent vaccine platform expressing a filovirus glycoprotein has been demonstrated to provide protection from lethal challenge with ebola (ebov) and marburg (marv) viruses both prophylactically and after exposure. this platform provides protection between heterologous strains within a species; however, protection from lethal challenge between species has been largely unsuccessful. to determine whether the rvsv-ebov vaccines have t ... | 2011 | 21987745 |
| 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 ... | 2011 | 21987751 |
| characterization of zaire ebolavirus glycoprotein-specific monoclonal antibodies. | zaire ebolavirus (zebov) can be transmitted by human-to-human contact and causes acute haemorrhagic fever with case fatality rates up to 90%. there are no effective therapeutic or prophylactic treatments available. the sole transmembrane glycoprotein (gp) is the key target for developing neutralizing antibodies. in this study, recombinant vsvδg/zebovgp was used to generate monoclonal antibodies (mabs) against the zebov gp. a total of 8 mabs were produced using traditional hybridoma cell fusion t ... | 2011 | 21925951 |
| filovirus infection of stat-1 knockout mice. | we evaluated the susceptibility to ebola and marburg virus infection of mice that cannot respond to interferon (ifn)-α/β and ifn-γ because of deletion of the stat-1 gene. a mouse-adapted zaire ebolavirus (zebov) caused rapidly lethal disease; wild-type zebov and sudan ebolavirus and 4 different marburg virus strains produced severe, but more slowly progressive illness; and reston ebolavirus caused mild disease that was late in onset. the virulence of each agent was mirrored by the pace and sever ... | 2011 | 21987780 |
| vesicular stomatitis virus-based ebola vaccines with improved cross-protective efficacy. | for ebola virus (ebov), 4 different species are known: zaire, sudan, côte d'ivoire, and reston ebolavirus. the newly discovered bundibugyo ebolavirus has been proposed as a 5th species. so far, no cross-neutralization among ebov species has been described, aggravating progress toward cross-species protective vaccines. with the use of recombinant vesicular stomatitis virus (rvsv)-based vaccines, guinea pigs could be protected against zaire ebolavirus (zebov) infection only when immunized with a v ... | 2011 | 21987743 |
| 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 ... | 2011 | 21858240 |
| evasion of the interferon-mediated antiviral response by filoviruses. | the members of the filoviruses are recognized as some of the most lethal viruses affecting human and non-human primates. the only two genera of the filoviridae family, marburg virus (marv) and ebola virus (ebov), comprise the main etiologic agents of severe hemorrhagic fever outbreaks in central africa, with case fatality rates ranging from 25 to 90%. fatal outcomes have been associated with a late and dysregulated immune response to infection, very likely due to the virus targeting key host imm ... | 2010 | 21994610 |
| drbp76 associates with ebola virus vp35 and suppresses viral polymerase function. | the zaire ebola virus (ebov) protein vp35 is multifunctional; it inhibits ifn-α/β production and functions as a cofactor of the viral rna polymerase. mass spectrometry identified the double stranded rna binding protein 76 (drbp76/nfar-1/nf90) as a cellular factor that associates with the vp35 c-terminal interferon inhibitory domain (iid). drbp76 is described to regulate host cell protein synthesis and play an important role in host defense. the vp35-iid-drbp76 interaction required the addition o ... | 2011 | 21987769 |
| Lethality and pathogenesis of airborne infection with filoviruses in A129 a/ß -/- interferon receptor-deficient mice. | Normal immunocompetent mice are not susceptible to non-adapted filoviruses. There are therefore two strategies available to establish a murine model of filovirus infection: adaptation of the virus to the host or the use of genetically modified mice that are susceptible to the virus. A number of knockout (KO) strains of mice with defects in either their adaptive or innate immunity are susceptible to non-adapted filoviruses. In this study, A129 a/ß -/- interferon receptor-deficient KO mice, strain ... | 2012 | 21852521 |
| protective efficacy of a bivalent recombinant vesicular stomatitis virus vaccine in the syrian hamster model of lethal ebola virus infection. | outbreaks of filoviral hemorrhagic fever occur sporadically and unpredictably across wide regions in central africa and overlap with the occurrence of other infectious diseases of public health importance. | 2011 | 21987746 |
| Host response dynamics following lethal infection of rhesus macaques with Zaire ebolavirus. | To gain further insight into the interdependent pathogenic processes in Ebola hemorrhagic fever (EHF), we have examined the dynamics of host responses in individual rhesus macaques infected with Zaire ebolavirus over the entire disease course. Examination of coagulation parameters revealed that decreased coagulation inhibitor activity triggered severe coagulopathy as indicated by prolonged coagulation times and decreased fibrinogen levels. This has been proposed as one of the significant mechani ... | 2011 | 21987781 |
| 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 ... | 2011 | 22028943 |
| sgp serves as a structural protein in ebola virus infection. | sgp, which is perceived as nonstructural, secretory glycoprotein, shares 295 amino acids at its n-terminal with gp(1,2), which include the specific residue necessary to interact with gp(2). in the present study, we tested whether the sgp protein of zaire ebolavirus (zebov) could substitute for gp(1) and form a complex with gp(2), thus serving as a structural protein. | 2011 | 21987767 |
| risk factors for zaire ebolavirus--specific igg in rural gabonese populations. | in gabon, several ebolavirus outbreaks have occurred exclusively in the northeastern region. we conducted a large serosurvey to identify areas and populations at risk and potential demographic, clinical, and behavioral risk factors. | 2011 | 21987749 |