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sequence analysis of the marburg virus nucleoprotein gene: comparison to ebola virus and other non-segmented negative-strand rna viruses.the first 3000 nucleotides from the 3' end of the marburg virus (mbg) genome were determined from cdna clones produced from genomic rna and mrna. identified in the sequence was a short putative leader sequence at the extreme 3' end, followed by the complete nucleoprotein (np) gene. the 5' end of the np mrna was determined as was the polyadenylation site for the np gene. the transcriptional start (3' uucuucuuauaauu..) and termination (3' ..uaauucuuuuu) signals of the mbg np gene are very similar ...19921538192
marburg virus, a filovirus: messenger rnas, gene order, and regulatory elements of the replication cycle.the genome of marburg virus (mbg), a filovirus, is 19.1 kb in length and thus the largest one found with negative-strand rna viruses. the gene order - 3' untranslated region-np-vp35-vp40-gp-vp30-vp24-l-5' untranslated region-resembles that of other non-segmented negative-strand (nns) rna viruses. six species of polyadenylated subgenomic rnas, isolated from mbg-infected cells, are complementary to the negative-strand rna genome. they can be translated in vitro into the known structural proteins n ...19921626422
hemorrhagic fever virus infections in an isolated rainforest area of central liberia. limitations of the indirect immunofluorescence slide test for antibody screening in africa.serum samples from 119 healthy individuals and 106 epilepsy patients inhabiting grand bassa county, liberia, were tested for antibodies to hemorrhagic fever viruses (hfv) by indirect immunofluorescence. e6 vero cells infected with lassa fever virus (las), rift valley fever virus (rvf), congo hemorrhagic fever virus (con), marburg virus (mbg) and the ebola (ebo) virus strains mayinga (may) and boniface (bon) were used as antigen. to obtain reproducible and specific test results sera had to be abs ...19863092415
physicochemical properties of marburg virus: evidence for three distinct virus strains and their relationship to ebola virus.the physicochemical and antigenic properties of three groups of marburg (mbg) virus isolates, separated temporally and geographically, were compared to each other and to another member of the same family, ebola (ebo) virus. each mbg isolate contained seven virion proteins, one of which was a glycosylated surface protein. peptide mapping of glycoproteins, nucleoproteins (np) and viral structural protein (vp40) demonstrated extensive sequence conservation in the proteins of viruses isolated over a ...19883404120
conservation of the 3' terminal nucleotide sequences of ebola and marburg virus.the 3' rna base sequences of several marburg (mbg) and ebola (ebo) virus isolates have been determined. a comparison of these 3' terminal noncoding sequences with those of other negative strand rna viruses suggests a unique phylogenic niche for marburg and ebola viruses. the translation initiation site and 35 n-terminal amino acids of the 3' proximal coding gene of a zaire strain of ebola virus was predicted. in addition, putative leader rna sequences preceding the first gene are discussed in te ...19863946083
a comparison of indirect immunofluorescence and electron microscopy for the diagnosis of some haemorrhagic viruses in cell cultures.yellow fever, dengue (types 1, 2 and 4), chikungunya, rift valley fever, ebola, marburg, and lassa viruses were inoculated into susceptible cell cultures and daily investigated by indirect immunofluorescence (ifa) and electron microscopy (em) with a view to achieve an early detection-identification of these agents. compared to the other cell lines tested (vero, bhk-21 and aedes albopictus), cv-1 cells were found to be more sensitive. viral antigens were detected by ifa from a few hours post inoc ...19817024293
the asialoglycoprotein receptor is a potential liver-specific receptor for marburg virus.the liver is one of the main target organs of marburg virus (mbg), a filovirus causing severe haemorrhagic fever with a high fatality rate in humans and non-human primates. mbg grown in certain cells does not contain neuraminic acid, but has terminal galactose on its surface glycoprotein. this observation indicated that the asialoglycoprotein receptor (asgp-r) of hepatocytes may serve as a receptor for mbg in the liver. binding studies revealed that the attachment of mbg to asgp-r-expressing hep ...19957844558
characterization of filoviruses based on differences in structure and antigenicity of the virion glycoprotein.eight different filovirus isolates, representing major episodes of filovirus hemorrhagic disease, were propagated for structural and antigenetic analyses of their glycoprotein (gp). carbohydrate analysis revealed that n- and o-glycosylation are features of filovirus gps. oligosaccharide side chains differed in their sialylation pattern and seemed to be cell line-dependent. marburg virus (mbg) isolates are clearly distinguished from ebola (ebo) and reston viruses by a lack of terminal sialic acid ...19948122375
the nucleoprotein of marburg virus is phosphorylated.the nucleoprotein (np) of marburg virus (mbg), a filovirus, is encoded by the gene closest to the 3' end of the non-segmented negative-strand rna genome. sequence comparison has indicated that np is the functional equivalent to the nucleoproteins of paramyxoviruses and rhabdoviruses. expression of recombinant np in two eukaryotic systems using vaccinia virus and baculovirus (vectors psc11 and pacymb1, respectively) and analysis of mbg-specific proteins have demonstrated that the np of mbg is pho ...19948151297
sequence analysis of the ebola virus genome: organization, genetic elements, and comparison with the genome of marburg virus.sequence analysis of the second through the sixth genes of the ebola virus (ebo) genome indicates that it is organized similarly to rhabdoviruses and paramyxoviruses and is virtually the same as marburg virus (mbg). in vitro translation experiments and predicted amino acid sequence comparisons showed that the order of the ebo genes is: 3'-np-vp35-vp40-gp-vp30-vp24-l. the transcriptional start and stop (polyadenylation) signals are conserved and all contain the sequence 3'-uaauu. three base inter ...19938237108
the vp35 and vp40 proteins of filoviruses. homology between marburg and ebola viruses.the fragments of genomic rna sequences of marburg (mbg) and ebola (ebo) viruses are reported. these fragments were found to encode the vp35 and vp40 proteins. the canonic sequences were revealed before and after each open reading frame. it is suggested that these sequences are mrna extremities and at the same time the regulatory elements for mrna transcription. homology between the mbg and ebo proteins was discovered.19938482365
filovirus-induced endothelial leakage triggered by infected monocytes/macrophages.the pathogenetic mechanisms underlying hemorrhagic fevers are not fully understood, but hemorrhage, activation of coagulation, and shock suggest vascular instability. here, we demonstrate that marburg virus (mbg), a filovirus causing a severe form of hemorrhagic fever in humans, replicates in human monocytes/macrophages, resulting in cytolytic infection and release of infectious virus particles. replication also led to intracellular budding and accumulation of viral particles in vacuoles, thus p ...19968642644
termini of all mrna species of marburg virus: sequence and secondary structure.the 3' and 5' ends of marburg virus (mbg)-specific mrna species have been determined using reverse transcription-pcr, rapid amplification of cdna ends, or the reverse ligation-mediated pcr procedure after removal of cap structures with tobacco acid pyrophosphatase. the polyadenylation sites of all mbg-specific mrnas were strictly conserved and corresponded to the predicted transcriptional stop signals of genomic rna. determination of the 5' ends of the mrna species showed that mrna synthesis sta ...19968806574
intracellular transport and processing of the marburg virus surface protein in vertebrate and insect cells.the surface protein (gp) of marburg virus (mbg) is synthesized as a 90-kda precursor protein which is cotranslationally modified by the addition of high-mannose sugars (140 kda). this step is followed by the conversion of the n-linked sugars to endoglycosidase h (endo h)-resistant species and the addition of o-linked oliosaccharides leading to a mature protein of 170-200 kda approximately 30 min after pulse labelling. the mature form of gp is efficiently transported to the plasma membrane. gp sy ...19968918541
antigenicity and vaccine potential of marburg virus glycoprotein expressed by baculovirus recombinants.there is no effective vaccine for marburg virus (mbgv) or any other filovirus, nor enough pertinent information to expedite rational vaccine development. to ascertain some of the minimal requirements for a mbgv vaccine, we determined whether whole inactivated mbgv, or a baculovirus-expressed virion subunit, could be used to immunize guinea pigs against a lethal infection. baculovirus recombinants were made to express the mbgv glycoprotein (gp) either as a full-length, cell-associated molecule or ...19979426460
three of the four nucleocapsid proteins of marburg virus, np, vp35, and l, are sufficient to mediate replication and transcription of marburg virus-specific monocistronic minigenomes.this paper describes the first reconstituted replication system established for a member of the filoviridae, marburg virus (mbgv). mbgv minigenomes containing the leader and trailer regions of the mbgv genome and the chloramphenicol acetyltransferase (cat) gene were constructed. in mbgv-infected cells, these minigenomes were replicated and encapsidated and could be passaged. unlike most other members of the order mononegavirales, filoviruses possess four proteins presumed to be components of the ...19989765419
interactions of marburg virus nucleocapsid proteins.in this study, the components of marburg virus nucleocapsid complex were determined, and interactions between the compounds were investigated. using salt dissociation of isolated virions, four proteins (np, vp35, vp30, and l) remained attached to the core complex. same proteins were detected intracellularly to be localized in mbgv-induced inclusion bodies, which are presumed to represent areas of nucleocapsid formation. to investigate interactions between the four proteins, immunofluorescence an ...19989791031
marburg virus vaccines based upon alphavirus replicons protect guinea pigs and nonhuman primates.marburg virus (mbgv), for which no vaccines or treatments currently exist, causes an acute hemorrhagic fever with a high mortality rate in humans. we previously showed that immunization with either killed mbgv or a glycoprotein (gp) subunit prevented lethal infection in guinea pigs. in the studies reported here, an rna replicon, based upon venezuelan equine encephalitis (vee) virus, was used as a vaccine vector; the vee structural genes were replaced by genes for mbgv gp, nucleoprotein (np), vp4 ...19989813200
comparison of the transcription and replication strategies of marburg virus and ebola virus by using artificial replication systems.the members of the family filoviridae, marburg virus (mbgv) and ebola virus (ebov), are very similar in terms of morphology, genome organization, and protein composition. to compare the replication and transcription strategies of both viruses, an artificial replication system based on the vaccinia virus t7 expression system was established for ebov. specific transcription and replication of an artificial monocistronic minireplicon was demonstrated by reporter gene expression and detection of the ...19999971816
[comparative study of the antigenic and immunogenic properties of native and recombinant marburg virus vp35 proteins].antigenic structure of marburg virus (mbg) vp35 was compared with that of the recombinant vp35 (f35) expressed in a prokaryotic system. for this purpose, a gene encoding the full-length vp35 was cloned in vector pqe31(qiagen) and expressed at about 70 mg/liter culture fluid in escherichia coli jm103 as a recombinant fusion protein f35. balb/c mice were immunized with soluble f35 or purified inactivated virions of mbg. antibodies cross-reacting with vp35 and f35 antigens were detected by elisa an ...199910544447
ebola and marburg virus antibody prevalence in selected populations of the central african republic.with the natural history of the filovirus family seemingly unknown, filovirus ecology in its natural environment remains a rudimentary field of research. in order to investigate the maintenance cycle of filovirus in central africa, a study was conducted within the rain forest of the central african republic. the epidemiological study determines the frequency and distribution of filovirus seroprevalence in a selected human population. using an elisa, serum samples from pygmy and non-pygmy populat ...200010717539
ultrastructural organization of recombinant marburg virus nucleoprotein: comparison with marburg virus inclusions.hela cells expressing the recombinant marburg virus (mbgv) nucleoprotein (np) have been studied by immunoelectron microscopy. it was found that mbgv nps assembled into large aggregates which were in close association with membranes of the rough endoplasmic reticulum. further analysis of these aggregates revealed that nps formed tubule-like structures which were arranged in a hexagonal pattern. a similar pattern of preformed nucleocapsids was detected in intracellular inclusions induced by mbgv i ...200010729166
distinct mechanisms of entry by envelope glycoproteins of marburg and ebola (zaire) viruses.since the marburg (mbg) and ebola (ebo) viruses have sequence homology and cause similar diseases, we hypothesized that they associate with target cells by similar mechanisms. pseudotype viruses prepared with a luciferase-containing human immunodeficiency virus type 1 backbone and packaged by the mbg virus or the zaire subtype ebo virus glycoproteins (gp) mediated infection of a comparable wide range of mammalian cell types, and both were inhibited by ammonium chloride. in contrast, they exhibit ...200010775638
differential induction of cellular detachment by envelope glycoproteins of marburg and ebola (zaire) viruses.human infection by marburg (mbg) or ebola (ebo) virus is associated with fatal haemorrhagic fevers. while these filoviruses may both incite disease as a result of explosive virus replication, we hypothesized that expression of individual viral gene products, such as the envelope glycoprotein (gp), may directly alter target cells and contribute to pathogenesis. we found that expression of ebo gp in 293t cells caused significant levels of cellular detachment in the absence of cell death or virus r ...200010950971
enzyme-linked immunosorbent assays for detection of antibodies to ebola and marburg viruses using recombinant nucleoproteins.the full-length nucleoprotein (np) of ebola virus (ebo) was expressed as a his-tagged recombinant protein (his-ebo-np) by a baculovirus system. carboxy-terminal halves of nps of ebo and marburg virus (mbg) were expressed as glutathione s-transferase-tagged recombinant proteins in an escherichia coli system. the antigenic regions on the nps of ebo and mbg were determined by both western blotting and enzyme-linked immunosorbent assay (elisa) to be located on the c-terminal halves. the c-terminal 1 ...200111136739
[detection of antiviral activity of monoclonal antibodies, specific to marburg virus proteins].monoclonal antibodies (mabs) specific to marburg virus (mbg), popp strain, have been previously produced and characterized by indirect elisa. protein specificity of mabs was determined by immunoblotting with sds-page proteins of mbg: one to np, four to vp40, and protein specificity of one antibody was not detected. the effect of mab binding to protein epitopes on viral functions was investigated in vitro and in vivo. none of antibodies neutralized the virus in the neutralization test in vitro, b ...200111233285
the role of the type i interferon response in the resistance of mice to filovirus infection.adult immunocompetent mice inoculated with ebola (ebo) or marburg (mbg) virus do not become ill. a suckling-mouse-passaged variant of ebo zaire '76 ('mouse-adapted ebo-z') causes rapidly lethal infection in adult mice after intraperitoneal (i.p.) inoculation, but does not cause apparent disease when inoculated subcutaneously (s.c.). a series of experiments showed that both forms of resistance to infection are mediated by the type i interferon response. mice lacking the cell-surface ifn-alpha/bet ...200111369881
folate receptor-alpha is a cofactor for cellular entry by marburg and ebola viruses.human infections by marburg (mbg) and ebola (ebo) viruses result in lethal hemorrhagic fever. to identify cellular entry factors employed by mbg virus, noninfectible cells transduced with an expression library were challenged with a selectable pseudotype virus packaged by mbg glycoproteins (gp). a cdna encoding the folate receptor-alpha (fr-alpha) was recovered from cells exhibiting reconstitution of viral entry. a fr-alpha cdna was recovered in a similar strategy employing ebo pseudotypes. fr-a ...200111461707
marburg virus vaccines: comparing classical and new approaches.an effort to develop a safe and effective vaccine for marburg virus (mbgv), one of the filoviruses known to cause high mortality rates in humans, led us to compare directly some of the merits of modern versus classical vaccine approaches for this agent. prior work had established the mbgv-glycoprotein (gp), the only known virion surface antigen, as a candidate for inclusion in a vaccine. in this study, we vaccinated groups of hartley guinea pigs with killed mbgv, live attenuated mbgv, soluble mb ...200111672925
vp40, the matrix protein of marburg virus, is associated with membranes of the late endosomal compartment.localization of vp40 in marburg virus (mbgv)-infected cells was studied by using immunofluorescence and immunoelectron microscopic analysis. vp40 was detected in association with nucleocapsid structures, present in viral inclusions and at sites of virus budding. additionally, vp40 was identified in the foci of virus-induced membrane proliferation and in intracellular membrane clusters which had the appearance of multivesicular bodies (mvbs). vp40-containing mvbs were free of nucleocapsids. when ...200211799178
morphology of marburg virus np-rna.when marburg virus (mbgv) nucleoprotein (np) is expressed in insect cells, it binds to cellular rna and forms np-rna complexes such as insect cell-expressed nucleoproteins from other nonsegmented negative-strand rna viruses. recombinant mbgv np-rna forms loose coils that resemble rabies virus n-rna. mbgv np monomers are rods that are spaced along the coil similar to the nucleoprotein monomers of the rabies virus n-rna. high salt treatment induces tight coiling of the mbgv np-rna, again a charact ...200212069528
rapid detection and quantification of rna of ebola and marburg viruses, lassa virus, crimean-congo hemorrhagic fever virus, rift valley fever virus, dengue virus, and yellow fever virus by real-time reverse transcription-pcr.viral hemorrhagic fevers (vhfs) are acute infections with high case fatality rates. important vhf agents are ebola and marburg viruses (mbgv/ebov), lassa virus (lasv), crimean-congo hemorrhagic fever virus (cchfv), rift valley fever virus (rvfv), dengue virus (denv), and yellow fever virus (yfv). vhfs are clinically difficult to diagnose and to distinguish; a rapid and reliable laboratory diagnosis is required in suspected cases. we have established six one-step, real-time reverse transcription- ...200212089242
mapping of two dominant sites of vp35 of marburg virus.five types of anti-vp35 monoclonal antibodies (mabs), four immune sera against marburg virus (mbgv), and 11 overlapping recombinant vp35 fragments were used to map the epitopes for vp35 of mbgv. the purified full-size recombinant vp35 was highly immunogenic and retained the b-cell epitopes that were identical to those of the viral vp35. two major sites on vp35 and a set of truncated vp35 fragments were found by use of an enzyme immunoassay and immunoblot. site i was located in a region between a ...200212479397
characterization of monoclonal antibodies to marburg virus (strain musoke) glycoprotein and identification of two protective epitopes.monoclonal antibodies (mabs) reactive with marburg virus (strain musoke) were evaluated for both biological activity and specificity. several of the marburg virus- (mbgv) specific mabs reduced the size and/or number of mbgv plaques in vitro. the ability of the mabs to affect plaque formation in vitro was demonstrated to be specific for the glycoprotein (gp) of the strain of mbgv used for vaccination. using deletion analysis and peptide mapping, the binding epitopes of several of these neutralizi ...200314517087
rapid detection protocol for filoviruses.the incidence of filovirus disease outbreaks has been increasing in recent years. although there have been advances in the developments of diagnostics, field tests are rare. apart from family members of infected patients, health care workers are at high risk of being infected during the initial phase of an outbreak. rt-pcr has been shown to be helpful in containing outbreaks.200415072761
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
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 ...200516355872
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 ...200616595665
multiagent vaccines vectored by venezuelan equine encephalitis virus replicon elicits immune responses to marburg virus and protection against anthrax and botulinum neurotoxin in mice.the development of multiagent vaccines offers the advantage of eliciting protection against multiple diseases with minimal inoculations over a shorter time span. we report here the results of using formulations of individual venezuelan equine encephalitis (vee) virus replicon-vectored vaccines against a bacterial disease, anthrax; a viral disease, marburg fever; and against a toxin-mediated disease, botulism. the individual vee replicon particles (vrp) expressed mature 83-kda protective antigen ...200616828936
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; ...200717940950
genomic differences between guinea pig lethal and nonlethal marburg virus variants.the complete genome sequences of 2 closely related plaque-derived variants of marburg virus (marv) species lake victoria marburgvirus, strain musoke, indicate only a few regions of the rna genome as underlying the differences between the 2 viruses. one variant is >90% lethal for guinea pigs and the other much less virulent, when guinea pigs are challenged with 1000 pfu of virus. only 4 mutations that result in amino acid changes were identified, 1 in viral matrix protein vp40 and 3 in l, the rna ...200717940965
quantification of lamivudine-resistant hepatitis b virus mutants by type-specific taqman minor groove binder probe assay in patients with chronic hepatitis b.lamivudine (lam)-resistant hepatitis b virus (hbv) with mutations in the polymerase region frequently appears after long-term use of lam. several methods allowing detection of mutant strains (yidd, yvdd) have been reported, but they have no quantitative characteristics. in this study, we explored a unique approach for quantification of each mutant strain.200818275675
monovalent virus-like particle vaccine protects guinea pigs and nonhuman primates against infection with multiple marburg viruses.virus-like particle (vlp)-based vaccines have the advantage of being morphologically and antigenically similar to the live virus from which they are derived. expression of the glycoprotein and vp40 matrix protein from lake victoria marburgvirus (marv) results in spontaneous production of vlps in mammalian cells. guinea pigs vaccinated with marburg virus vlps (mvlps) or inactivated marv (imarv) develop homologous humoral and t-cell responses and are completely protected from a lethal homologous m ...200818444889
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
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 ...201020686043
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 ...201021046175
marburg virus vp40 antagonizes interferon signaling in a species-specific manner.marburgviruses are zoonotic pathogens that cause lethal hemorrhagic fever in humans and nonhuman primates. however, they do not cause lethal disease in immunocompetent mice unless they are adapted to this species. the adaptation process can therefore provide insight into the specific virus-host interactions that determine virulence. in primate cells, the lake victoria marburgvirus musoke strain (marv) vp40 matrix protein antagonizes alpha/beta interferon (ifn-a/ß) and ifn-? signaling by inhibiti ...201121325424
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 ...201121536871
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 ...201221852521
viral immune surveillance: toward a th17/th9 gate to the central nervous system.viral cellular immune surveillance is a dynamic and fluid system that is driven by finely regulated cellular processes including cytokines and other factors locally in the microenvironment and systemically throughout the body. it is questionable as to what extent the central nervous system (cns) is an immune-privileged organ protected by the blood-brain barrier (bbb). recent evidence suggests converging pathways through which viral infection, and its associated immune surveillance processes, may ...201525780281
broad and temperature independent replication potential of filoviruses on cells derived from old and new world bat species.filoviruses are strongly associated with several species of bats as their natural reservoirs. in this study, we determined the replication potential of all filovirus species: marburg marburgvirus, taï forest ebolavirus, reston ebolavirus, sudan ebolavirus, zaire ebolavirus, and bundibugyo ebolavirus. filovirus replication was supported by all cell lines derived from 6 old and new world bat species: the hammer-headed fruit bat, buettikofer's epauletted fruit bat, the egyptian fruit bat, the jamai ...201627354372
sequencing ebola and marburg viruses genomes using microarrays.periodic outbreaks of ebola and marburg hemorrhagic fevers have occurred in africa over the past four decades with case fatality rates reaching as high as 90%. the latest ebola outbreak in west africa in 2014 raised concerns that these infections can spread across continents and pose serious health risks. early and accurate identification of the causative agents is necessary to contain outbreaks. in this report, we describe sequencing-by-hybridization (sbh) technique using high density microarra ...201626822839
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
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
[characterization of marburg virus morphology].ebola virus (ebov) and marburg virus (marv) belong to the family filoviridae. filoviruses cause severe filovirus hemorrhagic fever (fhf) in humans, with high case fatality rates, and represent potential agents for bioterrorism and biological weapons. it is necessary to keep surveillance of filoviruses, even though there is no report of their isolation and patients in china so far. to characterize marv morphology, the lake victoria marburgvirus--leiden was stained negatively and observed under a ...201425118385
a multiagent filovirus dna vaccine delivered by intramuscular electroporation completely protects mice from ebola and marburg virus challenge.we evaluated the immunogenicity and protective efficacy of dna vaccines expressing the codon-optimized envelope glycoprotein genes of zaire ebolavirus, sudan ebolavirus, and marburg marburgvirus (musoke and ravn). intramuscular or intradermal delivery of the vaccines in balb/c mice was performed using the trigrid™ electroporation device. mice that received dna vaccines against the individual viruses developed robust glycoprotein-specific antibody titers as determined by elisa and survived lethal ...201222922764
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
determination of specific antibody responses to the six species of ebola and marburg viruses by multiplexed protein microarrays.infectious hemorrhagic fevers caused by the marburg and ebola filoviruses result in human mortality rates of up to 90%, and there are no effective vaccines or therapeutics available for clinical use. the highly infectious and lethal nature of these viruses highlights the need for reliable and sensitive diagnostic methods. we assembled a protein microarray displaying nucleoprotein (np), virion protein 40 (vp40), and glycoprotein (gp) antigens from isolates representing the six species of filoviru ...201425230936
human survivors of disease outbreaks caused by ebola or marburg virus exhibit cross-reactive and long-lived antibody responses.a detailed understanding of serological immune responses to ebola and marburg virus infections will facilitate the development of effective diagnostic methods, therapeutics, and vaccines. we examined antibodies from ebola or marburg survivors 1 to 14 years after recovery from disease, by using a microarray that displayed recombinant nucleoprotein (np), viral protein 40 (vp40), envelope glycoprotein (gp), and inactivated whole virions from six species of filoviruses. all three outbreak cohorts ex ...201627335383
oral shedding of marburg virus in experimentally infected egyptian fruit bats (rousettus aegyptiacus).marburg virus (marburg marburgvirus; marv) causes sporadic outbreaks of marburg hemorrhagic fever (mhf) in africa. the egyptian fruit bat (rousettus aegyptiacus) has been identified as a natural reservoir based most-recently on the repeated isolation of marv directly from bats caught at two locations in southwestern uganda where miners and tourists separately contracted mhf from 2007-08. despite learning much about the ecology of marv through extensive field investigations, there remained unansw ...201525375951
induction of broad cytotoxic t cells by protective dna vaccination against marburg and ebola.marburg and ebola hemorrhagic fevers have been described as the most virulent viral diseases known to man due to associative lethality rates of up to 90%. death can occur within days to weeks of exposure and there is currently no licensed vaccine or therapeutic. recent evidence suggests an important role for antiviral t cells in conferring protection, but little detailed analysis of this response as driven by a protective vaccine has been reported. we developed a synthetic polyvalent-filovirus d ...201323670573
molecular evolution of viruses of the family filoviridae based on 97 whole-genome sequences.viruses in the ebolavirus and marburgvirus genera (family filoviridae) have been associated with large outbreaks of hemorrhagic fever in human and nonhuman primates. the first documented cases occurred in primates over 45 years ago, but the amount of virus genetic diversity detected within bat populations, which have recently been identified as potential reservoir hosts, suggests that the filoviruses are much older. here, detailed bayesian coalescent phylogenetic analyses are performed on 97 who ...201323255795
phosphorylation of marburg virus vp30 at serines 40 and 42 is critical for its interaction with np inclusions.the marburg virus (mbgv) nucleocapsid complex is composed of four viral proteins (np, l, vp35, and vp30) and the negative-strand nonsegmented genomic rna. np, l, and vp35 are functionally conserved among the order mononegavirales, whereas vp30, a phosphoprotein, represents a filovirus-specific nucleocapsid protein. in the present paper, we have characterized the localization and function of vp30 phosphorylation. the main phosphorylation sites are represented by seven serine residues in the regio ...200111504552
single dose trivalent vesiculovax vaccine protects macaques from lethal ebolavirus and marburgvirus challenge.previous studies demonstrated that a single intramuscular (im) dose of an attenuated vesicular stomatitis virus vector (vesiculovax™, rvsv-n4ct1) expressing the glycoprotein (gp) from the mayinga strain ofzaire ebolavirus(ebov) protected nonhuman primates (nhp) from lethal challenge with ebov kikwit and makona strains. here we studied the immunogenicity of an expanded range of attenuated rvsv vectors expressing filovirus gp in mice. based on data from those studies an optimal attenuated tri-vale ...201729142131
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
vaccinomics strategy for developing a unique multi-epitope monovalent vaccine against marburg marburgvirus.marburg virus is known to cause a severe hemorrhagic fever (mhf) in both humans and non-human primates with high degree of infectivity and lethality. to date no approved treatment is available for marburg virus infection. a study was employed to design a novel chimeric subunit vaccine against marburg virus by adopting reverse vaccinology approach. the entire viral proteome was retrieved from uniprotkb and assessed to design highly antigenic epitopes by antigenicity screening, transmembrane topol ...201930849525
identity and validity of conserved b cell epitopes of filovirus glycoprotein: towards rapid diagnostic testing for ebola and possibly marburg virus disease.ebolavirus and marburgvirus are genera of the virus family filoviridae. filoviruses cause rare but fatal viral hemorrhagic fevers (vhfs) in remote villages of equatorial africa with potential for regional and international spread. point-of-care (poc) rapid diagnostic tests (rdts) are critical for early epidemic detection, reponse and control. there are 2 rdts for zaire ebolavirus (ebov), but not other ebolavirus spp. or marburg marburgvirus (marv). we validate 3 conserved b cell epitopes of filo ...201830285648
preservation of quaternary structure in thermostable, lyophilized filovirus glycoprotein vaccines: a search for stability-indicating assays.the filoviruses zaire ebolavirus (ebov), marburg marburgvirus (marv), and sudan ebolavirus (sudv) are some of the most lethal infectious agents known. to date, the zaire ebolavirus vaccine (ervebo®) is the only united states food and drug administration (fda) approved vaccine available for any species of filovirus. however, the ervebo® vaccine requires cold-chain storage not to exceed -60 °c. such cold-chain requirements are difficult to maintain in low- and middle-income countries where filovir ...202032931778
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