Publications
| Title | Abstract | Year Filter | PMID(sorted ascending) Filter |
|---|
| analysis of human peripheral blood samples from fatal and nonfatal cases of ebola (sudan) hemorrhagic fever: cellular responses, virus load, and nitric oxide levels. | peripheral blood samples obtained from patients during an outbreak of ebola virus (sudan species) disease in uganda in 2000 were used to phenotype peripheral blood mononuclear cells (pbmc), quantitate gene expression, measure antigenemia, and determine nitric oxide levels. it was determined that as the severity of disease increased in infected patients, there was a corresponding increase in antigenemia and leukopenia. blood smears revealed thrombocytopenia, a left shift in neutrophils (in some c ... | 2004 | 15367603 |
| disulfide bond assignment of the ebola virus secreted glycoprotein sgp. | the non-structural glycoprotein (sgp) of ebola virus (ebov) is secreted in large amounts from infected cells as a disulfide-linked homodimer. in this communication, highly purified sgp, derived from vero e6 cultures infected with the zaire species of ebov, was used to determine the correct localization of inter- and intrachain disulfide bonds. matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry analysis of proteolytic cleavage fragments indicates that all cysteines (six ... | 2004 | 15369806 |
| ebola virus ecology: a continuing mystery. | 2004 | 15381189 | |
| ebola virus: new insights into disease aetiopathology and possible therapeutic interventions. | ebola virus (ebov) gained public notoriety in the last decade largely as a consequence of the highly publicized isolation of a new ebov species in a suburb of washington, dc, in 1989, together with the dramatic clinical presentation of ebov infection and high case-fatality rate in africa (near 90% in some outbreaks), and the unusual and striking morphology of the virus. furthermore, there are no vaccines or effective therapies currently available. progress in understanding the origins of the pat ... | 2004 | 15383160 |
| application of real-time pcr for testing antiviral compounds against lassa virus, sars coronavirus and ebola virus in vitro. | this report describes the application of real-time pcr for testing antivirals against highly pathogenic viruses such as lassa virus, sars coronavirus and ebola virus. the test combines classical cell culture with a quantitative real-time pcr read-out. the assay for lassa virus was validated with ribavirin, which showed an ic(50) of 9 micrograms/ml. small-scale screening identified a class of imidazole nucleoside/nucleotide analogues with antiviral activity against lassa virus. the analogues cont ... | 2004 | 15451189 |
| [functional activity of peritoneal macrophages in experimental ebola fever]. | the phagocytic activity of peritoneal macrophages (a representative of mononuclear phagocytes) as well as the tnf-alpha were studied in animals with different susceptibility to ebola virus (ev). the results denote the following: 1. phagocytosis activation by peritoneal macrophages after ev is introduced into the body correlates directly with a susceptibility degree of an animal to ev. 2. the ev content in peritoneal lavage is inversely dependent on a phagocytic activity of peritoneal macrophages ... | 2004 | 15455683 |
| flipping the switch from monomeric to dimeric cv-n has little effect on antiviral activity. | cyanovirin-n can exist in solution in monomeric and domain-swapped dimeric forms, with hiv-antiviral activity being reported for both. here we present results for cv-n variants that form stable solution dimers: the obligate dimer [deltaq50]cv-n and the preferential dimer [s52p]cv-n. these variants exhibit comparable deltag values (10.6 +/- 0.5 and 9.4 +/- 0.5 kcal.mol(-1), respectively), similar to that of stabilized, monomeric [p51g]cv-n (9.8 +/- 0.5 kcal.mol(-1)), but significantly higher than ... | 2004 | 15458629 |
| 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 |
| an uncertain defense. how do you test that a human ebola vaccine works? you don't. | 2004 | 15487661 | |
| transduction of satellite cells after prenatal intramuscular administration of lentiviral vectors. | we have previously reported long-term expression of lacz in myocytes after in utero intramuscular injection of mokola and ebola pseudotyped lentiviral vectors. in further experiments, we have noted that these vectors also transduce small cells at the periphery of the muscle fibers that have the morphology of satellite cells, or muscle stem cells. in this study we performed experiments to further define the morphology and function of these cells. | 2005 | 15515139 |
| 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 |
| ebola virus ecology. | 2004 | 15529250 | |
| a serological survey of ebola virus infection in central african nonhuman primates. | we used an elisa to determine the prevalence of igg antibodies specific for the zaire subtype of ebola virus in 790 nonhuman primates, belonging to 20 species, studied between 1985 and 2000 in cameroon, gabon, and the republic of congo. the seroprevalence rate of ebola antibody in wild-born chimpanzees was 12.9%, indicating that (1) ebola virus circulates in the forests of a large region of central africa, including countries such as cameroon, where no human cases of ebola infections have been r ... | 2004 | 15529251 |
| [threat or creation of panic? disease agents as terror weapons]. | 2004 | 15540528 | |
| optimized large-scale production of high titer lentivirus vector pseudotypes. | the goal of the present study was to develop an efficient transient transfection method for large-scale production of high titer lentivirus vector stocks of eight different pseudotypes. the envelope genes used for this purpose were those from vsv-g, mokola, rabies, mlv-ampho, mlv-10a1, lcmv-we, and lcmv-arm53b. all envelopes were cloned into phcmv, which yielded lentivirus vector titers one, two, or three orders of magnitude higher than the original plasmids for the rabies, mlv-10a1, and mlv-amp ... | 2004 | 15542136 |
| marburg and ebola viruses as aerosol threats. | ebola and marburg viruses are the sole members of the genus filovirus in the family filoviridae. there has been considerable media attention and fear generated by outbreaks of filoviruses because they can cause a severe viral hemorrhagic fever (vhf) syndrome that has a rapid onset and high mortality. although they are not naturally transmitted by aerosol, they are highly infectious as respirable particles under laboratory conditions. for these and other reasons, filoviruses are classified as cat ... | 2004 | 15588056 |
| ebola virus glycoprotein toxicity is mediated by a dynamin-dependent protein-trafficking pathway. | ebola virus infection causes a highly lethal hemorrhagic fever syndrome associated with profound immunosuppression through its ability to induce widespread inflammation and cellular damage. though gp, the viral envelope glycoprotein, mediates many of these effects, the molecular events that underlie ebola virus cytopathicity are poorly understood. here, we define a cellular mechanism responsible for ebola virus gp cytotoxicity. gp selectively decreased the expression of cell surface molecules th ... | 2005 | 15596847 |
| studies of ebola virus glycoprotein-mediated entry and fusion by using pseudotyped human immunodeficiency virus type 1 virions: involvement of cytoskeletal proteins and enhancement by tumor necrosis factor alpha. | the ebola filoviruses are aggressive pathogens that cause severe and often lethal hemorrhagic fever syndromes in humans and nonhuman primates. to date, no effective therapies have been identified. to analyze the entry and fusion properties of ebola virus, we adapted a human immunodeficiency virus type 1 (hiv-1) virion-based fusion assay by substituting ebola virus glycoprotein (gp) for the hiv-1 envelope. fusion was detected by cleavage of the fluorogenic substrate ccf2 by beta-lactamase-vpr inc ... | 2005 | 15613320 |
| [viral hemorrhagic fevers--ebola hemorrhagic fever, marburg virus disease, and lassa fever]. | 2004 | 15624463 | |
| containing the threat--don't forget ebola. | 2004 | 15630468 | |
| vp40 octamers are essential for ebola virus replication. | matrix protein vp40 of ebola virus is essential for virus assembly and budding. monomeric vp40 can oligomerize in vitro into rna binding octamers, and the crystal structure of octameric vp40 has revealed that residues phe125 and arg134 are the most important residues for the coordination of a short single-stranded rna. here we show that full-length wild-type vp40 octamers bind rna upon hek 293 cell expression. while the phe125-to-ala mutation resulted in reduced rna binding, the arg134-to-ala mu ... | 2005 | 15650213 |
| 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 |
| a reconstituted replication and transcription system for ebola virus reston and comparison with ebola virus zaire. | the only known filovirus, which presumably is not pathogenic for humans, is ebola virus (ebov) reston. when ebov reston and the highly pathogenic ebov zaire were grown in cell culture, comparison of the replication kinetics showed a clear growth impairment of ebov reston, indicating that the replication cycle of ebov reston might be delayed. in addition, the cytopathic effect caused by the virus was much milder with ebov reston than with ebov zaire. to compare replication and transcription of eb ... | 2005 | 15661171 |
| role of ebola virus secreted glycoproteins and virus-like particles in activation of human macrophages. | ebola virus, a member of the family filoviridae, causes one of the most severe forms of viral hemorrhagic fever. in the terminal stages of disease, symptoms progress to hypotension, coagulation disorders, and hemorrhages, and there is prominent involvement of the mononuclear phagocytic and reticuloendothelial systems. cells of the mononuclear phagocytic system are primary target cells and producers of inflammatory mediators. ebola virus efficiently produces four soluble glycoproteins during infe ... | 2005 | 15681442 |
| low seroprevalence of igg antibodies to ebola virus in an epidemic zone: ogooué-ivindo region, northeastern gabon, 1997. | a population-based serosurvey was performed to determine the seroprevalence of antibodies to ebola virus (ebo) in a region that has experienced multiple epidemics of ebo hemorrhagic fever. of 2533 residents in 8 villages, serum samples from 979 (38.6%) were tested by enzyme-linked immunosorbent assay for immunoglobulin (ig) g and igm antibodies to ebola-zaire (ebo-z) virus. fourteen samples (1.4%) were found positive for igg antibodies, and 4 of these (.4%) were samples from survivors of an epid ... | 2005 | 15717273 |
| communicable disease and health protection quarterly review: july to september 2004 from the health protection agency, communicable disease surveillance centre. | 2005 | 15749727 | |
| wild animal mortality monitoring and human ebola outbreaks, gabon and republic of congo, 2001-2003. | all human ebola virus outbreaks during 2001-2003 in the forest zone between gabon and republic of congo resulted from handling infected wild animal carcasses. after the first outbreak, we created an animal mortality monitoring network in collaboration with the gabonese and congolese ministries of forestry and environment and wildlife organizations (wildlife conservation society and programme de conservation et utilisation rationnelle des ecosystemes forestiers en afrique centrale) to predict and ... | 2005 | 15752448 |
| ebola virus antibody prevalence in dogs and human risk. | during the 2001-2002 outbreak in gabon, we observed that several dogs were highly exposed to ebola virus by eating infected dead animals. to examine whether these animals became infected with ebola virus, we sampled 439 dogs and screened them by ebola virus-specific immunoglobulin (ig) g assay, antigen detection, and viral polymerase chain reaction amplification. seven (8.9%) of 79 samples from the 2 main towns, 15 (15.2%) of 99 samples from mekambo, and 40 (25.2%) of 159 samples from villages i ... | 2005 | 15757552 |
| 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 |
| association of ebola virus matrix protein vp40 with microtubules. | viruses exploit a variety of cellular components to complete their life cycles, and it has become increasingly clear that use of host cell microtubules is a vital part of the infection process for many viruses. a variety of viral proteins have been identified that interact with microtubules, either directly or via a microtubule-associated motor protein. here, we report that ebola virus associates with microtubules via the matrix protein vp40. when transfected into mammalian cells, a fraction of ... | 2005 | 15795257 |
| comprehensive analysis of ebola virus gp1 in viral entry. | ebola virus infection is initiated by interactions between the viral glycoprotein gp1 and its cognate receptor(s), but little is known about the structure and function of gp1 in viral entry, partly due to the concern about safety when working with the live ebola virus and the difficulty of manipulating the rna genome of ebola virus. in this study, we have used a human immunodeficiency virus-based pseudotyped virus as a surrogate system to dissect the role of ebola virus gp1 in viral entry. analy ... | 2005 | 15795265 |
| nucleocapsid-like structures of ebola virus reconstructed using electron tomography. | electron tomography (et) is a new technique for high resolution, three-dimensional (3d) reconstruction of pleiomorphic macromolecular complexes, such as virus components. by employing this technique, we resolved the 3d structure of ebola virus nucleocapsid-like (nc-like) structures in the cytoplasm of cells expressing np, vp24, and vp35: the minimum components required to form these nc-like structures. reconstruction of these tubular nc-like structures of ebola virus showed them to be composed o ... | 2005 | 15805739 |
| virus-like particles exhibit potential as a pan-filovirus vaccine for both ebola and marburg viral infections. | a safe and effective pan-filovirus vaccine is highly desirable since the filoviruses ebola virus (ebov) and marburg virus (marv) cause highly lethal disease typified by unimpeded viral replication and severe hemorrhagic fever. previously, we showed that expression of the homologous glycoprotein (gp) and matrix protein vp40 from a single filovirus, either ebov or marv, resulted in formation of wild-type virus-like particles (vlps) in mammalian cells. when used as a vaccine, the wild-type vlps pro ... | 2005 | 15811650 |
| endosomal proteolysis of the ebola virus glycoprotein is necessary for infection. | ebola virus (ebov) causes rapidly fatal hemorrhagic fever in humans and there is currently no effective treatment. we found that the infection of african green monkey kidney (vero) cells by vesicular stomatitis viruses bearing the ebov glycoprotein (gp) requires the activity of endosomal cysteine proteases. using selective protease inhibitors and protease-deficient cell lines, we identified an essential role for cathepsin b (catb) and an accessory role for cathepsin l (catl) in ebov gp-dependent ... | 2005 | 15831716 |
| functional characterization of ebola virus l-domains using vsv recombinants. | vsv recombinants containing the overlapping l-domain sequences from ebola virus vp40 (ptappey) were recovered by reverse-genetics. replication kinetics of m40-wt, m40-p24l, and m40-y30a were indistinguishable from vsv-wt in bhk-21 cells, whereas the double mutant (m40-p2728a) was defective in budding. insertion of the ebola l-domain region into vsv m protein was sufficient to alter the dependence on host proteins for efficient budding. indeed, m40 recombinants containing a functional ptap motif ... | 2005 | 15892969 |
| analysis of ebola virus and vlp release using an immunocapture assay. | ebola virus (ebov), an emerging pathogen, is the causative agent of a rapidly progressive hemorrhagic fever with high mortality rates. there are currently no approved vaccines or treatments available for ebola hemorrhagic fever. standard plaque assays are currently the only reliable techniques for enumerating the virus. effective drug-discovery screening as well as target identification and validation require simple and more rapid detection methods. this report describes the development of a rap ... | 2005 | 15893559 |
| ebola virus: the role of macrophages and dendritic cells in the pathogenesis of ebola hemorrhagic fever. | ebola hemorrhagic fever is a severe viral infection characterized by fever, shock and coagulation defects. recent studies in macaques show that major features of illness are caused by effects of viral replication on macrophages and dendritic cells. infected macrophages produce proinflammatory cytokines, chemokines and tissue factor, attracting additional target cells and inducing vasodilatation, increased vascular permeability and disseminated intravascular coagulation. however, they cannot rest ... | 2005 | 15896665 |
| live attenuated recombinant vaccine protects nonhuman primates against ebola and marburg viruses. | vaccines and therapies are urgently needed to address public health needs stemming from emerging pathogens and biological threat agents such as the filoviruses ebola virus (ebov) and marburg virus (marv). here, we developed replication-competent vaccines against ebov and marv based on attenuated recombinant vesicular stomatitis virus vectors expressing either the ebov glycoprotein or marv glycoprotein. a single intramuscular injection of the ebov or marv vaccine elicited completely protective im ... | 2005 | 15937495 |
| marburg and ebola--arming ourselves against the deadly filoviruses. | 2005 | 15972860 | |
| how ebola virus infects cells. | 2005 | 15972874 | |
| induction of humoral and cd8+ t cell responses are required for protection against lethal ebola virus infection. | ebola virus (ebov)-like particles (evlp), composed of the ebov glycoprotein and matrix viral protein (vp)40 with a lipid membrane, are a highly efficacious method of immunization against ebov infection. the exact requirements for immunity against ebov infection are poorly defined at this time. the goal of this work was to determine the requirements for ebov immunity following evlp vaccination. vaccination of balb/c or c57bl/6 mice with evlps in conjunction with qs-21 adjuvant resulted in mixed i ... | 2005 | 16002721 |
| a single shot against ebola and marburg virus. | 2005 | 16015361 | |
| ebola virus vp40 late domains are not essential for viral replication in cell culture. | ebola virus particle formation and budding are mediated by the vp40 protein, which possesses overlapping ptap and ppxy late domain motifs (7-ptappxy-13). these late domain motifs have also been found in the gag proteins of retroviruses and the matrix proteins of rhabdo- and arenaviruses. while in vitro studies suggest a critical role for late domain motifs in the budding of these viruses, including ebola virus, it remains unclear as to whether the vp40 late domains play a role in ebola virus rep ... | 2005 | 16051823 |
| effects of ebola virus glycoproteins on endothelial cell activation and barrier function. | ebola virus causes severe hemorrhagic fever with high mortality rates in humans and nonhuman primates. vascular instability and dysregulation are disease-decisive symptoms during severe infection. while the transmembrane glycoprotein gp(1,2) has been shown to cause endothelial cell destruction, the role of the soluble glycoproteins in pathogenesis is largely unknown; however, they are hypothesized to be of biological relevance in terms of target cell activation and/or increase of endothelial per ... | 2005 | 16051836 |
| the ebola virus genomic replication promoter is bipartite and follows the rule of six. | in this work we investigated the cis-acting signals involved in replication of ebola virus (ebov) genomic rna. a set of mingenomes with mutant 3' ends were generated and used in a reconstituted replication and transcription system. our results suggest that the ebov genomic replication promoter is bipartite, consisting of a first element located within the leader region of the genome and a second, downstream element separated by a spacer region. while proper spacing of the two promoter elements i ... | 2005 | 16051858 |
| homo-oligomerization facilitates the interferon-antagonist activity of the ebolavirus vp35 protein. | we have identified a putative coiled-coil motif within the amino-terminal half of the ebolavirus vp35 protein. cross-linking studies demonstrated the ability of vp35 to form trimers, consistent with the presence of a functional coiled-coil motif. vp35 mutants lacking the coiled-coil motif or possessing a mutation designed to disrupt coiled-coil function were defective in oligomerization, as deduced by co-immunoprecipitation studies. vp35 inhibits signaling that activates interferon regulatory fa ... | 2005 | 16095644 |
| mannose-binding lectin binds to ebola and marburg envelope glycoproteins, resulting in blocking of virus interaction with dc-sign and complement-mediated virus neutralization. | mannose-binding lectin (mbl), a serum lectin that mediates innate immune functions including activation of the lectin complement pathway, binds to carbohydrates expressed on some viral glycoproteins. in this study, the ability of mbl to bind to virus particles pseudotyped with ebola and marburg envelope glycoproteins was evaluated. virus particles bearing either ebola (zaire strain) or marburg (musoke strain) envelope glycoproteins bound at significantly higher levels to immobilized mbl compared ... | 2005 | 16099912 |
| the contribution of the endothelium to the development of coagulation disorders that characterize ebola hemorrhagic fever in primates. | recently, there have been substantial developments in the understanding of ebola hemorrhagic fever pathogenesis, but there are still major gaps. these infections occur in underdeveloped areas of the world, and much of our knowledge of naturally occurring disease is derived from sporadic outbreaks that occurred decades in the past. recently conducted laboratory animal studies have provided insight into ebola pathogenesis and may help guide clinical investigations of disease using contemporary met ... | 2005 | 16113813 |
| complete genome sequence of an ebola virus (sudan species) responsible for a 2000 outbreak of human disease in uganda. | the entire genomic rna of the gulu (uganda 2000) strain of ebola virus was sequenced and compared to the genomes of other filoviruses. this data represents the first comprehensive genetic analysis for a representative isolate of the sudan species of ebola virus. the genome organization of the sudan species is nearly identical to that of the zaire species, but the presence of a gene overlap (between gp and vp30 genes) and a longer trailer sequence distinguish it from that of the reston species. a ... | 2005 | 16139097 |
| rab9 gtpase is required for replication of human immunodeficiency virus type 1, filoviruses, and measles virus. | rab proteins and their effectors facilitate vesicular transport by tethering donor vesicles to their respective target membranes. by using gene trap insertional mutagenesis, we identified rab9, which mediates late-endosome-to-trans-golgi-network trafficking, among several candidate host genes whose disruption allowed the survival of marburg virus-infected cells, suggesting that rab9 is utilized in marburg replication. although rab9 has not been implicated in human immunodeficiency virus (hiv) re ... | 2005 | 16140752 |
| human dendritic cells and macrophages exhibit different intracellular processing pathways for soluble and liposome-encapsulated antigens. | the intracellular fates of soluble and liposomal antigens in human macrophages and dendritic cells are not well defined. previous studies using murine macrophages have demonstrated that liposomal antigens can enter the mhc class i pathway. the golgi complex is a major organelle in this pathway. phagocytosis of the antigens is followed by translocation of antigen-derived peptides to the trans-golgi where they can complex with mhc class i molecules. in contrast, soluble antigens are normally proce ... | 2005 | 16164039 |
| analysis of the expressed heavy chain variable-region genes of macaca fascicularis and isolation of monoclonal antibodies specific for the ebola virus' soluble glycoprotein. | the cynomolgus macaque, macaca fascicularis, is frequently used in immunological and other biomedical research as a model for man; understanding it's antibody repertoire is, therefore, of fundamental interest. the expressed variable-region gene repertoire of a single m. fascicularis, which was immune to the ebola virus, was studied. using 5' rapid amplification of cdna ends with immunoglobulin (ig)g-specific primers, we obtained 30 clones encoding full-length variable, diversity, and joining dom ... | 2005 | 16215733 |
| 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 |
| [human recombinant antibodies to ebola virus: preparation and characteristics]. | human recombinant antibodies against a purified ebola virus (ev) lysate were selected from a combinatorial library of scfv-antibodies using the phage display technique. nine unique antibodies were identified after sequencing the vh- and vl-genes encoding the selected antibodies. solid-phase enzyme immunoassay (eia) indicated that these antibodies were able to bind both inactivated and native ev. immunoblotting showed that 6 antibodies identified nucleoprotein (np), one antibody did vp24 and anot ... | 2005 | 16250595 |
| protective cytotoxic t-cell responses induced by venezuelan equine encephalitis virus replicons expressing ebola virus proteins. | infection with ebola virus causes a severe disease accompanied by high mortality rates, and there are no licensed vaccines or therapies available for human use. filovirus vaccine research efforts still need to determine the roles of humoral and cell-mediated immune responses in protection from ebola virus infection. previous studies indicated that exposure to ebola virus proteins expressed from packaged venezuelan equine encephalitis virus replicons elicited protective immunity in mice and that ... | 2005 | 16254354 |
| laboratory diagnosis of ebola and marburg hemorrhagic fever. | the control of filovirus outbreaks can be greatly enhanced by timely laboratory confirmation of infection or the identification of alternative disease processes. the status of current laboratory diagnostics for ebola and marburg virus infections is discussed in terms of the assays available and their interpretation. in addition, the role of field-based laboratory support and its limitations and capabilities in an outbreak response setting, especially in regards to real-time pcr and immunofiltrat ... | 2005 | 16267962 |
| ebola virus circulation in africa: a balance between clinical expression and epidemiological silence. | nearly thirty years after the first epidemics, ebola virus (ebov) remains hardly described, its transmission unclear and its reservoir elusive. soon after the ebola fever outbreak and virus discovery in 1976 and in order to investigate the distribution of ebov in central africa, several countries including a range of ecological zones were investigated in the early 1980s, using extensive survey: central african republic (car), cameroon, chad, congo, gabon and equatorial guinea. since 1992, elisa ... | 2005 | 16267963 |
| [multiple ebola virus haemorrhagic fever outbreaks in gabon, from october 2001 to april 2002]. | outbreaks of ebola virus haemorrhagic fever have been reported from 1994 to 1996 in the province of ogooué ivindo, a forest zone situated in the northeast of gabon. each time, the great primates had been identified as the initial source of human infection. end of november 2001 a new alert came from this province, rapidly confirmed as a evhv outbreak. the response was given by the ministry of health with the help of an international team under the aegis of who. an active monitoring system was imp ... | 2005 | 16267965 |
| ebola and great apes in central africa: current status and future needs. | 2005 | 16267967 | |
| evidence that multiple defects in murine dc-sign inhibit a functional interaction with pathogens. | certain viruses, bacteria, fungi and parasites target dendritic cells through the interaction with the cellular attachment factor dc-sign, making this c-type lectin an attractive target for therapeutic intervention. studies on dc-sign function would be greatly aided by the establishment of a mouse model, however, it is unclear if the murine (m) homologue of human (h) dc-sign also binds to pathogens. here, we investigated the interaction of mdc-sign, also termed cire, with the ebolavirus glycopro ... | 2006 | 16297949 |
| fruit bats as reservoirs of ebola virus. | the first recorded human outbreak of ebola virus was in 1976, but the wild reservoir of this virus is still unknown. here we test for ebola in more than a thousand small vertebrates that were collected during ebola outbreaks in humans and great apes between 2001 and 2003 in gabon and the republic of the congo. we find evidence of asymptomatic infection by ebola virus in three species of fruit bat, indicating that these animals may be acting as a reservoir for this deadly virus. | 2005 | 16319873 |
| 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 |
| ebola and marburg viruses: pathogenesis and development of countermeasures. | ebola and marburg viruses, family filoviridae, are among the best known examples of emerging and re-emerging pathogens. although outbreaks have been sporadic and geographically restricted to areas of central africa, the hemorrhagic fevers caused by these viruses are remarkably severe and are associated with high case fatality rates often exceeding 80 percent. in addition to humans, these viruses have decimated populations of wild apes in central africa. currently, there are no vaccines or effect ... | 2005 | 16375711 |
| rescue of recombinant marburg virus from cdna is dependent on nucleocapsid protein vp30. | here we report recovery of infectious marburg virus (marv) from a full-length cdna clone. compared to the wild-type virus, recombinant marv showed no difference in terms of morphology of virus particles, intracellular distribution in infected cells, and growth kinetics. the nucleocapsid protein vp30 of marv and ebola virus (ebov) contains a zn-binding motif which is important for the function of vp30 as a transcriptional activator in ebov, whereas its role for marv is unclear. it has been report ... | 2006 | 16379005 |
| [bats, reserves of the ebola virus: the mystery is dissipated]. | 2006 | 16386226 | |
| impact of polymorphisms in the dc-signr neck domain on the interaction with pathogens. | the lectins dc-sign and dc-signr augment infection by human immunodeficiency virus (hiv), ebolavirus (ebov) and other pathogens. the neck domain of these proteins drives multimerization, which is believed to be required for efficient recognition of multivalent ligands. the neck domain of dc-sign consists of seven sequence repeats with rare variations. in contrast, the dc-signr neck domain is polymorphic and, in addition to the wild type (wt) allele with seven repeat units, allelic forms with fiv ... | 2006 | 16413044 |
| gene-specific countermeasures against ebola virus based on antisense phosphorodiamidate morpholino oligomers. | the filoviruses marburg virus and ebola virus (ebov) quickly outpace host immune responses and cause hemorrhagic fever, resulting in case fatality rates as high as 90% in humans and nearly 100% in nonhuman primates. the development of an effective therapeutic for ebov is a daunting public health challenge and is hampered by a paucity of knowledge regarding filovirus pathogenesis. this report describes a successful strategy for interfering with ebov infection using antisense phosphorodiamidate mo ... | 2006 | 16415982 |
| development of treatment strategies to combat ebola and marburg viruses. | ebola and marburg viruses are emerging/re-emerging pathogens that pose a significant threat to human health. these naturally occurring viral infections frequently cause a lethal hemorrhagic fever in humans and nonhuman primates. the disastrous consequences of infection with these viruses have been pursued as potential biological weapons. to date, there are no therapeutic options available for the prophylaxis or treatment of infected individuals. the recognition that ebola and marburg viruses may ... | 2006 | 16441210 |
| a single intranasal inoculation with a paramyxovirus-vectored vaccine protects guinea pigs against a lethal-dose ebola virus challenge. | to determine whether intranasal inoculation with a paramyxovirus-vectored vaccine can induce protective immunity against ebola virus (ev), recombinant human parainfluenza virus type 3 (hpiv3) was modified to express either the ev structural glycoprotein (gp) by itself (hpiv3/ebogp) or together with the ev nucleoprotein (np) (hpiv3/ebogp-np). expression of ev gp by these recombinant viruses resulted in its efficient incorporation into virus particles and increased cytopathic effect in vero cells. ... | 2006 | 16474134 |
| vp35 knockdown inhibits ebola virus amplification and protects against lethal infection in mice. | phosphorodiamidate morpholino oligomers (pmo) are a class of uncharged single-stranded dna analogs modified such that each subunit includes a phosphorodiamidate linkage and morpholine ring. pmo antisense agents have been reported to effectively interfere with the replication of several positive-strand rna viruses in cell culture. the filoviruses, marburg virus and ebola virus (ebov), are negative-strand rna viruses that cause up to 90% lethality in human outbreaks. there is currently no commerci ... | 2006 | 16495261 |
| 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 |
| detection of cell-cell fusion mediated by ebola virus glycoproteins. | ebola viruses (ebov) are enveloped rna viruses infecting cells by a ph-dependent process mediated by viral glycoproteins (gp) involving endocytosis of virions and their routing into acidic endosomes. as with well-characterized ph-dependent viral entry proteins, in particular influenza virus hemagglutinin, it is thought that ebov gp require activation by low ph in order to mediate fusion of the viral envelope with the membrane of endosomes. however, it has not yet been possible to confirm the dir ... | 2006 | 16501090 |
| 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 |
| functional comparison of mouse cire/mouse dc-sign and human dc-sign. | cire/mdc-sign is a c-type lectin we originally identified as a molecule differentially expressed by mouse dendritic cell (dc) populations. immunostaining with a cire/mdc-sign-specific mab revealed that cire/mdc-sign is indeed on the surface of some cd4+, cd4- 8- dcs and plasmacytoid pre-dcs, but not on cd8+ dcs. it has been proposed that cire/mdc-sign is the functional orthologue of human dc-sign (hdc-sign), a molecule that both enhances t cell responses and facilitates antigen uptake. we assess ... | 2006 | 16569675 |
| toxicological safety evaluation of dna plasmid vaccines against hiv-1, ebola, severe acute respiratory syndrome, or west nile virus is similar despite differing plasmid backbones or gene-inserts. | the vaccine research center has developed a number of vaccine candidates for different diseases/infectious agents (hiv-1, severe acute respiratory syndrome virus, west nile virus, and ebola virus, plus a plasmid cytokine adjuvant-il-2/ig) based on a dna plasmid vaccine platform. to support the clinical development of each of these vaccine candidates, preclinical studies were performed to screen for potential toxicities (intrinsic and immunotoxicities). all treatment-related toxicities identified ... | 2006 | 16569728 |
| biodistribution of dna plasmid vaccines against hiv-1, ebola, severe acute respiratory syndrome, or west nile virus is similar, without integration, despite differing plasmid backbones or gene inserts. | the vaccine research center has developed a number of vaccine candidates for different diseases/infectious agents (hiv-1, severe acute respiratory syndrome virus, west nile virus, and ebola virus, plus a plasmid cytokine adjuvant-il-2/ig) based on a dna plasmid vaccine platform. to support the clinical development of each of these vaccine candidates, preclinical studies have been performed in mice or rabbits to determine where in the body these plasmid vaccines would biodistribute and how rapidl ... | 2006 | 16569729 |
| functional mapping of the nucleoprotein of ebola virus. | at 739 amino acids, the nucleoprotein (np) of ebola virus is the largest nucleoprotein of the nonsegmented negative-stranded rna viruses, and like the nps of other viruses, it plays a central role in virus replication. huang et al. (y. huang, l. xu, y. sun, and g. j. nabel, mol. cell 10:307-316, 2002) previously demonstrated that np, together with the minor matrix protein vp24 and polymerase cofactor vp35, is necessary and sufficient for the formation of nucleocapsid-like structures that are mor ... | 2006 | 16571791 |
| role of endosomal cathepsins in entry mediated by the ebola virus glycoprotein. | using chemical inhibitors and small interfering rna (sirna), we have confirmed roles for cathepsin b (catb) and cathepsin l (catl) in ebola virus glycoprotein (gp)-mediated infection. treatment of ebola virus gp pseudovirions with catb and catl converts gp1 from a 130-kda to a 19-kda species. virus with 19-kda gp1 displays significantly enhanced infection and is largely resistant to the effects of the catb inhibitor and sirna, but it still requires a low-ph-dependent endosomal/lysosomal function ... | 2006 | 16571833 |
| 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 |
| [ebola and marburg viruses: the humans strike back]. | ebola and marburg viruses are the causative agents of rapidly progressive hemorrhagic fevers with high mortality rates. pre- or post-exposure treatments against the diseases are currently not available for human use. in the field, establishment of strict quarantine measures preventing further virus transmission are still the only way to fight the infections. however, our knowledge of ebola and marburg viruses has markedly increased as a result of two recent discoveries discussed in this review. ... | 2006 | 16597410 |
| ebola virus glycoprotein gp is not cytotoxic when expressed constitutively at a moderate level. | transient expression of ebola virus (ebov) glycoprotein gp causes downregulation of surface proteins, cell rounding and detachment, a phenomenon believed to play a central role in the pathogenicity of the virus. in this study, evidence that moderate expression of gp does not result in such morphological changes was provided. it was shown that gp continuously produced in 293t cells from the kunjin virus replicon was correctly processed and transported to the plasma membrane without affecting the ... | 2006 | 16603527 |
| laboratory diagnostic systems for ebola and marburg hemorrhagic fevers developed with recombinant proteins. | 2006 | 16603611 | |
| ebola virus: unravelling pathogenesis to combat a deadly disease. | ebola virus (ebov) causes severe haemorrhagic fever leading to up to 90% lethality. increasingly frequent outbreaks and the placement of ebov in the category a list of potential biothreat agents have boosted interest in this virus. furthermore, development of new technologies (e.g. reverse genetics systems) and extensive studies on ebola haemorrhagic fever (ehf) in animal models have substantially expanded the knowledge on the pathogenic mechanisms that underlie this disease. two major factors i ... | 2006 | 16616875 |
| good news for marburg virus workers. | 2006 | 16650630 | |
| detection of ebola virus in oral fluid specimens during outbreaks of ebola virus hemorrhagic fever in the republic of congo. | patients who have refused to provide blood samples has meant that there have been significant delays in confirming outbreaks of ebola virus hemorrhagic fever (evhf). during the 2 evhf outbreaks in the republic of congo in 2003, we assessed the use of oral fluid specimens versus serum samples for laboratory confirmation of cases of evhf. | 2006 | 16652308 |
| ebola virus-like particles produced in insect cells exhibit dendritic cell stimulating activity and induce neutralizing antibodies. | recombinant baculoviruses (rbv) expressing ebola virus vp40 (rbv-vp40) or gp (rbv-gp) proteins were generated. infection of sf9 insect cells by rbv-vp40 led to assembly and budding of filamentous particles from the cell surface as shown by electron microscopy. ebola virus-like particles (vlps) were produced by coinfection of sf9 cells with rbv-vp40 and rbv-gp, and incorporation of ebola gp into vlps was demonstrated by sds-page and western blot analysis. recombinant baculovirus infection of inse ... | 2006 | 16678231 |
| immune protection of nonhuman primates against ebola virus with single low-dose adenovirus vectors encoding modified gps. | ebola virus causes a hemorrhagic fever syndrome that is associated with high mortality in humans. in the absence of effective therapies for ebola virus infection, the development of a vaccine becomes an important strategy to contain outbreaks. immunization with dna and/or replication-defective adenoviral vectors (rad) encoding the ebola glycoprotein (gp) and nucleoprotein (np) has been previously shown to confer specific protective immunity in nonhuman primates. gp can exert cytopathic effects o ... | 2006 | 16683867 |
| ebola virus vp35-vp40 interaction is sufficient for packaging 3e-5e minigenome rna into virus-like particles. | the packaging of viral genomic rna into nucleocapsids and subsequently into virions is not completely understood. phosphoprotein (p) and nucleoprotein (np) interactions link np-rna complexes with p-l (polymerase) complexes to form viral nucleocapsids. the nucleocapsid then interacts with the viral matrix protein, leading to specific packaging of the nucleocapsid into the virion. a mammalian two-hybrid assay and confocal microscopy were used to demonstrate that ebola virus vp35 and vp40 interact ... | 2006 | 16698994 |
| ebola virus vp24 binds karyopherin alpha1 and blocks stat1 nuclear accumulation. | ebola virus (ebov) infection blocks cellular production of alpha/beta interferon (ifn-alpha/beta) and the ability of cells to respond to ifn-alpha/beta or ifn-gamma. the ebov vp35 protein has previously been identified as an ebov-encoded inhibitor of ifn-alpha/beta production. however, the mechanism by which ebov infection inhibits responses to ifns has not previously been defined. here we demonstrate that the ebov vp24 protein functions as an inhibitor of ifn-alpha/beta and ifn-gamma signaling. ... | 2006 | 16698996 |
| ebola virus vp35 protein binds double-stranded rna and inhibits alpha/beta interferon production induced by rig-i signaling. | the ebola virus (ebov) vp35 protein blocks the virus-induced phosphorylation and activation of interferon regulatory factor 3 (irf-3), a transcription factor critical for the induction of alpha/beta interferon (ifn-alpha/beta) expression. however, the mechanism(s) by which this blockage occurs remains incompletely defined. we now provide evidence that vp35 possesses double-stranded rna (dsrna)-binding activity. specifically, vp35 bound to poly(ri) . poly(rc)-coated sepharose beads but not contro ... | 2006 | 16698997 |
| 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 |
| functional expression of mouse relaxin and mouse relaxin-3 in the lung from an ebola virus glycoprotein-pseudotyped lentivirus via tracheal delivery. | the peptide hormone relaxin is a known modulator of connective tissue and the extracellular matrix by virtue of its ability to regulate matrix metalloproteinases (mmps). relaxin knockout mice exhibit age-related pulmonary fibrosis, and delivery of recombinant human h2 relaxin ameliorates fibrotic-like conditions in the mouse lung. we investigated whether lentiviral vectors (lvs) engineering the expression of murine relaxins could induce mmp activity in the mouse lung. mouse relaxin and mouse rel ... | 2006 | 16709614 |
| effect of ebola virus proteins gp, np and vp35 on vp40 vlp morphology. | recently we described a role for ebola virus proteins, np, gp, and vp35 in enhancement of vp40 vlp budding. to explore the possibility that vlp structure was altered by co-expression of ebov proteins leading to the observed enhancement of vp40 vlp budding, we performed density gradient analysis as well as electron microscopy studies. our data suggest that vp40 is the major determinant of vlp morphology, as co-expression of np, gp and vp35 did not significantly change vlp density, length, and dia ... | 2006 | 16719918 |
| 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 |
| marburgvirus genomics and association with a large hemorrhagic fever outbreak in angola. | in march 2005, the centers for disease control and prevention (cdc) investigated a large hemorrhagic fever (hf) outbreak in uige province in northern angola, west africa. in total, 15 initial specimens were sent to cdc, atlanta, ga., for testing for viruses associated with viral hfs known to be present in west africa, including ebolavirus. marburgvirus was also included despite the fact that the origins of all earlier outbreaks were linked directly to east africa. surprisingly, marburgvirus was ... | 2006 | 16775337 |
| modulation of virion incorporation of ebolavirus glycoprotein: effects on attachment, cellular entry and neutralization. | the filoviruses ebolavirus (ebov) and marburgvirus (marv) cause severe hemorrhagic fever in humans and are potential agents of biological warfare. the envelope glycoprotein (gp) of filoviruses mediates viral entry into cells and is an attractive target for therapeutic intervention and vaccine design. here, we asked if the efficiency of virion incorporation of ebov-gp impacts attachment and entry into target cells and modulates susceptibility to neutralizing antibodies. in order to control the le ... | 2006 | 16777170 |
| viral haemorrhagic fevers caused by lassa, ebola and marburg viruses. | 2006 | 16802617 | |
| activation of triggering receptor expressed on myeloid cells-1 on human neutrophils by marburg and ebola viruses. | marburg virus (marv) and ebola virus (ebov), members of the viral family filoviridae, cause fatal hemorrhagic fevers in humans and nonhuman primates. high viral burden is coincident with inadequate adaptive immune responses and robust inflammatory responses, and virus-mediated dysregulation of early host defenses has been proposed. recently, a novel class of innate receptors called the triggering receptors expressed in myeloid cells (trem) has been discovered and shown to play an important role ... | 2006 | 16809329 |