Publications

detection of antibodies against the four subtypes of ebola virus in sera from any species using a novel antibody-phage indicator assay.	the natural host for ebola virus, presumed to be an animal, has not yet been identified despite an extensive search following several major outbreaks in africa. a straightforward approach used to determine animal contact with ebola virus is by assessing the presence of specific antibodies in serum. this approach however has been made very difficult by the absence of specific reagents required for the detection of antibodies from the majority of wild animal species. in this study, we isolated a h ...	2002	12350354
development of an immunofluorescence method for the detection of antibodies to ebola virus subtype reston by the use of recombinant nucleoprotein-expressing hela cells.	an indirect immunofluorescent assay (ifa) to detect ebola virus subtype reston (ebo-r) antibodies was developed by the use of a hela cell line stably expressing ebo-r nucleoprotein (np). this ifa has a high specificity for the detection of ebo-r igg antibodies in both hyperimmune rabbit sera and monkey sera collected during an ebo-r outbreak in the philippines in 1996. furthermore, this ifa showed a higher sensitivity for the detection of ebo-r antibodies than did the ifa using hela cells expres ...	2002	12437031
3-deazaneplanocin a induces massively increased interferon-alpha production in ebola virus-infected mice.	3-deazaneplanocin a, an analog of adenosine, is a potent inhibitor of ebola virus replication. a single dose early in infection prevents illness and death in ebola virus-infected mice. the ability of this and similar compounds to block both rna and dna viruses has been attributed to the inhibition of a cellular enzyme, s-adenosylhomocysteine hydrolase (sah), indirectly resulting in reduced methylation of the 5' cap of viral messenger rna. however, we found that the protective effect of the drug ...	2002	12076759
histopathology of natural ebola virus subtype reston infection in cynomolgus macaques during the philippine outbreak in 1996.	we investigated the livers, spleens, kidneys and lungs collected from 24 cynomolgus macaques (macaca fascicularis) naturally infected with ebola virus subtype reston (ebo-r) during the philippine outbreak in 1996, in order to reveal the histopathologic findings. these macaques showed necrotic hepatocytes with inclusions, slight to massive fibrin deposition in splenic cords, depletion of lymphoid cells in the white pulp of the spleen, and fibrin thrombi in some organs. immunohistochemical analysi ...	2002	12451705
ebola at mbarara, uganda: aesthetic expressions of the lived worlds of people waiting to know.	the ebola epidemic of 2000 was a disastrous experience for the people of uganda. prior outbreaks in neighboring african sub-saharan countries heightened the realization of death from this devastating disease. waiting to know is a phenomenon described as an excruciating inactivity uniquely experienced by individuals who were exposed to persons with ebola but who had not yet exhibited signs and symptoms of the disease. in the recent ebola epidemic in uganda, contact persons described their experie ...	2002	11949481
ebola virus vp40 drives the formation of virus-like filamentous particles along with gp.	using biochemical assays, it has been demonstrated that expression of ebola virus vp40 alone in mammalian cells induced production of particles with a density similar to that of virions. to determine the morphological properties of these particles, cells expressing vp40 and the particles released from the cells were examined by electron microscopy. vp40 induced budding from the plasma membrane of filamentous particles, which differed in length but had uniform diameters of approximately 65 nm. wh ...	2002	11967302
inflammatory responses in ebola virus-infected patients.	ebola virus subtype zaire (ebo-z) induces acute haemorrhagic fever and a 60-80% mortality rate in humans. inflammatory responses were monitored in victims and survivors of ebo-z haemorrhagic fever during two recent outbreaks in gabon. survivors were characterized by a transient release in plasma of interleukin-1beta (il-1beta), il-6, tumour necrosis factor-alpha (tnfalpha), macrophage inflammatory protein-1alpha (mip-1alpha) and mip-1beta early in the disease, followed by circulation of il-1 rec ...	2002	11982604
lipid raft microdomains: a gateway for compartmentalized trafficking of ebola and marburg viruses.	spatiotemporal aspects of filovirus entry and release are poorly understood. lipid rafts act as functional platforms for multiple cellular signaling and trafficking processes. here, we report the compartmentalization of ebola and marburg viral proteins within lipid rafts during viral assembly and budding. filoviruses released from infected cells incorporated raft-associated molecules, suggesting that viral exit occurs at the rafts. ectopic expression of ebola matrix protein and glycoprotein supp ...	2002	11877482
re-emergence of ebola haemorrhagic fever in gabon.		2002	11879899
mitogen therapy for biological warfare/terrorist attacks and viral hemorrhagic fever control.	ken alibek was for 17 years a leader in biopreparat, the soviet union's top secret agency involved in developing and stockpiling the most lethal bacteria, viruses, and toxins in the history of mankind before he defected with his family to the united states in 1992. very contrite when he discovered he had been misled to believe that his efforts had been essential to the survival of his homeland, alibek has become active sounding an alarm about, among other things, thousands of unemployed russian ...	2002	11915170
viral rna-polymerases -- a predicted 2'-o-ribose methyltransferase domain shared by all mononegavirales.	the mononegavirales virus group comprises several major human pathogens, including measles, rabies and ebola viruses. this article reports a computational analysis of the c-terminal region of rna-dependent rna-polymerases from mononegavirales. using a combination of sequence similarity and threading analysis, a 2'-o-ribose methyltransferase domain was identified that is involved in the capping of viral mrnas.	2002	12076527
evaluation in nonhuman primates of vaccines against ebola virus.	ebola virus (ebov) causes acute hemorrhagic fever that is fatal in up to 90% of cases in both humans and nonhuman primates. no vaccines or treatments are available for human use. we evaluated the effects in nonhuman primates of vaccine strategies that had protected mice or guinea pigs from lethal ebov infection. the following immunogens were used: rna replicon particles derived from an attenuated strain of venezuelan equine encephalitis virus (veev) expressing ebov glycoprotein and nucleoprotein ...	2002	11996686
[sensitizing and virus-neutralizing characteristics of goat immunoglobulins to ebola virus].	sensitizing and virus-neutralizing properties of igg isolated from the sera of goats immunized with ebola virus and a relevant gammaglobulin prepared by ethanol fractionation were compared. the ratio of the virus-neutralizing activities of subclasses igg2, igg1a, and igg1b was 100:10:1. anaphylactogenic activity of igg2 in the immediate type hypersensitivity test in guinea pigs was 2-fold lower than that of igg1a and igg1b. goat gammaglobulin to ebola virus, consisting from igg2 antibodies by mo ...	2002	12046470
reverse genetics demonstrates that proteolytic processing of the ebola virus glycoprotein is not essential for replication in cell culture.	ebola virus, a prime example of an emerging pathogen, causes fatal hemorrhagic fever in humans and in nonhuman primates. identification of major determinants of ebola virus pathogenicity has been hampered by the lack of effective strategies for experimental mutagenesis. here we exploit a reverse genetics system that allows the generation of ebola virus from cloned cdna to engineer a mutant ebola virus with an altered furin recognition motif in the glycoprotein (gp). when expressed in cells, the ...	2002	11739705
late assembly domain function can exhibit context dependence and involves ubiquitin residues implicated in endocytosis.	retroviral gag polyproteins contain regions that promote the separation of virus particles from the plasma membrane and from each other. these gag regions are often referred to as late assembly (l) domains. the l domain of human immunodeficiency virus type 1 (hiv-1) is in the c-terminal p6(gag) domain and harbors an essential p(t/s)app motif, whereas the l domains of oncoretroviruses are in the n-terminal half of the gag precursor and have a ppxy core motif. we recently observed that l domains i ...	2002	11991975
evidence against an important role for infectivity-enhancing antibodies in ebola virus infections.	the neutralizing and enhancing activities of ebola virus (ebov)-specific antibodies were tested among four murine antibodies specific to the surface glycoprotein (gp), a recombinant human monoclonal antibody specific to gp, a polyclonal equine igg, and serum obtained from a convalescent monkey. all but one of these antibodies neutralized ebov infectivity of primary human monocytes/macrophages or vero cells. none of the antibodies enhanced ebov infectivity in these cells. taken together with in v ...	2002	11853394
hiv/ebola comparison could spur new treatments.	a researcher has discovered a link between hiv and ebola virus: both viruses use the same method to spread through the human body.	2002	11862746
ebola virus glycoproteins induce global surface protein down-modulation and loss of cell adherence.	the ebola virus envelope glycoprotein (gp) derived from the pathogenic zaire subtype mediates cell rounding and detachment from the extracellular matrix in 293t cells. in this study we provide evidence that gps from the other pathogenic subtypes, sudan and côte d'ivoire, as well as from reston, a strain thought to be nonpathogenic in humans, also induced cell rounding, albeit at lower levels than zaire gp. sequential removal of regions of potential o-linked glycosylation at the c terminus of gp1 ...	2002	11836430
requirements for budding of paramyxovirus simian virus 5 virus-like particles.	enveloped viruses are released from infected cells after coalescence of viral components at cellular membranes and budding of membranes to release particles. for some negative-strand rna viruses (e.g., vesicular stomatitis virus and ebola virus), the viral matrix (m) protein contains all of the information needed for budding, since virus-like particles (vlps) are efficiently released from cells when the m protein is expressed from cdna. to investigate the requirements for budding of the paramyxo ...	2002	11907235
proinflammatory response during ebola virus infection of primate models: possible involvement of the tumor necrosis factor receptor superfamily.	ebola virus (ebov) infections are characterized by dysregulation of normal host immune responses. insight into the mechanism came from recent studies in nonhuman primates, which showed that ebov infects cells of the mononuclear phagocyte system (mps), resulting in apoptosis of bystander lymphocytes. in this study, we evaluated serum levels of cytokines/chemokines in ebov-infected nonhuman primates, as possible correlates of this bystander apoptosis. increased levels of interferon (ifn)-alpha, if ...	2002	11803049
[the restructuring of national sanitary inspectorate with regard to environmental hazards and health needs of the population].	the article presents the history of polish sanitary and epidemiological services from 1918 until contemporary times. emphasizing many achievements of national sanitary inspectorate, which are responsible for the low sick-rate of infectious diseases in poland, the article also points to the increasing number and growing severity of environmental hazards in recent years. the article discusses problems caused by the "old" infectious diseases, which, though until recently regarded as passed, are pos ...	2002	17474584
[filovirus haemorrhagic fevers: ebola fever].	epidemiological issues, clinical course and laboratory diagnostics of ebola haemorrhagic fever are reviewed. the structural features of virions and genetic variants of the virus are described along with ecology of ebola virus. the data on ebola fever global morbidity are also presented.	2002	12525016
covalent modifications of the ebola virus glycoprotein.	the role of covalent modifications of the ebola virus glycoprotein (gp) and the significance of the sequence identity between filovirus and avian retrovirus gps were investigated through biochemical and functional analyses of mutant gps. the expression and processing of mutant gps with altered n-linked glycosylation, substitutions for conserved cysteine residues, or a deletion in the region of o-linked glycosylation were analyzed, and virus entry capacities were assayed through the use of pseudo ...	2002	12438572
polystyrene derivatives substituted with arginine interact with babanki (togaviridae) and kedougou (flaviviridae) viruses.	outbreaks of new or old diseases appear primarily in tropical zones such as africa, south and central america, or asia. among these diseases, those induced by arboviruses (the best known of which are being yellow fever, dengue, ebola, and sindbis) are under intensive observation by the world health organization. rapid isolation and identification of the viral species is the first step in the diagnosis, study, and control of epidemics. one major problem with the isolation of viruses is capturing ...	2003	12601758
experimental vaccine protects monkeys against ebola virus.		2003	11217674
examining unmet needs in infectious disease.	in the past 30 years, more than 30 new aetiological agents of infectious disease have been identified. some of these are responsible for entirely novel and life-threatening disorders, such as aids, ebola fever, hantavirus pulmonary syndrome and nipah virus encephalitis. during the same period, some longstanding infectious diseases (such as tuberculosis) have became resurgent, as a result of a combination of complacency, increased travel and social dislocation, and also increasing drug resistance ...	2003	12546988
the crystal structure of the proprotein processing proteinase furin explains its stringent specificity.	in eukaryotes, many essential secreted proteins and peptide hormones are excised from larger precursors by members of a class of calcium-dependent endoproteinases, the prohormone-proprotein convertases (pcs). furin, the best-characterized member of the mammalian pc family, has essential functions in embryogenesis and homeostasis but is also implicated in various pathologies such as tumor metastasis, neurodegeneration and various bacterial and viral diseases caused by such pathogens as anthrax an ...	2003	12794637
ebola virus matrix protein vp40 interaction with human cellular factors tsg101 and nedd4.	the ebola virus matrix protein vp40 is a major viral structural protein and plays a central role in virus assembly and budding at the plasma membrane of infected cells. for efficient budding, a full amino terminus of vp40 is required, which includes a ppxy and a pt/sap motif, both of which have been proposed to interact with cellular proteins. here, we report that ebola vp40 can interact with cellular factors human nedd4 and tsg101 in vitro. we show that ww domain 3 of human nedd4 is necessary a ...	2003	12559917
calcium-dependent conformational changes of membrane-bound ebola fusion peptide drive vesicle fusion.	the fusogenic subdomain of the ebola virus envelope glycoprotein is an internal sequence located ca. 20 residues downstream the n-terminus of the glycoprotein transmembrane subunit. partitioning of the ebola fusion peptide into membranes containing phosphatidylinositol in the absence of ca2+ stabilizes an alpha-helical conformation, and gives rise to vesicle efflux but not vesicle fusion. in the presence of millimolar ca2+ the membrane-bound peptide adopts an extended beta-structure, and induces ...	2003	12560072
[titration of ebola and marburg viruses by plaque formation under semi liquid agar].	the method of titration of ebola and marburg viruses using plaque formation under semifluid agar cover is considered. advantages of this method over conventional method of titration of these viruses with the use of hard agar cover are discussed.	2003	12608062
development, characterization and use of monoclonal vp40-antibodies for the detection of ebola virus.	ebola virus (ebov) causes uncommon but dramatic outbreaks in remote regions of africa, where diagnostic facilities are limited. in order to develop diagnostic tests, which can be handled and distributed easily, monoclonal antibodies (mabs) to ebov, species zaire, were produced from mice immunized with inactivated viral particles. nine stable hybridoma cell lines were obtained producing specific mabs directed against the viral structural protein vp40. these mabs were characterized by enzyme-linke ...	2003	12821193
ebola virus transcription activator vp30 is a zinc-binding protein.	ebola virus vp30 is an essential activator of viral transcription. in viral particles, vp30 is closely associated with the nucleocapsid complex. a conspicuous structural feature of vp30 is an unconventional zinc-binding cys(3)-his motif comprising amino acids 68 to 95. by using a colorimetric zinc-binding assay we found that the vp30-specific cys(3)-his motif stoichiometrically binds zinc ions in a one-to-one relationship. substitution of the conserved cysteines and the histidine within the moti ...	2003	12584359
defense against filoviruses used as biological weapons.	the filoviruses, marburg and ebola, are classified as category a biowarfare agents by the centers for disease control. most known human infections with these viruses have been fatal, and no vaccines or effective therapies are currently available. filoviruses are highly infectious by the airborne route in the laboratory, but investigations of african outbreaks have shown that person-to-person spread requires direct contact with virus-containing material. in consequence, filovirus epidemics can be ...	2003	12615303
therapeutic options for diseases due to potential viral agents of bioterrorism.	the etiologic agents of smallpox and viral hemorrhagic fever have emerged as potential agents of bioterrorism due to their virulence, potential for human to human dissemination and limited strategies for treatment and prevention. cidofovir has shown significant promise in animal models, and limited case reports in humans are encouraging. ribavirin is the treatment of choice for certain hemorrhagic fever viral infections, but has no current application to ebola and marburg infections. current vac ...	2003	12669378
biochemical and functional characterization of the ebola virus vp24 protein: implications for a role in virus assembly and budding.	the vp24 protein of ebola virus is believed to be a secondary matrix protein and minor component of virions. in contrast, the vp40 protein of ebola virus is the primary matrix protein and the most abundant virion component. the structure and function of vp40 have been well characterized; however, virtually nothing is known regarding the structure and function of vp24. wild-type and mutant forms of vp24 were expressed in mammalian cells to gain a better understanding of the biochemical and functi ...	2003	12525613
ebola glycoprotein: the key to successful gene therapy?		2003	12867139
vaccine for aids and ebola virus infection.	ebola virus and hiv present challenges for vaccine development because natural immunity to these viruses is difficult to find, and there are no immune correlates of protection in humans. modern molecular genetic, virologic and immune analyses have been used to rationally identify promising approaches based on animal model and human clinical studies. improved vaccine candidates have been defined for hiv, and a promising ebola vaccine have conferred protection in non-human primates. further evalua ...	2003	12686432
ape populations decimated by hunting and ebola virus.		2003	12686965
conservation biology. ebola, hunting push ape populations to the brink.		2003	12690159
catastrophic ape decline in western equatorial africa.	because rapidly expanding human populations have devastated gorilla (gorilla gorilla) and common chimpanzee (pan troglodytes) habitats in east and west africa, the relatively intact forests of western equatorial africa have been viewed as the last stronghold of african apes. gabon and the republic of congo alone are thought to hold roughly 80% of the world's gorillas and most of the common chimpanzees. here we present survey results conservatively indicating that ape populations in gabon decline ...	2003	12679788
role of escrt-i in retroviral budding.	retroviral late-budding (l) domains are required for the efficient release of nascent virions. the three known types of l domain, designated according to essential tetrapeptide motifs (ptap, ppxy, or ypdl), each bind distinct cellular cofactors. we and others have demonstrated that recruitment of an escrt-i subunit, tsg101, a component of the class e vacuolar protein sorting (vps) machinery, is required for the budding of viruses, such as human immunodeficiency virus type 1 (hiv-1) and ebola vir ...	2003	12663786
cyanovirin-n binds to the viral surface glycoprotein, gp1,2 and inhibits infectivity of ebola virus.	ebola virus (ebo) causes severe hemorrhagic fever and high mortality in humans. there are currently no effective therapies. here, we have explored potential anti-ebo activity of the human immunodeficiency virus (hiv)-inactivating protein cyanovirin-n (cv-n). cv-n is known to potently inhibit the infectivity of a broad spectrum of hiv strains at the level of viral entry. this involves cv-n binding to n-linked high-mannose oligossacharides on the viral glycoprotein gp120. the ebola envelope contai ...	2003	12719006
analysis of the role of predicted rna secondary structures in ebola virus replication.	thermodynamic modeling of ebola viral rna predicts the formation of rna stem-loop structures at the 3' and 5' termini and panhandle structures between the termini of the genomic (or antigenomic) rnas. sequence analysis showed a high degree of identity among ebola zaire, sudan, reston, and cote d'ivoire subtype viruses in their 3' and 5' termini (18 nucleotides in length) and within a second region (internal by approximately 20 nucleotides). while base pairing of the two conserved regions could l ...	2003	12642094
comparison of the protective efficacy of dna and baculovirus-derived protein vaccines for ebola virus in guinea pigs.	the filoviruses ebola virus (ebov) and marburg virus (marv) cause severe hemorrhagic fever in humans for which no vaccines are available. previously, a priming dose of a dna vaccine expressing the glycoprotein (gp) gene of marv followed by boosting with recombinant baculovirus-derived gp protein was found to confer protective immunity to guinea pigs (hevey et al., 2001. vaccine 20, 568-593). to determine whether a similar prime-boost vaccine approach would be effective for ebov, we generated and ...	2003	12686428
serological reactivity of baculovirus-expressed ebola virus vp35 and nucleoproteins.	ebola virus (ebov) is a member of the family filoviridae and is classified as a biosafety level 4 virus. this classification makes the preparation of antigen and performance of diagnostic assays time-consuming and complicated. the objective of this study was to evaluate the value of ebov immunoassays based on recombinant nucleoprotein (r-np) and recombinant vp35 (r-vp35) using large serum panels of african origin and from primates. furthermore, we investigated whether the results obtained with e ...	2003	12737993
ebola virus infection inversely correlates with the overall expression levels of promyelocytic leukaemia (pml) protein in cultured cells.	ebola virus causes severe, often fatal hemorrhagic fever in humans. the mechanism of escape from cellular anti-viral mechanisms is not yet fully understood. the promyelocytic leukaemia (pml) associated nuclear body is part of the interferon inducible cellular defense system. several rna viruses have been found to interfere with the anti-viral function of the pml body. the possible interaction between ebola virus and the pml bodies has not yet been explored.	2003	12697055
a current review of ebola virus: pathogenesis, clinical presentation, and diagnostic assessment.	ebola hemorrhagic fever (ehf) is an acute viral syndrome that presents with fever and an ensuing bleeding diathesis that is marked by high mortality in human and nonhuman primates. fatality rates are between 50% and 100%. due to its lethal nature, this filovirus is classified as a biological class 4 pathogen. the natural reservoir of the virus is unknown. as a result, little is understood about how ebola virus is transmitted or how it replicates in its host. although the primary source of infect ...	2003	12698919
ebola virus: immune mechanisms of protection and vaccine development.	vaccination is one of our most powerful antiviral strategies. despite the emergence of deadly viruses such as ebola virus, vaccination efforts have focused mainly on childhood communicable diseases. although ebola virus was once believed to be limited to isolated outbreaks in distant lands, forces of globalization potentiate outbreaks anywhere in the world through incidental transmission. moreover, since this virus has already been transformed into weapon-grade material, the potential exists for ...	2003	12698920
u.s. military officer participation in the centers for disease control and prevention's epidemic intelligence service (1951-2001).	the epidemic intelligence service (eis) was created in 1951 to provide epidemiologists to investigate natural and intentional disease epidemics. from an initial class of 23 u.s. citizens, the program has evolved into a globally recognized, hands-on learning experience, accepting approximately 65 to 75 new officers each year. the first u.s. military epidemic intelligence service officer (eiso) was accepted into the program in 1994. since that time, 12 such officers have completed, or have begun, ...	2003	12775171
a fatal attraction: mycobacterium tuberculosis and hiv-1 target dc-sign to escape immune surveillance.	dendritic cells (dcs) are vital in the defense against pathogens. however, it is becoming increasingly clear that some pathogens subvert dc functions to escape immune surveillance. for example, hiv-1 targets the dc-specific c-type lectin dc-sign (dc-specific intercellular-adhesion-molecule-3-grabbing nonintegrin) to hijack dcs for viral dissemination. binding to dc-sign protects hiv-1 from antigen processing and facilitates its transport to lymphoid tissues, where dc-sign promotes hiv-1 infectio ...	2003	12727141
analysis of linear b-cell epitopes of the nucleoprotein of ebola virus that distinguish ebola virus subtypes.	ebola virus consists of four genetically distinguishable subtypes. we developed monoclonal antibodies (mabs) to the nucleoprotein (np) of ebola virus zaire subtype and analyzed their cross-reactivities to the reston and sudan subtypes. we further determined the epitopes recognized by these mabs. three mabs reacted with the three major subtypes and recognized a fragment containing 110 amino acids (aa) at the c-terminal extremity. they did not show specific reactivities to any 10-aa short peptides ...	2003	12522044
[ebola virus and marburg virus].		2003	12718026
overcoming immunity to a viral vaccine by dna priming before vector boosting.	replication-defective adenovirus (adv) and poxvirus vectors have shown potential as vaccines for pathogens such as ebola or human immunodeficiency virus in nonhuman primates, but prior immunity to the viral vector in humans may limit their clinical efficacy. to overcome this limitation, the effect of prior viral exposure on immune responses to ebola virus glycoprotein (gp), shown previously to protect against lethal hemorrhagic fever in animals, was studied. prior exposure to adv substantially r ...	2003	12477888
identification of protective epitopes on ebola virus glycoprotein at the single amino acid level by using recombinant vesicular stomatitis viruses.	ebola virus causes lethal hemorrhagic fever in humans, but currently there are no effective vaccines or antiviral compounds for this infectious disease. passive transfer of monoclonal antibodies (mabs) protects mice from lethal ebola virus infection (j. a. wilson, m. hevey, r. bakken, s. guest, m. bray, a. l. schmaljohn, and m. k. hart, science 287:1664-1666, 2000). however, the epitopes responsible for neutralization have been only partially characterized because some of the mabs do not recogni ...	2003	12502822
pre-transmembrane sequence of ebola glycoprotein. interfacial hydrophobicity distribution and interaction with membranes.	the membrane-interacting domain that precedes the transmembrane anchor of ebola glycoprotein has been characterized. this aromatic-rich region is predicted to bind the membrane interface adopting an alpha-helical structure. peptides representing either the ebola glycoprotein pre-transmembrane sequence, or a 'scrambled' control with a different hydrophobic-at-interface moment, have been studied. insertion into lipid monolayers, changes in intrinsic fluorescence and in infrared spectra demonstrate ...	2003	12505157
[in vitro synthesis of immunoglobulins caused by an inactivated ebola virus].	an in vitro model ebola infection was used to study the humoral response of human mononuclear cells to stimulation by purified inactivated ebola virus antigen. inactivated ebola virus was cocultivated with human mononuclear cells in the presence or absence of b-cell mitogen lps e. coli: b5. an increase in the rate of synthesis of immunoglobulins (both igg and, to a less extent, other classes) was observed. the ebola virus proteins were suggested to exert no suppression effect on b-cells. the igm ...	2003	12608056
differential n-linked glycosylation of human immunodeficiency virus and ebola virus envelope glycoproteins modulates interactions with dc-sign and dc-signr.	the c-type lectins dc-sign and dc-signr [collectively referred to as dc-sign(r)] bind and transmit human immunodeficiency virus (hiv) and simian immunodeficiency virus to t cells via the viral envelope glycoprotein (env). other viruses containing heavily glycosylated glycoproteins (gps) fail to interact with dc-sign(r), suggesting some degree of specificity in this interaction. we show here that dc-sign(r) selectively interact with hiv env and ebola virus gps containing more high-mannose than co ...	2003	12502850
cutting edge: impairment of dendritic cells and adaptive immunity by ebola and lassa viruses.	acute infection of humans with ebola and lassa viruses, two principal etiologic agents of hemorrhagic fevers, often results in a paradoxical pattern of immune responses: early infection, characterized by an outpouring of inflammatory mediators such as tnf-alpha, il-1 beta, and il-6, vs late stage infections, which are associated with poor immune responses. the mechanisms underlying these diverse outcomes are poorly understood. in particular, the role played by cells of the innate immune system, ...	2003	12626527
newcastle disease virus (ndv)-based assay demonstrates interferon-antagonist activity for the ndv v protein and the nipah virus v, w, and c proteins.	we have generated a recombinant newcastle disease virus (ndv) that expresses the green fluorescence protein (gfp) in infected chicken embryo fibroblasts (cefs). this virus is interferon (ifn) sensitive, and pretreatment of cells with chicken alpha/beta ifn (ifn-alpha/beta) completely blocks viral gfp expression. prior transfection of plasmid dna induces an ifn response in cefs and blocks ndv-gfp replication. however, transfection of known inhibitors of the ifn-alpha/beta system, including the in ...	2003	12502864
dc-sign and dc-signr bind ebola glycoproteins and enhance infection of macrophages and endothelial cells.	ebola virus exhibits a broad cellular tropism in vitro. in humans and animal models, virus is found in most tissues and organs during the latter stages of infection. in contrast, a more restricted cell and tissue tropism is exhibited early in infection where macrophages, liver, lymph node, and spleen are major initial targets. this indicates that cellular factors other than the broadly expressed virus receptor(s) modulate ebola virus tropism. here we demonstrate that the c-type lectins dc-sign a ...	2003	12504546
pathogens target dc-sign to influence their fate dc-sign functions as a pathogen receptor with broad specificity.	dendritic cells (dc) are vital in the defense against pathogens. to sense pathogens dc express pathogen recognition receptors such as toll-like receptors (tlr) and c-type lectins that recognize different fragments of pathogens, and subsequently activate or present pathogen fragments to t cells. it is now becoming evident that some pathogens subvert dc functions to escape immune surveillance. hiv-1 targets the dc-specific c-type lectin dc-sign to hijack dc for viral dissemination. hiv-1 binding t ...	2003	12974773
elaboration of laboratory strains of ebola virus and study of pathophysiological reactions of animals inoculated with these strains.	selective passages in animals and cell cultures were used to produce a set of ebola virus (ebo) laboratory strains with changed virulence for some animal genera. comparative study of the genomes of wild-type ebo and selected variants formed the basis for studying the molecular causes of ebo virulence. investigation of pathophysiological reactions of the animals inoculated with these strains allowed some key factors in ebola fever pathogenesis to be determined.	2003	12875925
viral hemorrhagic fever--a vascular disease?	the syndrome of "viral hemorrhagic fever" in man caused by certain viruses, such as ebola, lassa, dengue, and crimean-congo hemorrhagic fever viruses, is often associated with a shock syndrome of undetermined pathogenesis. however, the vascular system, particularly the vascular endothelium, seems to be directly and indirectly targeted by all these viruses. here we briefly summarize the current knowledge on marburg and ebola virus infections, the prototype viral hemorrhagic fever agents, and form ...	2003	12783108
inactivation of ebola virus with a surfactant nanoemulsion.	hemorrhagic fever caused by ebola virus (ebo) is a highly contagious infection. this necessitates that the contaminated instruments, clothes, and hospital premises must be completely disinfected. nanoemulsions are a new form of disinfectant composed of detergents and vegetable oil suspended in water. the antiviral activity of nanoemulsion atb has been investigated against ebo. the nanoemulsion was tested against two preparations of ebo (strain zaire) obtained from vero cell culture fluid (ebo-zc ...	2003	12875924
antibody-dependent enhancement of ebola virus infection.	most strains of ebola virus cause a rapidly fatal hemorrhagic disease in humans, yet there are still no biologic explanations that adequately account for the extreme virulence of these emerging pathogens. here we show that ebola zaire virus infection in humans induces antibodies that enhance viral infectivity. plasma or serum from convalescing patients enhanced the infection of primate kidney cells by the zaire virus, and this enhancement was mediated by antibodies to the viral glycoprotein and ...	2003	12805454
conservation biology. can great apes be saved from ebola?		2003	12805515
crystal structure of the borna disease virus nucleoprotein.	borna disease virus (bdv) causes an infection of the central nervous system in a wide range of vertebrates, which can fatally progress to an immune-mediated disease, called borna disease. bdv is a member of the mononegavirales, which also includes the highly infectious measles and ebola viruses. the viral nucleoproteins are central to transcription, replication, and packaging of the rna genome. we present the x-ray structure of the bdv nucleoprotein determined at 1.76 a resolution. the structure ...	2003	14527390
pathogens: raft hijackers.	throughout evolution, organisms have developed immune-surveillance networks to protect themselves from potential pathogens. at the cellular level, the signalling events that regulate these defensive responses take place in membrane rafts--dynamic microdomains that are enriched in cholesterol and glycosphingolipids--that facilitate many protein-protein and lipid-protein interactions at the cell surface. pathogens have evolved many strategies to ensure their own survival and to evade the host immu ...	2003	12876558
fast vaccine offers hope in battle with ebola.		2003	12904747
immunoglobulin g enzyme-linked immunosorbent assay using truncated nucleoproteins of reston ebola virus.	we developed an immunoglobulin g (igg) enzyme-linked immunosorbent assay (elisa), using partial recombinant nucleoproteins (rnp) of reston ebola virus (ebo-r) and zaire ebola virus (ebo-z). we examined the reaction of 10 sera from cynomolgus macaques naturally infected with ebo-r to each of the partial rnp in the igg elisa. all the sera reacted to the c-terminal halves of the rnp of both ebo-r and ebo-z. most of the sera reacted to the rdeltac (amino acid (aa) 360-739), and rdelta6 (aa 451-551) ...	2003	12825739
accelerated vaccination for ebola virus haemorrhagic fever in non-human primates.	containment of highly lethal ebola virus outbreaks poses a serious public health challenge. although an experimental vaccine has successfully protected non-human primates against disease, more than six months was required to complete the immunizations, making it impractical to limit an acute epidemic. here, we report the development of accelerated vaccination against ebola virus in non-human primates. the antibody response to immunization with an adenoviral (adv) vector encoding the ebola glycop ...	2003	12904795
the ebola virus vp35 protein inhibits activation of interferon regulatory factor 3.	the ebola virus vp35 protein was previously found to act as an interferon (ifn) antagonist which could complement growth of influenza delns1 virus, a mutant influenza virus lacking the influenza virus ifn antagonist protein, ns1. the ebola virus vp35 could also prevent the virus- or double-stranded rna-mediated transcriptional activation of both the beta ifn (ifn-beta) promoter and the ifn-stimulated isg54 promoter (c. basler et al., proc. natl. acad. sci. usa 97:12289-12294, 2000). we now show ...	2003	12829834
ebola virus pathogenesis: implications for vaccines and therapies.		2003	12941881
antigen capture enzyme-linked immunosorbent assay for specific detection of reston ebola virus nucleoprotein.	antigen capture enzyme-linked immunosorbent assay (elisa) is one of the most useful methods to detect ebola virus rapidly. we previously developed an antigen capture elisa using a monoclonal antibody (mab), 3-3d, which reacted not only to the nucleoprotein (np) of zaire ebola virus (ebo-z) but also to the nps of sudan (ebo-s) and reston ebola (ebo-r) viruses. in this study, we developed antigen capture elisas using two novel mabs, res2-6c8 and res2-1d8, specific to the np of ebo-r. res2-6c8 and ...	2003	12853385
oligomerization of ebola virus vp30 is essential for viral transcription and can be inhibited by a synthetic peptide.	transcription of ebola virus (ebov)-specific mrna is driven by the nucleocapsid proteins np, vp35, and l. this process is further dependent on vp30, an essential ebov-specific transcription factor. the present study addresses the self-assembly of vp30 and the functional significance of this process for viral transcription and propagation. essential for oligomerization of vp30 is a region spanning amino acids 94-112. within this region a cluster of four leucine residues is of critical importance. ...	2003	12912982
folate receptor alpha and caveolae are not required for ebola virus glycoprotein-mediated viral infection.	folate receptor alpha (fralpha) has been described as a factor involved in mediating ebola virus entry into cells (6). furthermore, it was suggested that interaction with fralpha results in internalization and subsequent viral ingress into the cytoplasm via caveolae (9). descriptions of cellular receptors for ebola virus and its entry mechanisms are of fundamental importance, particularly with the advent of vectors bearing ebola virus glycoprotein (gp) being utilized for gene transfer into cell ...	2003	14645601
an ebola epidemic simmers in africa: in remote region, outbreak shows staying power.		2003	12865357
crystal structure of the measles virus phosphoprotein domain responsible for the induced folding of the c-terminal domain of the nucleoprotein.	measles virus is a negative-sense, single-stranded rna virus belonging to the mononegavirales order which comprises several human pathogens such as ebola, nipah, and hendra viruses. the phosphoprotein of measles virus is a modular protein consisting of an intrinsically disordered n-terminal domain (karlin, d., longhi, s., receveur, v., and canard, b. (2002) virology 296, 251-262) and of a c-terminal moiety (pct) composed of alternating disordered and globular regions. we report the crystal struc ...	2003	12944395
specific association of glycoprotein b with lipid rafts during herpes simplex virus entry.	herpes simplex virus (hsv) entry requires the interaction of glycoprotein d (gd) with a cellular receptor such as herpesvirus entry mediator (hvem or hvea) or nectin-1 (hvec). however, the fusion mechanism is still not understood. since cholesterol-enriched cell membrane lipid rafts are involved in the entry of other enveloped viruses such as human immunodeficiency virus and ebola virus, we tested whether hsv entry proceeds similarly. vero cells and cells expressing either hvem or nectin-1 were ...	2003	12915568
lentivirus vectors pseudotyped with filoviral envelope glycoproteins transduce airway epithelia from the apical surface independently of folate receptor alpha.	the practical application of gene therapy as a treatment for cystic fibrosis is limited by poor gene transfer efficiency with vectors applied to the apical surface of airway epithelia. recently, folate receptor alpha (fr alpha), a glycosylphosphatidylinositol-linked surface protein, was reported to be a cellular receptor for the filoviruses. we found that polarized human airway epithelia expressed abundant fr alpha on their apical surface. in an attempt to target these apical receptors, we pseud ...	2003	12719583
treatment of ebola virus infection with a recombinant inhibitor of factor viia/tissue factor: a study in rhesus monkeys.	infection with the ebola virus induces overexpression of the procoagulant tissue factor in primate monocytes and macrophages, suggesting that inhibition of the tissue-factor pathway could ameliorate the effects of ebola haemorrhagic fever. here, we tested the notion that blockade of fviia/tissue factor is beneficial after infection with ebola virus.	2003	14683653
oligomerization and polymerization of the filovirus matrix protein vp40.	the matrix protein vp40 from ebola virus plays an important role in the assembly process of virus particles by interacting with cellular factors, cellular membranes, and the ribonuclearprotein particle complex. here we show that the n-terminal domain of vp40 folds into a mixture of two different oligomeric states in vitro, namely hexameric and octameric ringlike structures, as detected by gel filtration chromatography, chemical cross-linking, and electron microscopy. octamer formation depends la ...	2003	12919741
protection from lethal infection is determined by innate immune responses in a mouse model of ebola virus infection.	a mouse-adapted strain of ebola zaire virus produces a fatal infection when balb/cj mice are infected intraperitoneally (ip) but subcutaneous (sc) infection with the same virus fails to produce illness and confers long-term protection from lethal ip rechallenge. to identify immune correlates of protection in this model, we compared viral replication and cytokine/chemokine responses to ebola virus in mice infected ip (10 pfu/mouse), or sc (100 pfu/mouse) and sc "immune" mice rechallenged ip (10(6 ...	2003	12919746
towards a vaccine against ebola virus.	ebola virus infection causes hemorrhagic fever with high mortality rates in humans and nonhuman primates. currently, there are no vaccines or therapies approved for human use. outbreaks of ebola virus have been infrequent, largely confined to remote locations in africa and quarantine of sick patients has been effective in controlling epidemics. in the past, this small global market has generated little commercial interest for developing an ebola virus vaccine. however, heightened awareness of bi ...	2003	14711361
comparison of individual and combination dna vaccines for b. anthracis, ebola virus, marburg virus and venezuelan equine encephalitis virus.	multiagent dna vaccines for highly pathogenic organisms offer an attractive approach for preventing naturally occurring or deliberately introduced diseases. few animal studies have compared the feasibility of combining unrelated gene vaccines. here, we demonstrate that dna vaccines to four dissimilar pathogens that are known biowarfare agents, bacillus anthracis, ebola (ebov), marburg (marv), and venezuelan equine encephalitis virus (veev), can elicit protective immunity in relevant animal model ...	2003	12922144
ebola virus: from discovery to vaccine.	ebola virus, being highly pathogenic for humans and non-human primates and the subject of former weapons programmes, is now one of the most feared pathogens worldwide. in addition, the lack of pre- and post-exposure interventions makes the development of rapid diagnostics, new antiviral agents and protective vaccines a priority for many nations. further insight into the ecology, immunology and pathogenesis of ebola virus will promote the delivery of these urgently required tools.	2003	12974482
a system of protein target sequences for anti-rna-viral chemotherapy by a vitamin b6-derived zinc-chelating trioxa-adamantane-triol.	the synthesis of the structurally unusual heterotricyclic compound 1-[3-hydroxy-5-(hydroxymethyl)-2-methyl-4-pyridinyl]-2,8,9-trioxaadamantane-3,5,7-triol (trivially named bananin, bn) from pyridoxylidenephloroglucinol and a theoretical prospect on possible biological activities of bn are presented in this report. pyridoxylidenephloroglucinol is synthesized by knoevenagel condensation of the vitamin b6 aldehyde pyridoxal with phloroglucinol. pyridoxylidenephloroglucinol rearranges to light-yello ...	2003	14527557
conference report - i. investigating new vaccines: ebola and hiv: highlights from the viral vaccine meeting; october 25-28, 2003; barcelona, spain.		2003	14745371
the small ring finger protein z drives arenavirus budding: implications for antiviral strategies.	by using a reverse genetics system that is based on the prototypic arenavirus lymphocytic choriomeningitis virus (lcmv), we have identified the arenavirus small ring finger z protein as the main driving force of virus budding. both lcmv and lassa fever virus (lfv) z proteins exhibited self-budding activity, and both substituted efficiently for the late domain that is present in the gag protein of rous sarcoma virus. lcmv and lfv z proteins contain proline-rich motifs that are characteristic of l ...	2003	14563923
lentiviral vectors pseudotyped with minimal filovirus envelopes increased gene transfer in murine lung.	a human immunodeficiency virus (hiv)-based vector pseudotyped with the ebola zaire (eboz) viral envelope glycoprotein (gp) was recently shown to transduce murine airway epithelia cells in vivo. in this study, the vector was further redesigned to improve gene transfer and also to increase safety. we used mutant eboz envelopes for pseudotyping, which resulted in higher titers and increased transduction of airway cells in vivo compared to vectors pseudotyped with wild-type eboz gp. as these envelop ...	2003	14599811
virology. new vaccine and treatment excite ebola researchers.		2003	14615510
pathogenesis of ebola hemorrhagic fever in primate models: evidence that hemorrhage is not a direct effect of virus-induced cytolysis of endothelial cells.	ebola virus (ebov) infection causes a severe and often fatal hemorrhagic disease in humans and nonhuman primates. whether infection of endothelial cells is central to the pathogenesis of ebov hemorrhagic fever (hf) remains unknown. to clarify the role of endothelial cells in ebov hf, we examined tissues of 21 ebov-infected cynomolgus monkeys throughout time, and also evaluated ebov infection of primary human umbilical vein endothelial cells and primary human lung-derived microvascular endothelia ...	2003	14633609
mannosyl glycodendritic structure inhibits dc-sign-mediated ebola virus infection in cis and in trans.	we have designed a glycodendritic structure, bh30sucman, that blocks the interaction between dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin (dc-sign) and ebola virus (ebov) envelope. bh30sucman inhibits dc-sign-mediated ebov infection at nanomolar concentrations. bh30sucman may counteract important steps of the infective process of ebov and, potentially, of microorganisms shown to exploit dc-sign for cell entry and infection.	2003	14638512
vaccine research efforts for filoviruses.	ebola and marburg viruses belong to the family filoviridae, and cause acute, frequently fatal, haemorrhagic fever in humans and non-human primates. no vaccines are available for human use. this review describes the status of research efforts to develop vaccines for these viruses and to identify the immune mechanisms of protection. the vaccine approaches discussed include dna-based vaccines, and subunit vaccines vectored by adenovirus, alphavirus replicons, and vaccinia virus.	2003	12782057
overlapping motifs (ptap and ppey) within the ebola virus vp40 protein function independently as late budding domains: involvement of host proteins tsg101 and vps-4.	the vp40 protein of ebola virus can bud from mammalian cells in the form of lipid-bound, virus-like particles (vlps), and late budding domains (l-domains) are conserved motifs (ptap, ppxy, or yxxl; where "x" is any amino acid) that facilitate the budding of vp40-containing vlps. vp40 is unique in that potential overlapping l-domains with the sequences ptap and ppey are present at amino acids 7 to 13 of vp40 (ptappey). l-domains are thought to function by interacting with specific cellular protei ...	2003	12525615
risk factors for marburg hemorrhagic fever, democratic republic of the congo.	we conducted two antibody surveys to assess risk factors for marburg hemorrhagic fever in an area of confirmed marburg virus transmission in the democratic republic of the congo. questionnaires were administered and serum samples tested for marburg-specific antibodies by enzyme-linked immunosorbent assay. fifteen (2%) of 912 participants in a general village cross-sectional antibody survey were positive for marburg immunoglobulin g antibody. thirteen (87%) of these 15 were men who worked in the ...	2003	14720391
changing world, changing doctors, changing education!	future developments in the community will underline the need to provide a community-oriented health care system in which public health doctors collaborate with general practitioners, as the hospital-based health care system that currently exists in many countries will not be able to solve the problems of health care in the future. increasing populations, increasing mobility all over the world, spread of new diseases (aids/hiv and ebola virus for example) will have great impact on our societies a ...	2003	12784489
measles virus 1998-2002: progress and controversy.	despite the extensive media exposure that viruses such as west nile, norwalk, and ebola have received lately, and the emerging threat that old pathogens may reappear as new agents of terrorism, measles virus (mv) persists as one of the leading causes of death by infectious agents worldwide, approaching the annual mortality rate of human immunodeficiency virus (hiv)-1. for most mv victims, fatality is indirect: virus-induced transient immunosuppression predisposes the individual to opportunistic ...	2003	14527283
[analysis of antigenic determinant profiles of the ebola virus vp35 protein n-terminal region using its short recombinant fragments].	cdna of fragments of gene vp35 of the ebola virus (ev) were expressed in vector pqe30 for the purpose of isolation of recombinant fragments of protein vp35. five short affinity-purified fragments of the ev vp35 protein were analyzed, by using the methods of iea and immunoblotting, with polyclonal antiviral sera (pas) against ev and with hybrid monoclonal antibodies (mabs) ic6 and 6f7 specific to ev vp35 protein. all fragments of protein vp35 with an intact n-terminal region and removed c-termina ...	2003	12800775
[outbreak of ebola hemorrhagic fever in the republic of the congo, 2003: a new strategy?].	this article describes the last ebola haemorrhagic fever (ehf) outbreak that occurred in the cuvette ouest region of the republic of congo from january to april 2003. epidemiological study demonstrated that the first patient, in whom diagnosis was made retrospectively, became ill on december 25, 2002. subsequently until may 7, 2003, a total of 143 cases were recorded in the mbomo and kéllé health districts including 129 fatalities. thirteen cases were laboratory confirmed and 130 were epidemiolo ...	2003	14579469