detection of ebola viral antigen by enzyme-linked immunosorbent assay using a novel monoclonal antibody to nucleoprotein.with the increase in international traffic, the risk of introducing rare but severe infectious diseases like ebola hemorrhagic fever is increasing all over the world. however, the system for the diagnosis of ebola virus infection is available in a limited number of countries. in the present study, we developed an ebola virus antigen-detection enzyme-linked immunosorbent assay (elisa) system using a novel monoclonal antibody (mab) to the nucleoprotein (np). this antibody recognized an epitope def ...200111526161
multiplex analysis of cytokines in the blood of cynomolgus macaques naturally infected with ebola virus (reston serotype).ebola virus (ebo) causes the most severe form of viral hemorrhagic fever in humans and nonhuman primates with up to 90% of infections culminating in death. the requirement of maximum containment laboratories for ebola virus research has limited opportunities to study the pathogenesis of ebo infections. while tissue damage does occur, often it would appear not to be sufficient to explain death, indicating that soluble mediators play an important role in disease progression. in previous studies, f ...200111596094
the pathogenesis of ebola hemorrhagic fever.ebola virus causes lethal hemorrhagic disease in humans, yet there are still no satisfactory biological explanations to account for its extreme virulence. this review focuses on recent findings relevant to understanding the pathogenesis of ebola virus infection and developing vaccines and effective therapy. the available data suggest that the envelope glycoprotein and the interaction of some viral proteins with the immune system are likely to play important roles in the extraordinary pathogenici ...200111597453
symposium on marburg and ebola viruses. 200111597757
ebola hemorrhagic fever (ehf): mechanism of transmission and pathogenicity.hemorrhagic fevers represent a wide spectrum of viral infectious diseases, out-breaking mostly as epidemics, some of them being highly lethal. they range from those caused by bunyaviridae, associated with renal or pulmonary syndromes and those recently emerging and caused by the filoviridae family of thread-like viruses. among the latter, ebola hemorrhagic fever (ehf) bears the highest mortality and morbidity rates. one form of the disease has been documented only in monkeys. the human form, has ...200111598619
infection and activation of monocytes by marburg and ebola this study we investigated the effects of marburg virus and ebola virus (species zaire and reston) infections on freshly isolated suspended monocytes in comparison to adherent macrophages under culture conditions. our data showed that monocytes are permissive for both filoviruses. as is the case in macrophages, infection resulted in the activation of monocytes which was largely independent of virus replication. the activation was triggered similarly by marburg and ebola viruses, species zaire ...200111602743
vaccine potential of ebola virus vp24, vp30, vp35, and vp40 proteins.previous vaccine efforts with ebola virus zaire (ebov-z) emphasized the potential protective efficacies of immune responses to the surface glycoprotein and the nucleoprotein. to determine whether the vp24, vp30, vp35, and vp40 proteins are also capable of eliciting protective immune responses, these genes were expressed from alphavirus replicons and used to vaccinate balb/c and c57bl/6 mice. although all of the vp proteins were capable of inducing protective immune responses, no single vp protei ...200111485406
folate receptor-alpha is a cofactor for cellular entry by marburg and ebola viruses.human infections by marburg (mbg) and ebola (ebo) viruses result in lethal hemorrhagic fever. to identify cellular entry factors employed by mbg virus, noninfectible cells transduced with an expression library were challenged with a selectable pseudotype virus packaged by mbg glycoproteins (gp). a cdna encoding the folate receptor-alpha (fr-alpha) was recovered from cells exhibiting reconstitution of viral entry. a fr-alpha cdna was recovered in a similar strategy employing ebo pseudotypes. fr-a ...200111461707
individual and bivalent vaccines based on alphavirus replicons protect guinea pigs against infection with lassa and ebola viruses.lassa and ebola viruses cause acute, often fatal, hemorrhagic fever diseases, for which no effective vaccines are currently available. although lethal human disease outbreaks have been confined so far to sub-saharan africa, they also pose significant epidemiological concern worldwide as demonstrated by several instances of accidental importation of the viruses into north america and europe. in the present study, we developed experimental individual vaccines for lassa virus and bivalent vaccines ...200111689649
identification, phylogeny, and evolution of retroviral elements based on their envelope genes.phylogenetic analyses of retroviral elements, including endogenous retroviruses, have relied essentially on the retroviral pol gene expressing the highly conserved reverse transcriptase. this enzyme is essential for the life cycle of all retroid elements, but other genes are also endowed with conserved essential functions. among them, the transmembrane (tm) subunit of the envelope gene is involved in virus entry through membrane fusion. it has also been reported to contain a domain, named the im ...200111689652
[the worldwide challenges of "new" or reemerging communicable diseases at the dawn of the 21st century].in the first part of this review, aids, prion diseases, hantavirus and arbovirus infections, ebola hemorrhagic fever, legionellosis, hepatitis c, enterotoxigenic escherichia coli infections, lyme disease, tuberculosis have provided alarming examples of emerging or reemerging infectious diseases. in this second part, the stress is placed on the reemergence of diphtheria and of serious streptococcal infections, on bartonelloses, chlamydia infections, fungal infections, while malaria and cholera ar ...200111468579
recombinant monoclonal human antibodies against ebola virus. 200111712178
[antigenic structure of ebola virus vp35 protein].antigenic structure of ebola virus (ev) (strain mayinga) nucleocapsid protein vp35 was analyzed using monoclonal antibodies to ev vp35 and polyclonal antibodies to ev. ev protein vp35 was shown to have antigenic sites inducing the production of antibodies in animals. for better characterization of protein vp35 antigenic structure. ev gene encoding the full-length vp35 was cloned in vector pqe31 as a recombinant fusion protein (rec.vp35). the antigenic and immunogenic properties of rec.vp35 and e ...200111715705
development and evaluation of a fluorogenic 5' nuclease assay to detect and differentiate between ebola virus subtypes zaire and sudan.the ability to rapidly recognize ebola virus infections is critical to quickly limit further spread of the disease. a rapid, sensitive, and specific laboratory diagnostic test is needed to confirm outbreaks of ebola virus infection and to distinguish it from other diseases that can cause similar clinical symptoms. a one-tube reverse transcription-pcr assay for the identification of ebola virus subtype zaire (ebola zaire) and ebola virus subtype sudan (ebola sudan) was developed and evaluated by ...200111682540
hiv-1 and ebola virus: the getaway driver nabbed. 200111726960
hiv-1 and ebola virus encode small peptide motifs that recruit tsg101 to sites of particle assembly to facilitate egress.retroviral gag proteins encode sequences, termed late domains, which facilitate the final stages of particle budding from the plasma membrane. we report here that interactions between tsg101, a factor involved in endosomal protein sorting, and short peptide motifs in the hiv-1 gag late domain and ebola virus matrix (ebvp40) proteins are essential for efficient egress of hiv-1 virions and ebola virus-like particles. ebvp40 recruits tsg101 to sites of particle assembly and a short, ebvp40-derived ...200111726971
outbreak of ebola hemorrhagic fever uganda, august 2000-january 2001.on october 8, 2000, an outbreak of an unusual febrile illness with occasional hemorrhage and significant mortality was reported to the ministry of health (moh) in kampala by the superintendent of st. mary's hospital in lacor, and the district director of health services in the gulu district. a preliminary assessment conducted by moh found additional cases in gulu district and in gulu hospital, the regional referral hospital. on october 15, suspicion of ebola hemorrhagic fever (ehf) was confirmed ...200111686289
the model of response to viral haemorrhagic fevers of the national institute for infectious diseases "lazzaro spallanzani".viral haemorrhagic fevers (vhf) are severe and life-threatening diseases caused by a range of viruses. however, only four agents of vhf are known to be readily capable of person-to-person spread: lassa virus, crimean/congo haemorrhagic fever virus, ebola and marburg viruses. diseases caused by these viruses are endemic only in few areas in the world, most notably africa and some rural parts of the middle east and eastern europe. nonetheless, the increasing volume of international travel presents ...200111693443
genome structure of ebola virus subtype reston: differences among ebola subtypes. brief report.we determined the complete genome sequence of ebola virus subtype reston (ebo-r) in the philippines in 1996. the deduced transcriptional signals were highly conserved among ebola viruses except for the stop signal of l genes. the intergenic regions were composed of 4 to 7 nucleotides, and of 2 characteristic overlaps and a long intergenic region. the glycoprotein (gp) had several amino acid differences from ebo-r isolated in 1989 and 1992. the variety of gp sequences strongly suggests the indepe ...200111722021
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 ...200211739705
biological agents: weapons of warfare and bioterrorism.the use of microorganisms as agents of biological warfare is considered inevitable for several reasons, including ease of production and dispersion, delayed onset, ability to cause high rates of morbidity and mortality, and difficulty in diagnosis. biological agents that have been identified as posing the greatest threat are variola major (smallpox), bacillus anthracis (anthrax), yersinia pestis (plague), clostridium botulinum toxin (botulism), francisella tularensis (tularaemia), filoviruses (e ...200111774197
ebola virus: the search for vaccines and treatments.ebola viruses belong to the family filoviridae, which are among the most virulent infectious agents known. these viruses cause acute, and frequently fatal, hemorrhagic fever in humans and nonhuman primates. currently, no vaccines or treatments are available for human use. this review describes ebola viruses, with a particular focus on the status of research efforts to develop vaccines and therapeutics and to identify the immune mechanisms of protection.200111766882
viral replication and host gene expression in alveolar macrophages infected with ebola virus (zaire strain).in order to characterize the cellular response to and identify potential diagnostic markers for the early detection of ebola virus, an in vitro culture system involving nonhuman primate alveolar macrophages was developed. ebola virus replication in the alveolar macrophages was characterized by plaque assay, immunohistochemical analysis, and in situ hybridization. fluorogenic 5'-nuclease assays specific for nonhuman primate proinflammatory cytokines and chemokines were designed and used to evalua ...200211777824
[dynamics of expression of marburg and ebola virus antigens in infected vero cells ].time course of marburg and ebola virus antigens expression in vero cells was studied by indirect immunofluorescence test. the maximum accumulation of virus specific antigens in vero cells infected with a high dose was observed after 48-54 h of incubation. it is essential for laboratory diagnosis that virus specific antigens can present as incorporations of different shape and size, starting from small hardly discernible granules (immediately after the virus adsorption) to large lumps, cords, acc ...200111785389
[microbiological surveillance: viral hemorrhagic fever in central african republic: current serological data in man].an investigation was conducted between 1994 and 1997 in forested areas of the central african republic (car) to determine the seroprevalence of igg antibodies against several haemorrhagic fever viruses present in the region. sera were obtained from 1762 individuals in two groups (pygmy and bantu locuted populations) living in 4 forested areas in the south of the country. sera were tested for igg antibodies against ebola, marburg, rift valley fever (rvf), yellow fever (yf) and hantaviruses by enz ...200011775321
sequence analysis of the gp, np, vp40 and vp24 genes of ebola virus isolated from deceased, surviving and asymptomatically infected individuals during the 1996 outbreak in gabon: comparative studies and phylogenetic characterization.the aims of this study were to determine if the clinical outcome of ebola virus (ebov) infection is associated with virus genetic structure and to document the genetic changes in the gabon strains of ebov by sequencing the gp, np, vp40 and vp24 genes from deceased and surviving symptomatic and asymptomatic individuals. gp and np sequences were identical in the three groups of patients and only one silent substitution occurred in the vp40 and vp24 genes in asymptomatic individuals. a strain from ...200211752702
intracellular phosphorylation of carbocyclic 3-deazaadenosine, an anti-ebola virus agent.carbocyclic 3-deazaadenosine (c-c3ado) is a potent inhibitor of ebola virus in mice by infrequent dosing, even though its half life in plasma is only 23-28 min. this prompted studies to determine whether c-c3ado undergoes intracellular metabolism to derivatives that may promote in vivo activity. in cells, radiolabelled compound readily underwent metabolism to monophosphate, diphosphate and triphosphate (c-c3atp) forms, with c-c3atp being the major metabolite detected. a non-polar metabolite was ...200111771734
haematological, biochemical and coagulation changes in mice, guinea-pigs and monkeys infected with a mouse-adapted variant of ebola zaire virus.ebola zaire virus from the 1976 outbreak (ebo-z) was recently adapted to the stage of lethal virulence in balb/c mice through serial passage. in the present study, various parameters were examined in groups of mice and guinea-pigs and in three rhesus monkeys after infection with mouse-adapted ebo-z. the virus caused fatal disease not only in mice but also in guinea-pigs, in which the course of illness resembled that produced by guinea-pig-adapted ebo-z. mice, guinea-pigs and monkeys showed simil ...200111798241
pathogenesis of experimental ebola zaire virus infection in balb/c mice.guinea-pigs and non-human primates have traditionally been used as animal models for studying ebola zaire virus (ebo-z) infections. the virus was also recently adapted to the stage of lethal virulence in balb/c mice. this murine model is now in use for testing antiviral medications and vaccines. however, the pathological features of ebo-z infection in mice have not yet been fully described. to identify sites of viral replication and characterize sequential morphological changes in balb/c mice, a ...200111798240
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 ...200211836430
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 ...200211803049
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.200211862746
the lived experience of waiting-to-know: ebola at mbarara, uganda--hoping for life, anticipating death.purpose pf the study: the purpose of the study was to describe the phenomenon of 'waiting to know'. it is a phenomenon uniquely experienced by persons who had been exposed to patients with ebola hemorrhagic fever (ebola) but who have not yet exhibited signs and symptoms of the disease. research method/analysis: the phenomenological human science approach was used using the four life worlds as guides for reflection. these are spatiality, corporeality, temporality, and relationality. participants: ...200211851785
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 ...200211853394
jungle conceals ebola origins. 200211901650
surprise finding spurs ebola researchers' hopes. 200211903010
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 ...200211907235
[microorganisms strike back--infectious diseases during the last 50 years].in the first half of the 20th century, improved living conditions, preventive measures, vaccines and antibiotics led to a marked reduction in morbidity and mortality from infectious diseases. it was predicted that the conquest of all infectious diseases was imminent. however, 50 years later, in 1999, they were still the major cause of disease worldwide, and caused nearly one third of all deaths (a total of 55.9 million). the eradication of smallpox in the 1970s and the approaching eradication of ...200111808014
ebola: preparing for the worst. 200111921713
ebola: small, but real progress. 200211927920
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 ...200211915170
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 ...200211877482
re-emergence of ebola haemorrhagic fever in gabon. 200211879899
virology. rafting with ebola. 200211951027
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 ...200211949481
targeted transduction patterns in the mouse brain by lentivirus vectors pseudotyped with vsv, ebola, mokola, lcmv, or mulv envelope proteins.lentiviral vectors have proven to be promising tools for transduction of central nervous system (cns) cells in vivo and in vitro. in this study, cns transduction patterns of lentiviral vectors pseudotyped with envelope glycoproteins from ebola virus, murine leukemia virus (mulv), lymphocytic choriomeningitis virus (lcmv), or the rabies-related mokola virus were compared to a vector pseudotyped with the vesicular stomatitis virus glycoprotein (vsv-g). mokola-, lcmv-, and vsv-g-pseudotyped vectors ...200211991743
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 ...200211991975
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 ...200211982604
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 ...200211996686
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 ...200211967302
pre- and postexposure prophylaxis of ebola virus infection in an animal model by passive transfer of a neutralizing human antibody.a neutralizing human monoclonal antibody, kz52, protects guinea pigs from lethal ebola zaire virus challenge. administration before or up to 1 h after challenge resulted in dose-dependent protection by the antibody. interestingly, some antibody-treated animals survived despite developing high-level viremia, suggesting that the mechanism of protection by kz52 may extend beyond reduction of viremia by virus neutralization. kz52 is a promising candidate for immunoprophylaxis of ebola virus infectio ...200212021376
association of the caveola vesicular system with cellular entry by filoviruses.the filoviruses ebola zaire virus and marburg virus are believed to infect target cells through endocytic vesicles, but the details of this pathway are unknown. we used a pseudotyping strategy to investigate the cell biology of filovirus entry. we observed that specific inhibitors of the caveola system, including cholesterol-sequestering drugs and phorbol esters, inhibited the entry of filovirus pseudotypes into human cells. we also measured slower cell entry kinetics for both filovirus pseudoty ...200211967340
c-type lectins dc-sign and l-sign mediate cellular entry by ebola virus in cis and in trans.ebola virus is a highly lethal pathogen responsible for several outbreaks of hemorrhagic fever. here we show that the primate lentiviral binding c-type lectins dc-sign and l-sign act as cofactors for cellular entry by ebola virus. furthermore, dc-sign on the surface of dendritic cells is able to function as a trans receptor, binding ebola virus-pseudotyped lentiviral particles and transmitting infection to susceptible cells. our data underscore a role for dc-sign and l-sign in the infective proc ...200212050398
phosphorylation of vp30 impairs ebola virus transcription.transcription of the highly pathogenic ebola virus (ebov) is dependent on vp30, a constituent of the viral nucleocapsid complex. here we present evidence that phosphorylation of vp30, which takes place at six n-terminal serine residues and one threonine residue, is of functional significance. replacement of the phosphoserines by alanines resulted in an only slightly phosphorylated vp30 (vp30(6a)) that is still able to activate ebov-specific transcription in a plasmid-based minigenome system. vp3 ...200212052831
chronological and spatial analysis of the 1996 ebola reston virus outbreak in a monkey breeding facility in the describe the transmission pattern of natural infection with ebola reston (ebo-r) virus in a breeding colony, the chronological and spatial analysis of mortality during the 1996 ebo-r virus outbreak was done in this study. the ebo-r virus infection among monkeys in the facility was widespread. over a period of 3 months, 14 out of 21 occupied units were contaminated with antigen positive animals. a large number of wild-caught monkeys were involved in this outbreak suggesting that wild-caught mo ...200212012728
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 ...200212076759
[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 ...200212046470
ebola vaccine gets corporate backer. 200212091886
representations of far-flung illnesses: the case of ebola in western cultures lay people are faced with a plethora of far-flung illnesses, relayed to them by the mass media. a number of social scientists have called for scrutiny of the link between people's patterns of thinking concerning such events, and the messages to which they are exposed. using the outbreaks of ebola in africa in the mid-1990s as a vehicle, the study examines how british broadsheets and their readers, and british tabloids and their readers, make sense of this far-flung illness. e ...200211996028
rapid detection and quantification of rna of ebola and marburg viruses, lassa virus, crimean-congo hemorrhagic fever virus, rift valley fever virus, dengue virus, and yellow fever virus by real-time reverse transcription-pcr.viral hemorrhagic fevers (vhfs) are acute infections with high case fatality rates. important vhf agents are ebola and marburg viruses (mbgv/ebov), lassa virus (lasv), crimean-congo hemorrhagic fever virus (cchfv), rift valley fever virus (rvfv), dengue virus (denv), and yellow fever virus (yfv). vhfs are clinically difficult to diagnose and to distinguish; a rapid and reliable laboratory diagnosis is required in suspected cases. we have established six one-step, real-time reverse transcription- ...200212089242
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.200212076527
dendritic cell (dc)-specific intercellular adhesion molecule 3 (icam-3)-grabbing nonintegrin (dc-sign, cd209), a c-type surface lectin in human dcs, is a receptor for leishmania amastigotes.dendritic cells (dcs) play a critical role in the initiation of the immunological response against leishmania parasites. however, the receptors involved in amastigote-dendritic cell interaction are unknown, especially in absence of opsonizing antibodies. we have studied the interaction of leishmania pifanoi axenic amastigotes with the c-type lectin dc-specific intercellular adhesion molecule (icam)-3-grabbing nonintegrin (dc-sign, cd209), a receptor for icam-2, icam-3, human immunodeficiency vir ...200212122001
ebola virus vp30-mediated transcription is regulated by rna secondary structure formation.the nucleocapsid protein vp30 of ebola virus (ebov), a member of the filovirus family, is known to act as a transcription activator. by using a reconstituted minigenome system, the role of vp30 during transcription was investigated. we could show that vp30-mediated transcription activation is dependent on formation of a stem-loop structure at the first gene start site. destruction of this secondary structure led to vp30-independent transcription. analysis of the transcription products of bicistr ...200212163572
quantitative expression and virus transmission analysis of dc-sign on monocyte-derived dendritic cells.the c-type lectins dc-sign and dc-signr efficiently bind human immunodeficiency virus (hiv) and simian immunodeficiency virus (siv) strains and can transmit bound virus to adjacent cd4-positive cells. dc-sign also binds efficiently to the ebola virus glycoprotein, enhancing ebola virus infection. dc-sign is thought to be responsible for the ability of dendritic cells (dcs) to capture hiv and transmit it to t cells, thus promoting hiv dissemination in vitro and perhaps in vivo as well. to investi ...200212186897
induction of immune responses in mice and monkeys to ebola virus after immunization with liposome-encapsulated irradiated ebola virus: protection in mice requires cd4(+) t cells.ebola zaire virus (ebo-z) causes severe hemorrhagic fever in humans, with a high mortality rate. it is thought that a vaccine against ebo-z may have to induce both humoral and cell-mediated immune responses to successfully confer protection. because it is known that liposome-encapsulated antigens induce both antibody and cellular responses, we evaluated the protective efficacy of liposome-encapsulated irradiated ebo-z [l(ev)], which contains all of the native ebo-z proteins. in a series of exper ...200212186901
defend the human rights of the ebola victims! 200212139173
study of the pathogenesis of ebola fever in laboratory animals with different sensitivity to this virus.pathophysiological parameters were compared in animals with different sensitivity to ebola virus infected with this virus. analysis of the results showed the differences in immune reactions underlying the difference between ebola-sensitive and ebola-resistant animals. no neutrophil activation in response to ebola virus injection was noted in ebola-sensitive animal. phagocytic activity of neutrophils in these animals inversely correlated with animal sensitivity to ebola virus. animal susceptibili ...200112152882
lentiviral vectors pseudotyped with a modified rd114 envelope glycoprotein show increased stability in sera and augmented transduction of primary lymphocytes and cd34+ cells derived from human and nonhuman primates.generating lentiviral vectors pseudotyped with different viral glycoproteins (gps) may modulate the physicochemical properties of the vectors, their interaction with the host immune system, and their host range. we have investigated the capacity of a panel of gps of both retroviral (amphotropic murine leukemia virus [mlv-a]; gibbon ape leukemia virus [galv]; rd114, feline endogenous virus) and nonretroviral (fowl plague virus [fpv]; ebola virus [ebov]; vesicular stomatitis virus [vsv]; lymphocyt ...200212130492
transcriptional control of the rna-dependent rna polymerase of vesicular stomatitis virus.the nonsegmented negative strand (nns) rna viruses include some of the mosr problematic human, animal and plant pathogens extant: for example, rabies virus, ebola virus, respiratory syncytial virus, the parainfluenza viruses, measles and infectious hemapoietic necrosis virus. the key feature of transcriptional control in the nns rna viruses is polymerase entry at a single 3' proximal site followed by obligatory sequential transcription of the linear array of genes. the levels of gene expression ...200212213662
molecular characterization of an isolate from the 1989/90 epizootic of ebola virus reston among macaques imported into the united states.we have determined the entire genomic sequence of the pennsylvania strain, which was isolated along with the virginia strain during the emergence of ebola virus reston in 1989/90 in the united states. thus, either the pennsylvania or virginia strain, neither of which had been previously molecularly characterized, can be considered as the prototype for ebola virus reston. comparative analysis showed a high degree of homology to the concomitantly analyzed and recently published philippine strain o ...200212191779
the assembly of ebola virus nucleocapsid requires virion-associated proteins 35 and 24 and posttranslational modification of nucleoprotein.ebola virus encodes seven viral structural and regulatory proteins that support its high rates of replication, but little is known about nucleocapsid assembly of this virus in infected cells. we report here that three viral proteins are necessary and sufficient for formation of ebola virus particles and that intracellular posttranslational modification regulates this process. expression of the nucleoprotein (np) and virion-associated proteins vp35 and vp24 led to spontaneous assembly of nucleoca ...200212191476
anthrax, tularemia, plague, ebola or smallpox as agents of bioterrorism: recognition in the emergency room.bioterrorism has become a potential diagnostic consideration in infectious diseases. this article reviews the clinical presentation and differential diagnosis of potential bioterrorist agents when first presenting to the hospital in the emergency room setting. the characteristic clinical features of inhalation anthrax, tularemic pneumonia, plague pneumonia, including laboratory and radiographic finding, are discussed. ebola vieus and smallpox are also discussed as potential bioterrorist-transmit ...200212197871
the role of dc-sign and dc-signr in hiv and ebola virus infection: can potential therapeutics block virus transmission and dissemination?sexual transmission of hiv requires that the virus crosses mucosal barriers and disseminates into lymphoid tissue, the major site of viral replication. to achieve this, hiv might engage dc-sign, a calcium dependent lectin that is expressed on mucosal dendritic cells (dcs), which binds avidly to hiv. dc-sign and other attachment factors are likely to account for the well-known ability of dcs to enhance infection of t cells by hiv. attachment of hiv to dc-sign might thus enhance viral spread in mu ...200212223058
[ebola fever, an out of control epidemic?]. 200212229031
efficient transduction of liver and muscle after in utero injection of lentiviral vectors with different this study we investigate the efficacy of lentiviral vectors of different pseudotypes for gene transfer to tissues of the preimmune fetus. balb/c fetuses at 14-15 days' gestation received lentiviral vectors carrying the transgene lacz under the control of the human cytomegalovirus (cmv) promoter by intramuscular (i.m.) or intrahepatic (i.h.) injection. we pseudotyped the lentiviral vectors with vesicular stomatitis virus (vsv-g), with mokola virus, or with ebola virus envelope glycoproteins. ...200212231171
[ebola: a virus endemic to central africa?].from october 2001 to march 2002, an outbreak of ebola haemorrhagic fever occurred in the north-eastern gabon (63 cases) and neighbouring congo (57 cases). it was the fourth epidemic in north eastern gabon since 1994. meanwhile this outbreak differed from the previous epidemics: at least five different emerging sources of the virus in the human population were observed from the local fauna resulting in fears of an endemic ebola virus in the area. the control of the outbreak was uneasy because of ...200212244929
[infections always present at the dawn of the 21st century].despite the many scientific achievements realized in recent years, infectious diseases still remain the main cause of premature mortality worldwide. it is also growing increasingly difficult to fight infections. tuberculosis and malaria are making a comeback, cholera and yellow fever are making new inroads into countries where they¿ve never been before, other diseases are developing resistance to antibiotics and have in some cases become incurable, and new diseases such as ebola-induced hemorrh ...199712322621
infection control in africa. nosocomial infection.this article discusses infection prevention and control in africa and describes an available manual for infection control. the effectiveness of prevention and control efforts is dependent on health care services and the prevalence of disease. funding for health care, the perceived economic impact of infection control, and trained administrators determine the availability of health services and the spread of disease. the challenge is to provide cleanliness, aseptic techniques in patient care, ...199712321236
un sec-gen on world health a speech on april 7, 1997, world health day, un secretary-general kofi annan stated that the globalization of trade, changes in ecology and climate, and mass movements of people are some factors which contribute to the spread of infectious diseases. as such, mr. annan called for international solidarity to combat such diseases. he believes that uncontrolled urbanization in many countries forces people to live in unhygienic and overcrowded conditions. in keeping with the day's theme of emer ...199712321711
a syringe that self-destructs.the reuse of unsterilized syringes is spreading aids, hepatitis b and the african ebola-marburg virus. in the us 25% of the aids cases are related to intravenous drug abuse. in developing countries syringe reuse is related to poor health care delivery systems. in these countries syringes are used over 5 times before sterilization; in some countries the syringes are distributed by people who sell injections of vitamins and antibiotics. in 1986 halsey challenged the medical community to design ...198912282933
the threat of emerging infections.a variety of newly discovered pathogens and new forms of older infectious agents threaten to reemerge. typical symptoms of acute infection are fever, headache, malaise, vomiting, and diarrhea. some of the better-known emerging viral infections include dengue, filoviruses (ebola, marburg), hantaviruses, hepatitis b, hepatitis c, hiv, influenza, lassa fever, measles, rift valley fever, rotavirus, and yellow fever. emerging bacterial infections include cholera, escherichia coli 0157:h7, leg ...199612349257
here to stay. an interview with dr. david satcher, director, u.s. centers for disease control and prevention.this paper presents an interview with dr. david satcher of the us centers for disease control and prevention (cdc) on the issue of infectious and chronic diseases. the problem of new and reemerging infectious diseases around the world, particularly in developing countries, is discussed. while drug resistant malaria and sporadic outbreaks of ebola in africa have alarmed health programs, aids is the major emerging infectious disease throughout the world. microorganisms have a way of surviv ...199612349258
emerging infectious disease: global response, global alert.despite spectacular progress in the eradication of infectious diseases, malaria and tuberculosis are making a comeback in many parts of the world. after years of decline, plague, diphtheria, dengue, meningococcal meningitis, yellow fever, and cholera have reappeared as public health threats. in the last 20 years [before 1997] more than 30 new and highly infectious diseases have been identified, including ebola-type hemorrhagic fever, hiv/aids, and hepatitis c. antibiotic resistance has also e ...199712348002
a decade after the generation of a negative-sense rna virus from cloned cdna - what have we learned?since the first generation of a negative-sense rna virus entirely from cloned cdna in 1994, similar reverse genetics systems have been established for members of most genera of the rhabdo- and paramyxoviridae families, as well as for ebola virus (filoviridae). the generation of segmented negative-sense rna viruses was technically more challenging and has lagged behind the recovery of nonsegmented viruses, primarily because of the difficulty of providing more than one genomic rna segment. a membe ...200212388800
development of an immunofluorescence method for the detection of antibodies to ebola virus subtype reston by the use of recombinant nucleoprotein-expressing hela 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 ...200212437031
furin at the cutting edge: from protein traffic to embryogenesis and disease.furin catalyses a simple biochemical reaction--the proteolytic maturation of proprotein substrates in the secretory pathway. but the simplicity of this reaction belies furin's broad and important roles in homeostasis, as well as in diseases ranging from alzheimer's disease and cancer to anthrax and ebola fever. this review summarizes various features of furin--its structural and enzymatic properties, intracellular localization, trafficking, substrates, and roles in vivo.200212360192
structure of the tsg101 uev domain in complex with the ptap motif of the hiv-1 p6 protein.the structural proteins of hiv and ebola display ptap peptide motifs (termed 'late domains') that recruit the human protein tsg101 to facilitate virus budding. here we present the solution structure of the uev (ubiquitin e2 variant) binding domain of tsg101 in complex with a ptap peptide that spans the late domain of hiv-1 p6(gag). the uev domain of tsg101 resembles e2 ubiquitin-conjugating enzymes, and the ptap peptide binds in a bifurcated groove above the vestigial enzyme active site. each pt ...200212379843
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 ...200212350354
evidence against ebola virus sgp binding to human neutrophils by a specific receptor.the issue of whether ebola secretory glycoprotein (sgp) binds to human neutrophils via the igg fc receptor iiib (fcgammariiib, cd16b) or other receptors has been controversial. to clarify this, facs analysis, an sgp absorption assay, and direct binding of (125)i-sgp to neutrophils were performed. results from facs analysis demonstrated that limited washing conditions leads to the nonspecific formation of immune complexes on the neutrophil surface and this, but not a specific interaction between ...200212482654
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 ...200312502822
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 ...200312502850
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 ...200312502864
ebola. 200212473930
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 ...200312477888
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 ...200212451705
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 ...200312505157
[sanitary control of the territory: data bases on the spread of some quarantine infections].the data bases (db) on the spread of plague, yellow fever and contagious virus hemorrhagic fevers (cvhf) in foreign countries have been created. these db contain information on the main international air and sea ports and their relationships with natural focal territories. the data base "sanitary control. yellow fever" contains information on different species serving as vectors for yellow fever virus. information on the circulation of the causative agents of ebola fever, lassa fever and marburg ...200212524996
[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.200212525016
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 ...200312522044
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 ...200312504546
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