PMID(sorted ascending)
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.200314683653
containing a haemorrhagic fever epidemic: the ebola experience in uganda (october 2000-january 2001).introduction: the ebola virus, belonging to the family of filoviruses, was first recognized in 1976 when it caused concurrent outbreaks in yambuku in the democratic republic of congo (drc), and in the town of nzara in sudan. both countries share borders with uganda. a total of 425 cases and 224 deaths attributed to ebola haemorrhagic fever (ehf) were recorded in uganda in 2000/01. although there was delayed detection at the community level, prompt and efficient outbreak investigation led to the ...200414690778
[ebola hemorrhagic fever: a unique efficacious vaccine dose in primates]. 200314691739
persistent infection with ebola virus under conditions of partial immunity.ebola hemorrhagic fever in humans is associated with high mortality; however, some infected hosts clear the virus and recover. the mechanisms by which this occurs and the correlates of protective immunity are not well defined. using a mouse model, we determined the role of the immune system in clearance of and protection against ebola virus. all cd8 t-cell-deficient mice succumbed to subcutaneous infection and had high viral antigen titers in tissues, whereas mice deficient in b cells or cd4 t c ...200414694127
production of novel ebola virus-like particles from cdnas: an alternative to ebola virus generation by reverse genetics.we established a plasmid-based system for generating infectious ebola virus-like particles (vlps), which contain an ebola virus-like minigenome consisting of a negative-sense copy of the green fluorescent protein gene. this system produced nearly 10(3) infectious particles per ml of supernatant, equivalent to the titer of ebola virus generated by a reverse genetics system. interestingly, infectious ebola vlps were generated, even without expression of vp24. transmission and scanning electron mic ...200414694131
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 ...200314711361
ebola hemorrhagic fever transmission and risk factors of contacts, uganda.from august 2000 through january 2001, a large epidemic of ebola hemorrhagic fever occurred in uganda, with 425 cases and 224 deaths. starting from three laboratory-confirmed cases, we traced the chains of transmission for three generations, until we reached the primary case-patients (i.e., persons with an unidentified source of infection). we then prospectively identified the other contacts in whom the disease had developed. to identify the risk factors associated with transmission, we intervie ...200314718087
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 ...200314720391
epidemiology. ebola outbreaks may have had independent sources. 200414726565
multiple ebola virus transmission events and rapid decline of central african wildlife.several human and animal ebola outbreaks have occurred over the past 4 years in gabon and the republic of congo. the human outbreaks consisted of multiple simultaneous epidemics caused by different viral strains, and each epidemic resulted from the handling of a distinct gorilla, chimpanzee, or duiker carcass. these animal populations declined markedly during human ebola outbreaks, apparently as a result of ebola infection. recovered carcasses were infected by a variety of ebola strains, suggest ...200414726594
space agency donates satellites to help study ebola. 200414733196
conference report - i. investigating new vaccines: ebola and hiv: highlights from the viral vaccine meeting; october 25-28, 2003; barcelona, spain. 200314745371
distribution of hydrophobic residues is crucial for the fusogenic properties of the ebola virus gp2 fusion peptide.the lipid-destabilizing properties of the n-terminal domain of the gp2 of ebola virus were investigated. our results suggest that the domain of ebola virus needed for fusion is shorter than that previously reported. the fusogenic properties of this domain are related to its oblique orientation at the lipid/water interface owing to an asymmetric distribution of the hydrophobic residues when helical.200414747578
ebola vaccines tested in humans, monkeys. 200414762022
identification of murine t-cell epitopes in ebola virus nucleoprotein.cd8 t cells play an important role in controlling ebola infection and in mediating vaccine-induced protective immunity, yet little is known about antigenic targets in ebola that are recognized by cd8 t cells. overlapping peptides were used to identify major histocompatibility complex class i-restricted epitopes in mice immunized with vectors encoding ebola nucleoprotein (np). cd8 t-cell responses were mapped to a h-2(d)-restricted epitope (np279-288) and two h-2(b)-restricted epitopes (np44-52 a ...200414972550
transduction of human islets with pseudotyped lentiviral vectors.type i diabetes is caused by an autoimmune-mediated elimination of insulin-secreting pancreatic islets. genetic modification of islets offers a powerful molecular tool for improving our understanding of islet biology. moreover, efficient genetic engineering of islets could allow for evaluation of new strategies aimed at preventing islet destruction. the present study evaluated the ability of a human immunodeficiency virus (hiv)-based lentiviral vector pseudotyped with various viral envelopes to ...200414975193
prediction of proprotein convertase cleavage sites.many secretory proteins and peptides are synthesized as inactive precursors that in addition to signal peptide cleavage undergo post-translational processing to become biologically active polypeptides. precursors are usually cleaved at sites composed of single or paired basic amino acid residues by members of the subtilisin/kexin-like proprotein convertase (pc) family. in mammals, seven members have been identified, with furin being the one first discovered and best characterized. recently, the ...200414985543
budding of ppxy-containing rhabdoviruses is not dependent on host proteins tgs101 and vps4a.viral matrix proteins of several enveloped rna viruses play important roles in virus assembly and budding and are by themselves able to bud from the cell surface in the form of lipid-enveloped, virus-like particles (vlps). three motifs (pt/sap, ppxy, and yxxl) have been identified as late budding domains (l-domains) responsible for efficient budding. l-domains can functionally interact with cellular proteins involved in vacuolar sorting (vps4a and tsg101) and endocytic pathways (nedd4), suggesti ...200414990685
human macrophage c-type lectin specific for galactose and n-acetylgalactosamine promotes filovirus entry.filoviruses cause lethal hemorrhagic disease in humans and nonhuman primates. an initial target of filovirus infection is the mononuclear phagocytic cell. calcium-dependent (c-type) lectins such as dendritic cell- or liver/lymph node-specific icam-3 grabbing nonintegrin (dc-sign or l-sign, respectively), as well as the hepatic asialoglycoprotein receptor, bind to ebola or marburg virus glycoprotein (gp) and enhance the infectivity of these viruses in vitro. here, we demonstrate that a recently i ...200414990712
ebola virus glycoproteins: guidance devices for targeting gene therapy vectors.replacing the native viral envelope protein on the surface of a retrovirus or lentivirus with the glycoprotein of a foreign enveloped virus, a process called pseudotyping, can expand the set of potential target cells for a viral vector or can restrict entry to specific cells. the ebola virus glycoprotein, because of its evolutionary origins and the route of viral entry promoted by it, possesses distinct advantages in forming the outer shell of such pseudotyped retroviruses for gene therapy appli ...200415006727
l-deaza-5'-noraisteromycin.(+/-)-1-deazaaristeromycin (4) has been reported to be an inactivator of s-adenosylhomocysteine (adohcy) hydrolase and, as a consequence, to affect s-adenosylmethionine (adomet) mediated macromolecular biomethylations. to extend this to our program focused on 5'-noraristeromycin derivatives as inhibitors of the same hydrolase enzyme as potential antiviral agents, both enantiomers of 1-deaza-5'-noraristeromycin (5 and 20) have been prepared. compounds 5 and 20 were evaluated against the following ...200415043137
rapid diagnosis of ebola hemorrhagic fever by reverse transcription-pcr in an outbreak setting and assessment of patient viral load as a predictor of outcome.the largest outbreak on record of ebola hemorrhagic fever (ehf) occurred in uganda from august 2000 to january 2001. the outbreak was centered in the gulu district of northern uganda, with secondary transmission to other districts. after the initial diagnosis of sudan ebolavirus by the national institute for virology in johannesburg, south africa, a temporary diagnostic laboratory was established within the gulu district at st. mary's lacor hospital. the laboratory used antigen capture and rever ...200415047846
[an effective vaccine against ebola hemorrhagic fever]. 200415049337
ebola virus glycoprotein-mediated anoikis of primary human cardiac microvascular endothelial cells.ebola virus glycoprotein (egp) has been implicated for the induction of cytotoxicity and injury in vascular cells. on the other hand, egp has also been suggested to induce massive cell rounding and detachment from the plastic surface by downregulating cell adhesion molecules without causing cytotoxicity. in this study, we have examined the cytotoxic role of egp in primary endothelial cells by transduction with a replication-deficient recombinant adenovirus expressing egp (ad-egp). primary human ...200415051379
dc-sign: binding receptor for hcv?dc-sign, a dendritic cell-specific adhesion receptor and a type ii transmembrane mannose-binding c-type lectin, is very important in the function of dc, both in mediating naive t cell interactions through icam-3 and as a rolling receptor that mediates the dc-specific icam-2-dependent migration processes. it can be used by viral and bacterial pathogens including human immunodeficiency virus (hiv), hcv, ebola virus, cmv and mycobacterium tuberculosis to facilitate infection. both dc-sign and dc-si ...200415052667
organisation of health care during an outbreak of marburg haemorrhagic fever in the democratic republic of congo, 1999.organising health care was one of the tasks of the international scientific and technical committee during the 1998-1999 outbreak in durba/watsa, in the north-eastern province (province orientale), democratic republic of congo. with the logistical support of médecins sans frontières (msf), two isolation units were created: one at the durba reference health centre and the other at the okimo hospital in watsa. between may 6th, the day the isolation unit was installed and may 19th, 15 patients were ...200415066337
rapid detection protocol for filoviruses.the incidence of filovirus disease outbreaks has been increasing in recent years. although there have been advances in the developments of diagnostics, field tests are rare. apart from family members of infected patients, health care workers are at high risk of being infected during the initial phase of an outbreak. rt-pcr has been shown to be helpful in containing outbreaks.200415072761
in vitro evaluation of cyanovirin-n antiviral activity, by use of lentiviral vectors pseudotyped with filovirus envelope glycoproteins.cyanovirin-n (cv-n) has been shown to inhibit ebola zaire virus (ebozv) infection, both in vitro and in vivo, through its ability to bind to oligomannoses-8/9 on the ebozv surface glycoprotein (gp). here, we report the in vitro potency of cv-n to inhibit ebozv gp- and marburg virus gp-pseudotyped viruses (ec50 approximately 40-60 nmol/l and approximately 6-25 nmol/l, respectively) from mediating gene transduction into hela cells. in addition, we provide evidence that cv-n can effectively inhibit ...200415073681
ecologic and geographic distribution of filovirus disease.we used ecologic niche modeling of outbreaks and sporadic cases of filovirus-associated hemorrhagic fever (hf) to provide a large-scale perspective on the geographic and ecologic distributions of ebola and marburg viruses. we predicted that filovirus would occur across the afrotropics: ebola hf in the humid rain forests of central and western africa, and marburg hf in the drier and more open areas of central and eastern africa. most of the predicted geographic extent of ebola hf appear to have b ...200415078595
the kindest cuts of all: crystal structures of kex2 and furin reveal secrets of precursor or pro-protein convertases are a conserved family of eukaryotic serine proteases found in the secretory pathway. these endoproteases mature precursors for peptides and proteins that perform a wide range of physiologically important and clinically relevant functions. the first member of this family to be identified was kex2 in the yeast saccharomyces cerevisiae. one mammalian member of this family - furin - is responsible for processing substrates that include insulin pro-receptor, hu ...200415102434
ectodomain shedding of the glycoprotein gp of ebola this study, release of abundant amounts of the ebola virus (ebov) surface glycoprotein gp in a soluble form from virus-infected cells was investigated. we demonstrate that the mechanism responsible for the release of gp is ectodomain shedding mediated by cellular sheddases. proteolytic cleavage taking place at amino-acid position d637 removes the transmembrane anchor and liberates complexes consisting of gp1 and truncated gp2 (gp(2delta)) subunits from the cell surface. we show that tumor nec ...200415103332
[strain differences related to ebola virus reproduction in peritoneal macrophages and in aorta explants of guinea pigs].reproduction of the ebola strains (es) virus causing lethality in guinea pigs as well as in peritoneal macrophages and aorta explants of animals was investigated in vitro and in vivo; besides, production of interferon-gamma (ifn-gamma) and of tumor necrosis factor-alpha (tnf-alpha) by macrophages and endotheliocytes of guinea pigs was also studied. the interplay "macrophage--es" by the example of 2 models of susceptibility to es demonstrates that the es lethality is not unambiguously related onl ...200415106377
[dynamics of complement hemolytic activity in experimental ebola infection].the dynamic hemolytic activity of complements (hac) was investigated in blood of guinea pigs in lethal and non-lethal ebola infection. the increasing hac dynamic activity in the animal blood was found to correlate with the infection lethal course. hac as observed in animals with lethal infection was sweepingly increasing after they, were infected with ebola virus, and yet after 15 hours from the infection time the complement activity parameters topped 2-fold the basic values in 100% of guinea pi ...200415106379
structural studies on the ebola virus matrix protein vp40 indicate that matrix proteins of enveloped rna viruses are analogues but not homologues.matrix proteins are the driving force of assembly of enveloped viruses. their main function is to interact with and polymerize at cellular membranes and link other viral components to the matrix-membrane complex resulting in individual particle shapes and ensuring the integrity of the viral particle. although matrix proteins of different virus families show functional analogy, they share no sequence or structural homology, their diversity is also evident in that they use a variety of late domain ...200415108720
case definitions. ebola-marburg viral diseases. 200315112622
properties of replication-competent vesicular stomatitis virus vectors expressing glycoproteins of filoviruses and arenaviruses.replication-competent recombinant vesicular stomatitis viruses (rvsvs) expressing the type i transmembrane glycoproteins and selected soluble glycoproteins of several viral hemorrhagic fever agents (marburg virus, ebola virus, and lassa virus) were generated and characterized. all recombinant viruses exhibited rhabdovirus morphology and replicated cytolytically in tissue culture. unlike the rvsvs with an additional transcription unit expressing the soluble glycoproteins, the viruses carrying the ...200415113924
context-dependent effects of l domains and ubiquitination on viral budding.many enveloped viruses encode late assembly domains, or l domains, that facilitate virion egress. ptap-type l domains act by recruiting the escrt-i (endosomal sorting complex required for transport i) component tsg101, and ypxl/lxxlf-type l domains recruit aip-1/alix, both of which are class e vacuolar protein sorting (vps) factors, normally required for the generation of vesicles within endosomes. the binding cofactors for ppxy-type l domains have not been unambiguously resolved but may include ...200415140952
the basic reproductive number of ebola and the effects of public health measures: the cases of congo and uganda.despite improved control measures, ebola remains a serious public health risk in african regions where recurrent outbreaks have been observed since the initial epidemic in 1976. using epidemic modeling and data from two well-documented ebola outbreaks (congo 1995 and uganda 2000), we estimate the number of secondary cases generated by an index case in the absence of control interventions r0. our estimate of r0 is 1.83 (sd 0.06) for congo (1995) and 1.34 (sd 0.03) for uganda (2000). we model the ...200415178190
use of recombinant cytokines for optimized induction of antiviral immunity against siv in the nonhuman primate model of human aids.outbreaks of infectious diseases such as hiv and the much televised and attention-getting outbreaks of diseases such as ebola, hantaviruses, and the most recent outbreak of sars have induced a significant new interest in the formulations and more importantly the science of vaccinology, which has previously to a large extent been conducted empirically. our laboratory has focused on the use of recombinant nonhuman primate cytokines as adjunctive therapies for inducing antigen-specific immune respo ...200415181266
molecular dynamics simulation of lipid reorientation at bilayer edges.understanding cellular membrane processes is critical for the study of events such as viral entry, neurotransmitter exocytosis, and immune activation. supported lipid bilayers are commonly used to model these membrane processes experimentally. despite the relative simplicity of such a system, many important structural and dynamic parameters are not experimentally observable with current techniques. computational approaches allow the development of a high-resolution model of bilayer processes. we ...200415189870
other viral bioweapons: ebola and marburg hemorrhagic fever.the term viral hemorrhagic fever refers to a clinical syndrome characterized by acute onset of fever accompanied by nonspecific findings of malaise, prostration, diarrhea,and headache. patients frequently show signs of increased vascular permeability, and many develop bleeding diatheses. the hemorrhagic fever viruses represent potential agents for biologic warfare because of capability of aerosol transmission, high morbidity,and mortality associated with infection, and ability to replicate in ce ...200415207310
contribution of ebola virus glycoprotein, nucleoprotein, and vp24 to budding of vp40 virus-like particles.the vp40 matrix protein of ebola virus buds from cells in the form of virus-like particles (vlps) and plays a central role in virus assembly and budding. in this study, we utilized a functional budding assay and cotransfection experiments to examine the contributions of the glycoprotein (gp), nucleoprotein (np), and vp24 of ebola virus in facilitating release of vp40 vlps. we demonstrate that vp24 alone does not affect vp40 vlp release, whereas np and gp enhance release of vp40 vlps, individuall ...200415220407
roles of a conserved proline in the internal fusion peptide of ebola glycoprotein.the structural determinants underlying the functionality of viral internal fusion peptides (ifps) are not well understood. we have compared ebowt (gaaiglawipyfgpaae), representing the ifp of the ebola fusion protein gp, and ebowt (gaaiglawipyfgraae) derived from a non-functional mutant with conserved pro537 substituted by arg. p537r substitution did not abrogate peptide-membrane association, but interfered with the ability to induce bilayer destabilization. structural determinations suggest that ...200415225645
crimean-congo hemorrhagic fever: prevention and control limitations in a resource-poor autumn 2000, an outbreak of crimean-congo hemorrhagic fever (cchf) occurred in pakistan and involved nosocomial cases due to human-to-human transmission at a tertiary care hospital in karachi. during a hospital-based investigation, 6 serologically confirmed cases (i.e., patients seropositive for cchf antigen or anti-cchf immunoglobulin m antibodies by means of a capture enzyme-linked immunosorbent assay [elisa]) and 3 clinically confirmed cases (i.e., patients with negative elisa for cchf but ...200415227619
role of natural killer cells in innate protection against lethal ebola virus infection.ebola virus is a highly lethal human pathogen and is rapidly driving many wild primate populations toward extinction. several lines of evidence suggest that innate, nonspecific host factors are potentially critical for survival after ebola virus infection. here, we show that nonreplicating ebola virus-like particles (vlps), containing the glycoprotein (gp) and matrix protein virus protein (vp)40, administered 1-3 d before ebola virus infection rapidly induced protective immunity. vlp injection e ...200415249592
sudan ebola outbreak of known strain. 200415252932
high resolution crystal structure of human rab9 gtpase: a novel antiviral drug target.rab gtpases and their effectors facilitate vesicular transport by tethering donor vesicles to their respective target membranes. rab9 mediates late endosome to trans-golgi transport and has recently been found to be a key cellular component for human immunodeficiency virus-1, ebola, marburg, and measles virus replication, suggesting that it may be a novel target in the development of broad spectrum antiviral drugs. as part of our structure-based drug design program, we have determined the crysta ...200415263003
ebola and marburg virus-like particles activate human myeloid dendritic cells.the filoviruses, ebola (ebov) and marburg (marv), are potential global health threats, which cause deadly hemorrhagic fevers. although both ebov and marv logarithmically replicate in dendritic cells (dcs), these viruses do not elicit dc cytokine secretion and fail to activate and mature infected dcs. here, we employed virus-like particles (vlps) of ebov and marv to investigate whether these genome-free particles maintain similar immune evasive properties as authentic filoviruses. confocal micros ...200415302213
marburg virus-like particles protect guinea pigs from lethal marburg virus infection.ongoing outbreaks of filoviruses in africa and concerns about their use in bioterrorism attacks have led to intense efforts to find safe and effective vaccines to prevent the high mortality associated with these viruses. we previously reported the generation of virus-like particles (vlps) for the filoviruses, marburg (marv) and ebola (ebov) virus, and that vaccinating mice with ebola vlps (evlps) results in complete survival from a lethal ebov challenge. the objective of this study was to determ ...200415308377
glycodendritic structures: promising new antiviral drugs.dc-sign, a c-type lectin expressed by dendritic cells, is able to recognize high mannosylated glycoproteins at the surface of a broad range of pathogens including viruses, bacteria, fungi and parasites. for at least some of these agents this interaction appears to be an important part of the infection process. therefore, this lectin might be considered in the design of new antiviral drugs. in this manner, multivalent carbohydrate systems based on dendrimers and dendritic polymers are promising c ...200415308605
emerging roles of tissue factor in viral hemorrhagic fever.activation of coagulation by tissue factor (tf) is frequently observed in sepsis syndrome and is documented in certain viral hemorrhagic fevers. coagulation protease complexes signal by activating the g-protein coupled, protease-activated receptors that regulate inflammation. blockade of tf attenuates lethality in experimental models of ebola virus infection but - similar to findings in bacterial sepsis - reduction of inflammation, rather than attenuation of coagulation, predicts survival of tre ...200415324737
emerging infections in animals--potential new zoonoses?it is well recognized that most emerging diseases of humans are zoonotic, and that the forces working to create emerging diseases in humans are also operating in animal populations. however, what is often overlooked is that emerging human diseases are usually preceded by the emergence of the same pathogen in an animal population. in fact, the developing disease in animals acts as a link allowing the disease to take hold and wreck havoc in public health. numerous examples--rift valley fever, monk ...200415325066
depletion of peripheral blood t lymphocytes and nk cells during the course of ebola hemorrhagic fever in cynomolgus macaques.during the course of an experimentally induced ebola virus (ebova) infection of cynomolgus macaques, peripheral blood mononuclear cells were isolated and characterized by multi-color flow cytometry. both cd4+ and cd8+ lymphocyte counts decreased 60-70% during the first 4 days after infection. among cd8+ lymphocytes, this decline was greatest among the cd8(lo) population, which was composed mostly of cd3- cd16+ nk cells. in contrast, the number of cd20+ b lymphocytes in the blood did not signific ...200415357905
analysis of human peripheral blood samples from fatal and nonfatal cases of ebola (sudan) hemorrhagic fever: cellular responses, virus load, and nitric oxide levels.peripheral blood samples obtained from patients during an outbreak of ebola virus (sudan species) disease in uganda in 2000 were used to phenotype peripheral blood mononuclear cells (pbmc), quantitate gene expression, measure antigenemia, and determine nitric oxide levels. it was determined that as the severity of disease increased in infected patients, there was a corresponding increase in antigenemia and leukopenia. blood smears revealed thrombocytopenia, a left shift in neutrophils (in some c ...200415367603
disulfide bond assignment of the ebola virus secreted glycoprotein sgp.the non-structural glycoprotein (sgp) of ebola virus (ebov) is secreted in large amounts from infected cells as a disulfide-linked homodimer. in this communication, highly purified sgp, derived from vero e6 cultures infected with the zaire species of ebov, was used to determine the correct localization of inter- and intrachain disulfide bonds. matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry analysis of proteolytic cleavage fragments indicates that all cysteines (six ...200415369806
sequence and structure relatedness of matrix protein of human respiratory syncytial virus with matrix proteins of other negative-sense rna viruses.matrix proteins of viruses within the order mononegavirales have similar functions and play important roles in virus assembly. protein sequence alignment, phylogenetic tree derivation, hydropathy profiles and secondary structure prediction were performed on selected matrix protein sequences, using human respiratory syncytial virus matrix protein as the reference. no general conservation of primary, secondary or tertiary structure was found, except for a broad similarity in the hydropathy pattern ...200415373896
dc-sign: binding receptors for hepatitis c review the recent developments in and research into binding receptors of hepatitis c virus (hcv) and especially the role of dendritic cell-specific adhesion receptor (dc-sign) in hcv.200415377434
ebola virus ecology: a continuing mystery. 200415381189
ebola virus: new insights into disease aetiopathology and possible therapeutic interventions.ebola virus (ebov) gained public notoriety in the last decade largely as a consequence of the highly publicized isolation of a new ebov species in a suburb of washington, dc, in 1989, together with the dramatic clinical presentation of ebov infection and high case-fatality rate in africa (near 90% in some outbreaks), and the unusual and striking morphology of the virus. furthermore, there are no vaccines or effective therapies currently available. progress in understanding the origins of the pat ...200415383160
application of real-time pcr for testing antiviral compounds against lassa virus, sars coronavirus and ebola virus in vitro.this report describes the application of real-time pcr for testing antivirals against highly pathogenic viruses such as lassa virus, sars coronavirus and ebola virus. the test combines classical cell culture with a quantitative real-time pcr read-out. the assay for lassa virus was validated with ribavirin, which showed an ic(50) of 9 micrograms/ml. small-scale screening identified a class of imidazole nucleoside/nucleotide analogues with antiviral activity against lassa virus. the analogues cont ...200415451189
[functional activity of peritoneal macrophages in experimental ebola fever].the phagocytic activity of peritoneal macrophages (a representative of mononuclear phagocytes) as well as the tnf-alpha were studied in animals with different susceptibility to ebola virus (ev). the results denote the following: 1. phagocytosis activation by peritoneal macrophages after ev is introduced into the body correlates directly with a susceptibility degree of an animal to ev. 2. the ev content in peritoneal lavage is inversely dependent on a phagocytic activity of peritoneal macrophages ...200415455683
flipping the switch from monomeric to dimeric cv-n has little effect on antiviral activity.cyanovirin-n can exist in solution in monomeric and domain-swapped dimeric forms, with hiv-antiviral activity being reported for both. here we present results for cv-n variants that form stable solution dimers: the obligate dimer [deltaq50]cv-n and the preferential dimer [s52p]cv-n. these variants exhibit comparable deltag values (10.6 +/- 0.5 and 9.4 +/- 0.5 kcal.mol(-1), respectively), similar to that of stabilized, monomeric [p51g]cv-n (9.8 +/- 0.5 kcal.mol(-1)), but significantly higher than ...200415458629
[new form of hemorraghic fever in zaire].the purpose of this report is to describe the events that occurred immediately before and during the first weeks of the ebola virus epicemic in the democratic republic of the congo (formerly zaire) in september and october 1976. by october 4 dr raffier and dr ruppol were already on hand at the epicenter of the epicemic in the equator region about 1000 km from kinshasa. they had been mandated by the state health commissioner to conduct a firsthand assessment of the reportedly disastrous local con ...200415460138
[practical guidelines for the management of ebola infected patients in the field].ebola hemorrhagic fever appears after an incubation of 3 days to 3 weeks. the first symptoms are fever accompanied by general and hemorrhagic signs leading to death in 50 to 90% of cases. during epidemics definition of cases permits prompt diagnosis. due to the high risk of person-to-person and nosocomial transmission associated with ebola hemorrhagic fever, management is based on isolation of patients and institution of protected care. hands and soiled material are often decontaminated using so ...200415460155
[epidemics of ebola haemorrhagic fever in gabon (1994-2002). epidemiologic aspects and considerations on control measures].based on the description of the four ebola haemorrhagic fever epidemics (ehf) occurred in gabon between 1994 and 2002, the authors are considering the cultural and psycho-sociological aspects accounting for the difficulty to implement control measures. on the whole, the result of these raging epidemics came up to 207 cases and 150 dead (lethality: 72%). analysing precisely the aspects of the third epidemic and pointing up the possible factors explaining its spreading far beyond its epicentre, th ...200415462203
[bacterial and viral epidemics of zoonotic origin; the role of hunting and cutting up wild animals].since the prehistoric times hunting has been a vital activity for man. however, this may account for the contamination of the hunter, his family and relatives. infections may occur by direct contact with blood or tissues of infected animal during handling and cutting up preys and when preparing or eating meat, or also when bitten by injured animal. apes and antelopes hunting in sub-saharan africa proves to be particularly important since it has been well established that the recent or previous e ...200415462204
representations of sars in the british the spring of 2003, there was a huge interest in the global news media following the emergence of a new infectious disease: severe acute respiratory syndrome (sars). this study examines how this novel disease threat was depicted in the uk newspapers, using social representations theory and in particular existing work on social representations of hiv/aids and ebola to analyse the meanings of the epidemic. it investigates the way that sars was presented as a dangerous threat to the uk public, w ...200415474209
dc-sign and dc-signr interact with the glycoprotein of marburg virus and the s protein of severe acute respiratory syndrome coronavirus.the lectins dc-sign and dc-signr can augment viral infection; however, the range of pathogens interacting with these attachment factors is incompletely defined. here we show that dc-sign and dc-signr enhance infection mediated by the glycoprotein (gp) of marburg virus (marv) and the s protein of severe acute respiratory syndrome coronavirus and might promote viral dissemination. signr1, a murine dc-sign homologue, also enhanced infection driven by marv and ebola virus gp and could be targeted to ...200415479853
an uncertain defense. how do you test that a human ebola vaccine works? you don't. 200415487661
cd209l (l-sign) is a receptor for severe acute respiratory syndrome coronavirus.angiotensin-converting enzyme 2 (ace2) is a receptor for sars-cov, the novel coronavirus that causes severe acute respiratory syndrome [li, w. moore, m. j., vasilieva, n., sui, j., wong, s. k., berne, m. a., somasundaran, m., sullivan, j. l., luzuriaga, k., greenough, t. c., et al. (2003) nature 426, 450-454]. we have identified a different human cellular glycoprotein that can serve as an alternative receptor for sars-cov. a human lung cdna library in vesicular stomatitis virus g pseudotyped ret ...200415496474
multivesicular bodies as a platform for formation of the marburg virus envelope.the marburg virus (marv) envelope consists of a lipid membrane and two major proteins, the matrix protein vp40 and the glycoprotein gp. both proteins use different intracellular transport pathways: gp utilizes the exocytotic pathway, while vp40 is transported through the retrograde late endosomal pathway. it is currently unknown where the proteins combine to form the viral envelope. in the present study, we identified the intracellular site where the two major envelope proteins of marv come toge ...200415507615
transduction of satellite cells after prenatal intramuscular administration of lentiviral vectors.we have previously reported long-term expression of lacz in myocytes after in utero intramuscular injection of mokola and ebola pseudotyped lentiviral vectors. in further experiments, we have noted that these vectors also transduce small cells at the periphery of the muscle fibers that have the morphology of satellite cells, or muscle stem cells. in this study we performed experiments to further define the morphology and function of these cells.200515515139
rescue of ebola virus from cdna using heterologous support proteins.using the infectious clone for zaire ebolavirus, the functional specificity of viral proteins of the ribonucleoprotein complex in transcription/replication was investigated by substituting them with heterologous proteins derived from closely (reston ebolavirus) and distantly related filoviruses (marburgvirus). the data clearly demonstrated that transcription/replication are neither strictly species-specific nor genus-specific. protein interactions between the nucleoprotein np and the virion prot ...200415522446
seasonality of infectious diseases and severe acute respiratory syndrome-what we don't know can hurt us.the novel severe acute respiratory syndrome (sars) coronavirus caused severe disease and heavy economic losses before apparently coming under complete control. our understanding of the forces driving seasonal disappearance and recurrence of infectious diseases remains fragmentary, thus limiting any predictions about whether, or when, sars will recur. it is true that most established respiratory pathogens of human beings recur in wintertime, but a new appreciation for the high burden of disease i ...200415522683
ebola virus ecology. 200415529250
a serological survey of ebola virus infection in central african nonhuman primates.we used an elisa to determine the prevalence of igg antibodies specific for the zaire subtype of ebola virus in 790 nonhuman primates, belonging to 20 species, studied between 1985 and 2000 in cameroon, gabon, and the republic of congo. the seroprevalence rate of ebola antibody in wild-born chimpanzees was 12.9%, indicating that (1) ebola virus circulates in the forests of a large region of central africa, including countries such as cameroon, where no human cases of ebola infections have been r ...200415529251
filovirus filoviridae, which includes ebola virus (ebov) and marburg virus (marv), is a growing threat to human and non-human primate populations in central africa. although many facets of the filovirus life cycle remain to be deciphered, a great deal has been learned in recent years. in particular, a clearer understanding of the roles played by viral, as well as cellular, proteins in the assembly and budding processes has been achieved. this review will discuss the current state of filovirus buddi ...200415567496
trigger events: enviroclimatic coupling of ebola hemorrhagic fever outbreaks.we use spatially continuous satellite data as a correlate of precipitation within tropical africa and show that the majority of documented ebola hemorrhagic fever outbreaks were closely associated with sharply drier conditions at the end of the rainy season. we propose that these trigger events may enhance transmission of ebola virus from its cryptic reservoir to humans. these findings suggest specific directions to help understand the sylvatic cycle of the virus and may provide early warning to ...200415569802
outbreak(s) of ebola haemorrhagic fever, congo and gabon, october 2001-july 2002. 200315571171
exotic emerging viral diseases: progress and challenges.the agents causing viral hemorrhagic fever (vhf) are a taxonomically diverse group of viruses that may share commonalities in the process whereby they produce systemic and frequently fatal disease. significant progress has been made in understanding the biology of the ebola virus, one of the best known examples. this knowledge has guided our thinking about other vhf agents, including marburg, lassa, the south american arenaviruses, yellow fever, crimean-congo and rift valley fever viruses. compa ...200415577929
sequencing needs for viral diagnostics.we built a system to guide decisions regarding the amount of genomic sequencing required to develop diagnostic dna signatures, which are short sequences that are sufficient to uniquely identify a viral species. we used our existing dna diagnostic signature prediction pipeline, which selects regions of a target species genome that are conserved among strains of the target (for reliability, to prevent false negatives) and unique relative to other species (for specificity, to avoid false positives) ...200415583268
marburg and ebola viruses as aerosol threats.ebola and marburg viruses are the sole members of the genus filovirus in the family filoviridae. there has been considerable media attention and fear generated by outbreaks of filoviruses because they can cause a severe viral hemorrhagic fever (vhf) syndrome that has a rapid onset and high mortality. although they are not naturally transmitted by aerosol, they are highly infectious as respirable particles under laboratory conditions. for these and other reasons, filoviruses are classified as cat ...200415588056
ebola virus glycoprotein toxicity is mediated by a dynamin-dependent protein-trafficking pathway.ebola virus infection causes a highly lethal hemorrhagic fever syndrome associated with profound immunosuppression through its ability to induce widespread inflammation and cellular damage. though gp, the viral envelope glycoprotein, mediates many of these effects, the molecular events that underlie ebola virus cytopathicity are poorly understood. here, we define a cellular mechanism responsible for ebola virus gp cytotoxicity. gp selectively decreased the expression of cell surface molecules th ...200515596847
studies of ebola virus glycoprotein-mediated entry and fusion by using pseudotyped human immunodeficiency virus type 1 virions: involvement of cytoskeletal proteins and enhancement by tumor necrosis factor alpha.the ebola filoviruses are aggressive pathogens that cause severe and often lethal hemorrhagic fever syndromes in humans and nonhuman primates. to date, no effective therapies have been identified. to analyze the entry and fusion properties of ebola virus, we adapted a human immunodeficiency virus type 1 (hiv-1) virion-based fusion assay by substituting ebola virus glycoprotein (gp) for the hiv-1 envelope. fusion was detected by cleavage of the fluorogenic substrate ccf2 by beta-lactamase-vpr inc ...200515613320
[ebola virus hemorrhagic fever: another deadly strike in sudan]. 200415615380
[viral hemorrhagic fevers--ebola hemorrhagic fever, marburg virus disease, and lassa fever]. 200415624463
containing the threat--don't forget ebola. 200415630468
ebola haemorrhagic fever--fact sheet revised in may 2004. 200415638356
the highly specific carbohydrate-binding protein cyanovirin-n: structure, anti-hiv/ebola activity and possibilities for therapy.cyanovirin-n (cv-n), a cyanobacterial lectin, is a potent viral entry inhibitor currently under development as a microbicide against a broad spectrum of enveloped viruses. cv-n was originally identified as a highly active anti-hiv agent and later, as a virucidal agent against other unrelated enveloped viruses such as ebola, and possibly other viruses. cv-n's antiviral activity appears to involve unique recognition of n-linked high-mannose oligosaccharides, man-8 and man-9, on the viral surface g ...200515638789
epidemiology: past, present and future.epidemiology in the past was concerned essentially by the study of infectious diseases which were the cause of huge mortalities especially since urbanisation was initiated. epidemics of pest, typhus, cholera, influenza a.o. were common. the epidemics were halted by better hygiene, vaccination and antibiotics. since the second world war epidemiology was dominated by an "epidemic" of new chronic diseases, especially heart disease and cancer. this was due to an increase in life span and to an incre ...200415641567
demand for nonhuman primate resources in the age of biodefense.the demand for nonhuman primates will undoubtedly increase to meet biomedical needs in this current age of biodefense. the availability of funding has increased the research on select agents and has created a requirement to validate results in relevant primate models. this review provides a description of current and potential biological threats that are likely to require nonhuman primates for the development of vaccines and therapeutics. primates have been an invaluable resource in the dissecti ...200515644560
vp40 octamers are essential for ebola virus replication.matrix protein vp40 of ebola virus is essential for virus assembly and budding. monomeric vp40 can oligomerize in vitro into rna binding octamers, and the crystal structure of octameric vp40 has revealed that residues phe125 and arg134 are the most important residues for the coordination of a short single-stranded rna. here we show that full-length wild-type vp40 octamers bind rna upon hek 293 cell expression. while the phe125-to-ala mutation resulted in reduced rna binding, the arg134-to-ala mu ...200515650213
the disease profile of poverty: morbidity and mortality in northern uganda in the context of war, population displacement and hiv/aids.the population of gulu district (northern uganda) has been severely incapacitated by war, epidemics and social disruption. this study is aimed at describing disease patterns and trends in this area through a retrospective analysis of discharge records for 155205 in-patients of lacor hospital in the period 1992-2002. the burden of infectious diseases in childhood is overwhelming, with malaria accounting for the steepest increase in admissions. admissions for war-related injuries and malnutrition ...200515653126
generation of egfp expressing recombinant zaire ebolavirus for analysis of early pathogenesis events and high-throughput antiviral drug screening.zaire ebolavirus causes large outbreaks of severe and usually fatal hemorrhagic disease in humans for which there is no effective treatment or cure. to facilitate examination of early critical events in viral pathogenesis and to identify antiviral compounds, a recombinant zaire ebolavirus was engineered to express a foreign protein, egfp, to provide a rapid and sensitive means to monitor virus replication in infected cells. this genetically engineered virus represents the first insertion of a fo ...200515661137
a reconstituted replication and transcription system for ebola virus reston and comparison with ebola virus zaire.the only known filovirus, which presumably is not pathogenic for humans, is ebola virus (ebov) reston. when ebov reston and the highly pathogenic ebov zaire were grown in cell culture, comparison of the replication kinetics showed a clear growth impairment of ebov reston, indicating that the replication cycle of ebov reston might be delayed. in addition, the cytopathic effect caused by the virus was much milder with ebov reston than with ebov zaire. to compare replication and transcription of eb ...200515661171
potential mammalian filovirus reservoirs.ebola and marburg viruses are maintained in unknown reservoir species; spillover into human populations results in occasional human cases or epidemics. we attempted to narrow the list of possibilities regarding the identity of those reservoir species. we made a series of explicit assumptions about the reservoir: it is a mammal; it supports persistent, largely asymptomatic filovirus infections; its range subsumes that of its associated filovirus; it has coevolved with the virus; it is of small bo ...200415663841
exposure to nonhuman primates in rural cameroon.exposure to nonhuman primates has led to the emergence of important diseases, including ebola hemorrhagic fever, aids, and adult t-cell leukemia. to determine the extent of exposure to nonhuman primates, persons were examined in 17 remote villages in cameroon that represented three habitats (savanna, gallery forest, and lowland forest). questionnaire data were collected to assess whether persons kept wild animal pets; hunted and butchered wild game; had experienced bites, scratches, or injuries ...200415663844
bichat guidelines for the clinical management of haemorrhagic fever viruses and bioterrorism-related haemorrhagic fever viruses.haemorrhagic fever viruses (hfvs) are a diverse group of viruses that cause a clinical disease associated with fever and bleeding disorder. hfvs that are associated with a potential biological threat are ebola and marburg viruses (filoviridae), lassa fever and new world arenaviruses (machupo, junin, guanarito and sabia viruses) (arenaviridae), rift valley fever (bunyaviridae) and yellow fever, omsk haemorrhagic fever, and kyanasur forest disease (flaviviridae). in terms of biological warfare con ...200415677844
role of ebola virus secreted glycoproteins and virus-like particles in activation of human macrophages.ebola virus, a member of the family filoviridae, causes one of the most severe forms of viral hemorrhagic fever. in the terminal stages of disease, symptoms progress to hypotension, coagulation disorders, and hemorrhages, and there is prominent involvement of the mononuclear phagocytic and reticuloendothelial systems. cells of the mononuclear phagocytic system are primary target cells and producers of inflammatory mediators. ebola virus efficiently produces four soluble glycoproteins during infe ...200515681442
the role of wildlife in emerging and re-emerging zoonoses.there are huge numbers of wild animals distributed throughout the world and the diversity of wildlife species is immense. each landscape and habitat has a kaleidoscope of niches supporting an enormous variety of vertebrate and invertebrate species, and each species or taxon supports an even more impressive array of macro- and micro-parasites. infectious pathogens that originate in wild animals have become increasingly important throughout the world in recent decades, as they have had substantial ...200415702716
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