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characterization of the l gene and 5' trailer region of ebola virus.the nucleotide sequences of the l gene and 5' trailer region of ebola virus strain mayinga (subtype zaire) have been determined, thus completing the sequence of the ebola virus genome. the putative transcription start signal of the l gene was identical to the determined 5' terminus of the l mrna (5' gaggaagauuaa) and showed a high degree of similarity to the corresponding regions of other ebola virus genes. the 3' end of the l mrna terminated with 5' auuauaaaaaa, a sequence which is distinct fro ...199910073695
ebola virus selectively inhibits responses to interferons, but not to interleukin-1beta, in endothelial cells.ebola virus infection is highly lethal and leads to severe immunosuppression. in this study, we demonstrate that infection of human umbilical vein endothelial cells (huvecs) with ebola virus zaire (ez) suppressed basal expression of the major histocompatibility complex class i (mhc i) family of proteins and inhibited the induction of multiple genes by alpha interferon (ifn-alpha) and ifn-gamma, including those coding for mhc i proteins, 2'-5' oligoadenylate synthetase [2'-5'(a)n], and ifn regula ...199910074208
core structure of the envelope glycoprotein gp2 from ebola virus at 1.9-a resolution.ebola virions contain a surface transmembrane glycoprotein (gp) that is responsible for binding to target cells and subsequent fusion of the viral and host-cell membranes. gp is expressed as a single-chain precursor that is posttranslationally processed into the disulfide-linked fragments gp1 and gp2. the gp2 subunit is thought to mediate membrane fusion. a soluble fragment of the gp2 ectodomain, lacking the fusion-peptide region and the transmembrane helix, folds into a stable, highly helical s ...199910077567
[ebola hemorrhagic fever and marburg virus disease: their virological and clinical aspects]. 199910088344
[effects of repeated administration of ebola virus preparations on dynamics of immunologic parameters]. 199910190013
defective humoral responses and extensive intravascular apoptosis are associated with fatal outcome in ebola virus-infected patients.ebola virus is very pathogenic in humans. it induces an acute hemorrhagic fever that leads to death in about 70% of patients. we compared the immune responses of patients who died from ebola virus disease with those who survived during two large outbreaks in 1996 in gabon. in survivors, early and increasing levels of igg, directed mainly against the nucleoprotein and the 40-kda viral protein, were followed by clearance of circulating viral antigen and activation of cytotoxic t cells, which was i ...199910202932
ebola: the virus and the disease. 199910207327
[intramuscular injections in sub-saharan african children, apropos of a frequently misunderstood pathology: the complications related to intramuscular quinine injections].in west africa, the incidence of poliomyelitis has decreased in the past years thanks to intensive immunization campaigns. nowadays intramuscular injection is the main reason for paralysis of the legs in african children as well as attendance at rehabilitation centres. intramuscular injection of quinine is the most frequently reported. faced with the lack of sterile material, health workers do not rationalize the use of intramuscular injections. although the use of the same needle has decreased, ...199910214519
sicarius (six-eyed crab spider): a homeopathic treatment for ebola haemorrhagic fever and disseminated intravascular coagulation? 199910228601
structural basis for membrane fusion by enveloped viruses.enveloped viruses such as hiv-1, influenza virus, and ebola virus express a surface glycoprotein that mediates both cell attachment and fusion of viral and cellular membranes. the membrane fusion process leads to the release of viral proteins and the rna genome into the host cell, initiating an infectious cycle. this review focuses on the hiv-1 gp41 membrane fusion protein and discusses the structural similarities of viral membrane fusion proteins from diverse families such as retroviridae (hiv- ...199910332732
are the fusion processes involved in birth, life and death of the cell depending on tilted insertion of peptides into membranes?various peptide segments have been modeled as asymmetric amphipathic alpha-helices. theoretical calculations have shown that they insert obliquely into model membranes. they have been named "tilted peptides". molecular modeling results reported here also evidence the presence of tilted peptides in adm-1 protein of caenorhabditis elegans that may be involved in fusion events, in meltrin alpha, a protein implicated in myoblast fusion, in hemagglutinin of influenza virus, in the e2 glycoprotein of ...199910339392
leptospirosis and ebola virus infection in five gold-panning villages in northeastern gabon.an exhaustive epidemiologic and serologic survey was carried out in five gold-panning villages situated in northeastern gabon to estimate the degree of exposure of to leptospirosis and ebola virus. the seroprevalence was 15.7% for leptospirosis and 10.2% for ebola virus. sixty years after the last seroepidemiologic survey of leptospirosis in gabon, this study demonstrates the persistence of this infection among the endemic population and the need to consider it as a potential cause of hemorrhagi ...199910348236
ebola virus can be effectively neutralized by antibody produced in natural human infection.the activity of antibodies against filoviruses is poorly understood but has important consequences for vaccine design and passive prophylaxis. to investigate this activity, a panel of recombinant human monoclonal antibodies to ebola virus antigens was isolated from phage display libraries constructed from rna from donors who recovered from infection in the 1995 ebola virus outbreak in kikwit, democratic republic of congo. antibodies reactive with nucleoprotein (np), envelope glycoprotein (gp), a ...199910364354
threat to humans from virus infections of non-human primates.several hundred distinct non human primate species are recognised, and they are likely to harbour a similar range of viruses to humans. simians such as cynomolgus and rhesus macaques, african green monkeys, and marmosets are widely used for biomedical research, but despite this extensive close contact very few simian viruses have been shown to pose a threat of infection or illness to humans. herpesvirus simiae is the best recognised zoonotic hazard of simians. it is an alphaherpes virus of asiat ...199710398488
suppressive effect of ebola virus on t cell proliferation in vitro is provided by a 125-kda gp viral protein.ebola virus (ev), an extremely infectious pathogen, causes severe hemorrhagic fever in humans and nonhuman primates. the disease pattern includes damage of parenchymal cells of vital organs in association with hemostatic and immune disorders. vaccination with the inactivated virions does not provide an effective immune protection against the disease. the inadequate immune response may be directly caused by the virus, and, hence, it may presumably be crucial in the pathogenic process and prophyla ...199910424429
cytotoxic t lymphocytes to ebola zaire virus are induced in mice by immunization with liposomes containing lipid a.an eight amino acid sequence (telrtfsi) present in the carboxy terminal end (aa 577-584) of membrane-anchored gp, the major structural protein of ebola virus, was identified as an h-2k-specific murine cytotoxic t cell epitope. cytotoxic t lymphocytes (ctls) to this epitope were induced by immunizing b10.br mice intravenously with either irradiated ebola virus or with irradiated ebola virus encapsulated in liposomes containing lipid a. the ctl response induced by irradiated ebola virus could not ...199910462234
the glycoproteins of marburg and ebola virus and their potential roles in pathogenesis.filoviruses cause systemic infections that can lead to severe hemorrhagic fever in human and non-human primates. the primary target of the virus appears to be the mononuclear phagocytic system. as the virus spreads through the organism, the spectrum of target cells increases to include endothelial cells, fibroblasts, hepatocytes, and many other cells. there is evidence that the filovirus glycoprotein plays an important role in cell tropism, spread of infection, and pathogenicity. biosynthesis of ...199910470276
mutational analysis of the putative fusion domain of ebola virus glycoprotein.ebola viruses contain a single glycoprotein (gp) spike, which functions as a receptor binding and membrane fusion protein. it contains a highly conserved hydrophobic region (amino acids 524 to 539) located 24 amino acids downstream of the n terminus of the ebola virus gp2 subunit. comparison of this region with the structural features of the transmembrane subunit of avian retroviral gps suggests that the conserved ebola virus hydrophobic region may, in fact, serve as the fusion peptide. to test ...199910482652
[emergence of "new" viral zoonoses].in the last two to three decades a significant increase of viral zoonotic infections was observed. these zoonoses are not only newly (or previously unrecognized) emerging diseases, but also due to the reappearance of diseases thought to have been defeated (re-emerging diseases). "new" viral diseases can arise when viruses broaden their host-range (monkey poxvirus; equine morbillivirus), or can be a consequence of intrinsic properties of the virus itself, such as high mutation rates (influenza a ...199910488638
ebola virus defective interfering particles and persistent infection.ebola virus (zaire subtype) is associated with high mortality disease outbreaks that commonly involve human to human transmission. surviving patients can show evidence of prolonged virus persistence. the potential for ebola virus to generate defective interfering (di) particles and establish persistent infections in tissue culture was investigated. it was found that serial undiluted virus passages quickly resulted in production of an evolving population of virus minireplicons possessing both del ...199910489346
lassa and mopeia virus replication in human monocytes/macrophages and in endothelial cells: different effects on il-8 and tnf-alpha gene expression.cells of the mononuclear and endothelial lineages are targets for viruses which cause hemorrhagic fevers (hf) such as the filoviruses marburg and ebola, and the arenaviruses lassa and junin. a recent model of marburg hf pathogenesis proposes that virus directly causes endothelial cell damage and macrophage release of tnf-alpha which increases the permeability of endothelial monolayers [feldmann et al. , 1996]. we show that lassa virus replicates in human monocytes/macrophages and endothelial cel ...199910534741
[effect of an infections dose of the ebola virus on survivability and immunologic indicators in guinea pigs].analysis of the time course of immunological parameters in intact guinea pigs and animals immunized with inactivated ebola virus (ev) inoculated with high and low doses of ev strain lethal for guinea pigs showed that high doses induced a higher resistance of the lymphocytic component of immunity than low doses, but activation of the neutrophil phagocytosis was far less expressed after high doses than after low ones. this indicates a qualitative effect of the infective dose of ev on the developme ...199910544449
identification of ebola virus sequences present as rna or dna in organs of terrestrial small mammals of the central african republic.the life cycle of the ebola (ebo) virus remains enigmatic. we tested for ebo virus in the organs of 242 small mammals captured during ecological studies in the central african republic. ebo virus glycoprotein or polymerase gene sequences were detected by reverse transcription pcr in rna extracts of the organs of seven animals and by pcr in dna extract of one animal. neither live virus nor virus antigen was detected in any organ sample. direct sequencing of amplicons identified the virus as being ...199910580275
unsafe injections in the developing world and transmission of bloodborne pathogens: a review.unsafe injections are suspected to occur routinely in developing countries. we carried out a literature review to quantify the prevalence of unsafe injections and to assess the disease burden of bloodborne infections attributable to this practice. quantitative information on injection use and unsafe injections (defined as the reuse of syringe or needle between patients without sterilization) was obtained by reviewing the published literature and unpublished who reports. the transmissibility of h ...199910593026
delta-peptide is the carboxy-terminal cleavage fragment of the nonstructural small glycoprotein sgp of ebola virus.in the present study we have investigated processing and maturation of the nonstructural small glycoprotein (sgp) of ebola virus. when sgp expressed from vaccinia virus vectors was analyzed by pulse-chase experiments using sds-page under reducing conditions, the mature form and two different precursors have been identified. first, the endoplasmic reticulum form sgp(er), full-length sgp with oligomannosidic n-glycans, was detected, sgp(er) was then replaced by the golgi-specific precursor pre-sgp ...199910603327
ebola virus secretory glycoprotein (sgp) diminishes fc gamma riiib-to-cr3 proximity on neutrophils.previous studies have shown that ebola virus' secretory glycoprotein (sgp) binds to fc gamma riiib (cd16b) and inhibits l-selectin shedding. in this study, we test the hypothesis that sgp interferes with the physical linkage between cr3 and fc gamma riiib. neutrophils were stained with rhodamine-conjugated anti-cd16b mab (which does not inhibit sgp binding) and fluorescein-conjugated anti-cr3 mab reagents and then incubated in media with or without sgp. physical proximity between fluorochrome-la ...200010623844
latest developments in gene transfer technology: achievements, perspectives, and controversies over therapeutic applications.over the last decade, more than 300 phase i and phase ii gene-based clinical trials have been conducted worldwide for the treatment of cancer and monogenic disorders. lately, these trials have been extended to the treatment of aids and, to a lesser extent, cardiovascular diseases. there are 27 currently active gene therapy protocols for the treatment of hiv-1 infection in the usa. preclinical studies are currently in progress to evaluate the possibility of increasing the number of gene therapy c ...200010661569
unexpected ebola virus in a tertiary setting: clinical and epidemiologic aspects.to describe the clinical manifestations of viral hemorrhagic fever, and to increase clinicians' awareness and knowledge of these illnesses.200010667531
diagnosis of ebola haemorrhagic fever by rt-pcr in an epidemic setting.this study reports the first field evaluation of a new diagnostic technique for ebola virus disease with sensitivity and specificity. ebola virus causes rare but fulminating outbreaks in equatorial africa. rapid differentiation from other infections is critical for timely implementation of public health measures. patients usually die before developing antibodies, necessitating rapid virus detection. a reverse transcriptase-polymerase chain reaction (rt-pcr) assay was developed, implemented and e ...200010686031
epitopes involved in antibody-mediated protection from ebola virus.to determine the ability of antibodies to provide protection from ebola viruses, monoclonal antibodies (mabs) to the ebola glycoprotein were generated and evaluated for efficacy. we identified several protective mabs directed toward five unique epitopes on ebola glycoprotein. one of the epitopes is conserved among all ebola viruses that are known to be pathogenic for humans. some protective mabs were also effective therapeutically when administered to mice 2 days after exposure to lethal ebola v ...200010698744
apoptosis induced in vitro and in vivo during infection by ebola and marburg viruses.induction of apoptosis has been documented during infection with a number of different viruses. in this study, we used transmission electron microscopy (tem) and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling to investigate the effects of ebola and marburg viruses on apoptosis of different cell populations during in vitro and in vivo infections. tissues from 18 filovirus-infected nonhuman primates killed in extremis were evaluated. apoptotic lymphocyte ...200010701687
immune and pathophysiological processes in baboons experimentally infected with ebola virus adapted to guinea pigs.the dynamics of pathophysiological and immunological parameters monitored in monkeys papio hamadryas infected with the guinea pig-adapted ebola virus strain demonstrated that this viral strain preserved its virulence for monkeys and caused the disease with characteristic features similar to those caused by non-adapted ebola virus. however, certain previously unknown patterns have been observed: (1) prolongation of the febrile period by two days; (2) extended period was characterized by stability ...200010714441
ebola and marburg virus antibody prevalence in selected populations of the central african republic.with the natural history of the filovirus family seemingly unknown, filovirus ecology in its natural environment remains a rudimentary field of research. in order to investigate the maintenance cycle of filovirus in central africa, a study was conducted within the rain forest of the central african republic. the epidemiological study determines the frequency and distribution of filovirus seroprevalence in a selected human population. using an elisa, serum samples from pygmy and non-pygmy populat ...200010717539
ebola haemorrhagic fever--a review. 200010762106
distinct mechanisms of entry by envelope glycoproteins of marburg and ebola (zaire) viruses.since the marburg (mbg) and ebola (ebo) viruses have sequence homology and cause similar diseases, we hypothesized that they associate with target cells by similar mechanisms. pseudotype viruses prepared with a luciferase-containing human immunodeficiency virus type 1 backbone and packaged by the mbg virus or the zaire subtype ebo virus glycoproteins (gp) mediated infection of a comparable wide range of mammalian cell types, and both were inhibited by ammonium chloride. in contrast, they exhibit ...200010775638
evolutionary conservation of the membrane fusion machine.recent structural studies of proteins mediating membrane fusion reveal intriguing similarities between diverse viral and mammalian systems. particularly striking is the close similarity between the transmembrane envelope glycoproteins from the retrovirus htlv-1 and the filovirus ebola. these similarities suggest similar mechanisms of membrane fusion. the model that fits most currently available data suggests fusion activation in viral systems is driven by a symmetrical conformational change trig ...199910794590
treatment of lethal ebola virus infection in mice with a single dose of an s-adenosyl-l-homocysteine hydrolase inhibitor.ebola zaire virus causes lethal hemorrhagic fever in humans, for which there is no effective treatment. a variety of adenosine analogues inhibit the replication of ebola virus in vitro, probably by blocking the cellular enzyme, s-adenosyl-l-homocysteine hydrolase, thereby indirectly limiting methylation of the 5' cap of viral messenger rna. we previously observed that adult, immunocompetent mice treated thrice daily for 9 days with 2.2-20 mg/kg of an adenosine analogue, carbocyclic 3-deazaadenos ...200010809022
crystallization and preliminary x-ray analysis of the matrix protein from ebola virus.the matrix protein from ebola virus is a membrane-associated molecule that plays a role in viral budding. despite its functional similarity to other viral matrix proteins, it displays no sequence similarity and hence may have a distinct fold. x-ray diffraction quality crystals of the ebola vp40 matrix protein were grown by the hanging-drop vapour-diffusion method. the crystals belong to the monoclinic space group c2, with unit-cell parameters a = 64.4, b = 91.1, c = 47.9 a, beta = 96.3 degrees. ...200010818356
antibodies in human infectious disease.investigation of human antibody responses to viral pathogens at the molecular level is revealing novel aspects of the interplay of viruses with the humoral immune system. in viral infection, at least two types of human antibody responses exist: a response to mature envelope on virions that is neutralizing and a response to immature forms of envelope (viral debris) that is not. many pathogens have, to varying degrees, evolved envelopes to minimize antibody responses against epitopes exposed on th ...200010852127
marburg and ebola virus infections in laboratory non-human primates: a literature review.background and purpose: several non-human primate species are used as laboratory animals for various types of studies. although importation of monkeys may introduce different diseases, special attention has recently been drawn to marburg and ebola viruses. this review presented here discusses the potential risk of these viruses for persons working with non-human primates as laboratory animals by focusing on epidemiology, virology, symptoms, pathogenesis, natural reservoir, transmission, quaranti ...200010857001
structural characterization and membrane binding properties of the matrix protein vp40 of ebola virus.the matrix protein vp40 of ebola virus is believed to play a central role in viral assembly as it targets the plasma membrane of infected cells and subsequently forms a tightly packed layer on the inner side of the viral envelope. expression of vp40 in escherichia coli and subsequent proteolysis yielded two structural variants differing by a c-terminal truncation 114 amino acid residues long. as indicated by chemical cross-linking studies and electron microscopy, the larger polypeptide was prese ...200010864502
[monoclonal antibodies to ebola virus: isolation, characteristics, and study of cross reactivity with marburg virus].thirteen hybridoma strains producing monoclonal antibodies (mabs) to ebola virus were prepared by fusion of ns-o mouse myeloma cells with splenocytes of balb/c mice immunized with purified and inactivated ebola virus (mayinga strain). mabs directed against viral proteins were selected and tested by elisa. protein specificity of 13 mabs was determined by immunoblotting with sds-page proteins of ebola virus. of these, 11 hybridoma mabs reacted with 116 kda protein (np) and 2 with ebola virus vp35. ...200010867995
symptomless infection with ebola virus. 200010881884
human asymptomatic ebola infection and strong inflammatory response.ebola virus is one of the most virulent pathogens, killing a very high proportion of patients within 5-7 days. two outbreaks of fulminating haemorrhagic fever occurred in northern gabon in 1996, with a 70% case-fatality rate. during both outbreaks we identified some individuals in direct contact with sick patients who never developed symptoms. we aimed to determine whether these individuals were indeed infected with ebola virus, and how they maintained asymptomatic status.200010881895
[introduction to sterilization and disinfection of medical wastes contaminated with human virus].in this paper, we describe sterilization and disinfection of medical wastes contaminated with blood borne-virus, such as ebola virus, marburg virus, crimean-congo hemorrhagic fever virus, lassa virus, hepatitis b virus and human immunodeficiency virus.200010901040
communicable disease surveillance with limited resources: the scope to link human and veterinary programmes.zoonoses are an important cause of human disease in much of africa, but limitations in current diagnosis and surveillance strategies restrict the effectiveness of control and prevention programmes. outbreaks of disease, ranging from ebola virus infection to rift valley fever, that have occurred recently in africa have demonstrated the need for improved disease surveillance and monitoring. strategies are suggested for co-ordinating human and animal disease surveillance programmes, at the district ...200010913758
recombinant rna replicons derived from attenuated venezuelan equine encephalitis virus protect guinea pigs and mice from ebola hemorrhagic fever virus.rna replicons derived from an attenuated strain of venezuelan equine encephalitis virus (vee), an alphavirus, were configured as candidate vaccines for ebola hemorrhagic fever. the ebola nucleoprotein (np) or glycoprotein (gp) genes were introduced into the vee rna downstream from the vee 26s promoter in place of the vee structural protein genes. the resulting recombinant replicons, expressing the np or gp genes, were packaged into vee replicon particles (np-vrp and gp-vrp, respectively) using a ...200010924796
identification of the ebola virus glycoprotein as the main viral determinant of vascular cell cytotoxicity and injury.here we defined the main viral determinant of ebola virus pathogenicity; synthesis of the virion glycoprotein (gp) of ebola virus zaire induced cytotoxic effects in human endothelial cells in vitro and in vivo. this effect mapped to a serine-threonine-rich, mucin-like domain of this type i transmembrane glycoprotein, one of seven gene products of the virus. gene transfer of gp into explanted human or porcine blood vessels caused massive endothelial cell loss within 48 hours that led to a substan ...200010932225
crystal structure of the matrix protein vp40 from ebola virus.ebola virus maturation occurs at the plasma membrane of infected cells and involves the clustering of the viral matrix protein vp40 at the assembly site as well as its interaction with the lipid bilayer. here we report the x-ray crystal structure of vp40 from ebola virus at 2.0 a resolution. the crystal structure reveals that ebola virus vp40 is topologically distinct from all other known viral matrix proteins, consisting of two domains with unique folds, connected by a flexible linker. the c-te ...200010944105
differential induction of cellular detachment by envelope glycoproteins of marburg and ebola (zaire) viruses.human infection by marburg (mbg) or ebola (ebo) virus is associated with fatal haemorrhagic fevers. while these filoviruses may both incite disease as a result of explosive virus replication, we hypothesized that expression of individual viral gene products, such as the envelope glycoprotein (gp), may directly alter target cells and contribute to pathogenesis. we found that expression of ebo gp in 293t cells caused significant levels of cellular detachment in the absence of cell death or virus r ...200010950971
critical role for the cysteines flanking the internal fusion peptide of avian sarcoma/leukosis virus envelope glycoprotein.the transmembrane subunit (tm) of the envelope glycoprotein (env) of the oncovirus avian sarcoma/leukosis virus (aslv) contains an internal fusion peptide flanked by two cysteines (c9 and c45). these cysteines, as well as an analogous pair in the ebola virus gp glycoprotein, are predicted to be joined by a disulfide bond. to examine the importance of these cysteines, we mutated c9 and c45 in the aslv subtype a env (enva), individually and together, to serine. all of the mutant envas formed trime ...200011000247
the poison center role in biological and chemical terrorism.nuclear, biological and chemical (nbc) terrorism countermeasures are a major priority with municipalities, healthcare providers, and the federal government. significant resources are being invested to enhance civilian domestic preparedness by conducting education at every response level in anticipation of a nbc terroristic incident. the key to a successful response, in addition to education, is integration of efforts as well as thorough communication and understanding the role that each agency w ...200011003124
passive immunity in prevention and treatment of infectious diseases.antibodies have been used for over a century in the prevention and treatment of infectious disease. they are used most commonly for the prevention of measles, hepatitis a, hepatitis b, tetanus, varicella, rabies, and vaccinia. although their use in the treatment of bacterial infection has largely been supplanted by antibiotics, antibodies remain a critical component of the treatment of diptheria, tetanus, and botulism. high-dose intravenous immunoglobulin can be used to treat certain viral infec ...200011023960
functional importance of the coiled-coil of the ebola virus glycoprotein.ebola virus contains a single glycoprotein (gp) that is responsible for receptor binding and membrane fusion and is proteolytically cleaved into disulfide-linked gp1 and gp2 subunits. the gp2 subunit possesses a coiled-coil motif, which plays an important role in the oligomerization and fusion activity of other viral gps. to determine the functional significance of the coiled-coil motif of gp2, we examined the effects of peptides corresponding to the coiled-coil motif of gp2 on the infectivity o ...200011024148
the ebola virus vp35 protein functions as a type i ifn antagonist.an assay has been developed that allows the identification of molecules that function as type i ifn antagonists. using this assay, we have identified an ebola virus-encoded inhibitor of the type i ifn response, the ebola virus vp35 protein. the assay relies on the properties of an influenza virus mutant, influenza delns1 virus, which lacks the ns1 orf and, therefore, does not produce the ns1 protein. when cells are infected with influenza delns1 virus, large amounts of type i ifn are produced. a ...200011027311
[circulation of virus and interspecies contamination in wild animals].paradoxically, just when we have succeeded in eradicating and/or bringing under control the major viral infections (smallpox, poliomyelitis, measles) numerous viral infections are emerging in man and in animals. changes in our social environment, technological and ecological equilibrium have facilitated this phenomenon. furthermore, certain of these viruses have demonstrated an almost unlimited capacity to adapt genetically to environmental change. hiv has already infected 40 million individuals ...200011030047
[forest ecosystems and ebola virus].despite data collected since the emergence of the ebola virus in 1976, its natural transmission cycle and especially the nature of its reservoirs and means of transmission are still an enigma. this means that effective epidemiological surveillance and prevention are difficult to implement. the location of outbreak areas has suggested that the reservoir and the transmission cycle of the ebola virus are closely linked to the rainforest ecosystem. the fact that outbreaks seldom occur suggests the p ...200011030051
molecular characterization of guinea pig-adapted variants of ebola virus.serial passage of initially nonlethal ebola virus (ebov) in outbred guinea pigs resulted in the selection of variants with high pathogenicity. nucleotide sequence analysis of the complete genome of the guinea pig-adapted variant 8mc revealed that it differed from wild-type virus by eight mutations. no mutations were identified in nontranscribed regions, including leader, trailer, and intragenic sequences. among noncoding regions the only base change was found in the vp30 gene. two silent base ch ...200011062045
a role for ubiquitin ligase recruitment in retrovirus release.retroviral gag polyproteins have specific regions, commonly referred to as late assembly (l) domains, which are required for the efficient separation of assembled virions from the host cell. the l domain of hiv-1 is in the c-terminal p6(gag) domain and contains an essential p(t/s)ap core motif that is widely conserved among lentiviruses. in contrast, the l domains of oncoretroviruses such as rous sarcoma virus (rsv) have a more n-terminal location and a ppxy core motif. in the present study, we ...200011087860
a ppxy motif within the vp40 protein of ebola virus interacts physically and functionally with a ubiquitin ligase: implications for filovirus budding.vp40, the putative matrix protein of both ebola and marburg viruses, possesses a conserved proline-rich motif (py motif) at its n terminus. we demonstrate that the vp40 protein can mediate its own release from mammalian cells, and that the py motif is important for this self-exocytosis (budding) function. in addition, we used western-ligand blotting to demonstrate that the py motif of vp40 can mediate interactions with specific cellular proteins that have type i ww-domains, including the mammali ...200011095724
comments on the article "marburg and ebola virus infections in laboratory non-human primates: a literature review". soren schou and axel kornerup hansen. comparative medicine, 2000. 50:108-123. 200011099125
epidemiology of the ebola virus: facts and hypotheses.marburg and ebola viruses are emerging pathogens recognized since 1967, and in 1976, when they were first identified. these viruses are the only members of the filoviridae family. they cause severe, frequently fatal, hemorrhagic fever. each genus includes some serotypes with the distinctive characteristics to cause high mortality rate during outbreaks. the ebola-zaire subtype is the most lethal variant. the epidemiology of human pathogenic filovirus is reviewed in this paper considering the most ...199811103018
downregulation of beta1 integrins by ebola virus glycoprotein: implication for virus entry.filoviruses, including ebola virus, are cytotoxic. to investigate the role of the ebola virus glycoprotein (gp) in this cytopathic effect, we transiently expressed the gp in human kidney 293t cells. expression of wild-type gp, but not the secretory form of the molecule lacking a membrane anchor, induced rounding and detachment of the cells, as did a chimeric gp containing its ectodomain and influenza virus hemagglutinin transmembrane-cytoplasmic domain. these results indicate that the gp ectodom ...200011112476
fighting the ebola virus. 200011117724
development of a preventive vaccine for ebola virus infection in primates.outbreaks of haemorrhagic fever caused by the ebola virus are associated with high mortality rates that are a distinguishing feature of this human pathogen. the highest lethality is associated with the zaire subtype, one of four strains identified to date. its rapid progression allows little opportunity to develop natural immunity, and there is currently no effective anti-viral therapy. therefore, vaccination offers a promising intervention to prevent infection and limit spread. here we describe ...200011117750
membrane association induces a conformational change in the ebola virus matrix protein.the matrix protein vp40 from ebola virus is targeted to the plasma membrane, where it is thought to induce assembly and budding of virions through its association with the lipid bilayer. ebola virus vp40 is expressed as a monomeric molecule in solution, consisting of two loosely associated domains. here we show that a c-terminal truncation of seven residues destabilizes the monomeric closed conformation and induces spontaneous hexamerization in solution, as indicated by chemical cross-linking an ...200011118208
dermatological infectiology--quo vadis? symposium, ruhr-university, september 29-30, 2000. abstracts.infectious diseases remain a major cause of morbidity and mortality in the year 2000. 17 million deaths per year or roughly a third of all deaths are caused by infections. infectious diseases also pose a serious economic threat. while many well-established pathogens have not been contained several new infectious agents have been discovered within the past 27 years which include rotavirus, legionella, hiv, ebola, campylobacter, helicobacter, nipah, hhv8, hepatitis c, and many others. additionally ...200011121370
enzyme-linked immunosorbent assays for detection of antibodies to ebola and marburg viruses using recombinant nucleoproteins.the full-length nucleoprotein (np) of ebola virus (ebo) was expressed as a his-tagged recombinant protein (his-ebo-np) by a baculovirus system. carboxy-terminal halves of nps of ebo and marburg virus (mbg) were expressed as glutathione s-transferase-tagged recombinant proteins in an escherichia coli system. the antigenic regions on the nps of ebo and mbg were determined by both western blotting and enzyme-linked immunosorbent assay (elisa) to be located on the c-terminal halves. the c-terminal 1 ...200111136739
the rhetorical construction of the predatorial virus: a burkian analysis of nonfiction accounts of the ebola virus.over the past 5 years, a new subgenre of horror films, referred to as plague films, has turned our focus to the threat of a hemorrhagic viral pandemic, comparable to the spanish flu epidemic of 1916. based on the ebola viral outbreaks of 1976, various writers have presented their accounts under the guise of increasing interest and prevention strategies. disregarding inappropriate health care practices as the cause of these epidemics, accountability is refocused onto the rhetorically constructed, ...200111147163
ebola virus glycoprotein: proteolytic processing, acylation, cell tropism, and detection of neutralizing antibodies.using the vesicular stomatitis virus (vsv) pseudotype system, we studied the functional properties of the ebola virus glycoprotein (gp). amino acid substitutions at the gp cleavage site, which reduce glycoprotein cleavability and viral infectivity in some viruses, did not appreciably change the infectivity of vsv pseudotyped with gp. likewise, removal of two acylated cysteine residues in the transmembrane region of gp showed no discernible effects on infectivity. although most filoviruses are be ...200111152533
immunofluorescence method for detection of ebola virus immunoglobulin g, using hela cells which express recombinant nucleoprotein.a novel recombinant baculovirus which expresses ebola virus (ebo) nucleoprotein (np) under the control of the cytomegalovirus immediate-early promoter was constructed. hela cells abortively infected with the baculovirus expressed ebo np, and this was used as an immunofluorescent (if) antigen to detect ebo immunoglobulin g (igg) antibody. this if method has high efficacy in detecting ebo igg antibody in clinical specimens, indicating its usefulness in the diagnosis of ebo infections and seroepide ...200111158150
infectivity-enhancing antibodies to ebola virus glycoprotein.ebola virus causes severe hemorrhagic fever in primates, resulting in mortality rates of up to 100%, yet there are no satisfactory biologic explanations for this extreme virulence. here we show that antisera produced by dna immunization with a plasmid encoding the surface glycoprotein (gp) of the zaire strain of ebola virus enhances the infectivity of vesicular stomatitis virus pseudotyped with the gp. substantially weaker enhancement was observed with antiserum to the gp of the reston strain, w ...200111160735
risks and prevention of nosocomial transmission of rare zoonotic diseases.americans are increasingly exposed to exotic zoonotic diseases through travel, contact with exotic pets, occupational exposure, and leisure pursuits. appropriate isolation precautions are required to prevent nosocomial transmission of rare zoonotic diseases for which person-to-person transmission has been documented. this minireview provides guidelines for the isolation of patients and management of staff exposed to the following infectious diseases with documented person-to-person transmission: ...200111170953
implication of the proprotein convertases furin, pc5 and pc7 in the cleavage of surface glycoproteins of hong kong, ebola and respiratory syncytial viruses: a comparative analysis with fluorogenic peptides.fluorogenic peptides encompassing the processing sites of envelope glycoproteins of the infectious influenza a hong kong virus (hkv), ebola virus (ebov) and respiratory syncytial virus (rsv) were tested for cleavage by soluble recombinants of the proprotein convertases furin, pc5 and pc7. kinetic studies with these intramolecularly quenched fluorogenic peptides revealed selective cleavages at the physiological dibasic sites. the hkv peptide is cleaved by both furin and pc5 with similar efficacy; ...200111171050
emerging diseases. on the trail of ebola and marburg viruses. 200011184732
public health implications of emerging zoonoses.many new, emerging and re-emerging diseases of humans are caused by pathogens which originate from animals or products of animal origin. a wide variety of animal species, both domestic and wild, act as reservoirs for these pathogens, which may be viruses, bacteria or parasites. given the extensive distribution of the animal species affected, the effective surveillance, prevention and control of zoonotic diseases pose a significant challenge. the authors describe the direct and indirect implicati ...200011189723
infections by viruses of the families bunyaviridae and filoviridae.rift valley fever is the most important bunyaviral disease of animals in africa. the virus, transmitted by mosquitoes, causes abortions and mortality in young animals in addition to haemorrhagic fevers in humans. although vaccines against this virus are available, the uses of these vaccines are limited because of deleterious effects or incomplete protection, justifying further studies to improve the existing vaccines or to develop others. nairobi sheep disease is transmitted by ticks. the diseas ...200011189728
the viral transmembrane superfamily: possible divergence of arenavirus and filovirus glycoproteins from a common rna virus ancestor.recent studies of viral entry proteins from influenza, measles, human immunodeficiency virus, type 1 (hiv-1), and ebola virus have shown, first with molecular modeling, and then x-ray crystallographic or other biophysical studies, that these disparate viruses share a coiled-coil type of entry protein.200111208257
experimental vaccine protects monkeys against ebola virus. 200311217674
in vitro dissection of the membrane and rnp binding activities of influenza virus m1 protein.spontaneous proteolysis of influenza virus m1 protein during crystallisation has defined an n-terminal domain of amino acids 1--164. full-length m1, the n-terminal domain, and the c-terminal part of m1 (residues 165--252) were produced in escherichia coli. in vitro tests showed that only full-length m1 and its n-terminal domain bind to negatively charged liposomes and that only full-length m1 and its c-terminal part bind to rnp. however, only full-length m1 had transcription inhibition activity. ...200111222100
protection from ebola virus mediated by cytotoxic t lymphocytes specific for the viral nucleoprotein.cytotoxic t lymphocytes (ctls) are proposed to be critical for protection from intracellular pathogens such as ebola virus. however, there have been no demonstrations that protection against ebola virus is mediated by ebola virus-specific ctls. here, we report that c57bl/6 mice vaccinated with venezuelan equine encephalitis virus replicons encoding the ebola virus nucleoprotein (np) survived lethal challenge with ebola virus. vaccination induced both antibodies to the np and a major histocompati ...200111222689
apoptosis in fatal ebola infection. does the virus toll the bell for immune system?in fatal ebola virus hemorrhagic fever massive intravascular apoptosis develops rapidly following infection and progressing relentlessly until death. while data suggest that t lymphocytes are mainly deleted by apoptosis in pbmc of human fatal cases, experimental ebola infection in animal models have shown some evidence of destruction of lymphocytes in spleen and lymph nodes probably involving both t and b cells. nevertheless, we are able to conclude from the accumulated evidence that early inter ...200011227491
recovery of infectious ebola virus from complementary dna: rna editing of the gp gene and viral cytotoxicity.to study the mechanisms underlying the high pathogenicity of ebola virus, we have established a system that allows the recovery of infectious virus from cloned cdna and thus permits genetic manipulation. we created a mutant in which the editing site of the gene encoding envelope glycoprotein (gp) was eliminated. this mutant no longer expressed the nonstructural glycoprotein sgp. synthesis of gp increased, but most of it accumulated in the endoplasmic reticulum as immature precursor. the mutant w ...200111239157
[ebola and marburg virus: entomologic hypothesis to confirm]. 200011258069
2001 aspet otto krayer award lecture. molecular targets for antiviral agents.there are a number of virus-specific processes within the virus replicative cycle or virus-infected cell that have proven to be attractive targets for chemotherapeutic intervention, i.e., virus adsorption and entry into the cells, reverse (rna --> dna) transcription, viral dna polymerization, and cellular enzymatic reactions that are associated with viral dna and rna synthesis and viral mrna maturation (i.e., methylation). a variety of chemotherapeutic agents, both nucleoside (and nucleotide) an ...200111259521
human immunodeficiency virus type 1 particles pseudotyped with envelope proteins that fuse at low ph no longer require nef for optimal infectivity.we have investigated the effects of nef on infectivity in the context of various viral envelope proteins. these experiments were performed with a minimal vector system where nef is the only accessory protein present. our results support the hypothesis that the route of entry influences the ability of nef to enhance human immunodeficiency virus (hiv) infectivity. we show that hiv particles pseudotyped with ebola virus glycoprotein or vesicular stomatitis virus glycoprotein (vsv-g), which fuse at ...200111264394
cutaneous dna vaccination against ebola virus by particle bombardment: histopathology and alteration of cd3-positive dendritic epidermal cells.we analyzed the localization of gold particles, expression of immunogenic protein, and histopathologic changes after vaccinating guinea pigs and mice with a dna vaccine to the ebola virus glycoprotein administered by cutaneous particle bombardment. gold particles were deposited in all layers of the epidermis and in the dermis. those in the epidermis were lost as the damaged layers sloughed, while those in the dermis were phagocytized by macrophages. glycoprotein was demonstrated by immunohistoch ...200111280377
ebola virus glycoprotein demonstrates differential cellular localization in infected cell types of nonhuman primates and guinea pigs.in vitro studies have previously shown that ebola virus glycoprotein (gp) is rapidly processed and largely released from infected cells, whereas other viral proteins, such as vp40, accumulate within cells.200111300932
passive transfer of antibodies protects immunocompetent and imunodeficient mice against lethal ebola virus infection without complete inhibition of viral replication.ebola hemorrhagic fever is a severe, usually fatal illness caused by ebola virus, a member of the filovirus family. the use of nonhomologous immune serum in animal studies and blood from survivors in two anecdotal reports of ebola hemorrhagic fever in humans has shown promise, but the efficacy of these treatments has not been demonstrated definitively. we have evaluated the protective efficacy of polyclonal immune serum in a mouse model of ebola virus infection. our results demonstrate that mice ...200111312335
vesicular release of ebola virus matrix protein vp40.we have analysed the expression and cellular localisation of the matrix protein vp40 from ebola virus. full-length vp40 and an n-terminal truncated construct missing the first 31 residues [vp40(31-326)] both locate to the plasma membrane of 293t cells when expressed transiently, while a c-terminal truncation of residues 213 to 326 [vp40(31-212)] shows only expression in the cytoplasm, when analysed by indirect immunofluorescence and plasma membrane preparations. in addition, we find that full-le ...200111312656
[ebola fever: an emerging disease].one of the most fatal diseases encountered by mankind so far is ebola fever. ebola fever is caused by a highly pathogenic virus from the filoviridae family which is found in nature in four different sub-types which differ among others also by their pathogenicity for man. the hitherto detected ebo sub-types are stable do not change in the course of an epidemic nor in the course of the patient's illness, nor during passage of the virus from one subject to another. the author presents a historical ...200111329728
ebola virus vp40-induced particle formation and association with the lipid bilayer.viral protein 40 (vp40) of ebola virus appears equivalent to matrix proteins of other viruses, yet little is known about its role in the viral life cycle. to elucidate the functions of vp40, we investigated its ability to induce the formation of membrane-bound particles when it was expressed apart from other viral proteins. we found that vp40 is indeed able to induce particle formation when it is expressed in mammalian cells, and this process appeared to rely on a conserved n-terminal ppxy motif ...200111333902
monocyte-derived human macrophages and peripheral blood mononuclear cells infected with ebola virus secrete mip-1alpha and tnf-alpha and inhibit poly-ic-induced ifn-alpha in vitro.ebola virus infection of humans is associated with high levels of circulating inflammatory chemokines and cytokines. we demonstrate that direct infection of human pbmc results in the induction of mcp-1, mip-1alpha, rantes, and tnf-alpha as early as 24 h p.i. in response to live virus. monocyte-derived macrophages infected with live ebola-virus secreted mip-1alpha and tnf-alpha specifically while rantes and mcp-1 were secreted by with both live or inactivated virus stimulation and do not require ...200111352664
the role of the type i interferon response in the resistance of mice to filovirus infection.adult immunocompetent mice inoculated with ebola (ebo) or marburg (mbg) virus do not become ill. a suckling-mouse-passaged variant of ebo zaire '76 ('mouse-adapted ebo-z') causes rapidly lethal infection in adult mice after intraperitoneal (i.p.) inoculation, but does not cause apparent disease when inoculated subcutaneously (s.c.). a series of experiments showed that both forms of resistance to infection are mediated by the type i interferon response. mice lacking the cell-surface ifn-alpha/bet ...200111369881
[hope for a vaccine against ebola virus]. 200111400662
the gordon wilson lecture: viruses and human disease.in many ways, ebola virus infection provides a model for understanding the toxicity of viruses and their causal role in human disease. the highly aggressive course of ebola virus infection provides a model for understanding the molecular mechanisms of viral cytotoxicity. in addition, the use of animal models and definition of immune correlates, which lead to protection, may provide lessons that are applicable to other viral infections. perhaps the greatest challenge facing biomedical science tod ...200111413785
virus membrane fusion proteins: biological machines that undergo a metamorphosis.fusion proteins from a group of widely disparate viruses, including the paramyxovirus f protein, the hiv and siv gp160 proteins, the retroviral env protein, the ebola virus gp, and the influenza virus haemagglutinin, share a number of common features. all contain multiple glycosylation sites, and must be trimeric and undergo proteolytic cleavage to be fusogenically active. subsequent to proteolytic cleavage, the subunit containing the transmembrane domain in each case has an extremely hydrophobi ...200011426696
[the worldwide challenges of "new" or reemerging communicable diseases at the dawn of the 21st century].in spite of the very significant advances made during the 20 th century in the prevention and the treatment of communicable diseases, infections are still today, even in developed countries, a major cause of morbidity and mortality. new infectious diseases have emerged (aids, legionellosis, exterotoxigenic e. coli, ebola fever), others have significantly reemerged (tuberculosis, diphtheria, bartonella infections) or have seen their geographic distribution widen considerably (dengue, hantavirus, ...200111427818
outbreak of ebola hemorrhagic fever, uganda, august 2000-january 2001. 200111428235
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
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