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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
ebola: preparing for the worst. 200111921713
[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
[the worldwide challenges of "new" or reemerging communicable diseases at the dawn of the 21st century].in the first part of this review, aids, prion diseases, hantavirus and arbovirus infections, ebola hemorrhagic fever, legionellosis, hepatitis c, enterotoxigenic escherichia coli infections, lyme disease, tuberculosis have provided alarming examples of emerging or reemerging infectious diseases. in this second part, the stress is placed on the reemergence of diphtheria and of serious streptococcal infections, on bartonelloses, chlamydia infections, fungal infections, while malaria and cholera ar ...200111468579
early immune responses accompanying human asymptomatic ebola infections.in a recent study we identified certain asymptomatic individuals infected by ebola virus (ebov) who mounted specific igg and early and strong inflammatory responses. here, we further characterized the primary immune response to ebov during the course of asymptomatic infection in humans. inflammatory responses occurred in temporal association with anti-inflammatory phase composed by soluble antagonist il-1ra, circulating tnf receptors, il-10 and cortisol. at the end of the inflammatory process, m ...200111472407
vaccine potential of ebola virus vp24, vp30, vp35, and vp40 proteins.previous vaccine efforts with ebola virus zaire (ebov-z) emphasized the potential protective efficacies of immune responses to the surface glycoprotein and the nucleoprotein. to determine whether the vp24, vp30, vp35, and vp40 proteins are also capable of eliciting protective immune responses, these genes were expressed from alphavirus replicons and used to vaccinate balb/c and c57bl/6 mice. although all of the vp proteins were capable of inducing protective immune responses, no single vp protei ...200111485406
detection of ebola viral antigen by enzyme-linked immunosorbent assay using a novel monoclonal antibody to nucleoprotein.with the increase in international traffic, the risk of introducing rare but severe infectious diseases like ebola hemorrhagic fever is increasing all over the world. however, the system for the diagnosis of ebola virus infection is available in a limited number of countries. in the present study, we developed an ebola virus antigen-detection enzyme-linked immunosorbent assay (elisa) system using a novel monoclonal antibody (mab) to the nucleoprotein (np). this antibody recognized an epitope def ...200111526161
multiplex analysis of cytokines in the blood of cynomolgus macaques naturally infected with ebola virus (reston serotype).ebola virus (ebo) causes the most severe form of viral hemorrhagic fever in humans and nonhuman primates with up to 90% of infections culminating in death. the requirement of maximum containment laboratories for ebola virus research has limited opportunities to study the pathogenesis of ebo infections. while tissue damage does occur, often it would appear not to be sufficient to explain death, indicating that soluble mediators play an important role in disease progression. in previous studies, f ...200111596094
the pathogenesis of ebola hemorrhagic fever.ebola virus causes lethal hemorrhagic disease in humans, yet there are still no satisfactory biological explanations to account for its extreme virulence. this review focuses on recent findings relevant to understanding the pathogenesis of ebola virus infection and developing vaccines and effective therapy. the available data suggest that the envelope glycoprotein and the interaction of some viral proteins with the immune system are likely to play important roles in the extraordinary pathogenici ...200111597453
symposium on marburg and ebola viruses. 200111597757
ebola hemorrhagic fever (ehf): mechanism of transmission and pathogenicity.hemorrhagic fevers represent a wide spectrum of viral infectious diseases, out-breaking mostly as epidemics, some of them being highly lethal. they range from those caused by bunyaviridae, associated with renal or pulmonary syndromes and those recently emerging and caused by the filoviridae family of thread-like viruses. among the latter, ebola hemorrhagic fever (ehf) bears the highest mortality and morbidity rates. one form of the disease has been documented only in monkeys. the human form, has ...200111598619
infection and activation of monocytes by marburg and ebola viruses.in this study we investigated the effects of marburg virus and ebola virus (species zaire and reston) infections on freshly isolated suspended monocytes in comparison to adherent macrophages under culture conditions. our data showed that monocytes are permissive for both filoviruses. as is the case in macrophages, infection resulted in the activation of monocytes which was largely independent of virus replication. the activation was triggered similarly by marburg and ebola viruses, species zaire ...200111602743
development and evaluation of a fluorogenic 5' nuclease assay to detect and differentiate between ebola virus subtypes zaire and sudan.the ability to rapidly recognize ebola virus infections is critical to quickly limit further spread of the disease. a rapid, sensitive, and specific laboratory diagnostic test is needed to confirm outbreaks of ebola virus infection and to distinguish it from other diseases that can cause similar clinical symptoms. a one-tube reverse transcription-pcr assay for the identification of ebola virus subtype zaire (ebola zaire) and ebola virus subtype sudan (ebola sudan) was developed and evaluated by ...200111682540
outbreak of ebola hemorrhagic fever uganda, august 2000-january 2001.on october 8, 2000, an outbreak of an unusual febrile illness with occasional hemorrhage and significant mortality was reported to the ministry of health (moh) in kampala by the superintendent of st. mary's hospital in lacor, and the district director of health services in the gulu district. a preliminary assessment conducted by moh found additional cases in gulu district and in gulu hospital, the regional referral hospital. on october 15, suspicion of ebola hemorrhagic fever (ehf) was confirmed ...200111686289
individual and bivalent vaccines based on alphavirus replicons protect guinea pigs against infection with lassa and ebola viruses.lassa and ebola viruses cause acute, often fatal, hemorrhagic fever diseases, for which no effective vaccines are currently available. although lethal human disease outbreaks have been confined so far to sub-saharan africa, they also pose significant epidemiological concern worldwide as demonstrated by several instances of accidental importation of the viruses into north america and europe. in the present study, we developed experimental individual vaccines for lassa virus and bivalent vaccines ...200111689649
identification, phylogeny, and evolution of retroviral elements based on their envelope genes.phylogenetic analyses of retroviral elements, including endogenous retroviruses, have relied essentially on the retroviral pol gene expressing the highly conserved reverse transcriptase. this enzyme is essential for the life cycle of all retroid elements, but other genes are also endowed with conserved essential functions. among them, the transmembrane (tm) subunit of the envelope gene is involved in virus entry through membrane fusion. it has also been reported to contain a domain, named the im ...200111689652
the model of response to viral haemorrhagic fevers of the national institute for infectious diseases "lazzaro spallanzani".viral haemorrhagic fevers (vhf) are severe and life-threatening diseases caused by a range of viruses. however, only four agents of vhf are known to be readily capable of person-to-person spread: lassa virus, crimean/congo haemorrhagic fever virus, ebola and marburg viruses. diseases caused by these viruses are endemic only in few areas in the world, most notably africa and some rural parts of the middle east and eastern europe. nonetheless, the increasing volume of international travel presents ...200111693443
recombinant monoclonal human antibodies against ebola virus. 200111712178
[antigenic structure of ebola virus vp35 protein].antigenic structure of ebola virus (ev) (strain mayinga) nucleocapsid protein vp35 was analyzed using monoclonal antibodies to ev vp35 and polyclonal antibodies to ev. ev protein vp35 was shown to have antigenic sites inducing the production of antibodies in animals. for better characterization of protein vp35 antigenic structure. ev gene encoding the full-length vp35 was cloned in vector pqe31 as a recombinant fusion protein (rec.vp35). the antigenic and immunogenic properties of rec.vp35 and e ...200111715705
genome structure of ebola virus subtype reston: differences among ebola subtypes. brief report.we determined the complete genome sequence of ebola virus subtype reston (ebo-r) in the philippines in 1996. the deduced transcriptional signals were highly conserved among ebola viruses except for the stop signal of l genes. the intergenic regions were composed of 4 to 7 nucleotides, and of 2 characteristic overlaps and a long intergenic region. the glycoprotein (gp) had several amino acid differences from ebo-r isolated in 1989 and 1992. the variety of gp sequences strongly suggests the indepe ...200111722021
hiv-1 and ebola virus: the getaway driver nabbed. 200111726960
hiv-1 and ebola virus encode small peptide motifs that recruit tsg101 to sites of particle assembly to facilitate egress.retroviral gag proteins encode sequences, termed late domains, which facilitate the final stages of particle budding from the plasma membrane. we report here that interactions between tsg101, a factor involved in endosomal protein sorting, and short peptide motifs in the hiv-1 gag late domain and ebola virus matrix (ebvp40) proteins are essential for efficient egress of hiv-1 virions and ebola virus-like particles. ebvp40 recruits tsg101 to sites of particle assembly and a short, ebvp40-derived ...200111726971
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
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
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
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
[microorganisms strike back--infectious diseases during the last 50 years].in the first half of the 20th century, improved living conditions, preventive measures, vaccines and antibiotics led to a marked reduction in morbidity and mortality from infectious diseases. it was predicted that the conquest of all infectious diseases was imminent. however, 50 years later, in 1999, they were still the major cause of disease worldwide, and caused nearly one third of all deaths (a total of 55.9 million). the eradication of smallpox in the 1970s and the approaching eradication of ...200111808014
study of the pathogenesis of ebola fever in laboratory animals with different sensitivity to this virus.pathophysiological parameters were compared in animals with different sensitivity to ebola virus infected with this virus. analysis of the results showed the differences in immune reactions underlying the difference between ebola-sensitive and ebola-resistant animals. no neutrophil activation in response to ebola virus injection was noted in ebola-sensitive animal. phagocytic activity of neutrophils in these animals inversely correlated with animal sensitivity to ebola virus. animal susceptibili ...200112152882
ebola haemorrhagic fever among hospitalised children and adolescents in northern uganda: epidemiologic and clinical observations.a unique feature of previous ebola outbreaks has been the relative sparing of children. for the first time, an out break of an unusual illness-ebola haemorrhagic fever occurred in northern uganda gulu district.200112789118
viral hemorrhagic fever hazards for travelers in africa.this short review covers 6 viral hemorrhagic fevers (vhfs) that are known to occur in africa: yellow fever, rift valley fever, crimean-congo hemorrhagic fever, lassa fever, marburg virus disease, and ebola hemorrhagic fever. all of these have at one time or another affected travelers, often the adventurous kind who are "roughing it" in rural areas, who should therefore be made aware by their physicians or travel health clinics about their potential risk of exposure to any vhf along their travel ...200111595975
[epidemics and related cultural factors for ebola hemorrhagic fever in gabon].the republic of gabon experienced epidemics of ebola hemorrhagic fever (ehf) three times between 1994 and 1997. this study aimed at exploring cultural factors related to the outbreaks.200111725529
ebola-athens preemergence? 200111388345
[ebola: second or third when it comes to the most lethal viral infections]. 200111374012
[alarmingly protracted ebola epidemics in uganda]. 200111374011
canada's ebola scare over but questions just beginning. 200111314433
role of the red cross movement in uganda's ebola outbreak. 200111285677
from the centers for disease control and prevention. outbreak of ebola hemorrhagic fever--uganda, august 2000-january 2001. 200111263418
ebola erupts again. 200111258226
outbreak of ebola haemorrhagic fever, uganda, august 2000-january 2001. 200111233580
ebola and marburg hemorrhagic fevers. 200111930600
caring for the survivors of uganda's ebola epidemic one year on. 200111684230
management of viral haemorrhagic fevers in switzerland.over the past years, there have been very few imported cases of vhf in switzerland: one confirmed and four suspected cases of ebola fever in basel in 1994, two suspected cases of ebola and lassa fevers in lausanne in 2000, and in the same year, six suspected cases of lassa fever in geneva. given the considerable diversity in the management of patients with suspected or confirmed vhf, national guidelines are needed, as well as the establishment of a national reference centre.200212631944
ebola in africa--discoveries in the past decade.within the past decade, ebola haemorrhagic fever (ehf) has been recognised for the first time in four countries. our understanding of the epidemiology, clinical aspects, laboratory diagnosis and control measures for ehf has improved considerably as a result of the outbreaks in these countries and the re-emergence that has occurred in another. the coordinated international responses to several of the large ehf outbreaks serve as models for controlling epidemics of other communicable diseases. thi ...200212631942
viral haemorrhagic fevers in europe--effective control requires a co-ordinated response.viral haemorrhagic fevers (vhf) have attracted the attention of the medical world and general public for many reasons, some based in reality and more on misinformation. they are amongst the highest profile infections in the public mind, because they are thought to be highly infectious and to kill most of their victims in a dramatic way (1,2). to add to the intrigue, mysteries remain about the source of some of the viruses involved. they emerge and re-emerge in many countries, most recently ebola ...200212631941
the outbreak and control of ebola viral haemorrhagic fever in a ugandan medical school.uganda has just experienced the largest outbreak of ebola haemorrhagic fever (ehf) ever recorded. mbarara university teaching hospital (muth) is responsible for training approximately one-third of uganda's doctors. mbarara is located in southwest uganda, 614 km from gulu, the main epicentre of the outbreak. on 23 october a patient was admitted to the medical ward of muth with an acute fever. he soon exhibited haemorrhagic symptoms and died. he was later confirmed to have suffered ebola. three mo ...200211991014
ebola-poe: a modern-day parallel of the red death? 200212508799
an outbreak of ebola in uganda.an outbreak of ebola disease was reported from gulu district, uganda, on 8 october 2000. the outbreak was characterized by fever and haemorrhagic manifestations, and affected health workers and the general population of rwot-obillo, a village 14 km north of gulu town. later, the outbreak spread to other parts of the country including mbarara and masindi districts. response measures included surveillance, community mobilization, case and logistics management. three coordination committees were fo ...200212460399
[how to treat a patient with indications for an infectious viral hemorrhagic fever].lassa, ebola, marburg and crimean-congo haemorrhagic fever viruses are the most important causes of viral haemorrhagic fever which is transmitted from person to person through contact with blood or excreta. a non-specific fever may be the initial symptom of viral haemorrhagic fever. by means of carefully noting where the patient has travelled, possible exposure to ill persons, vectors or an animal reservoir, and the incubation period (< or = 21 days versus longer), it is possible to estimate the ...200212467160
serious, frightening and interesting conditions: differences in values and attitudes between first-year and final-year medical students.during medical education and training, the values and attitudes of medical students are shaped both by knowledge and by role models. in this study, the aim was to compare the views of first- and final-year students concerning patients with different medical conditions.200212047671
ebola virus vp30-mediated transcription is regulated by rna secondary structure formation.the nucleocapsid protein vp30 of ebola virus (ebov), a member of the filovirus family, is known to act as a transcription activator. by using a reconstituted minigenome system, the role of vp30 during transcription was investigated. we could show that vp30-mediated transcription activation is dependent on formation of a stem-loop structure at the first gene start site. destruction of this secondary structure led to vp30-independent transcription. analysis of the transcription products of bicistr ...200212163572
quantitative expression and virus transmission analysis of dc-sign on monocyte-derived dendritic cells.the c-type lectins dc-sign and dc-signr efficiently bind human immunodeficiency virus (hiv) and simian immunodeficiency virus (siv) strains and can transmit bound virus to adjacent cd4-positive cells. dc-sign also binds efficiently to the ebola virus glycoprotein, enhancing ebola virus infection. dc-sign is thought to be responsible for the ability of dendritic cells (dcs) to capture hiv and transmit it to t cells, thus promoting hiv dissemination in vitro and perhaps in vivo as well. to investi ...200212186897
induction of immune responses in mice and monkeys to ebola virus after immunization with liposome-encapsulated irradiated ebola virus: protection in mice requires cd4(+) t cells.ebola zaire virus (ebo-z) causes severe hemorrhagic fever in humans, with a high mortality rate. it is thought that a vaccine against ebo-z may have to induce both humoral and cell-mediated immune responses to successfully confer protection. because it is known that liposome-encapsulated antigens induce both antibody and cellular responses, we evaluated the protective efficacy of liposome-encapsulated irradiated ebo-z [l(ev)], which contains all of the native ebo-z proteins. in a series of exper ...200212186901
the assembly of ebola virus nucleocapsid requires virion-associated proteins 35 and 24 and posttranslational modification of nucleoprotein.ebola virus encodes seven viral structural and regulatory proteins that support its high rates of replication, but little is known about nucleocapsid assembly of this virus in infected cells. we report here that three viral proteins are necessary and sufficient for formation of ebola virus particles and that intracellular posttranslational modification regulates this process. expression of the nucleoprotein (np) and virion-associated proteins vp35 and vp24 led to spontaneous assembly of nucleoca ...200212191476
molecular characterization of an isolate from the 1989/90 epizootic of ebola virus reston among macaques imported into the united states.we have determined the entire genomic sequence of the pennsylvania strain, which was isolated along with the virginia strain during the emergence of ebola virus reston in 1989/90 in the united states. thus, either the pennsylvania or virginia strain, neither of which had been previously molecularly characterized, can be considered as the prototype for ebola virus reston. comparative analysis showed a high degree of homology to the concomitantly analyzed and recently published philippine strain o ...200212191779
anthrax, tularemia, plague, ebola or smallpox as agents of bioterrorism: recognition in the emergency room.bioterrorism has become a potential diagnostic consideration in infectious diseases. this article reviews the clinical presentation and differential diagnosis of potential bioterrorist agents when first presenting to the hospital in the emergency room setting. the characteristic clinical features of inhalation anthrax, tularemic pneumonia, plague pneumonia, including laboratory and radiographic finding, are discussed. ebola vieus and smallpox are also discussed as potential bioterrorist-transmit ...200212197871
transcriptional control of the rna-dependent rna polymerase of vesicular stomatitis virus.the nonsegmented negative strand (nns) rna viruses include some of the mosr problematic human, animal and plant pathogens extant: for example, rabies virus, ebola virus, respiratory syncytial virus, the parainfluenza viruses, measles and infectious hemapoietic necrosis virus. the key feature of transcriptional control in the nns rna viruses is polymerase entry at a single 3' proximal site followed by obligatory sequential transcription of the linear array of genes. the levels of gene expression ...200212213662
the role of dc-sign and dc-signr in hiv and ebola virus infection: can potential therapeutics block virus transmission and dissemination?sexual transmission of hiv requires that the virus crosses mucosal barriers and disseminates into lymphoid tissue, the major site of viral replication. to achieve this, hiv might engage dc-sign, a calcium dependent lectin that is expressed on mucosal dendritic cells (dcs), which binds avidly to hiv. dc-sign and other attachment factors are likely to account for the well-known ability of dcs to enhance infection of t cells by hiv. attachment of hiv to dc-sign might thus enhance viral spread in mu ...200212223058
[ebola fever, an out of control epidemic?]. 200212229031
efficient transduction of liver and muscle after in utero injection of lentiviral vectors with different pseudotypes.in this study we investigate the efficacy of lentiviral vectors of different pseudotypes for gene transfer to tissues of the preimmune fetus. balb/c fetuses at 14-15 days' gestation received lentiviral vectors carrying the transgene lacz under the control of the human cytomegalovirus (cmv) promoter by intramuscular (i.m.) or intrahepatic (i.h.) injection. we pseudotyped the lentiviral vectors with vesicular stomatitis virus (vsv-g), with mokola virus, or with ebola virus envelope glycoproteins. ...200212231171
[ebola: a virus endemic to central africa?].from october 2001 to march 2002, an outbreak of ebola haemorrhagic fever occurred in the north-eastern gabon (63 cases) and neighbouring congo (57 cases). it was the fourth epidemic in north eastern gabon since 1994. meanwhile this outbreak differed from the previous epidemics: at least five different emerging sources of the virus in the human population were observed from the local fauna resulting in fears of an endemic ebola virus in the area. the control of the outbreak was uneasy because of ...200212244929
ebola virus glycoproteins induce global surface protein down-modulation and loss of cell adherence.the ebola virus envelope glycoprotein (gp) derived from the pathogenic zaire subtype mediates cell rounding and detachment from the extracellular matrix in 293t cells. in this study we provide evidence that gps from the other pathogenic subtypes, sudan and côte d'ivoire, as well as from reston, a strain thought to be nonpathogenic in humans, also induced cell rounding, albeit at lower levels than zaire gp. sequential removal of regions of potential o-linked glycosylation at the c terminus of gp1 ...200211836430
the lived experience of waiting-to-know: ebola at mbarara, uganda--hoping for life, anticipating death.purpose pf the study: the purpose of the study was to describe the phenomenon of 'waiting to know'. it is a phenomenon uniquely experienced by persons who had been exposed to patients with ebola hemorrhagic fever (ebola) but who have not yet exhibited signs and symptoms of the disease. research method/analysis: the phenomenological human science approach was used using the four life worlds as guides for reflection. these are spatiality, corporeality, temporality, and relationality. participants: ...200211851785
evidence against an important role for infectivity-enhancing antibodies in ebola virus infections.the neutralizing and enhancing activities of ebola virus (ebov)-specific antibodies were tested among four murine antibodies specific to the surface glycoprotein (gp), a recombinant human monoclonal antibody specific to gp, a polyclonal equine igg, and serum obtained from a convalescent monkey. all but one of these antibodies neutralized ebov infectivity of primary human monocytes/macrophages or vero cells. none of the antibodies enhanced ebov infectivity in these cells. taken together with in v ...200211853394
hiv/ebola comparison could spur new treatments.a researcher has discovered a link between hiv and ebola virus: both viruses use the same method to spread through the human body.200211862746
lipid raft microdomains: a gateway for compartmentalized trafficking of ebola and marburg viruses.spatiotemporal aspects of filovirus entry and release are poorly understood. lipid rafts act as functional platforms for multiple cellular signaling and trafficking processes. here, we report the compartmentalization of ebola and marburg viral proteins within lipid rafts during viral assembly and budding. filoviruses released from infected cells incorporated raft-associated molecules, suggesting that viral exit occurs at the rafts. ectopic expression of ebola matrix protein and glycoprotein supp ...200211877482
re-emergence of ebola haemorrhagic fever in gabon. 200211879899
jungle conceals ebola origins. 200211901650
surprise finding spurs ebola researchers' hopes. 200211903010
requirements for budding of paramyxovirus simian virus 5 virus-like particles.enveloped viruses are released from infected cells after coalescence of viral components at cellular membranes and budding of membranes to release particles. for some negative-strand rna viruses (e.g., vesicular stomatitis virus and ebola virus), the viral matrix (m) protein contains all of the information needed for budding, since virus-like particles (vlps) are efficiently released from cells when the m protein is expressed from cdna. to investigate the requirements for budding of the paramyxo ...200211907235
mitogen therapy for biological warfare/terrorist attacks and viral hemorrhagic fever control.ken alibek was for 17 years a leader in biopreparat, the soviet union's top secret agency involved in developing and stockpiling the most lethal bacteria, viruses, and toxins in the history of mankind before he defected with his family to the united states in 1992. very contrite when he discovered he had been misled to believe that his efforts had been essential to the survival of his homeland, alibek has become active sounding an alarm about, among other things, thousands of unemployed russian ...200211915170
evidence against ebola virus sgp binding to human neutrophils by a specific receptor.the issue of whether ebola secretory glycoprotein (sgp) binds to human neutrophils via the igg fc receptor iiib (fcgammariiib, cd16b) or other receptors has been controversial. to clarify this, facs analysis, an sgp absorption assay, and direct binding of (125)i-sgp to neutrophils were performed. results from facs analysis demonstrated that limited washing conditions leads to the nonspecific formation of immune complexes on the neutrophil surface and this, but not a specific interaction between ...200212482654
detection of antibodies against the four subtypes of ebola virus in sera from any species using a novel antibody-phage indicator assay.the natural host for ebola virus, presumed to be an animal, has not yet been identified despite an extensive search following several major outbreaks in africa. a straightforward approach used to determine animal contact with ebola virus is by assessing the presence of specific antibodies in serum. this approach however has been made very difficult by the absence of specific reagents required for the detection of antibodies from the majority of wild animal species. in this study, we isolated a h ...200212350354
furin at the cutting edge: from protein traffic to embryogenesis and disease.furin catalyses a simple biochemical reaction--the proteolytic maturation of proprotein substrates in the secretory pathway. but the simplicity of this reaction belies furin's broad and important roles in homeostasis, as well as in diseases ranging from alzheimer's disease and cancer to anthrax and ebola fever. this review summarizes various features of furin--its structural and enzymatic properties, intracellular localization, trafficking, substrates, and roles in vivo.200212360192
structure of the tsg101 uev domain in complex with the ptap motif of the hiv-1 p6 protein.the structural proteins of hiv and ebola display ptap peptide motifs (termed 'late domains') that recruit the human protein tsg101 to facilitate virus budding. here we present the solution structure of the uev (ubiquitin e2 variant) binding domain of tsg101 in complex with a ptap peptide that spans the late domain of hiv-1 p6(gag). the uev domain of tsg101 resembles e2 ubiquitin-conjugating enzymes, and the ptap peptide binds in a bifurcated groove above the vestigial enzyme active site. each pt ...200212379843
a decade after the generation of a negative-sense rna virus from cloned cdna - what have we learned?since the first generation of a negative-sense rna virus entirely from cloned cdna in 1994, similar reverse genetics systems have been established for members of most genera of the rhabdo- and paramyxoviridae families, as well as for ebola virus (filoviridae). the generation of segmented negative-sense rna viruses was technically more challenging and has lagged behind the recovery of nonsegmented viruses, primarily because of the difficulty of providing more than one genomic rna segment. a membe ...200212388800
development of an immunofluorescence method for the detection of antibodies to ebola virus subtype reston by the use of recombinant nucleoprotein-expressing hela cells.an indirect immunofluorescent assay (ifa) to detect ebola virus subtype reston (ebo-r) antibodies was developed by the use of a hela cell line stably expressing ebo-r nucleoprotein (np). this ifa has a high specificity for the detection of ebo-r igg antibodies in both hyperimmune rabbit sera and monkey sera collected during an ebo-r outbreak in the philippines in 1996. furthermore, this ifa showed a higher sensitivity for the detection of ebo-r antibodies than did the ifa using hela cells expres ...200212437031
histopathology of natural ebola virus subtype reston infection in cynomolgus macaques during the philippine outbreak in 1996.we investigated the livers, spleens, kidneys and lungs collected from 24 cynomolgus macaques (macaca fascicularis) naturally infected with ebola virus subtype reston (ebo-r) during the philippine outbreak in 1996, in order to reveal the histopathologic findings. these macaques showed necrotic hepatocytes with inclusions, slight to massive fibrin deposition in splenic cords, depletion of lymphoid cells in the white pulp of the spleen, and fibrin thrombi in some organs. immunohistochemical analysi ...200212451705
ebola. 200212473930
reverse genetics demonstrates that proteolytic processing of the ebola virus glycoprotein is not essential for replication in cell culture.ebola virus, a prime example of an emerging pathogen, causes fatal hemorrhagic fever in humans and in nonhuman primates. identification of major determinants of ebola virus pathogenicity has been hampered by the lack of effective strategies for experimental mutagenesis. here we exploit a reverse genetics system that allows the generation of ebola virus from cloned cdna to engineer a mutant ebola virus with an altered furin recognition motif in the glycoprotein (gp). when expressed in cells, the ...200211739705
sequence analysis of the gp, np, vp40 and vp24 genes of ebola virus isolated from deceased, surviving and asymptomatically infected individuals during the 1996 outbreak in gabon: comparative studies and phylogenetic characterization.the aims of this study were to determine if the clinical outcome of ebola virus (ebov) infection is associated with virus genetic structure and to document the genetic changes in the gabon strains of ebov by sequencing the gp, np, vp40 and vp24 genes from deceased and surviving symptomatic and asymptomatic individuals. gp and np sequences were identical in the three groups of patients and only one silent substitution occurred in the vp40 and vp24 genes in asymptomatic individuals. a strain from ...200211752702
ebola: small, but real progress. 200211927920
ebola at mbarara, uganda: aesthetic expressions of the lived worlds of people waiting to know.the ebola epidemic of 2000 was a disastrous experience for the people of uganda. prior outbreaks in neighboring african sub-saharan countries heightened the realization of death from this devastating disease. waiting to know is a phenomenon described as an excruciating inactivity uniquely experienced by individuals who were exposed to persons with ebola but who had not yet exhibited signs and symptoms of the disease. in the recent ebola epidemic in uganda, contact persons described their experie ...200211949481
virology. rafting with ebola. 200211951027
ebola virus vp40 drives the formation of virus-like filamentous particles along with gp.using biochemical assays, it has been demonstrated that expression of ebola virus vp40 alone in mammalian cells induced production of particles with a density similar to that of virions. to determine the morphological properties of these particles, cells expressing vp40 and the particles released from the cells were examined by electron microscopy. vp40 induced budding from the plasma membrane of filamentous particles, which differed in length but had uniform diameters of approximately 65 nm. wh ...200211967302
association of the caveola vesicular system with cellular entry by filoviruses.the filoviruses ebola zaire virus and marburg virus are believed to infect target cells through endocytic vesicles, but the details of this pathway are unknown. we used a pseudotyping strategy to investigate the cell biology of filovirus entry. we observed that specific inhibitors of the caveola system, including cholesterol-sequestering drugs and phorbol esters, inhibited the entry of filovirus pseudotypes into human cells. we also measured slower cell entry kinetics for both filovirus pseudoty ...200211967340
inflammatory responses in ebola virus-infected patients.ebola virus subtype zaire (ebo-z) induces acute haemorrhagic fever and a 60-80% mortality rate in humans. inflammatory responses were monitored in victims and survivors of ebo-z haemorrhagic fever during two recent outbreaks in gabon. survivors were characterized by a transient release in plasma of interleukin-1beta (il-1beta), il-6, tumour necrosis factor-alpha (tnfalpha), macrophage inflammatory protein-1alpha (mip-1alpha) and mip-1beta early in the disease, followed by circulation of il-1 rec ...200211982604
targeted transduction patterns in the mouse brain by lentivirus vectors pseudotyped with vsv, ebola, mokola, lcmv, or mulv envelope proteins.lentiviral vectors have proven to be promising tools for transduction of central nervous system (cns) cells in vivo and in vitro. in this study, cns transduction patterns of lentiviral vectors pseudotyped with envelope glycoproteins from ebola virus, murine leukemia virus (mulv), lymphocytic choriomeningitis virus (lcmv), or the rabies-related mokola virus were compared to a vector pseudotyped with the vesicular stomatitis virus glycoprotein (vsv-g). mokola-, lcmv-, and vsv-g-pseudotyped vectors ...200211991743
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