PMID(sorted ascending)
ebola virus vp35-vp40 interaction is sufficient for packaging 3e-5e minigenome rna into virus-like particles.the packaging of viral genomic rna into nucleocapsids and subsequently into virions is not completely understood. phosphoprotein (p) and nucleoprotein (np) interactions link np-rna complexes with p-l (polymerase) complexes to form viral nucleocapsids. the nucleocapsid then interacts with the viral matrix protein, leading to specific packaging of the nucleocapsid into the virion. a mammalian two-hybrid assay and confocal microscopy were used to demonstrate that ebola virus vp35 and vp40 interact ...200616698994
ebola virus vp24 binds karyopherin alpha1 and blocks stat1 nuclear accumulation.ebola virus (ebov) infection blocks cellular production of alpha/beta interferon (ifn-alpha/beta) and the ability of cells to respond to ifn-alpha/beta or ifn-gamma. the ebov vp35 protein has previously been identified as an ebov-encoded inhibitor of ifn-alpha/beta production. however, the mechanism by which ebov infection inhibits responses to ifns has not previously been defined. here we demonstrate that the ebov vp24 protein functions as an inhibitor of ifn-alpha/beta and ifn-gamma signaling. ...200616698996
ebola virus vp35 protein binds double-stranded rna and inhibits alpha/beta interferon production induced by rig-i signaling.the ebola virus (ebov) vp35 protein blocks the virus-induced phosphorylation and activation of interferon regulatory factor 3 (irf-3), a transcription factor critical for the induction of alpha/beta interferon (ifn-alpha/beta) expression. however, the mechanism(s) by which this blockage occurs remains incompletely defined. we now provide evidence that vp35 possesses double-stranded rna (dsrna)-binding activity. specifically, vp35 bound to poly(ri) . poly(rc)-coated sepharose beads but not contro ...200616698997
postexposure protection of guinea pigs against a lethal ebola virus challenge is conferred by rna interference.ebola virus (ebov) infection causes a frequently fatal hemorrhagic fever (hf) that is refractory to treatment with currently available antiviral therapeutics. rna interference represents a powerful, naturally occurring biological strategy for the inhibition of gene expression and has demonstrated utility in the inhibition of viral replication. here, we describe the development of a potential therapy for ebov infection that is based on small interfering rnas (sirnas).200616703508
functional expression of mouse relaxin and mouse relaxin-3 in the lung from an ebola virus glycoprotein-pseudotyped lentivirus via tracheal delivery.the peptide hormone relaxin is a known modulator of connective tissue and the extracellular matrix by virtue of its ability to regulate matrix metalloproteinases (mmps). relaxin knockout mice exhibit age-related pulmonary fibrosis, and delivery of recombinant human h2 relaxin ameliorates fibrotic-like conditions in the mouse lung. we investigated whether lentiviral vectors (lvs) engineering the expression of murine relaxins could induce mmp activity in the mouse lung. mouse relaxin and mouse rel ...200616709614
effect of ebola virus proteins gp, np and vp35 on vp40 vlp morphology.recently we described a role for ebola virus proteins, np, gp, and vp35 in enhancement of vp40 vlp budding. to explore the possibility that vlp structure was altered by co-expression of ebov proteins leading to the observed enhancement of vp40 vlp budding, we performed density gradient analysis as well as electron microscopy studies. our data suggest that vp40 is the major determinant of vlp morphology, as co-expression of np, gp and vp35 did not significantly change vlp density, length, and dia ...200616719918
interaction of amsh with escrt-iii and deubiquitination of endosomal cargo.the "class e" vacuolar protein sorting (vps) pathway mediates sorting of ubiquitinated cargo into the forming vesicles of the multivesicular bodies (mvb), and it is essential for down-regulation of signaling by growth factors and budding of enveloped viruses such as ebola and hiv-1. work in yeast has identified doa4 as a gene that is recruited by the class e machinery to remove ubiquitin from the endosomal cargo before it is incorporated into mvb vesicles, but the identity of the mammalian count ...200616760479
reverse genetic generation of recombinant zaire ebola viruses containing disrupted irf-3 inhibitory domains results in attenuated virus growth in vitro and higher levels of irf-3 activation without inhibiting viral transcription or replication.the vp35 protein of zaire ebola virus is an essential component of the viral rna polymerase complex and also functions to antagonize the cellular type i interferon (ifn) response by blocking activation of the transcription factor irf-3. we previously mapped the irf-3 inhibitory domain within the c terminus of vp35. in the present study, we show that mutations that disrupt the irf-3 inhibitory function of vp35 do not disrupt viral transcription/replication, suggesting that the two functions of vp ...200616775331
[chiroptera and zoonosis: an emerging problem on all five continents].zoonosis is the cause of the vast majority of emerging diseases. bats that occupy the second place in the mammal class play an important role. whether they belong to the microchiroptera suborder or to the megachiroptera suborder, bats on all five continents have been implicated in transmission of numerous pathogens including not only viruses such as lyssavirus (e.g. rabies), hepanivirus (e.g. hendra and nipah virus) and recently coronavirus (e.g. sars-like coronavirus and ebola virus) but also f ...200616775933
viral haemorrhagic fevers caused by lassa, ebola and marburg viruses. 200616802617
activation of triggering receptor expressed on myeloid cells-1 on human neutrophils by marburg and ebola viruses.marburg virus (marv) and ebola virus (ebov), members of the viral family filoviridae, cause fatal hemorrhagic fevers in humans and nonhuman primates. high viral burden is coincident with inadequate adaptive immune responses and robust inflammatory responses, and virus-mediated dysregulation of early host defenses has been proposed. recently, a novel class of innate receptors called the triggering receptors expressed in myeloid cells (trem) has been discovered and shown to play an important role ...200616809329
infection of naive target cells with virus-like particles: implications for the function of ebola virus vp24.infectious virus-like particle (ivlp) systems have recently been established for several negative-strand rna viruses, including the highly pathogenic zaire ebolavirus (zebov), and allow study of the viral life cycle under biosafety level 2 conditions. however, current systems depend on the expression of viral helper nucleocapsid proteins in target cells, thus making it impossible to determine whether ribonucleoprotein complexes transferred by ivlps are able to facilitate initial transcription, a ...200616809331
complex adenovirus-vectored vaccine protects guinea pigs from three strains of marburg virus challenges.the marburg virus (marv), an african filovirus closely related to the ebola virus, causes a deadly hemorrhagic fever in humans, with up to 90% mortality. currently, treatment of disease is only supportive, and no vaccines are available to prevent spread of marv infections. in order to address this need, we have developed and characterized a novel recombinant vaccine that utilizes a single complex adenovirus-vectored vaccine (cadvax) to overexpress a marv glycoprotein (gp) fusion protein derived ...200616820184
gorilla susceptibility to ebola virus: the cost of sociality. 200616824905
a luciferase-based budding assay for ebola virus.the vp40 matrix protein of ebola virus (ebov) is capable of budding from mammalian cells as a virus-like particle (vlp) and is the major protein involved in virus egress. a functional budding assay has been developed based upon this characteristic of vp40 to assess the contributions of vp40 sequences as well as host proteins to the budding process. this well-defined assay has been modified for potential use in a high-throughput format in which the detection and quantification of firefly lucifera ...200616837071
identification of two amino acid residues on ebola virus glycoprotein 1 critical for cell entry.using site-directed mutagenesis and retroviral vector pseudotyping of the wild type or mutated glycoprotein of zaire ebolavirus (zebov), we analyzed 15 conserved residues in the n-terminus of the filovirus glycoprotein 1 (gp1) in order to identify residues critical for cell entry. results from infectivity assays and western blot analyses identified two phenylalanine residues at positions 88 and 159 that appear to be critical for zebov entry in vitro. we extended this observation by introduction ...200616839637
peptides derived from hiv-1, hiv-2, ebola virus, sars coronavirus and coronavirus 229e exhibit high affinity binding to the formyl peptide receptor.peptides derived from the membrane proximal region of fusion proteins of human immunodeficiency viruses 1 and 2, coronavirus 229 e, severe acute respiratory syndrome coronavirus and ebola virus were all potent antagonists of the formyl peptide receptor expressed in chinese hamster ovary cells. binding of viral peptides was affected by the naturally occurring polymorphisms at residues 190 and 192, which are located at second extracellular loop-transmembrane helix 5 interface. substitution of r190 ...200616842982
molecular determinants of ebola virus virulence in mice.zaire ebolavirus (zebov) causes severe hemorrhagic fever in humans and nonhuman primates, with fatality rates in humans of up to 90%. the molecular basis for the extreme virulence of zebov remains elusive. while adult mice resist zebov infection, the mayinga strain of the virus has been adapted to cause lethal infection in these animals. to understand the pathogenesis underlying the extreme virulence of ebola virus (ebov), here we identified the mutations responsible for the acquisition of the h ...200616848640
detection of ebola virus envelope using monoclonal and polyclonal antibodies in elisa, surface plasmon resonance and a quartz crystal microbalance immunosensor.ebola virus (ebov) zaire, sudan, as well as ivory coast are virulent human ebov species. both polyclonal and monoclonal antibodies (mabs) were developed against soluble ebov envelope glycoprotein (gp) for the study of ebov envelope diversity and development of diagnostic reagents. three ebov sudan-gulu gp peptides, from the n-terminus, mid-gp, and c-terminus regions were used to immunize rabbits for the generation of anti-ebov polyclonal antibodies. polyclonal antisera raised against the c-termi ...200616857271
aids: caused by development of resistance to drugs in a non-target intracellular parasite.the origin of acquired immune disorder syndrome (aids) has been the subject of substantial controversy both in the scientific community and in the popular press. the debate involves the mode of transmission of a simian virus (siv) to humans. both major camps in the argument presume that humans are normally free of such viruses and assume that once the simian virus was transmitted, it immediately infected some t-cells and caused the release of toxic agents that killed off bystander (uninfected) t ...200716893612
generation of an adenoviral vaccine vector based on simian adenovirus 21.adenoviral vectors can be used to generate potent humoral and cellular immune responses to transgene products. use of adenoviral vectors based on non-human isolates may allow for their utilization in populations harbouring neutralizing antibodies to common human serotypes. a vector chimera was constructed using simian adenovirus 22 (a serotype belonging to the species human adenovirus e) and simian adenovirus 21 (a serotype belonging to the species human adenovirus b) expressing the ebola (zaire ...200616894185
anthrax in western and central african great apes.during the period of december 2004 to january 2005, bacillus anthracis killed three wild chimpanzees (pan troglodytes troglodytes) and one gorilla (gorilla gorilla gorilla) in a tropical forest in cameroon. while this is the second anthrax outbreak in wild chimpanzees, this is the first case of anthrax in gorillas ever reported. the number of great apes in central africa is dramatically declining and the populations are seriously threatened by diseases, mainly ebola. nevertheless, a considerable ...200616900500
permeabilization of the plasma membrane by ebola virus gp2.the glycoprotein (gp) of ebola virus (ebov) is a multifunctional protein known to play a role in virus attachment and entry, cell rounding and cytotoxicity, down-regulation of host surface proteins, and enhancement of virus assembly and budding. ebov gp is synthesized as a precursor which is subsequently cleaved to yield two disulfide-linked subunits: gp1 (surface-exposed [su] subunit) and gp2 (membrane-anchored [tm] subunit). we sought to determine the effect of membrane-anchored gp2 protein ex ...200716927113
[hematological and immunological parameters during ebola virus passages in guinea-pigs].the trend in hematological and immunological parameters during ebola virus passages in guinea-pigs indicated that pathophysiological changes occurred just during the second passage and further became stronger. the increase of some parameters and their correlation with the occurrence of fatal outcomes allowed the authors to reveal the most significant changes as increased juvenile platelets, whole blood virus appearance, higher echinocytes, a rise in the pro mil of blast cells and megakaryocytes ...200616929596
structure-function analysis of the soluble glycoprotein, sgp, of ebola addition to the transmembrane protein, gp(1,2), the ebola virus glycoprotein gene encodes the soluble glycoproteins sgp and delta-peptide. two more soluble proteins, gp(1) and gp(1,2deltatm), are generated from gp(1,2) as a result of disulfide-bond instability and proteolytic cleavage, respectively, and are shed from the surface of infected cells. the sgp glycoprotein is secreted as a disulfide-linked homodimer, but there have been conflicting reports on whether it is arranged in a parallel o ...200616977667
release of cellular proteases into the acidic extracellular milieu exacerbates ebola virus-induced cell damage.ebola virus is highly cytopathic through mechanisms that are largely unknown. we present evidence that progressive acidification of the extracellular milieu by ebola virus-infected cells combined with reduced levels of natural cysteine protease inhibitor makes the cells vulnerable to uncontrolled proteolysis of extracellular matrix components by released active endosomal cathepsins, thereby exacerbating ebola virus-induced cell destruction. the cell surface microenvironment was shown to be cruci ...200716982079
emergency medicine and the public's health: emerging infectious recent years, multiple global forces have contributed to the emergence and widespread distribution of previously unknown disease entities. this article discusses ebola virus, west nile virus, and hantavirus as representative emerging infectious diseases. smallpox is discussed along with concerns about the safety of the smallpox vaccine, given the uncertain risk of bioterrorism and smallpox exposure. ed physicians must become familiar with the presentation, management, and public health impact ...200616982350
a dna vaccine for ebola virus is safe and immunogenic in a phase i clinical trial.ebola viruses represent a class of filoviruses that causes severe hemorrhagic fever with high mortality. recognized first in 1976 in the democratic republic of congo, outbreaks continue to occur in equatorial africa. a safe and effective ebola virus vaccine is needed because of its continued emergence and its potential for use for biodefense. we report the safety and immunogenicity of an ebola virus vaccine in its first phase i human study. a three-plasmid dna vaccine encoding the envelope glyco ...200616988008
characterization of marburg virus glycoprotein in viral major determinant of host tropism for filoviruses is viral glycoprotein (gp), which is involved in receptor binding and viral entry. compared to ebola gp (egp), marburg gp (mgp) is less well characterized in viral entry. in this study, using a human immunodeficiency virus-based pseudotyped virus as a surrogate system, we have characterized the role of mgp in viral entry. we have shown that like egp, the mucin-like region of mgp (289-501) is not essential for virus entry. we have developed a ...200716989883
understanding the dynamics of ebola epidemics.ebola is a highly lethal virus, which has caused at least 14 confirmed outbreaks in africa between 1976 and 2006. using data from two epidemics [in democratic republic of congo (drc) in 1995 and in uganda in 2000], we built a mathematical model for the spread of ebola haemorrhagic fever epidemics taking into account transmission in different epidemiological settings. we estimated the basic reproduction number (r0) to be 2.7 (95% ci 1.9-2.8) for the 1995 epidemic in drc, and 2.7 (95% ci 2.5-4.1) ...200716999875
mutation of ymyl in the nipah virus matrix protein abrogates budding and alters subcellular localization.matrix (m) proteins reportedly direct the budding of paramyxoviruses from infected cells. in order to begin to characterize the assembly process for the highly lethal, emerging paramyxovirus nipah virus (niv), we have examined the budding of niv m. we demonstrated that expression of the niv m protein is sufficient to produce budding virus-like particles (vlps) that are physically and morphologically similar to niv. we identified in niv m a sequence, ymyl, with similarity to the ypdl late domain ...200617005661
tyro3 family-mediated cell entry of ebola and marburg viruses.filoviruses, represented by the genera ebolavirus and marburgvirus, cause a lethal hemorrhagic fever in humans and in nonhuman primates. although filovirus can replicate in various tissues or cell types in these animals, the molecular mechanisms of its broad tropism remain poorly understood. here we show the involvement of members of the tyro3 receptor tyrosine kinase family-axl, dtk, and mer-in cell entry of filoviruses. ectopic expression of these family members in lymphoid cells, which otherw ...200617005688
bile salt-stimulated lipase from human milk binds dc-sign and inhibits human immunodeficiency virus type 1 transfer to cd4+ t cells.a wide range of pathogens, including human immunodeficiency virus type 1 (hiv-1), hepatitis c virus, ebola virus, cytomegalovirus, dengue virus, mycobacterium, leishmania, and helicobacter pylori, can interact with dendritic cell (dc)-specific icam3-grabbing nonintegrin (dc-sign), expressed on dcs and a subset of b cells. more specifically, the interaction of the gp120 envelope protein of hiv-1 with dc-sign can facilitate the transfer of virus to cd4+ t lymphocytes in trans and enhance infection ...200617005819
morbidity and mortality of wild animals in relation to outbreaks of ebola haemorrhagic fever in gabon, 1994-2003.antibody to ebola virus was found in 14 (1.2%) of 1147 human sera collected in gabon in 1981-1997. six seropositive subjects were bled in the northeast in 1991, more than 3 years prior to recognition of the first known outbreak of ebola haemorrhagic fever (ehf), whilst eight came from the southwest where the disease has not been recognised. it has been reported elsewhere that 98 carcasses of wild animals were found in systematic studies in northeastern gabon and adjoining northwestern republic o ...200717010400
evaluation of promed-mail as an electronic early warning system for emerging animal diseases: 1996 to identify emerging animal and zoonotic diseases and associated geographic distribution, disease agents, animal hosts, and seasonality of reporting in the program for monitoring emerging diseases (promed)-mail electronic early warning system.200617014355
implication of a retrovirus-like glycoprotein peptide in the immunopathogenesis of ebola and marburg viruses.ebola and marburg viruses can cause hemorrhagic fever (hf) outbreaks with high mortality in primates. whereas marburg (marv), ebola zaire (zebov), and ebola sudan (sebov) viruses are pathogenic in humans, apes, and monkeys, ebola reston (rebov) is pathogenic only in monkeys. early immunosuppression may contribute to pathogenesis by facilitating viral replication. lymphocyte depletion, intravascular apoptosis, and cytokine dysregulation are prominent in fatal cases. here we functionally character ...200617023517
[properties of the ebola virus glycoprotein].in central and west africa, ebola virus, a member of the filovirus group, has produced sporadic outbreaks of lethal disease. this virus causes hemorrhagic fever in humans and nonhuman primates, resulting in mortality rates of up to 90%. although there are no satisfactory biologic explanations for this extreme virulence, it has been suggested that functions of the envelope glycoprotein are likely to play important roles in the pathogenicity of ebola virus.200617038820
zoonotic viral diseases and the frontier of early diagnosis, control and prevention.public awareness of the human health risks of zoonotic infections has grown in recent years. currently, concern of h5n1 flu transmission from migratory bird populations has increased with foci of fatal human cases. this comes on the heels of other major zoonotic viral epidemics in the last decade. these include other acute emerging or re-emerging viral diseases such as severe acute respiratory syndrome (sars), west-nile virus, ebola virus, monkeypox, as well as the more inapparent insidious slow ...200617040245
bats as a continuing source of emerging infections in humans.amongst the 60 viral species reported to be associated with bats, 59 are rna viruses, which are potentially important in the generation of emerging and re-emerging infections in humans. the prime examples of these are the lyssaviruses and henipavirus. the transmission of nipah, hendra and perhaps sars coronavirus and ebola virus to humans may involve intermediate amplification hosts such as pigs, horses, civets and primates, respectively. understanding of the natural reservoir or introductory ho ...200717042030
protective efficacy of neutralizing antibodies against ebola virus infection.ebola virus causes lethal hemorrhagic fever in humans and nonhuman primates, but no effective antiviral compounds are available for the treatment of this infection. the surface glycoprotein (gp) of ebola virus is an important target of neutralizing antibodies. although passive transfer of gp-specific antibodies has been evaluated in mouse and guinea pig models, protection was achieved only by treatment shortly before or after virus challenge. using these animal models, we evaluated the protectiv ...200717055127
the vp35 protein of ebola virus inhibits the antiviral effect mediated by double-stranded rna-dependent protein kinase pkr.the vp35 protein of ebola virus is a viral antagonist of interferon. it acts to block virus or double-stranded rna-mediated activation of interferon regulatory factor 3, a transcription factor that facilitates the expression of interferon and interferon-stimulated genes. in this report, we show that the vp35 protein is also able to inhibit the antiviral response induced by alpha interferon. this depends on the vp35 function that interferes with the pathway regulated by double-stranded rna-depend ...200717065211
recent common ancestry of ebola zaire virus found in a bat reservoir. 200617069458
[hemorrhagic (marburg, ebola, lassa, and bolivian) fevers: epidemiology, clinical pictures, and treatment].the evaluation of the biological and epidemiological properties of ebola, marburg, lassa, and machupo viruses suggests that they are of social importance for health care authorities. the studies have created prerequisites to the development of reliable biosafety means against these pathogens. particular emphasis is laid on the methods for infection diagnosis and on the studies to design specific protective agents--immunoglobulins and inactivated vaccines.200617087059
progress towards the treatment of ebola haemorrhagic fever.being highly pathogenic for human and nonhuman primates and the subject of former weapon programmes makes ebola virus one of the most feared pathogens worldwide today. due to a lack of licensed pre- and postexposure intervention, the current response depends on rapid diagnostics, proper isolation procedures and supportive care of case patients. consequently, the development of more specific countermeasures is of high priority for the preparedness of many nations. over the past years, enhanced re ...200617107278
the erk mitogen-activated protein kinase pathway contributes to ebola virus glycoprotein-induced cytotoxicity.ebola virus is a highly lethal pathogen that causes hemorrhagic fever in humans and nonhuman primates. among the seven known viral gene products, the envelope glycoprotein (gp) alone induces cell rounding and detachment that ultimately leads to cell death. cellular cytoxicity is not seen with comparable levels of expression of a mutant form of gp lacking a mucin-like domain (gpdeltamuc). gp-induced cell death is nonapoptotic and is preceded by downmodulation of cell surface molecules involved in ...200717108034
computational prediction and identification of hla-a2.1-specific ebola virus ctl epitopes.ebola virus (ebov) is known to cause a severe hemorrhagic fever resulting in high mortality. although the precise host defense mechanism(s) that afford protection against ebov is not completely understood, t cell-mediated immune responses is believed to play a pivotal role in controlling virus replication and ebov infection. there have been no reports on mapping of mhc class i-binding ctl epitopes for ebov till to date. in this study, we identified five hla-a2-binding 9-mer peptides of ebov nucl ...200717123567
structural studies of algal lectins with anti-hiv activity.a number of antiviral lectins, small proteins that bind carbohydrates found on viral envelopes, are currently in pre-clinical trials as potential drugs for prevention of transmission of human immunodeficiency virus (hiv) and other enveloped viruses, such as the ebola virus and the coronavirus responsible for severe acute respiratory syndrome (sars). lectins of algal origin whose antiviral properties make them candidate agents for prevention of viral transmission through topical applications incl ...200617128290
[emerging viral diseases].emerging and re-emerging infectious diseases have again entered the public arena in recent years. this is due to factors such as evolving lifestyles, ecological and socio-political upheavals, and recent diagnostic advances. numerous pathogens, including viruses like west nile, chikungunya and japanese encephalitis on the one hand, and hemorrhagic fever viruses like ebola and maburg, are particular concerns. recently, the corona virus responsible for sars, which caused an epidemic sufficiently wo ...200617140098
influences of glycosylation on antigenicity, immunogenicity, and protective efficacy of ebola virus gp dna vaccines.the ebola virus (ebov) envelope glycoprotein (gp) is the primary target of protective immunity. mature gp consists of two disulfide-linked subunits, gp1 and membrane-bound gp2. gp is highly glycosylated with both n- and o-linked carbohydrates. we measured the influences of gp glycosylation on antigenicity, immunogenicity, and protection by testing dna vaccines comprised of gp genes with deleted n-linked glycosylation sites or with deletions in the central hypervariable mucin region. we showed th ...200717151111
statistical inference in a stochastic epidemic seir model with control intervention: ebola as a case study.a stochastic discrete-time susceptible-exposed-infectious-recovered (seir) model for infectious diseases is developed with the aim of estimating parameters from daily incidence and mortality time series for an outbreak of ebola in the democratic republic of congo in 1995. the incidence time series exhibit many low integers as well as zero counts requiring an intrinsically stochastic modeling approach. in order to capture the stochastic nature of the transitions between the compartmental populati ...200617156292
ebola outbreak killed 5000 gorillas.over the past decade, the zaire strain of ebola virus (zebov) has repeatedly emerged in gabon and congo. each human outbreak has been accompanied by reports of gorilla and chimpanzee carcasses in neighboring forests, but both the extent of ape mortality and the causal role of zebov have been hotly debated. here, we present data suggesting that in 2002 and 2003 zebov killed about 5000 gorillas in our study area. the lag between neighboring gorilla groups in mortality onset was close to the zebov ...200617158318
antiviral properties of deazaadenine nucleoside derivatives.viral infections have menaced human beings since time immemorial, and even today new viral strains that cause lethal diseases are being discovered with alarming frequency. one major example is hiv, the etiological agent of aids, which spread up in the last two decades. very recently, other virus based diseases such as avian flu have spread fear around the world, and hemorrhagic fevers from central africa serious threaten human health because of their very deadly effects. new antiviral agents are ...200617168721
inhibition of filovirus replication by the zinc finger antiviral protein.the zinc finger antiviral protein (zap) was recently shown to inhibit moloney murine leukemia virus and sindbis virus replication. we tested whether zap also acts against ebola virus (ebov) and marburg virus (marv). antiviral effects were observed after infection of cells expressing the n-terminal part of zap fused to the product of the zeocin resistance gene (nzap-zeo) as well as after infection of cells inducibly expressing full-length zap. ebov was inhibited by up to 4 log units, whereas marv ...200717182693
public health awareness of emerging zoonotic viruses of bats: a european perspective.bats classified in the order chiroptera are the most abundant and widely distributed non-human mammalian species in the world. several bat species are reservoir hosts of zoonotic viruses and therefore can be a public health hazard. lyssaviruses of different genotypes have emerged from bats in america (genotype 1 rabies virus; rabv), europe (european bat lyssavirus; eblv), and australia (australian bat lyssavirus; ablv), whereas nipah virus is the most important recent zoonosis of bat origin in a ...200617187565
rapid and simple detection of ebola virus by reverse transcription-loop-mediated isothermal amplification.ebola virus (ebov) causes severe hemorrhagic fever in humans and nonhuman primates with high mortality rates. rapid identification of the virus is required to prevent spread of the infection. in this study, we developed and evaluated a one-step simple reverse transcription-loop mediated isothermal amplification (rt-lamp) assay for the rapid detection of zaire ebolavirus (zebov), the most virulent species of ebov, targeting the trailer region of the viral genome. the assay could detect 20 copies ...200717194485
[detection of anti-lassa antibodies in the western forest area of the ivory coast].lassa fever is an african viral hemorrhagic fever (vhf) known to be endemic in a number of west african countries including nigeria, sierra leone, liberia and guinea. despite having common borders with liberia and guinea, côte d'ivoire has never reported any cases of lassa fever. in march 2000, as part of a research project on vhf--mainly yellow fever, lassa fever and ebola fever--in guinea and cote d'ivoire, an exploratory survey was conducted to assess knowledge about vhf and immunological sta ...200617201291
filoviruses and the balance of innate, adaptive, and inflammatory responses.the filoviruses marburg virus and ebola virus are among the deadliest of human pathogens, causing fulminant hemorrhagic fevers typified by overmatched specific immune responses and profuse inflammatory responses. keys to both vaccination and treatment may reside, first, in the understanding of immune dysfunctions that parallel filoviral disease and, second, in devising ways to redirect and restore normal immune function as well as to mitigate inflammation. here, we describe how filoviral infecti ...200617201655
crystal structure of the c-terminal domain of ebola virus vp30 reveals a role in transcription and nucleocapsid association.transcription of the highly pathogenic ebola virus depends on vp30, a nucleocapsid-associated ebola virus-specific transcription factor. the transcription activator vp30 was shown to play an essential role in ebola virus replication, most likely by stabilizing nascent mrna. here we present the crystal structure of the c-terminal domain (ctd) of vp30 (vp30(ctd)) at 2.0-a resolution. vp30(ctd) folds independently into a dimeric helical assembly. the vp30(ctd) dimers assemble into hexamers that are ...200717202263
[the properties of ebola virus proteins].the paper describes the structure and functions of ebola virus properties. it also presents information on the role of structural (np, vp40, vp35, gp, vp30, vp24, and l) and secreted (sgp, delta-peptide, gp1, gp(1,2delta), ssgp) proteins in the viral replication cycle and in the pathogenesis of ebola hemorrhagic fever.200617214074
unconventional mechanism of mrna capping by the rna-dependent rna polymerase of vesicular stomatitis virus.all known eukaryotic and some viral mrna capping enzymes (ces) transfer a gmp moiety of gtp to the 5'-diphosphate end of the acceptor rna via a covalent enzyme-gmp intermediate to generate the cap structure. in striking contrast, the putative ce of vesicular stomatitis virus (vsv), a prototype of nonsegmented negative-strand (nns) rna viruses including rabies, measles, and ebola, incorporates the gdp moiety of gtp into the cap structure of transcribing mrnas. here, we report that the rna-depende ...200717218273
mapping of the vp40-binding regions of the nucleoprotein of ebola virus.expression of ebola virus nucleoprotein (np) in mammalian cells leads to the formation of helical structures, which serve as a scaffold for the nucleocapsid. we recently found that np binding with the matrix protein vp40 is important for nucleocapsid incorporation into virions (t. noda, h. ebihara, y. muramoto, k. fujii, a. takada, h. sagara, j. h. kim, h. kida, h. feldmann, and y. kawaoka, plos pathog. 2:e99, 2006). to identify the region(s) on the np molecule required for vp40 binding, we exam ...200717229682
proteolytic processing of the ebola virus glycoprotein is not critical for ebola virus replication in nonhuman primates.enveloped viruses often require cleavage of a surface glycoprotein by a cellular endoprotease such as furin for infectivity and virulence. previously, we showed that ebola virus glycoprotein does not require the furin cleavage motif for virus replication in cell culture. here, we show that there are no appreciable differences in disease progression, hematology, serum biochemistry, virus titers, or lethality in nonhuman primates infected with an ebola virus lacking the furin recognition sequence ...200717229700
[ebola and marburg fever--outbreaks of viral haemorrhagic fever].with an increasing frequency of traveling and tourism to exotic countries, a new threat-import of rare, very dangerous infections-emerges in humane medicine. ebola fever and marburg fever, whose agents come from the same group of filoviridae family, belong among these diseases. the natural reservoir of these viruses has not yet been precisely determined. the pathogenesis of the diseases is not absolutely clear, there is neither a possibility of vaccination, nor an effective treatment. fever and ...200617230375
effective post-exposure treatment of ebola infection.ebola viruses are highly lethal human pathogens that have received considerable attention in recent years due to an increasing re-emergence in central africa and a potential for use as a biological weapon. there is no vaccine or treatment licensed for human use. in the past, however, important advances have been made in developing preventive vaccines that are protective in animal models. in this regard, we showed that a single injection of a live-attenuated recombinant vesicular stomatitis virus ...200717238284
neutralizing antibody fails to impact the course of ebola virus infection in monkeys.prophylaxis with high doses of neutralizing antibody typically offers protection against challenge with viruses producing acute infections. in this study, we have investigated the ability of the neutralizing human monoclonal antibody, kz52, to protect against ebola virus in rhesus macaques. this antibody was previously shown to fully protect guinea pigs from infection. four rhesus macaques were given 50 mg/kg of neutralizing human monoclonal antibody kz52 intravenously 1 d before challenge with ...200717238286
status and challenges of filovirus vaccines.vaccines that could protect humans against the highly lethal marburg and ebola viruses have eluded scientists for decades. classical approaches have been generally unsuccessful for marburg and ebola viruses and pose enormous safety concerns as well. modern approaches, in particular those using vector-based approaches have met with success in nonhuman primate models although success against ebola has been more difficult to achieve than marburg. despite these successes, more work remains to be don ...200717241710
rift valley fever outbreak--kenya, november 2006-january mid-december 2006, several unexplained fatalities associated with fever and generalized bleeding were reported to the kenya ministry of health (kmoh) from garissa district in north eastern province (nep). by december 20, a total of 11 deaths had been reported. of serum samples collected from the first 19 patients, rift valley fever (rvf) virus rna or immunoglobulin m (igm) antibodies against rvf virus were found in samples from 10 patients; all serum specimens were negative for yellow fever, ...200717268404
gene transfer in human skin with different pseudotyped hiv-based vectors.pseudotyping lentiviral vector with other viral surface proteins could be applied for treating genetic anomalies in human skin. in this study, the modification of hiv vector tropism by pseudotyping with the envelope glycoprotein from vesicular stomatitis virus (vsv), the zaire ebola (eboz) virus, murine leukemia virus (mulv), lymphocytic choriomeningitis virus (lcmv), rabies or the rabies-related mokola virus encoding lacz as a reporter gene was evaluated qualitatively and quantitatively in huma ...200717268532
development of vaccines for marburg hemorrhagic fever.marburg (marv) and ebola viruses (ebov) emerged from the rainforests of central africa more than 30 years ago causing outbreaks of severe and, usually, fatal hemorrhagic fever. ebov has garnered the lion's share of the attention, fueled by the higher frequency of ebov outbreaks, high mortality rates and importation into the usa, documented in such popular works as the best-selling novel 'the hot zone'. however, recent large outbreaks of hundreds of cases of marv infection in the democratic repub ...200717280479
interaction of tsg101 with marburg virus vp40 depends on the pppy motif, but not the pt/sap motif as in the case of ebola virus, and tsg101 plays a critical role in the budding of marburg virus-like particles induced by vp40, np, and gp.marburg virus (marv) vp40 is a matrix protein that can be released from mammalian cells in the form of virus-like particles (vlps) and contains the pppy sequence, which is an l-domain motif. here, we demonstrate that the pppy motif is important for vp40-induced vlp budding and that vlp production is significantly enhanced by coexpression of np and gp. we show that tsg101 interacts with vp40 depending on the presence of the pppy motif, but not the pt/sap motif as in the case of ebola virus, and p ...200717301151
identification of inhibitors using a cell-based assay for monitoring golgi-resident protease activity.noninvasive real-time quantification of cellular protease activity allows monitoring of enzymatic activity and identification of activity modulators within the protease's natural milieu. we developed a protease activity assay based on differential localization of a recombinant reporter consisting of a golgi retention signal and a protease cleavage sequence fused to alkaline phosphatase (ap). when expressed in mammalian cells, this protein localizes to golgi bodies and, on protease-mediated cleav ...200717316541
mechanism of ad5 vaccine immunity and toxicity: fiber shaft targeting of dendritic cells.recombinant adenoviral (rad) vectors elicit potent cellular and humoral immune responses and show promise as vaccines for hiv-1, ebola virus, tuberculosis, malaria, and other infections. these vectors are now widely used and have been generally well tolerated in vaccine and gene therapy clinical trials, with many thousands of people exposed. at the same time, dose-limiting adverse responses have been observed, including transient low-grade fevers and a prior human gene therapy fatality, after sy ...200717319743
[molecular mechanisms of ebola virus reproduction].the review presents recent data on the molecular mechanisms of the stages of an ebola virus replication cycle, on the interaction of viral and cellular components at each stage, as well as on the mechanisms responsible for he realization of viral genetic information in the infected cell.200717338228
the dc-sign-related lectin lsectin mediates antigen capture and pathogen binding by human myeloid cells.liver and lymph node sinusoidal endothelial cell c-type lectin (lsectin [clec4g]) is a c-type lectin encoded within the liver/lymph node-specific intercellular adhesion molecule-3-grabbing nonintegrin (l-sign)/dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (dc-sign)/cd23 gene cluster. lsectin expression has been previously described as restricted to sinusoidal endothelial cells of the liver and lymph node. we now report lsectin expression in human peripheral blood ...200717339424
viral exanthems in the tropics.viral exanthems are a common problem in tropical regions, particularly affecting children. most exanthems are transient and harmless, but some are potentially very dangerous. pregnant women and malnourished or immunocompromised infants carry the greatest risk of adverse outcome. in this article, parvovirus b19; dengue and yellow fever; west nile, barmah forest, marburg, and ebola viruses, and human herpesviruses; asymmetric periflexural exanthema of childhood; measles; rubella; enteroviruses; la ...200717350501
[new reflections on inflammation and coagulation].inflammation is the host's defense mechanism to infection or injury, including surgical procedures. in the clinical setting non-infectious inflammation, activation of the coagulation cascade and deterioration of endothelial function play an important role in cardiology (e.g. percutaneous transluminal coronary angioplasty, ptca), intensive care medicine (e.g. polytrauma), cardiac (e.g. extracorporal circulation) and vascular surgery (e.g. reperfusion injury). imbalances in the inflammatory respon ...200717364187
production and characterization of monoclonal antibodies against different epitopes of ebola virus antigens.ebola virus (ebov) causes hemorrhagic fever in humans and nonhuman primates with up to 90% mortality rate. in this study, ebola virus like particles (evlps) and the aglycosyl subfragment of glycoprotein (gp(1) subfragment d) were used to generate monoclonal antibodies (mabs) against different epitopes of the viral antigens. such mabs could be useful in diagnostics and potential therapeutics of viral infection and its hemorrhagic symptoms. hybridoma cell fusion technology was used for production ...200717368819
nkp30-dependent cytolysis of filovirus-infected human dendritic cells.understanding how protective innate immune responses are generated is crucial to defeating highly lethal emerging pathogens. accumulating evidence suggests that potent innate immune responses are tightly linked to control of ebola and marburg filoviral infections. here, we report that unlike authentic or inactivated ebola and marburg, filovirus-derived virus-like particles directly activated human natural killer (nk) cells in vitro, evidenced by pro-inflammatory cytokine production and enhanced ...200717381429
differential expression of the ebola virus gp(1,2) protein and its fragments in e. coli.bacterial expression platforms are frequently used for the expression and production of different recombinant proteins. the full length ebola virus (ebov) gp(1,2) gene and subfragments of the gp(1) gene were cloned in a bacterial expression vector as a c-terminal his(6) fusion protein. surprisingly, the full length ebov gp(1,2) gene could not be expressed in escherichia coli. the subfragments of gp(1) were only expressed in small amounts with the exception of one small fragment (subfragment d) w ...200717383893
ebola virus infection of human pbmcs causes massive death of macrophages, cd4 and cd8 t cell sub-populations in vitro.ebola virus causes an often fatal disease characterized by poor immune response and high inflammatory reaction in the patients. one of the causes for poor immunity is virus-mediated apoptosis of lymphocytes in the host. in this study, we infected human pbmcs with ebola zaire virus and study apoptosis of different cell types using flow cytometry. we have shown that ebola virus causes bystander death of cd4 and cd8 t cells. cells infected with virus had 30-40% active caspase 3(+), annexin-v(+) and ...200717391724
potential for ebola transmission between gorilla and chimpanzee social groups.over the past decade ebola hemorrhagic fever has emerged repeatedly in gabon and congo, causing numerous human outbreaks and massive die-offs of gorillas and chimpanzees. why ebola has emerged so explosively remains poorly understood. previous studies have tended to focus on exogenous factors such as habitat disturbance and climate change as drivers of ebola emergence while downplaying the contribution of transmission between gorilla or chimpanzee social groups. here we report recent observation ...200717427138
successful topical respiratory tract immunization of primates against ebola virus.ebola virus causes outbreaks of severe viral hemorrhagic fever with high mortality in humans. the virus is highly contagious and can be transmitted by contact and by the aerosol route. these features make ebola virus a potential weapon for bioterrorism and biological warfare. therefore, a vaccine that induces both systemic and local immune responses in the respiratory tract would be highly beneficial. we evaluated a common pediatric respiratory pathogen, human parainfluenza virus type 3 (hpiv3), ...200717428868
ebola virus-like particle-induced activation of nf-kappab and erk signaling in human dendritic cells requires the glycoprotein mucin domain.dendritic cells (dcs), important early targets of ebola virus (ebov) infection in vivo, are activated by ebola virus-like particles (vlps). to better understand this phenomenon, we have systematically assessed the response of dcs to vlps of different compositions. vlps containing the viral matrix protein (vp40) and the viral glycoprotein (gp), were found to induce a proinflammatory response highly similar to a prototypical dc activator, lps. this response included the production of several proin ...200717434557
[the primordial reservoir in the infectious contagion cicle. the avian influenza model].an update of the role of the primordial reservoir in the biological cycle of the process of infection and contagion is made, using diseases of very frequent incidence at the present moment in the mediterranean area and the iberian peninsula. these diseases are, amongst others severe and acute respiratory syndrome (sars), rabies, lyme disease, african horse sickness, blue tongue, african swine fever, ebola hemorrhagic fever, hantavirosis, and avian influenza. the zoonoses classification proposed ...200617451102
hemorrhagic fevers: few clues after 25 years.there is a high prevalence of ebola antibodies found in the kenya population, related to geographical area and season, although the clinical disease was never found and the virus was not isolated. a field study was carried out in 7 hospitals in western kenya, 1986 -1987 (including surveillance studies in suspect areas), to intensify collection and transport of samples, testing facilities, patient observation with record keeping and follow-up. this study involved 1109 admitted patients with fever ...199617451318
[the restructuring of national sanitary inspectorate with regard to environmental hazards and health needs of the population].the article presents the history of polish sanitary and epidemiological services from 1918 until contemporary times. emphasizing many achievements of national sanitary inspectorate, which are responsible for the low sick-rate of infectious diseases in poland, the article also points to the increasing number and growing severity of environmental hazards in recent years. the article discusses problems caused by the "old" infectious diseases, which, though until recently regarded as passed, are pos ...200217474584
ebola virus glycoprotein 1: identification of residues important for binding and postbinding events.the filoviruses ebola virus (ebov) and marburg virus (marv) are responsible for devastating hemorrhagic fever outbreaks. no therapies are available against these viruses. an understanding of filoviral glycoprotein 1 (gp1) residues involved in entry events would facilitate the development of antivirals. towards this end, we performed alanine scanning mutagenesis on selected residues in the amino terminus of gp1. mutant gps were evaluated for their incorporation onto feline immunodeficiency virus ...200717475648
prevention of immune cell apoptosis as potential therapeutic strategy for severe infections.some labile cell types whose numbers are normally controlled through programmed cell death are subject to markedly increased destruction during some severe infections. lymphocytes, in particular, undergo massive and apparently unregulated apoptosis in human patients and laboratory animals with sepsis, potentially playing a major role in the severe immunosuppression that characterizes the terminal phase of fatal illness. extensive lymphocyte apoptosis has also occurred in humans and animals infec ...200717479879
dynamics of filamentous viral rnps prior to egress.the final step in the maturation of paramyxoviruses, orthomyxoviruses and viruses of several other families, entails the budding of the viral nucleocapsid through the plasma membrane of the host cell. many medically important viruses, such as influenza, parainfluenza, respiratory syncytial virus (rsv) and ebola, can form filamentous particles when budding. although filamentous virions have been previously studied, details of how viral filaments bud from the plasma membrane remain largely unknown ...200717485480
[ebola hemorrhagic fever]. 200717491360
1,2-mannobioside mimic: synthesis, dc-sign interaction by nmr and docking, and antiviral activity.the design and preparation of carbohydrate ligands for dc-sign is a topic of high interest because of the role played by this c-type lectin in immunity and infection processes. the low chemical stability of carbohydrates against enzymatic hydrolysis by glycosylases has stimulated the search for new alternatives more stable in vivo. herein, we present a good alternative for a dc-sign ligand based on a mannobioside mimic with a higher enzymatic stability than the corresponding disaccharide. nmr an ...200717508368
a deadly mystery. a savage outbreak of ebola virus is killing gorillas and chimps. epidemiologists have just figured out why. 200717511316
structure of the ebola fusion peptide in a membrane-mimetic environment and the interaction with lipid rafts.the fusion peptide ebo(16) (gaaiglawipyfgpaa) comprises the fusion domain of an internal sequence located in the envelope fusion glycoprotein (gp2) of the ebola virus. this region interacts with the cellular membrane of the host and leads to membrane fusion. to gain insight into the mechanism of the peptide-membrane interaction and fusion, insertion of the peptide was modeled by experiments in which the tryptophan fluorescence and (1)h nmr were monitored in the presence of sodium dodecyl sulfate ...200717545161
ebola virus vp30 is an rna binding protein.the ebola virus (ebov) genome encodes for several proteins that are necessary and sufficient for replication and transcription of the viral rnas in vitro; np, vp30, vp35, and l. vp30 acts in trans with an rna secondary structure upstream of the first transcriptional start site to modulate transcription. using a bioinformatics approach, we identified a region within the n terminus of vp30 with sequence features that typify intrinsically disordered regions and a putative rna binding site. to exper ...200717567691
influence of calcium/calmodulin on budding of ebola vlps: implications for the involvement of the ras/raf/mek/erk pathway.the vp40 matrix protein of ebola virus is able to bud from mammalian cells as a virus-like particle (vlp). interactions between l-domain motifs of vp40 and host proteins such as tsg101 and nedd4 serve to facilitate budding of vp40 vlps. since intracellular levels of calcium are known to influence localization and function of host proteins involved in virus budding, we sought to determine, whether alterations of calcium or calmodulin levels in cells would affect budding of vp40 vlps. vp40 vlp rel ...200717570046
the eighteenth african health sciences congress: dissemination of research results for utilisation.the african health sciences congress for 1997 will be held in cape town, south africa, from 14 to 18 april. this congress has been an annual event where scientists from across the world meet to present research results and to discuss meaningful approaches to solving some of the world's pressing health problems. the congress which is under the aegis of the african forum for health sciences (afhes), focusses special attention on ways of finding solutions for problems that afflict the african. the ...199717583970
how ebola and marburg viruses battle the immune system.the filoviruses ebola and marburg have emerged in the past decade from relative obscurity to serve now as archetypes for some of the more intriguing and daunting challenges posed by such agents. public imagination is captured by deadly outbreaks of these viruses and reinforced by the specter of bioterrorism. as research on these agents has accelerated, it has been found increasingly that filoviruses use a combination of familiar and apparently new ways to baffle and battle the immune system. fil ...200717589545
the ebola virus vp35 protein is a suppressor of rna silencing.rna silencing or interference (rnai) is a gene regulation mechanism in eukaryotes that controls cell differentiation and developmental processes via expression of micrornas. rnai also serves as an innate antiviral defence response in plants, nematodes, and insects. this antiviral response is triggered by virus-specific double-stranded rna molecules (dsrnas) that are produced during infection. to overcome antiviral rnai responses, many plant and insect viruses encode rna silencing suppressors (rs ...200717590081
ebola virus update. 199517590596
[development of a method for rapid detection of ebola virus antibodies and antigen].despite the wide spectrum of reliable methods for identifying ebola virus, their performance requires highly-skilled personnel, specialized laboratories, complicated equipment, and much time. therefore, there is a need for a method that allows a physician or a medical attendant to identify the causative agent in field or bedside tests without special equipment as soon as possible. the immunoassay involving nitrocellulose membrane immuno-filtration, by using a fixed antigen (antibodies) or their ...200717601052
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