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
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
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
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 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
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
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
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
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
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
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
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
[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
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
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
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
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
[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
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
a deadly mystery. a savage outbreak of ebola virus is killing gorillas and chimps. epidemiologists have just figured out why. 200717511316
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
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
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
[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
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
ebola sgp--the first viral glycoprotein shown to be c-mannosylated.mass spectrometry analysis of the ebola virus soluble glycoprotein sgp identified a rare post-translation modification, c-mannosylation, which was found on tryptophan (w) 288. this modification has not been described for any other viral protein; however, many viral transmembrane glycoproteins contain one or more of the recognition motifs (w-x-x-w). elimination of the c-mannose on sgp did not significantly alter protein biosynthesis, processing or structure. furthermore, the protective effect of ...200717659315
[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
current knowledge on lower virulence of reston ebola virus (in french: connaissances actuelles sur la moindre virulence du virus ebola reston).ebola viruses (ebov) and marburg virus belong to the family filoviridae, order mononegavirales. the genus ebolavirus consists of four species: zaire ebolavirus (zebov), sudan ebolavirus (sebov), ivory coast ebolavirus (icebov) and reston ebolavirus (rebov). three species of ebolaviruses, zebov, sebov, icebov, and marburg virus are known to be extremely pathogenic in primates and humans and cause severe hemorrhagic fever leading up to case fatality rate of some 90%, while rebov is thought to be p ...200717610952
marburg virus infection detected in a common african bat.marburg and ebola viruses can cause large hemorrhagic fever (hf) outbreaks with high case fatality (80-90%) in human and great apes. identification of the natural reservoir of these viruses is one of the most important topics in this field and a fundamental key to understanding their natural history. despite the discovery of this virus family almost 40 years ago, the search for the natural reservoir of these lethal pathogens remains an enigma despite numerous ecological studies. here, we report ...200717712412
[risk of nosocomial infection in intertropical africa--part 3: health care workers].parts of the nosocomial infections issue are the professionally-acquired infections of health care workers. this problem is widely neglected in sub-saharan africa, and little is known on the subject, in spite of the high prevalence of blood-borne infections such as hiv or hepatitis b and c, and air-borne diseases like tuberculosis. besides, unsafe practices and accidents like blood exposures are more frequent than in western countries. this is due to the lack of political concern, of safer equip ...200717784685
ebolavirus and other filoviruses.since ebola fever emerged in central africa in 1976, a number of studies have been undertaken to investigate its natural history and to characterize its transmission from a hypothetical reservoir host(s) to humans. this research has comprised investigations on a variety of animals and their characterization as intermediate, incidental, amplifying, reservoir, or vector hosts. a viral transmission chain was recently unveiled after a long absence of epidemic ebola fever. animal trapping missions we ...200717848072
outbreak news. ebola virus haemorrhagic fever, democratic republic of the congo. 200717886402
ebola virus vp24 proteins inhibit the interaction of npi-1 subfamily karyopherin alpha proteins with activated stat1.the zaire ebolavirus protein vp24 was previously demonstrated to inhibit alpha/beta interferon (ifn-alpha/beta)- and ifn-gamma-induced nuclear accumulation of tyrosine-phosphorylated stat1 (py-stat1) and to inhibit ifn-alpha/beta- and ifn-gamma-induced gene expression. these properties correlated with the ability of vp24 to interact with the nuclear localization signal receptor for py-stat1, karyopherin alpha1. here, vp24 is demonstrated to interact not only with overexpressed but also with endo ...200717928350
proteolysis of the ebola virus glycoproteins enhances virus binding and infectivity.cellular cathepsins are required for ebola virus infection and are believed to proteolytically process the ebola virus glycoprotein (gp) during entry. however, the significance of cathepsin cleavage during infection remains unclear. here we demonstrate a role for cathepsin l (catl) cleavage of ebola virus gp in the generation of a stable 18-kda gp1 viral intermediate that exhibits increased binding to and infectivity for susceptible cell targets. cell binding to a lymphocyte line was increased w ...200717928356
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
the ecology of ebola virus.since ebola virus was first identified more than 30 years ago, tremendous progress has been made in understanding the molecular biology and pathogenesis of this virus. however, the means by which ebola virus is maintained and transmitted in nature remains unclear despite dedicated efforts to answer these questions. recent work has provided new evidence that fruit bats might have a role as a reservoir species, but it is not clear whether other species are also involved or how transmission to huma ...200717698361
role for amino acids 212klr214 of ebola virus vp40 in assembly and budding.ebola virus vp40 is able to produce virus-like particles (vlps) in the absence of other viral proteins. at least three domains within vp40 are thought to be required for efficient vlp release: the late domain (l-domain), membrane association domain (m-domain), and self-interaction domain (i-domain). while the l-domain of ebola vp40 has been well characterized, the exact mechanism by which vp40 mediates budding through the m- and i-domains remains unclear. to identify additional domains important ...200717699576
outbreaks of filovirus hemorrhagic fever: time to refocus on the the 40 years since the recognition of filoviruses as agents of lethal human disease, there have been no specific advances in antiviral therapies or vaccines and few clinical studies on the efficacy of supportive care. on 20 september 2006, experts from 14 countries representing 68 institutions integrally involved in the response to outbreaks of filovirus hemorrhagic fever gathered at the national microbiology laboratory of the public health agency of canada in winnipeg to discuss possible rem ...200717940941
high-throughput molecular detection of hemorrhagic fever virus threats with applications for outbreak settings.within the past dozen years, outbreaks of filoviral hemorrhagic fever within the human population have been occurring with increasing frequency, with an average of 1 epidemic now occurring every 1-2 years. many of the outbreaks have been large (involving >150 cases), necessitating rapid responses from the international community to help implement infection control and surveillance. this increased activity, combined with today's climate of bioterrorism threats, has heightened the need for high-th ...200717940951
rapid assembly of sensitive antigen-capture assays for marburg virus, using in vitro selection of llama single-domain antibodies, at biosafety level 4.there is a pressing need for rapid and reliable approaches to the delivery of sensitive yet rugged diagnostic assays specific for emerging viruses, to hasten containment of outbreaks when and wherever they occur. within 3 weeks, we delivered an antigen-capture assay for marburg virus (marv) that was based on llama single-domain antibodies (sdabs) selected at biosafety level 4. four unique sdabs were capable of independently detecting marv variants musoke, ravn, and angola without cross-reactivit ...200717940952
analysis of the interaction of ebola virus glycoprotein with dc-sign (dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin) and its homologue dc-signr.the lectin dc-sign (dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin) augments ebola virus (ebov) infection. however, it its unclear whether dc-sign promotes only ebov attachment (attachment factor function, nonessential) or actively facilitates ebov entry (receptor function, essential).200717940955
regions in ebola virus vp24 that are important for nucleocapsid formation.ebola virus (ebov) vp24, together with nucleoprotein and vp35, is an essential component of viral rna-protein complexes called "nucleocapsids." in this study, using a series of deletion mutants of vp24, we identified regions within vp24 that are important for the formation of nucleocapsid-like structures and determined that both termini of vp24 are essential for nucleocapsid formation. this finding advances our knowledge of both ebov morphogenesis and the nature of vp24 molecules in nucleocapsid ...200717940956
the mechanism of axl-mediated ebola virus infection.we previously reported that expression of the receptor-type tyrosine kinase axl, which regulates cell survival and activation, enhances both pseudotype and live ebola virus (ebov) infection. to clarify the mechanistic basis of this enhancement, we created a series of axl mutants and identified amino acids/domains necessary for this function, by using a pseudotype virus carrying the ebov glycoprotein (gp). analyses of the axl mutants showed the importance of extracellular and intracellular region ...200717940958
involvement of vacuolar protein sorting pathway in ebola virus release independent of tsg101 interaction.budding of ebola virus (ebov) particles from the plasma membrane of infected cells requires viral and host proteins. ebov virus matrix protein vp40 recruits tsg101, an escrt-1 (host cell endosomal sorting complex required for transport-1) complex protein in the vacuolar protein sorting (vps) pathway, to the plasma membrane during budding. involvement of other vps proteins in ebov budding has not been established. therefore, we used vp40 deletion analysis, virus-like particle-release assays, and ...200717940959
blockage of filoviral glycoprotein processing by use of a protein-based inhibitor.cleavage of the glycoproteins of many virus species by furin and other host cell proteases is required for virus infectivity and, hence, determines viral pathogenicity. proteolytic processing of marburg virus and ebola virus glycoproteins is also mediated by furin; however, for ebola virus, in contrast to other viruses, glycoprotein cleavage is dispensable for replication in vitro, as has been shown in previous studies. in the present study, by use of a highly potent and selective furin inhibito ...200717940960
ebola virus inactivation with preservation of antigenic and structural integrity by a photoinducible alkylating agent.current methods for inactivating filoviruses are limited to high doses of irradiation or formalin treatment, which may cause structural perturbations that are reflected by poor immunogenicity. in this report, we describe a novel inactivation technique for zaire ebola virus (zebov) that uses the photoinduced alkylating probe 1,5-iodonaphthylazide (ina). ina is incorporated into lipid bilayers and, when activated by ultraviolet irradiation, alkylates the proteins therein. ina treatment of zebov re ...200717940961
ebola virus (ebov) vp24 inhibits transcription and replication of the ebov genome.the roles of ebola virus (ebov) vp24 in nucleocapsid (nc) formation and the effect of vp24 on transcription and replication of the viral genome during nc formation remain unknown. we therefore examined the effect of vp24 on the expression of a reporter gene (luciferase), viral rna, and messenger rna from the ebov minigenome. vp24 inhibited the expression of luciferase and both rnas in a dose-dependent manner, suggesting that vp24 inhibits transcription and replication of the ebov genome. by cont ...200717940962
mapping of a region of ebola virus vp40 that is important in the production of virus-like particles.ebola virus vp40 contains 2 overlapping late domains (7-ptap-10 and 10-ppey-13) that are essential for its interaction with tsg101 and nedd4 in the promotion of viral egress. deletion of the late domains inhibits vp40-induced virus-like particles (vlps). however, a truncated form of vp40, which lacks a late domain because of the deletion of amino acids 1-30, is released into supernatant as a vlp, indicating that the remaining portion of vp40 contains the structural elements required for vlp rele ...200717940963
lymphocyte death in a mouse model of ebola virus infection.a striking feature of zaire ebola virus (zebov) infection in nonhuman primates is the rapid depletion of t and nk lymphocytes by apoptosis. in a mouse model of zebov infection, lymphocyte death is a prominent finding; however, the mechanism of death and the lymphocyte subsets that are targeted remain unknown.200717940964
in vitro and in vivo characterization of recombinant ebola viruses expressing enhanced green fluorescent facilitate an understanding of the molecular aspects of the pathogenesis of zaire ebolavirus (zebov) infection, we generated 2 different recombinant viruses expressing enhanced green fluorescent protein (egfp) from additional transcription units inserted at different positions in the virus genome. these viruses showed in vitro phenotypes similar to that of wild-type zebov (wt-zebov) and were stable over multiple passages. infection with one of the viruses expressing egfp produced only mild di ...200717940966
pathologic findings associated with delayed death in nonhuman primates experimentally infected with zaire ebola virus.zaire ebola virus infection in macaques causes a fatal disease with a pathogenesis similar to that in humans. during several independent therapy studies, we noted altered tissue tropism in 6 rhesus macaques that survived longer than those with a typical disease course. the mean time to death for these 6 macaques was 21.7 days, which is significantly longer than the average mean time to death of 8.3 days for 20 untreated historical control animals. in addition to living significantly longer, thes ...200717940967
sequence-based human leukocyte antigen-b typing of patients infected with ebola virus in uganda in 2000: identification of alleles associated with fatal and nonfatal disease outcomes.the sudan species of ebola virus (sebov) causes severe, often fatal infection in approximately 50% of infected humans. we sought to determine whether the human leukocyte antigen-b (hla-b) locus has a role in the outcome of sebov disease by typing 77 cases from an outbreak in northern uganda in 2000-2001. sequence-based hla-b typing was performed using leukocytes isolated from 77 patients. statistical analysis and a predictive discriminant analysis (pda) were applied to typing data. epitope predi ...200717940968
epitopes required for antibody-dependent enhancement of ebola virus infection.we have shown that antibody-dependent enhancement (ade) of infection with zaire ebola virus (zebov) is mediated by interaction of virus-specific antibodies with fc receptors or complement component c1q and its receptors in vitro. ade activities of the antisera to the viral glycoprotein (gp) were virus species specific and were primarily correlated with immunoglobulin (ig) g2a and igm levels but not with igg1 levels. interestingly, compared with zebov, reston ebola virus (rebov) had substantially ...200717940970
cytokine and chemokine expression in humans infected with sudan ebola virus.the size and duration of the 2000 outbreak of sudan ebola virus (sebov) infection in uganda made it possible to collect serial serum samples from 87 patients (53 survivors and 34 nonsurvivors). surprisingly, the levels of tumor necrosis factor- alpha and interferon (ifn)- gamma , which had been found to be increased in patients with fatal zaire ebola virus infection, were not increased in any of the patients with sebov infection. the levels of interleukin (il)-1 beta , ifn- gamma -inducible prot ...200717940971
blood chemistry measurements and d-dimer levels associated with fatal and nonfatal outcomes in humans infected with sudan ebola virus.blood samples from patients infected with the sudan species of ebola virus (ebov), obtained during an outbreak of disease in uganda in 2000, were tested for a panel of analytes to evaluate their clinical condition and to compare values obtained for patients with fatal and nonfatal cases and for uninfected (hospitalized control) patients. liver function tests showed higher levels of aspartate aminotransferase (ast) in blood samples from patients with fatal cases than in samples from patients with ...200717940972
marburg virus angola infection of rhesus macaques: pathogenesis and treatment with recombinant nematode anticoagulant protein c2.the procoagulant tissue factor (tf) is thought to play a role in the coagulation disorders that characterize filoviral infections. in this study, we evaluated the pathogenesis of lethal infection with the angola strain of marburg virus (marv-ang) in rhesus macaques and tested the efficacy of recombinant nematode anticoagulant protein c2 (rnapc2), an inhibitor of tf/factor viia, as a potential treatment.200717940973
recombinant human activated protein c for the postexposure treatment of ebola hemorrhagic fever.infection of primates with zaire ebolavirus (zebov) leads to hypotension, coagulation disorders, and an impaired immune response and, in many ways, resembles severe sepsis. rapid decreases in plasma levels of protein c are a prominent feature of severe sepsis and zebov hemorrhagic fever (zhf). currently, recombinant human activated protein c (rhapc [xigris; eli lilly]) is licensed for treating human patients with severe sepsis who are at high risk of death. the aim of this study was to test the ...200717940975
ebola hemorrhagic fever: evaluation of passive immunotherapy in nonhuman primates.the survival of 7 of 8 patients with ebola virus (ebov) infection after transfusions of convalescent-phase blood during a 1995 outbreak of ebov infection is frequently cited as evidence that passive immunotherapy is a viable treatment option. to test whether whole-blood transfusions were more efficacious than passively administered immunoglobulins or monoclonal antibodies, we transfused convalescent-phase blood from ebov-immune monkeys into naive animals shortly after challenge with ebov. althou ...200717940976
assessment of a vesicular stomatitis virus-based vaccine by use of the mouse model of ebola virus hemorrhagic humans and nonhuman primates, ebola virus causes a virulent viral hemorrhagic fever for which no licensed vaccines or therapeutic drugs exist. in the present study, we used the mouse model for ebola hemorrhagic fever to assess the safety and efficacy of a vaccine based on a live attenuated vesicular stomatitis virus expressing the zaire ebolavirus (zebov) glycoprotein.200717940977
mucosal delivery of adenovirus-based vaccine protects against ebola virus infection in mice.mucosal vaccination can offer several advantages over conventional intramuscular immunization to protect against ebola virus (ebov) infection, such as immune protection at sites of viral entry into susceptible individuals, and can be administered using needle-free devices.200717940978
filovirus-like particles produced in insect cells: immunogenicity and protection in rodents.virus-like particles (vlps) of ebola virus (ebov) and marburg virus (marv) produced in human 293t embryonic kidney cells have been shown to be effective vaccines against filoviral infection. in this study, we explored alternative strategies for production of filovirus-like particle-based vaccines, to accelerate the development process. the goal of this work was to increase the yield of vlps, while retaining their immunogenic properties.200717940979
ebola virus-like particle-based vaccine protects nonhuman primates against lethal ebola virus challenge.currently, there are no licensed vaccines or therapeutics for the prevention or treatment of infection by the highly lethal filoviruses, ebola virus (ebov) and marburg virus (marv), in humans. we previously had demonstrated the protective efficacy of virus-like particle (vlp)-based vaccines against ebov and marv infection in rodents.200717940980
immunopathology of highly virulent pathogens: insights from ebola virus.ebola virus is a highly virulent pathogen capable of inducing a frequently lethal hemorrhagic fever syndrome. accumulating evidence indicates that the virus actively subverts both innate and adaptive immune responses and triggers harmful inflammatory responses as it inflicts direct tissue damage. the host immune system is ultimately overwhelmed by a combination of inflammatory factors and virus-induced cell damage, particularly in the liver and vasculature, often leading to death from septic sho ...200717952040
development of a model for marburgvirus based on severe-combined immunodeficiency mice.the filoviruses, ebola (ebov) and marburg (marv), cause a lethal hemorrhagic fever. human isolates of marv are not lethal to immmunocompetent adult mice and, to date, there are no reports of a mouse-adapted marv model. previously, a uniformly lethal ebov-zaire mouse-adapted virus was developed by performing 9 sequential passages in progressively older mice (suckling to adult). evaluation of this model identified many similarities between infection in mice and nonhuman primates, including viral t ...200717961252
a novel mechanism for lsectin binding to ebola virus surface glycoprotein through truncated glycans.lsectin is a member of the c-type lectin family of glycan-binding receptors that is expressed on sinusoidal endothelial cells of the liver and lymph nodes. to compare the sugar and pathogen binding properties of lsectin with those of related but more extensively characterized receptors, such as dc-sign, a soluble fragment of lsectin consisting of the c-terminal carbohydrate-recognition domain has been expressed in bacteria. a biotin-tagged version of the protein was also generated and complexed ...200817984090
spatial and temporal patterns of zaire ebolavirus antibody prevalence in the possible reservoir bat characterize the distribution of zaire ebolavirus (zebov) infection within the 3 bat species (epomops franqueti, hypsignathus monstrosus, and myonycteris torquata) that are possible reservoirs, we collected 1390 bats during 2003-2006 in gabon and the republic of the congo. detection of zebov immunoglobulin g (igg) in 40 specimens supports the role of these bat species as the zebov reservoirs. zebov igg prevalence rates (5%) were homogeneous across epidemic and nonepidemic regions during outbr ...200717940947
an interferon-alpha-induced tethering mechanism inhibits hiv-1 and ebola virus particle release but is counteracted by the hiv-1 vpu protein.type 1 interferon (ifn) inhibits the release of hiv-1 virus particles via poorly defined mechanisms. here, we show that ifnalpha induces retention of viral particles on the surface of fibroblasts, t cells, or primary lymphocytes infected with hiv-1 lacking the vpu protein. retained particles are tethered to cell surfaces, can be endocytosed, appear fully assembled, exhibit mature morphology, and can be detached by protease. strikingly, expression of the hiv-1 vpu protein attenuates the ability o ...200718005734
complex of a protective antibody with its ebola virus gp peptide epitope: unusual features of a v lambda x light chain.13f6-1-2 is a murine monoclonal antibody that recognizes the heavily glycosylated mucin-like domain of the ebola virus virion-attached glycoprotein (gp) and protects animals against lethal viral challenge. here we present the crystal structure, at 2.0 a, of 13f6-1-2 in complex with its ebola virus gp peptide epitope. the gp peptide binds in an extended conformation, anchored primarily by interactions with the heavy chain. two gp residues, gln p406 and arg p409, make extensive side-chain hydrogen ...200818005986
[feline immunodeficiency virus tropism].feline immunodeficiency virus (fiv) induces a disease similar to acquired immunodeficiency syndrome (aids) in cats, yet in contrast to human immunodeficiency virus (hiv), cd4 is not the viral receptor. we identified a primary receptor for fiv as cd134 (ox40), a t cell activation antigen and costimulatory molecule. cd134 expression promotes viral binding and renders cells permissive for viral entry, productive infection, and syncytium formation. infection is cxcr4-dependent, analogous to infectio ...200718040157
niaid resources for developing new therapies for severe viral infections.severe viral infections, including hemorrhagic fever and encephalitis, occur throughout the world, but are most prevalent in developing areas that are most vulnerable to infectious diseases. some of these can also infect related species as illustrated by the threatened extinction of gorillas by ebola infection in west and central africa. there are no safe and effective treatments available for these serious infections. in addition to the logistical difficulties inherent in developing a drug for ...200818061283
assessment of the risk of ebola virus transmission from bodily fluids and fomites.although ebola virus (ebov) is transmitted by unprotected physical contact with infected persons, few data exist on which specific bodily fluids are infected or on the risk of fomite transmission. therefore, we tested various clinical specimens from 26 laboratory-confirmed cases of ebola hemorrhagic fever, as well as environmental specimens collected from an isolation ward, for the presence of ebov. virus was detected by culture and/or reverse-transcription polymerase chain reaction in 16 of 54 ...200717940942
ebola outbreak in uganda "atypical", say experts. 200718161067
[recombinant full-size human antibody to ebola virus].a full-size human antibody to ebola virus was constructed by joining genes encoding the constant domains of the heavy and light chains of human immunoglobulin with the corresponding dna fragments encoding variable domains of the single-chain antibody 4d1 specific to ebola virus, which was chosen from a combinatorial phage display library of single-strand human antibodies. two expression plasmids. pch1 and pcl1, containing the artificial genes encoding the light and heavy chains of human immunogl ...200718173122
comparing ape densities and habitats in northern congo: surveys of sympatric gorillas and chimpanzees in the odzala and ndoki regions.the conservation status of western lowland gorillas and central chimpanzees in western equatorial africa remains largely speculative because many remote areas have never been surveyed and the impact of emergent diseases in the region has not been well documented. in this study, we compared ape densities and habitats in the lokoué study area in odzala national park and the goualougo triangle in nouabalé-ndoki national park in northern republic of congo. both of these sites have long been consider ...200818176937
viral genome sequencing by random priming methods.most emerging health threats are of zoonotic origin. for the overwhelming majority, their causative agents are rna viruses which include but are not limited to hiv, influenza, sars, ebola, dengue, and hantavirus. of increasing importance therefore is a better understanding of global viral diversity to enable better surveillance and prediction of pandemic threats; this will require rapid and flexible methods for complete viral genome sequencing.200818179705
laboratory diagnosis of ebola hemorrhagic fever during an outbreak in yambio, sudan, 2004.between the months of april and june 2004, an ebola hemorrhagic fever (ehf) outbreak was reported in yambio county, southern sudan. blood samples were collected from a total of 36 patients with suspected ehf and were tested by enzyme-linked immunosorbent assay (elisa) for immunoglobulin g and m antibodies, antigen elisa, and reverse-transcription polymerase chain reaction (pcr) of a segment of the ebolavirus (ebov) polymerase gene. a total of 13 patients were confirmed to be infected with ebov. ...200717940949
inhibition of irf-3 activation by vp35 is critical for the high level of virulence of ebola virus.zaire ebolavirus causes a rapidly progressing hemorrhagic disease with high mortality. identification of the viral virulence factors that contribute to the severity of disease induced by ebola virus is critical for the design of therapeutics and vaccines against the disease. given the rapidity of disease progression, virus interaction with the innate immune system early in the course of infection likely plays an important role in determining the outcome of the disease. the ebola virus vp35 prote ...200818199658
[bad bats?].for many centuries, man is fascinated by bats, the only flying mammals. probably because of their particular immune system, bats can be considered an important reservoir for new emerging viral diseases like sars-coronavirus, marburg fever, ebola fever and nipah virus encephalitis. during closer contact, they can transmit rabies and probably other nonviral infectious diseases. bats get closer to man due to ecological modifications like deforestation, so that transmission of new infectious agents ...200717985603
vaccine to confer to nonhuman primates complete protection against multistrain ebola and marburg virus infections.filoviruses (ebola and marburg viruses) are among the deadliest viruses known to mankind, with mortality rates nearing 90%. these pathogens are highly infectious through contact with infected body fluids and can be easily aerosolized. additionally, there are currently no licensed vaccines available to prevent filovirus outbreaks. their high mortality rates and infectious capabilities when aerosolized and the lack of licensed vaccines available to prevent such infectious make ebola and marburg vi ...200818216185
[important issues of biological safety].the problem of biological security raises alarm due to the real growth of biological threats. biological security includes a wide scope of problems, the solution of which becomes a part of national security as a necessary condition for the constant development of the country. a number of pathogens, such as human immunodeficiency virus, exotic ebola and lassa viruses causing hemorrhagic fever,rotaviruses causing acute intestinal diseases, etc. were first discovered in the last century. terrorist ...200718225506
Displaying items 801 - 900 of 7763