PMID(sorted ascending)
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
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 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
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
the temporal program of peripheral blood gene expression in the response of nonhuman primates to ebola hemorrhagic fever.infection with ebola virus (ebov) causes a fulminant and often fatal hemorrhagic fever. in order to improve our understanding of ebov pathogenesis and ebov-host interactions, we examined the molecular features of ebov infection in vivo.200717725815
[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
conservation. scientists say ebola has pushed western gorillas to the brink. 200717872416
outbreak news. ebola virus haemorrhagic fever, democratic republic of the congo. 200717886402
outbreak news. ebola virus haemorrhagic fever, democratic republic of the congo--update. 200717918654
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
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
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
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
development of an immunofiltration-based antigen-detection assay for rapid diagnosis of ebola virus infection.ebola virus (ebov) has caused outbreaks of severe viral hemorrhagic fever in regions of central africa where medical facilities are ill equipped and diagnostic capabilities are limited. to obtain a reliable test that can be implemented easily under these conditions, monoclonal antibodies to the ebov matrix protein (vp40), which previously had been found to work in a conventional enzyme-linked immunosorbent assay, were used to develop an immunofiltration assay for the detection of ebov antigen in ...200717940948
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
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
analysis of filovirus entry into vero e6 cells, using inhibitors of endocytosis, endosomal acidification, structural integrity, and cathepsin (b and l) activity.ebola and marburg viruses are believed to enter host cells by receptor-mediated endocytosis. the process has been studied through the use of inhibitors that affect host cell properties and recombinant pseudotyping systems in which filovirus structural glycoproteins mediate entry of foreign virus particles. the aim of the present study was to determine the effects of such treatments on the entry of wild-type filoviruses. vero e6 cells were exposed to various inhibitors before, during, and after i ...200717940957
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
development of a novel one-tube isothermal reverse transcription thermophilic helicase-dependent amplification platform for rapid rna detection.the high complexity and cost of polymerase chain reaction-based molecular diagnostics sometimes limits their use in the clinical diagnostics setting. a new helicase-based isothermal amplification method offers an alternative to standard polymerase chain reaction, allowing amplification and detection of specific dna sequences at a constant reaction temperature without thermocycling equipment. herein, we describe the development of a novel one-tube isothermal reverse transcription-thermophilic hel ...200717975029
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
[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
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
interactions of lsectin and dc-sign/dc-signr with viral ligands: differential ph dependence, internalization and virion binding.the calcium-dependent lectins dc-sign and dc-signr (collectively termed dc-sign/r) bind to high-mannose carbohydrates on a variety of viruses. in contrast, the related lectin lsectin does not recognize mannose-rich glycans and interacts with a more restricted spectrum of viruses. here, we analyzed whether these lectins differ in their mode of ligand engagement. lsectin and dc-signr, which we found to be co-expressed by liver, lymph node and bone marrow sinusoidal endothelial cells, bound to solu ...200818083206
filoviruses: interactions with the host cell.the highly pathogenic filoviruses, marburg and ebola virus, are difficult to handle and knowledge of the interactions between filoviruses and their host cells remained enigmatic for many years. two developments were crucial for the presented advances in our understanding of the cell biology of filoviruses, which is still fragmentary. on the one hand, the number of high containment laboratories increased where handling of the highly pathogenic filoviruses is possible. on the other hand, molecular ...200818158582
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
cysteines flanking the internal fusion peptide are required for the avian sarcoma/leukosis virus glycoprotein to mediate the lipid mixing stage of fusion with high efficiency.we previously showed that the cysteines flanking the internal fusion peptide of the avian sarcoma/leukosis virus subtype a (aslv-a) env (enva) are important for infectivity and cell-cell fusion. here we define the stage of fusion at which the cysteines are required. the flanking cysteines are dispensable for receptor-triggered membrane association but are required for the lipid mixing step of fusion, which, interestingly, displays a high ph onset and a biphasic profile. second-site mutations tha ...200818184714
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
generation of biologically contained ebola viruses.ebola virus (ebov), a public health concern in africa and a potential biological weapon, is classified as a biosafety level-4 agent because of its high mortality rate and the lack of approved vaccines and antivirals. basic research into the mechanisms of ebov pathogenicity and the development of effective countermeasures are restricted by the current biosafety classification of ebovs. we therefore developed biologically contained ebov that express a reporter gene instead of the vp30 gene, which ...200818212124
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
[medicine and health in the democratic republic of congo: from independence to the third republic].the birth and mortality rates in the democratic republic of congo (drc), a former belgian colony, are high, i.e., 48.9/1000 and 17/1000 respectively. the drc also has one of the highest maternal death rates in the world, i.e., 1289/100,000 live births. health conditions have not improved since independence. access to drinking water is limited, living conditions are poor, and food availability in households is low. the mean health services utilization rate in the drc is estimated to be 0.15 visit ...200718225727
the creation of stable cell lines expressing ebola virus glycoproteins and the matrix protein vp40 and generating ebola virus-like particles utilizing an ecdysone inducible mammalian expression system.ebola virus is a filovirus that causes hemorrhagic fever in humans and is associated with case fatality rates of up to 90%. the lack of therapeutic interventions in combination with the threat of weaponizing this organism has enhanced research investigations. the expression of key viral proteins and the production of virus-like particles in mammalian systems are often pursued for characterization and functional studies. common practice is to express these proteins through transient transfection ...200818242720
viral haemorrhagic fever and vascular alterations.pathogenesis of viral haemorrhagic fever (vhf) is closely associated with alterations of the vascular system. among the virus families causing vhf, filoviruses (marburg and ebola) are the most fatal, and will be focused on here. after entering the body, ebola primarily targets monocytes/macrophages and dendritic cells. infected dendritic cells are largely impaired in their activation potency, likely contributing to the immune suppression that occurs during filovirus infection. monocytes/macropha ...200818278167
isg15 inhibits nedd4 ubiquitin e3 activity and enhances the innate antiviral response.interferons regulate diverse immune functions through the transcriptional activation of hundreds of genes involved in anti-viral responses. the interferon-inducible ubiquitin-like protein isg15 is expressed in cells in response to a variety of stress conditions like viral or bacterial infection and is present in its free form or is conjugated to cellular proteins. in addition, protein ubiquitination plays a regulatory role in the immune system. many viruses modulate the ubiquitin (ub) pathway to ...200818287095
global trends in emerging infectious diseases.emerging infectious diseases (eids) are a significant burden on global economies and public health. their emergence is thought to be driven largely by socio-economic, environmental and ecological factors, but no comparative study has explicitly analysed these linkages to understand global temporal and spatial patterns of eids. here we analyse a database of 335 eid 'events' (origins of eids) between 1940 and 2004, and demonstrate non-random global patterns. eid events have risen significantly ove ...200818288193
isg15 inhibits ebola vp40 vlp budding in an l-domain-dependent manner by blocking nedd4 ligase activity.ebola virus budding is mediated by the vp40 matrix protein. vp40 can bud from mammalian cells independent of other viral proteins, and efficient release of vp40 virus-like particles (vlps) requires interactions with host proteins such as tsg101 and nedd4, an e3 ubiquitin ligase. ubiquitin itself is thought to be exploited by ebola virus to facilitate efficient virus egress. disruption of vp40 function and thus virus budding remains an attractive target for the development of novel antiviral ther ...200818305167
functional cd8+ t cell responses in lethal ebola virus infection.ebola virus (ebov) causes highly lethal hemorrhagic fever that leads to death in up to 90% of infected humans. like many other infections, ebov induces massive lymphocyte apoptosis, which is thought to prevent the development of a functional adaptive immune response. in a lethal mouse model of ebov infection, we show that there is an increase in expression of the activation/maturation marker cd44 in cd4(+) and cd8(+) t cells late in infection, preceding a dramatic rebound of lymphocyte numbers i ...200818322215
nonhuman primate quarantine: its evolution and practice.nonhuman primates (nhps) are imported to the united states for use in research, domestic breeding, and propagation of endangered populations in zoological gardens. during the past 60 years, individuals responsible for nhp importation programs have observed morbidity and mortality typically associated with infectious disease outbreaks. these outbreaks have included infectious agents such as tuberculosis, herpesvirus sp., simian hemorrhagic fever, and filovirus infections such as the ebola and mar ...200818323577
outbreak news. ebola haemorrhagic fever, uganda--end of the outbreak. 200818326109
ebola virus matrix protein vp40 uses the copii transport system for its intracellular transport.the ebola virus matrix protein vp40 plays an important role in virion formation and viral egress from cells. however, the host cell proteins and mechanisms responsible for intracellular transport of vp40 prior to its contribution to virion formation remain to be elucidated. therefore we used coimmunoprecipitation and mass spectrometric analyses to identify host proteins interacting with vp40. we found that sec24c, a component of the host copii vesicular transport system, interacts specifically w ...200818329616
treatment of marburg and ebola hemorrhagic fevers: a strategy for testing new drugs and vaccines under outbreak conditions.the filoviruses, marburg and ebola, have the dubious distinction of being associated with some of the highest case-fatality rates of any known infectious disease--approaching 90% in many outbreaks. in recent years, laboratory research on the filoviruses has produced treatments and vaccines that are effective in laboratory animals and that could potentially drastically reduce case-fatality rates and curtail outbreaks in humans. however, there are significant challenges in clinical testing of thes ...200818336927
whole-genome expression profiling reveals that inhibition of host innate immune response pathways by ebola virus can be reversed by a single amino acid change in the vp35 protein.ebola hemorrhagic fever is a rapidly progressing acute febrile illness characterized by high virus replication, severe immunosuppression, and case fatalities of ca. 80%. inhibition of phosphorylation of interferon regulatory factor 3 (irf-3) by the ebola vp35 protein may block the host innate immune response and play an important role in the severity of disease. we used two precisely defined reverse genetics-generated ebola viruses to investigate global host cell responses resulting from the inh ...200818353943
recombinant vesicular stomatitis virus vector mediates postexposure protection against sudan ebola hemorrhagic fever in nonhuman primates.recombinant vesicular stomatitis virus (vsv) vectors expressing homologous filoviral glycoproteins can completely protect rhesus monkeys against marburg virus when administered after exposure and can partially protect macaques after challenge with zaire ebolavirus. here, we administered a vsv vector expressing the sudan ebolavirus (sebov) glycoprotein to four rhesus macaques shortly after exposure to sebov. all four animals survived sebov challenge, while a control animal that received a nonspec ...200818385248
protection against filovirus infection: virus-like particle vaccines.significant progress has been made in vaccine development against infection by ebola and marburg viruses, members of the filoviridae, which cause severe hemorrhagic fevers in humans with no effective treatment and a mortality rate of up to 90%. several vaccine strategies have been shown to effectively protect immunized animals against filovirus infection. among these candidate vaccine strategies, virus-like particles represent a promising approach and have been shown to protect small laboratory ...200818393603
a filovirus-unique region of ebola virus nucleoprotein confers aberrant migration and mediates its incorporation into virions.the ebola virus nucleoprotein (np) is an essential component of the nucleocapsid, required for filovirus particle formation and replication. together with virion protein 35 (vp35) and vp24, this gene product gives rise to the filamentous nucleocapsid within transfected cells. ebola virus np migrates aberrantly, with an apparent molecular mass of 115 kda, although it is predicted to encode an approximately 85-kda protein. in this report, we show that two domains of this protein determine this abe ...200818417588
processing of genome 5' termini as a strategy of negative-strand rna viruses to avoid rig-i-dependent interferon induction.innate immunity is critically dependent on the rapid production of interferon in response to intruding viruses. the intracellular pathogen recognition receptors rig-i and mda5 are essential for interferon induction by viral rnas containing 5' triphosphates or double-stranded structures, respectively. viruses with a negative-stranded rna genome are an important group of pathogens causing emerging and re-emerging diseases. we investigated the ability of genomic rnas from substantial representative ...200818446221
what caused lymphopenia in sars and how reliable is the lymphokine status in glucocorticoid-treated patients?severe acute respiratory syndrome (sars) outbreak in 2002-03 caused morbidity in over 8000 individuals and mortality in 744 in 29 countries. lymphopenia along with neutrophilia was a feature of sars, as it is in respiratory syncytial virus (rsv) and ebola infections, to name a few. direct infestation of lymphocytes, neutrophils and macrophages by sars coronavirus (cov) has been debated as a cause of lymphopenia, but there is no convincing data. lymphopenia can be caused by glucocorticoids, and t ...200818448259
cell adhesion promotes ebola virus envelope glycoprotein-mediated binding and infection.ebola virus infects a wide variety of adherent cell types, while nonadherent cells are found to be refractory. to explore this correlation, we compared the ability of pairs of related adherent and nonadherent cells to bind a recombinant ebola virus receptor binding domain (ebov rbd) and to be infected with ebola virus glycoprotein (gp)-pseudotyped particles. both human 293f and thp-1 cells can be propagated as adherent or nonadherent cultures, and in both cases adherent cells were found to be si ...200818448524
the strains of ebola. 200818458253
hiv-1 assembly: viral glycoproteins segregate quantally to lipid rafts that associate individually with hiv-1 capsids and assembly depends on its structural protein, gag, which after synthesis on ribosomes, traffics to the late endosome/plasma membrane, associates with hiv env glycoprotein, and forms infectious virions. while env and gag migrate to lipid microdomains, their stoichiometry and specificity of interaction are unknown. pseudotyped viral particles can be made with one viral core surrounded by heterologous envelope proteins. taking advantage of this property, we analyzed the association of hiv env a ...200818474355
the 1995 kikwit ebola outbreak--model of virus properties on system capacity and function: a lesson for future viral epidemics.the 1995 kikwit ebola outbreak in the democratic republic of the congo is one of the first ebola outbreaks to be treated in a hospital setting and is one of the most well-studied ebola epidemics to have occurred to date. many of the lessons learned from identifying, containing, and treating the epidemic are applicable to future viral outbreaks. this article looks at the characteristics of the ebola virus and health system issues, which affected the healthcare providers' ability to contain and tr ...200718491842
managing potential laboratory exposure to ebola virus by using a patient biocontainment care 2004, a scientist from the us army medical research institute of infectious diseases (usamriid) was potentially exposed to a mouse-adapted variant of the zaire species of ebola virus. the circumstances surrounding the case are presented, in addition to an update on historical admissions to the medical containment suite at usamriid. research facilities contemplating work with pathogens requiring biosafety level 4 laboratory precautions should be mindful of the occupational health issues highli ...200818507897
a dna vaccine for the prevention of ebola virus infection.the nih and vical inc are developing an intramuscular needle-free dna vaccine containing plasmids encoding the envelope glycoprotein of ebola virus (ebov) from the sudan and zaire strains, and the nucleoprotein of ebov zaire strain. a phase i clinical trial demonstrated a good safety profile, with most adverse events limited to the site of injection and largely attributable to the delivery.200818535936
novel astroviruses in insectivorous bats.bats are increasingly recognized to harbor a wide range of viruses, and in most instances these viruses appear to establish long-term persistence in these animals. they are the reservoir of a number of human zoonotic diseases including nipah, ebola, and severe acute respiratory syndrome. we report the identification of novel groups of astroviruses in apparently healthy insectivorous bats found in hong kong, in particular, bats belonging to the genera miniopterus and myotis. astroviruses are impo ...200818550669
potent in vitro activity of the albumin fusion type 1 interferons (albumin-interferon-alpha and albumin-interferon-beta) against rna viral agents of bioterrorism and the severe acute respiratory syndrome (sars) virus.the type 1 interferons (inf-alpha and inf-beta) are potent antiviral agents. albumin-inf-alpha and albumin-inf-beta are novel recombinant proteins consisting of ifn-alpha or ifn-beta genetically fused to human albumin.200818560223
a paramyxovirus-vectored intranasal vaccine against ebola virus is immunogenic in vector-immune animals.ebola virus (ebov) causes outbreaks of a highly lethal hemorrhagic fever in humans. the virus can be transmitted by direct contact as well as by aerosol and is considered a potential bioweapon. because direct immunization of the respiratory tract should be particularly effective against infection of mucosal surfaces, we previously developed an intranasal vaccine based on replication-competent human parainfluenza virus type 3 (hpiv3) expressing ebov glycoprotein gp (hpiv3/ebogp) and showed that i ...200818570964
dc-sign mediates avian h5n1 influenza virus infection in cis and in trans.dc-sign, a c-type lectin receptor expressed in dendritic cells (dcs), has been identified as a receptor for human immunodeficiency virus type 1, hepatitis c virus, ebola virus, cytomegalovirus, dengue virus, and the sars coronavirus. we used h5n1 pseudotyped and reverse-genetics (rg) virus particles to study their ability to bind with dc-sign. electronic microscopy and functional assay results indicate that pseudotyped viruses containing both ha and na proteins express hemagglutination and are c ...200818593570
molecular ecology and natural history of simian foamy virus infection in wild-living chimpanzees.identifying microbial pathogens with zoonotic potential in wild-living primates can be important to human health, as evidenced by human immunodeficiency viruses types 1 and 2 (hiv-1 and hiv-2) and ebola virus. simian foamy viruses (sfvs) are ancient retroviruses that infect old and new world monkeys and apes. although not known to cause disease, these viruses are of public health interest because they have the potential to infect humans and thus provide a more general indication of zoonotic expo ...200818604273
[vaccines, biotechnology and their connection with induced abortion].diploid cells (wi-38, mrc-5) vaccines have their origin in induced abortions. among these vaccines we fi nd the following: rubella, measles, mumps, rabies, polio, smallpox, hepatitis a, chickenpox, and herpes zoster. nowadays, other abortion tainted vaccines cultivated on transformed cells (293, per.c6) are in the pipeline: flu, respiratory syncytial and parainfluenza viruses, hiv, west nile virus, ebola, marburg and lassa, hepatitis b and c, foot and mouth disease, japanese encephalitis, dengue ...200818611078
structure of the ebola virus glycoprotein bound to an antibody from a human survivor.ebola virus (ebov) entry requires the surface glycoprotein (gp) to initiate attachment and fusion of viral and host membranes. here we report the crystal structure of ebov gp in its trimeric, pre-fusion conformation (gp1+gp2) bound to a neutralizing antibody, kz52, derived from a human survivor of the 1995 kikwit outbreak. three gp1 viral attachment subunits assemble to form a chalice, cradled by the gp2 fusion subunits, while a novel glycan cap and projected mucin-like domain restrict access to ...200818615077
docking, synthesis, and nmr studies of mannosyl trisaccharide ligands for dc-sign lectin.dc-sign, a lectin, which presents at the surface of immature dendritic cells, constitutes nowadays a promising target for the design of new antiviral drugs. this lectin recognizes highly glycosylated proteins present at the surface of several pathogens such as hiv, ebola virus, candida albicans, mycobacterium tuberculosis, etc. understanding the binding mode of this lectin is a topic of tremendous interest and will permit a rational design of new and more selective ligands. here, we present comp ...200818633532
[the strategic plan for preparedness and response to bioterrorism in korea].following the anthrax bioterrorism attacks in the us in 2001, the korean government established comprehensive countermeasures against bioterrorism. these measures included the government assuming management of all infectious agents that cause diseases, including smallpox, anthrax, plaque, botulism, and the causative agents of viral hemorrhagic fevers (ebola fever, marburg fever, and lassa fever) for national security. in addition, the korean government is reinforcing the ability to prepare and r ...200818664725
ebola images emerge from the cave.ebola virus causes a lethal hemorrhagic disease for which no therapy or vaccine is currently approved. recently, the crystal structure of the ebola virus glycoprotein in complex with a human neutralizing antibody was illuminated, providing a path from the shadows toward understanding cellular attachment, viral fusion, and immune evasion.200818692765
rna viruses and the mitogenic raf/mek/erk signal transduction cascade.the raf/mek/erk signal transduction cascade belongs to the mitogen-activated protein kinase (mapk) cascades. raf/mek/erk signaling leads to stimulus-specific changes in gene expression, alterations in cell metabolism or induction of programmed cell death (apoptosis), and thus controls cell differentiation and proliferation. it is induced by extracellular agents, including pathogens such as rna viruses. many dna viruses are known to induce cellular signaling via this pathway. as these pathogens p ...200818713014
adaptive modeling of viral diseases in bats with a focus on rabies.many emerging and reemerging viruses, such as rabies, sars, marburg, and ebola have bat populations as disease reservoirs. understanding the spillover from bats to humans and other animals, and the associated health risks requires an analysis of the disease dynamics in bat populations. traditional compartmental epizootic models, which are relatively easy to implement and analyze, usually impose unrealistic aggregation assumptions about disease-related structure and depend on parameters that freq ...200818761020
phosphoinositide-3 kinase-akt pathway controls cellular entry of ebola virus.the phosphoinositide-3 kinase (pi3k) pathway regulates diverse cellular activities related to cell growth, migration, survival, and vesicular trafficking. it is known that ebola virus requires endocytosis to establish an infection. however, the cellular signals that mediate this uptake were unknown for ebola virus as well as many other viruses. here, the involvement of pi3k in ebola virus entry was studied. a novel and critical role of the pi3k signaling pathway was demonstrated in cell entry of ...200818769720
the 1995 kikwit ebola outbreak: lessons hospitals and physicians can apply to future viral epidemics.this article looks at lessons learned from the 1995 kikwit ebola outbreak and suggests how modern hospitals should apply these lessons to the next lethal viral epidemic that occurs.200818774428
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