dc-sign: binding receptor for hcv?dc-sign, a dendritic cell-specific adhesion receptor and a type ii transmembrane mannose-binding c-type lectin, is very important in the function of dc, both in mediating naive t cell interactions through icam-3 and as a rolling receptor that mediates the dc-specific icam-2-dependent migration processes. it can be used by viral and bacterial pathogens including human immunodeficiency virus (hiv), hcv, ebola virus, cmv and mycobacterium tuberculosis to facilitate infection. both dc-sign and dc-si ...200415052667
organisation of health care during an outbreak of marburg haemorrhagic fever in the democratic republic of congo, 1999.organising health care was one of the tasks of the international scientific and technical committee during the 1998-1999 outbreak in durba/watsa, in the north-eastern province (province orientale), democratic republic of congo. with the logistical support of médecins sans frontières (msf), two isolation units were created: one at the durba reference health centre and the other at the okimo hospital in watsa. between may 6th, the day the isolation unit was installed and may 19th, 15 patients were ...200415066337
rapid detection protocol for filoviruses.the incidence of filovirus disease outbreaks has been increasing in recent years. although there have been advances in the developments of diagnostics, field tests are rare. apart from family members of infected patients, health care workers are at high risk of being infected during the initial phase of an outbreak. rt-pcr has been shown to be helpful in containing outbreaks.200415072761
in vitro evaluation of cyanovirin-n antiviral activity, by use of lentiviral vectors pseudotyped with filovirus envelope glycoproteins.cyanovirin-n (cv-n) has been shown to inhibit ebola zaire virus (ebozv) infection, both in vitro and in vivo, through its ability to bind to oligomannoses-8/9 on the ebozv surface glycoprotein (gp). here, we report the in vitro potency of cv-n to inhibit ebozv gp- and marburg virus gp-pseudotyped viruses (ec50 approximately 40-60 nmol/l and approximately 6-25 nmol/l, respectively) from mediating gene transduction into hela cells. in addition, we provide evidence that cv-n can effectively inhibit ...200415073681
the kindest cuts of all: crystal structures of kex2 and furin reveal secrets of precursor or pro-protein convertases are a conserved family of eukaryotic serine proteases found in the secretory pathway. these endoproteases mature precursors for peptides and proteins that perform a wide range of physiologically important and clinically relevant functions. the first member of this family to be identified was kex2 in the yeast saccharomyces cerevisiae. one mammalian member of this family - furin - is responsible for processing substrates that include insulin pro-receptor, hu ...200415102434
ectodomain shedding of the glycoprotein gp of ebola this study, release of abundant amounts of the ebola virus (ebov) surface glycoprotein gp in a soluble form from virus-infected cells was investigated. we demonstrate that the mechanism responsible for the release of gp is ectodomain shedding mediated by cellular sheddases. proteolytic cleavage taking place at amino-acid position d637 removes the transmembrane anchor and liberates complexes consisting of gp1 and truncated gp2 (gp(2delta)) subunits from the cell surface. we show that tumor nec ...200415103332
[strain differences related to ebola virus reproduction in peritoneal macrophages and in aorta explants of guinea pigs].reproduction of the ebola strains (es) virus causing lethality in guinea pigs as well as in peritoneal macrophages and aorta explants of animals was investigated in vitro and in vivo; besides, production of interferon-gamma (ifn-gamma) and of tumor necrosis factor-alpha (tnf-alpha) by macrophages and endotheliocytes of guinea pigs was also studied. the interplay "macrophage--es" by the example of 2 models of susceptibility to es demonstrates that the es lethality is not unambiguously related onl ...200415106377
[dynamics of complement hemolytic activity in experimental ebola infection].the dynamic hemolytic activity of complements (hac) was investigated in blood of guinea pigs in lethal and non-lethal ebola infection. the increasing hac dynamic activity in the animal blood was found to correlate with the infection lethal course. hac as observed in animals with lethal infection was sweepingly increasing after they, were infected with ebola virus, and yet after 15 hours from the infection time the complement activity parameters topped 2-fold the basic values in 100% of guinea pi ...200415106379
structural studies on the ebola virus matrix protein vp40 indicate that matrix proteins of enveloped rna viruses are analogues but not homologues.matrix proteins are the driving force of assembly of enveloped viruses. their main function is to interact with and polymerize at cellular membranes and link other viral components to the matrix-membrane complex resulting in individual particle shapes and ensuring the integrity of the viral particle. although matrix proteins of different virus families show functional analogy, they share no sequence or structural homology, their diversity is also evident in that they use a variety of late domain ...200415108720
properties of replication-competent vesicular stomatitis virus vectors expressing glycoproteins of filoviruses and arenaviruses.replication-competent recombinant vesicular stomatitis viruses (rvsvs) expressing the type i transmembrane glycoproteins and selected soluble glycoproteins of several viral hemorrhagic fever agents (marburg virus, ebola virus, and lassa virus) were generated and characterized. all recombinant viruses exhibited rhabdovirus morphology and replicated cytolytically in tissue culture. unlike the rvsvs with an additional transcription unit expressing the soluble glycoproteins, the viruses carrying the ...200415113924
context-dependent effects of l domains and ubiquitination on viral budding.many enveloped viruses encode late assembly domains, or l domains, that facilitate virion egress. ptap-type l domains act by recruiting the escrt-i (endosomal sorting complex required for transport i) component tsg101, and ypxl/lxxlf-type l domains recruit aip-1/alix, both of which are class e vacuolar protein sorting (vps) factors, normally required for the generation of vesicles within endosomes. the binding cofactors for ppxy-type l domains have not been unambiguously resolved but may include ...200415140952
the basic reproductive number of ebola and the effects of public health measures: the cases of congo and uganda.despite improved control measures, ebola remains a serious public health risk in african regions where recurrent outbreaks have been observed since the initial epidemic in 1976. using epidemic modeling and data from two well-documented ebola outbreaks (congo 1995 and uganda 2000), we estimate the number of secondary cases generated by an index case in the absence of control interventions r0. our estimate of r0 is 1.83 (sd 0.06) for congo (1995) and 1.34 (sd 0.03) for uganda (2000). we model the ...200415178190
use of recombinant cytokines for optimized induction of antiviral immunity against siv in the nonhuman primate model of human aids.outbreaks of infectious diseases such as hiv and the much televised and attention-getting outbreaks of diseases such as ebola, hantaviruses, and the most recent outbreak of sars have induced a significant new interest in the formulations and more importantly the science of vaccinology, which has previously to a large extent been conducted empirically. our laboratory has focused on the use of recombinant nonhuman primate cytokines as adjunctive therapies for inducing antigen-specific immune respo ...200415181266
molecular dynamics simulation of lipid reorientation at bilayer edges.understanding cellular membrane processes is critical for the study of events such as viral entry, neurotransmitter exocytosis, and immune activation. supported lipid bilayers are commonly used to model these membrane processes experimentally. despite the relative simplicity of such a system, many important structural and dynamic parameters are not experimentally observable with current techniques. computational approaches allow the development of a high-resolution model of bilayer processes. we ...200415189870
other viral bioweapons: ebola and marburg hemorrhagic fever.the term viral hemorrhagic fever refers to a clinical syndrome characterized by acute onset of fever accompanied by nonspecific findings of malaise, prostration, diarrhea,and headache. patients frequently show signs of increased vascular permeability, and many develop bleeding diatheses. the hemorrhagic fever viruses represent potential agents for biologic warfare because of capability of aerosol transmission, high morbidity,and mortality associated with infection, and ability to replicate in ce ...200415207310
contribution of ebola virus glycoprotein, nucleoprotein, and vp24 to budding of vp40 virus-like particles.the vp40 matrix protein of ebola virus buds from cells in the form of virus-like particles (vlps) and plays a central role in virus assembly and budding. in this study, we utilized a functional budding assay and cotransfection experiments to examine the contributions of the glycoprotein (gp), nucleoprotein (np), and vp24 of ebola virus in facilitating release of vp40 vlps. we demonstrate that vp24 alone does not affect vp40 vlp release, whereas np and gp enhance release of vp40 vlps, individuall ...200415220407
roles of a conserved proline in the internal fusion peptide of ebola glycoprotein.the structural determinants underlying the functionality of viral internal fusion peptides (ifps) are not well understood. we have compared ebowt (gaaiglawipyfgpaae), representing the ifp of the ebola fusion protein gp, and ebowt (gaaiglawipyfgraae) derived from a non-functional mutant with conserved pro537 substituted by arg. p537r substitution did not abrogate peptide-membrane association, but interfered with the ability to induce bilayer destabilization. structural determinations suggest that ...200415225645
crimean-congo hemorrhagic fever: prevention and control limitations in a resource-poor autumn 2000, an outbreak of crimean-congo hemorrhagic fever (cchf) occurred in pakistan and involved nosocomial cases due to human-to-human transmission at a tertiary care hospital in karachi. during a hospital-based investigation, 6 serologically confirmed cases (i.e., patients seropositive for cchf antigen or anti-cchf immunoglobulin m antibodies by means of a capture enzyme-linked immunosorbent assay [elisa]) and 3 clinically confirmed cases (i.e., patients with negative elisa for cchf but ...200415227619
role of natural killer cells in innate protection against lethal ebola virus infection.ebola virus is a highly lethal human pathogen and is rapidly driving many wild primate populations toward extinction. several lines of evidence suggest that innate, nonspecific host factors are potentially critical for survival after ebola virus infection. here, we show that nonreplicating ebola virus-like particles (vlps), containing the glycoprotein (gp) and matrix protein virus protein (vp)40, administered 1-3 d before ebola virus infection rapidly induced protective immunity. vlp injection e ...200415249592
sudan ebola outbreak of known strain. 200415252932
high resolution crystal structure of human rab9 gtpase: a novel antiviral drug target.rab gtpases and their effectors facilitate vesicular transport by tethering donor vesicles to their respective target membranes. rab9 mediates late endosome to trans-golgi transport and has recently been found to be a key cellular component for human immunodeficiency virus-1, ebola, marburg, and measles virus replication, suggesting that it may be a novel target in the development of broad spectrum antiviral drugs. as part of our structure-based drug design program, we have determined the crysta ...200415263003
ebola and marburg virus-like particles activate human myeloid dendritic cells.the filoviruses, ebola (ebov) and marburg (marv), are potential global health threats, which cause deadly hemorrhagic fevers. although both ebov and marv logarithmically replicate in dendritic cells (dcs), these viruses do not elicit dc cytokine secretion and fail to activate and mature infected dcs. here, we employed virus-like particles (vlps) of ebov and marv to investigate whether these genome-free particles maintain similar immune evasive properties as authentic filoviruses. confocal micros ...200415302213
marburg virus-like particles protect guinea pigs from lethal marburg virus infection.ongoing outbreaks of filoviruses in africa and concerns about their use in bioterrorism attacks have led to intense efforts to find safe and effective vaccines to prevent the high mortality associated with these viruses. we previously reported the generation of virus-like particles (vlps) for the filoviruses, marburg (marv) and ebola (ebov) virus, and that vaccinating mice with ebola vlps (evlps) results in complete survival from a lethal ebov challenge. the objective of this study was to determ ...200415308377
glycodendritic structures: promising new antiviral drugs.dc-sign, a c-type lectin expressed by dendritic cells, is able to recognize high mannosylated glycoproteins at the surface of a broad range of pathogens including viruses, bacteria, fungi and parasites. for at least some of these agents this interaction appears to be an important part of the infection process. therefore, this lectin might be considered in the design of new antiviral drugs. in this manner, multivalent carbohydrate systems based on dendrimers and dendritic polymers are promising c ...200415308605
emerging infections in animals--potential new zoonoses?it is well recognized that most emerging diseases of humans are zoonotic, and that the forces working to create emerging diseases in humans are also operating in animal populations. however, what is often overlooked is that emerging human diseases are usually preceded by the emergence of the same pathogen in an animal population. in fact, the developing disease in animals acts as a link allowing the disease to take hold and wreck havoc in public health. numerous examples--rift valley fever, monk ...200415325066
analysis of human peripheral blood samples from fatal and nonfatal cases of ebola (sudan) hemorrhagic fever: cellular responses, virus load, and nitric oxide levels.peripheral blood samples obtained from patients during an outbreak of ebola virus (sudan species) disease in uganda in 2000 were used to phenotype peripheral blood mononuclear cells (pbmc), quantitate gene expression, measure antigenemia, and determine nitric oxide levels. it was determined that as the severity of disease increased in infected patients, there was a corresponding increase in antigenemia and leukopenia. blood smears revealed thrombocytopenia, a left shift in neutrophils (in some c ...200415367603
disulfide bond assignment of the ebola virus secreted glycoprotein sgp.the non-structural glycoprotein (sgp) of ebola virus (ebov) is secreted in large amounts from infected cells as a disulfide-linked homodimer. in this communication, highly purified sgp, derived from vero e6 cultures infected with the zaire species of ebov, was used to determine the correct localization of inter- and intrachain disulfide bonds. matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry analysis of proteolytic cleavage fragments indicates that all cysteines (six ...200415369806
sequence and structure relatedness of matrix protein of human respiratory syncytial virus with matrix proteins of other negative-sense rna viruses.matrix proteins of viruses within the order mononegavirales have similar functions and play important roles in virus assembly. protein sequence alignment, phylogenetic tree derivation, hydropathy profiles and secondary structure prediction were performed on selected matrix protein sequences, using human respiratory syncytial virus matrix protein as the reference. no general conservation of primary, secondary or tertiary structure was found, except for a broad similarity in the hydropathy pattern ...200415373896
dc-sign: binding receptors for hepatitis c review the recent developments in and research into binding receptors of hepatitis c virus (hcv) and especially the role of dendritic cell-specific adhesion receptor (dc-sign) in hcv.200415377434
ebola virus ecology: a continuing mystery. 200415381189
ebola virus: new insights into disease aetiopathology and possible therapeutic interventions.ebola virus (ebov) gained public notoriety in the last decade largely as a consequence of the highly publicized isolation of a new ebov species in a suburb of washington, dc, in 1989, together with the dramatic clinical presentation of ebov infection and high case-fatality rate in africa (near 90% in some outbreaks), and the unusual and striking morphology of the virus. furthermore, there are no vaccines or effective therapies currently available. progress in understanding the origins of the pat ...200415383160
application of real-time pcr for testing antiviral compounds against lassa virus, sars coronavirus and ebola virus in vitro.this report describes the application of real-time pcr for testing antivirals against highly pathogenic viruses such as lassa virus, sars coronavirus and ebola virus. the test combines classical cell culture with a quantitative real-time pcr read-out. the assay for lassa virus was validated with ribavirin, which showed an ic(50) of 9 micrograms/ml. small-scale screening identified a class of imidazole nucleoside/nucleotide analogues with antiviral activity against lassa virus. the analogues cont ...200415451189
[functional activity of peritoneal macrophages in experimental ebola fever].the phagocytic activity of peritoneal macrophages (a representative of mononuclear phagocytes) as well as the tnf-alpha were studied in animals with different susceptibility to ebola virus (ev). the results denote the following: 1. phagocytosis activation by peritoneal macrophages after ev is introduced into the body correlates directly with a susceptibility degree of an animal to ev. 2. the ev content in peritoneal lavage is inversely dependent on a phagocytic activity of peritoneal macrophages ...200415455683
flipping the switch from monomeric to dimeric cv-n has little effect on antiviral activity.cyanovirin-n can exist in solution in monomeric and domain-swapped dimeric forms, with hiv-antiviral activity being reported for both. here we present results for cv-n variants that form stable solution dimers: the obligate dimer [deltaq50]cv-n and the preferential dimer [s52p]cv-n. these variants exhibit comparable deltag values (10.6 +/- 0.5 and 9.4 +/- 0.5 kcal.mol(-1), respectively), similar to that of stabilized, monomeric [p51g]cv-n (9.8 +/- 0.5 kcal.mol(-1)), but significantly higher than ...200415458629
[bacterial and viral epidemics of zoonotic origin; the role of hunting and cutting up wild animals].since the prehistoric times hunting has been a vital activity for man. however, this may account for the contamination of the hunter, his family and relatives. infections may occur by direct contact with blood or tissues of infected animal during handling and cutting up preys and when preparing or eating meat, or also when bitten by injured animal. apes and antelopes hunting in sub-saharan africa proves to be particularly important since it has been well established that the recent or previous e ...200415462204
representations of sars in the british the spring of 2003, there was a huge interest in the global news media following the emergence of a new infectious disease: severe acute respiratory syndrome (sars). this study examines how this novel disease threat was depicted in the uk newspapers, using social representations theory and in particular existing work on social representations of hiv/aids and ebola to analyse the meanings of the epidemic. it investigates the way that sars was presented as a dangerous threat to the uk public, w ...200415474209
dc-sign and dc-signr interact with the glycoprotein of marburg virus and the s protein of severe acute respiratory syndrome coronavirus.the lectins dc-sign and dc-signr can augment viral infection; however, the range of pathogens interacting with these attachment factors is incompletely defined. here we show that dc-sign and dc-signr enhance infection mediated by the glycoprotein (gp) of marburg virus (marv) and the s protein of severe acute respiratory syndrome coronavirus and might promote viral dissemination. signr1, a murine dc-sign homologue, also enhanced infection driven by marv and ebola virus gp and could be targeted to ...200415479853
an uncertain defense. how do you test that a human ebola vaccine works? you don't. 200415487661
cd209l (l-sign) is a receptor for severe acute respiratory syndrome coronavirus.angiotensin-converting enzyme 2 (ace2) is a receptor for sars-cov, the novel coronavirus that causes severe acute respiratory syndrome [li, w. moore, m. j., vasilieva, n., sui, j., wong, s. k., berne, m. a., somasundaran, m., sullivan, j. l., luzuriaga, k., greenough, t. c., et al. (2003) nature 426, 450-454]. we have identified a different human cellular glycoprotein that can serve as an alternative receptor for sars-cov. a human lung cdna library in vesicular stomatitis virus g pseudotyped ret ...200415496474
multivesicular bodies as a platform for formation of the marburg virus envelope.the marburg virus (marv) envelope consists of a lipid membrane and two major proteins, the matrix protein vp40 and the glycoprotein gp. both proteins use different intracellular transport pathways: gp utilizes the exocytotic pathway, while vp40 is transported through the retrograde late endosomal pathway. it is currently unknown where the proteins combine to form the viral envelope. in the present study, we identified the intracellular site where the two major envelope proteins of marv come toge ...200415507615
transduction of satellite cells after prenatal intramuscular administration of lentiviral vectors.we have previously reported long-term expression of lacz in myocytes after in utero intramuscular injection of mokola and ebola pseudotyped lentiviral vectors. in further experiments, we have noted that these vectors also transduce small cells at the periphery of the muscle fibers that have the morphology of satellite cells, or muscle stem cells. in this study we performed experiments to further define the morphology and function of these cells.200515515139
rescue of ebola virus from cdna using heterologous support proteins.using the infectious clone for zaire ebolavirus, the functional specificity of viral proteins of the ribonucleoprotein complex in transcription/replication was investigated by substituting them with heterologous proteins derived from closely (reston ebolavirus) and distantly related filoviruses (marburgvirus). the data clearly demonstrated that transcription/replication are neither strictly species-specific nor genus-specific. protein interactions between the nucleoprotein np and the virion prot ...200415522446
seasonality of infectious diseases and severe acute respiratory syndrome-what we don't know can hurt us.the novel severe acute respiratory syndrome (sars) coronavirus caused severe disease and heavy economic losses before apparently coming under complete control. our understanding of the forces driving seasonal disappearance and recurrence of infectious diseases remains fragmentary, thus limiting any predictions about whether, or when, sars will recur. it is true that most established respiratory pathogens of human beings recur in wintertime, but a new appreciation for the high burden of disease i ...200415522683
ebola virus ecology. 200415529250
a serological survey of ebola virus infection in central african nonhuman primates.we used an elisa to determine the prevalence of igg antibodies specific for the zaire subtype of ebola virus in 790 nonhuman primates, belonging to 20 species, studied between 1985 and 2000 in cameroon, gabon, and the republic of congo. the seroprevalence rate of ebola antibody in wild-born chimpanzees was 12.9%, indicating that (1) ebola virus circulates in the forests of a large region of central africa, including countries such as cameroon, where no human cases of ebola infections have been r ...200415529251
filovirus filoviridae, which includes ebola virus (ebov) and marburg virus (marv), is a growing threat to human and non-human primate populations in central africa. although many facets of the filovirus life cycle remain to be deciphered, a great deal has been learned in recent years. in particular, a clearer understanding of the roles played by viral, as well as cellular, proteins in the assembly and budding processes has been achieved. this review will discuss the current state of filovirus buddi ...200415567496
sequencing needs for viral diagnostics.we built a system to guide decisions regarding the amount of genomic sequencing required to develop diagnostic dna signatures, which are short sequences that are sufficient to uniquely identify a viral species. we used our existing dna diagnostic signature prediction pipeline, which selects regions of a target species genome that are conserved among strains of the target (for reliability, to prevent false negatives) and unique relative to other species (for specificity, to avoid false positives) ...200415583268
marburg and ebola viruses as aerosol threats.ebola and marburg viruses are the sole members of the genus filovirus in the family filoviridae. there has been considerable media attention and fear generated by outbreaks of filoviruses because they can cause a severe viral hemorrhagic fever (vhf) syndrome that has a rapid onset and high mortality. although they are not naturally transmitted by aerosol, they are highly infectious as respirable particles under laboratory conditions. for these and other reasons, filoviruses are classified as cat ...200415588056
ebola virus glycoprotein toxicity is mediated by a dynamin-dependent protein-trafficking pathway.ebola virus infection causes a highly lethal hemorrhagic fever syndrome associated with profound immunosuppression through its ability to induce widespread inflammation and cellular damage. though gp, the viral envelope glycoprotein, mediates many of these effects, the molecular events that underlie ebola virus cytopathicity are poorly understood. here, we define a cellular mechanism responsible for ebola virus gp cytotoxicity. gp selectively decreased the expression of cell surface molecules th ...200515596847
studies of ebola virus glycoprotein-mediated entry and fusion by using pseudotyped human immunodeficiency virus type 1 virions: involvement of cytoskeletal proteins and enhancement by tumor necrosis factor alpha.the ebola filoviruses are aggressive pathogens that cause severe and often lethal hemorrhagic fever syndromes in humans and nonhuman primates. to date, no effective therapies have been identified. to analyze the entry and fusion properties of ebola virus, we adapted a human immunodeficiency virus type 1 (hiv-1) virion-based fusion assay by substituting ebola virus glycoprotein (gp) for the hiv-1 envelope. fusion was detected by cleavage of the fluorogenic substrate ccf2 by beta-lactamase-vpr inc ...200515613320
[viral hemorrhagic fevers--ebola hemorrhagic fever, marburg virus disease, and lassa fever]. 200415624463
containing the threat--don't forget ebola. 200415630468
the highly specific carbohydrate-binding protein cyanovirin-n: structure, anti-hiv/ebola activity and possibilities for therapy.cyanovirin-n (cv-n), a cyanobacterial lectin, is a potent viral entry inhibitor currently under development as a microbicide against a broad spectrum of enveloped viruses. cv-n was originally identified as a highly active anti-hiv agent and later, as a virucidal agent against other unrelated enveloped viruses such as ebola, and possibly other viruses. cv-n's antiviral activity appears to involve unique recognition of n-linked high-mannose oligosaccharides, man-8 and man-9, on the viral surface g ...200515638789
epidemiology: past, present and future.epidemiology in the past was concerned essentially by the study of infectious diseases which were the cause of huge mortalities especially since urbanisation was initiated. epidemics of pest, typhus, cholera, influenza a.o. were common. the epidemics were halted by better hygiene, vaccination and antibiotics. since the second world war epidemiology was dominated by an "epidemic" of new chronic diseases, especially heart disease and cancer. this was due to an increase in life span and to an incre ...200415641567
demand for nonhuman primate resources in the age of biodefense.the demand for nonhuman primates will undoubtedly increase to meet biomedical needs in this current age of biodefense. the availability of funding has increased the research on select agents and has created a requirement to validate results in relevant primate models. this review provides a description of current and potential biological threats that are likely to require nonhuman primates for the development of vaccines and therapeutics. primates have been an invaluable resource in the dissecti ...200515644560
vp40 octamers are essential for ebola virus replication.matrix protein vp40 of ebola virus is essential for virus assembly and budding. monomeric vp40 can oligomerize in vitro into rna binding octamers, and the crystal structure of octameric vp40 has revealed that residues phe125 and arg134 are the most important residues for the coordination of a short single-stranded rna. here we show that full-length wild-type vp40 octamers bind rna upon hek 293 cell expression. while the phe125-to-ala mutation resulted in reduced rna binding, the arg134-to-ala mu ...200515650213
the disease profile of poverty: morbidity and mortality in northern uganda in the context of war, population displacement and hiv/aids.the population of gulu district (northern uganda) has been severely incapacitated by war, epidemics and social disruption. this study is aimed at describing disease patterns and trends in this area through a retrospective analysis of discharge records for 155205 in-patients of lacor hospital in the period 1992-2002. the burden of infectious diseases in childhood is overwhelming, with malaria accounting for the steepest increase in admissions. admissions for war-related injuries and malnutrition ...200515653126
generation of egfp expressing recombinant zaire ebolavirus for analysis of early pathogenesis events and high-throughput antiviral drug screening.zaire ebolavirus causes large outbreaks of severe and usually fatal hemorrhagic disease in humans for which there is no effective treatment or cure. to facilitate examination of early critical events in viral pathogenesis and to identify antiviral compounds, a recombinant zaire ebolavirus was engineered to express a foreign protein, egfp, to provide a rapid and sensitive means to monitor virus replication in infected cells. this genetically engineered virus represents the first insertion of a fo ...200515661137
a reconstituted replication and transcription system for ebola virus reston and comparison with ebola virus zaire.the only known filovirus, which presumably is not pathogenic for humans, is ebola virus (ebov) reston. when ebov reston and the highly pathogenic ebov zaire were grown in cell culture, comparison of the replication kinetics showed a clear growth impairment of ebov reston, indicating that the replication cycle of ebov reston might be delayed. in addition, the cytopathic effect caused by the virus was much milder with ebov reston than with ebov zaire. to compare replication and transcription of eb ...200515661171
potential mammalian filovirus reservoirs.ebola and marburg viruses are maintained in unknown reservoir species; spillover into human populations results in occasional human cases or epidemics. we attempted to narrow the list of possibilities regarding the identity of those reservoir species. we made a series of explicit assumptions about the reservoir: it is a mammal; it supports persistent, largely asymptomatic filovirus infections; its range subsumes that of its associated filovirus; it has coevolved with the virus; it is of small bo ...200415663841
exposure to nonhuman primates in rural cameroon.exposure to nonhuman primates has led to the emergence of important diseases, including ebola hemorrhagic fever, aids, and adult t-cell leukemia. to determine the extent of exposure to nonhuman primates, persons were examined in 17 remote villages in cameroon that represented three habitats (savanna, gallery forest, and lowland forest). questionnaire data were collected to assess whether persons kept wild animal pets; hunted and butchered wild game; had experienced bites, scratches, or injuries ...200415663844
bichat guidelines for the clinical management of haemorrhagic fever viruses and bioterrorism-related haemorrhagic fever viruses.haemorrhagic fever viruses (hfvs) are a diverse group of viruses that cause a clinical disease associated with fever and bleeding disorder. hfvs that are associated with a potential biological threat are ebola and marburg viruses (filoviridae), lassa fever and new world arenaviruses (machupo, junin, guanarito and sabia viruses) (arenaviridae), rift valley fever (bunyaviridae) and yellow fever, omsk haemorrhagic fever, and kyanasur forest disease (flaviviridae). in terms of biological warfare con ...200415677844
role of ebola virus secreted glycoproteins and virus-like particles in activation of human macrophages.ebola virus, a member of the family filoviridae, causes one of the most severe forms of viral hemorrhagic fever. in the terminal stages of disease, symptoms progress to hypotension, coagulation disorders, and hemorrhages, and there is prominent involvement of the mononuclear phagocytic and reticuloendothelial systems. cells of the mononuclear phagocytic system are primary target cells and producers of inflammatory mediators. ebola virus efficiently produces four soluble glycoproteins during infe ...200515681442
the role of wildlife in emerging and re-emerging zoonoses.there are huge numbers of wild animals distributed throughout the world and the diversity of wildlife species is immense. each landscape and habitat has a kaleidoscope of niches supporting an enormous variety of vertebrate and invertebrate species, and each species or taxon supports an even more impressive array of macro- and micro-parasites. infectious pathogens that originate in wild animals have become increasingly important throughout the world in recent decades, as they have had substantial ...200415702716
transduction of the choroid plexus and ependyma in neonatal mouse brain by vesicular stomatitis virus glycoprotein-pseudotyped lentivirus and adeno-associated virus type 5 vectors.evaluation of gene transfer into the developing mouse brain has shown that when adeno-associated virus serotype 1 (aav1) or aav2 vectors are injected into the cerebral lateral ventricles at birth, widespread parenchymal transduction occurs. lentiviral vectors have not been tested by this route. in this study, we found that injection of lentiviral vectors pseudotyped with vesicular stomatitis virus glycoprotein (vsv-g) resulted in targeted transduction of the ependymal cells lining the ventricula ...200515703488
low seroprevalence of igg antibodies to ebola virus in an epidemic zone: ogooué-ivindo region, northeastern gabon, 1997.a population-based serosurvey was performed to determine the seroprevalence of antibodies to ebola virus (ebo) in a region that has experienced multiple epidemics of ebo hemorrhagic fever. of 2533 residents in 8 villages, serum samples from 979 (38.6%) were tested by enzyme-linked immunosorbent assay for immunoglobulin (ig) g and igm antibodies to ebola-zaire (ebo-z) virus. fourteen samples (1.4%) were found positive for igg antibodies, and 4 of these (.4%) were samples from survivors of an epid ...200515717273
wild animal mortality monitoring and human ebola outbreaks, gabon and republic of congo, 2001-2003.all human ebola virus outbreaks during 2001-2003 in the forest zone between gabon and republic of congo resulted from handling infected wild animal carcasses. after the first outbreak, we created an animal mortality monitoring network in collaboration with the gabonese and congolese ministries of forestry and environment and wildlife organizations (wildlife conservation society and programme de conservation et utilisation rationnelle des ecosystemes forestiers en afrique centrale) to predict and ...200515752448
ebola virus antibody prevalence in dogs and human risk.during the 2001-2002 outbreak in gabon, we observed that several dogs were highly exposed to ebola virus by eating infected dead animals. to examine whether these animals became infected with ebola virus, we sampled 439 dogs and screened them by ebola virus-specific immunoglobulin (ig) g assay, antigen detection, and viral polymerase chain reaction amplification. seven (8.9%) of 79 samples from the 2 main towns, 15 (15.2%) of 99 samples from mekambo, and 40 (25.2%) of 159 samples from villages i ...200515757552
rna polymerase i-driven minigenome system for ebola general, ebola viruses are well known for their ability to cause severe hemorrhagic fever in both human and nonhuman primates. however, despite substantial sequence homology to other members of the family filoviridae, reston ebolavirus displays reduced pathogenicity for nonhuman primates and has never been demonstrated to cause clinical disease in humans, despite its ability to cause infection. in order to develop a tool to explore potential roles for transcription and replication in the redu ...200515767442
cd8-mediated protection against ebola virus infection is perforin dependent.cd8 t cells have been shown to play an important role in the clearance and protection against fatal ebola virus infection. in this study, we examined the mechanisms by which cd8 t cells mediate this protection. our data demonstrate that all normal mice infected s.c. with a mouse-adapted ebola virus survived the infection, as did 100% of mice deficient in fas and 90% of those deficient in ifn-gamma. in contrast, perforin-deficient mice uniformly died after s.c. challenge. perforin-deficient mice ...200515778381
association of ebola virus matrix protein vp40 with microtubules.viruses exploit a variety of cellular components to complete their life cycles, and it has become increasingly clear that use of host cell microtubules is a vital part of the infection process for many viruses. a variety of viral proteins have been identified that interact with microtubules, either directly or via a microtubule-associated motor protein. here, we report that ebola virus associates with microtubules via the matrix protein vp40. when transfected into mammalian cells, a fraction of ...200515795257
comprehensive analysis of ebola virus gp1 in viral entry.ebola virus infection is initiated by interactions between the viral glycoprotein gp1 and its cognate receptor(s), but little is known about the structure and function of gp1 in viral entry, partly due to the concern about safety when working with the live ebola virus and the difficulty of manipulating the rna genome of ebola virus. in this study, we have used a human immunodeficiency virus-based pseudotyped virus as a surrogate system to dissect the role of ebola virus gp1 in viral entry. analy ...200515795265
nucleocapsid-like structures of ebola virus reconstructed using electron tomography.electron tomography (et) is a new technique for high resolution, three-dimensional (3d) reconstruction of pleiomorphic macromolecular complexes, such as virus components. by employing this technique, we resolved the 3d structure of ebola virus nucleocapsid-like (nc-like) structures in the cytoplasm of cells expressing np, vp24, and vp35: the minimum components required to form these nc-like structures. reconstruction of these tubular nc-like structures of ebola virus showed them to be composed o ...200515805739
virus-like particles exhibit potential as a pan-filovirus vaccine for both ebola and marburg viral infections.a safe and effective pan-filovirus vaccine is highly desirable since the filoviruses ebola virus (ebov) and marburg virus (marv) cause highly lethal disease typified by unimpeded viral replication and severe hemorrhagic fever. previously, we showed that expression of the homologous glycoprotein (gp) and matrix protein vp40 from a single filovirus, either ebov or marv, resulted in formation of wild-type virus-like particles (vlps) in mammalian cells. when used as a vaccine, the wild-type vlps pro ...200515811650
endosomal proteolysis of the ebola virus glycoprotein is necessary for infection.ebola virus (ebov) causes rapidly fatal hemorrhagic fever in humans and there is currently no effective treatment. we found that the infection of african green monkey kidney (vero) cells by vesicular stomatitis viruses bearing the ebov glycoprotein (gp) requires the activity of endosomal cysteine proteases. using selective protease inhibitors and protease-deficient cell lines, we identified an essential role for cathepsin b (catb) and an accessory role for cathepsin l (catl) in ebov gp-dependent ...200515831716
functional characterization of ebola virus l-domains using vsv recombinants.vsv recombinants containing the overlapping l-domain sequences from ebola virus vp40 (ptappey) were recovered by reverse-genetics. replication kinetics of m40-wt, m40-p24l, and m40-y30a were indistinguishable from vsv-wt in bhk-21 cells, whereas the double mutant (m40-p2728a) was defective in budding. insertion of the ebola l-domain region into vsv m protein was sufficient to alter the dependence on host proteins for efficient budding. indeed, m40 recombinants containing a functional ptap motif ...200515892969
analysis of ebola virus and vlp release using an immunocapture assay.ebola virus (ebov), an emerging pathogen, is the causative agent of a rapidly progressive hemorrhagic fever with high mortality rates. there are currently no approved vaccines or treatments available for ebola hemorrhagic fever. standard plaque assays are currently the only reliable techniques for enumerating the virus. effective drug-discovery screening as well as target identification and validation require simple and more rapid detection methods. this report describes the development of a rap ...200515893559
ebola virus: the role of macrophages and dendritic cells in the pathogenesis of ebola hemorrhagic fever.ebola hemorrhagic fever is a severe viral infection characterized by fever, shock and coagulation defects. recent studies in macaques show that major features of illness are caused by effects of viral replication on macrophages and dendritic cells. infected macrophages produce proinflammatory cytokines, chemokines and tissue factor, attracting additional target cells and inducing vasodilatation, increased vascular permeability and disseminated intravascular coagulation. however, they cannot rest ...200515896665
particulate delivery systems for biodefense subunit vaccines.expanding identification of potentially protective subunit antigens and correlates of protection has provided a basis for the introduction of safer vaccines. despite encouraging results in animal models, the significant potential of particulate delivery systems in vaccine design has not yet translated into effective vaccines available for use in humans. this review article will focus on the current status of the development of particulate vaccines, mainly liposomes and bio-degradable polymers, a ...200515935873
live attenuated recombinant vaccine protects nonhuman primates against ebola and marburg viruses.vaccines and therapies are urgently needed to address public health needs stemming from emerging pathogens and biological threat agents such as the filoviruses ebola virus (ebov) and marburg virus (marv). here, we developed replication-competent vaccines against ebov and marv based on attenuated recombinant vesicular stomatitis virus vectors expressing either the ebov glycoprotein or marv glycoprotein. a single intramuscular injection of the ebov or marv vaccine elicited completely protective im ...200515937495
novel innate immune functions for galectin-1: galectin-1 inhibits cell fusion by nipah virus envelope glycoproteins and augments dendritic cell secretion of proinflammatory cytokines.galectin-1 (gal-1), an endogenous lectin secreted by a variety of cell types, has pleiotropic immunomodulatory functions, including regulation of lymphocyte survival and cytokine secretion in autoimmune, transplant disease, and parasitic infection models. however, the role of gal-1 in viral infections is unknown. nipah virus (niv) is an emerging pathogen that causes severe, often fatal, febrile encephalitis. the primary targets of niv are endothelial cells. niv infection of endothelial cells res ...200515972675
marburg and ebola--arming ourselves against the deadly filoviruses. 200515972860
how ebola virus infects cells. 200515972874
the natural history of ebola virus in africa.several countries spanning the equatorial forest regions of africa have had outbreaks of ebola hemorrhagic fever over the last three decades. this article is an overview of the many published investigations of how ebola virus circulates in its natural environment, focusing on the viral reservoir, susceptible animal species, environmental conditions favoring inter-species transmission, and how the infection is transmitted to humans. major breakthroughs have been made in recent years but many outs ...200516002313
induction of humoral and cd8+ t cell responses are required for protection against lethal ebola virus infection.ebola virus (ebov)-like particles (evlp), composed of the ebov glycoprotein and matrix viral protein (vp)40 with a lipid membrane, are a highly efficacious method of immunization against ebov infection. the exact requirements for immunity against ebov infection are poorly defined at this time. the goal of this work was to determine the requirements for ebov immunity following evlp vaccination. vaccination of balb/c or c57bl/6 mice with evlps in conjunction with qs-21 adjuvant resulted in mixed i ...200516002721
vaccines against ebola and marburg viruses show promise in primate studies. 200516014579
a single shot against ebola and marburg virus. 200516015361
filovirus-like particles as vaccines and discovery tools.ebola and marburg viruses are members of the family filoviridae, which cause severe hemorrhagic fevers in humans. filovirus outbreaks have been sporadic, with mortality rates currently ranging from 30 to 90%. unfortunately, there is no efficacious human therapy or vaccine available to treat disease caused by either ebola or marburg virus infection. expression of the filovirus matrix protein, vp40, is sufficient to drive spontaneous production and release of virus-like particles (vlps) that resem ...200516026254
the intrinsically disordered c-terminal domain of the measles virus nucleoprotein interacts with the c-terminal domain of the phosphoprotein via two distinct sites and remains predominantly unfolded.measles virus is a negative-sense, single-stranded rna virus within the mononegavirales order,which includes several human pathogens, including rabies, ebola, nipah, and hendra viruses. the measles virus nucleoprotein consists of a structured n-terminal domain, and of an intrinsically disordered c-terminal domain, n(tail) (aa 401-525), which undergoes induced folding in the presence of the c-terminal domain (xd, aa 459-507) of the viral phosphoprotein. with in n(tail), an alpha-helical molecular ...200516046624
ebola virus vp40 late domains are not essential for viral replication in cell culture.ebola virus particle formation and budding are mediated by the vp40 protein, which possesses overlapping ptap and ppxy late domain motifs (7-ptappxy-13). these late domain motifs have also been found in the gag proteins of retroviruses and the matrix proteins of rhabdo- and arenaviruses. while in vitro studies suggest a critical role for late domain motifs in the budding of these viruses, including ebola virus, it remains unclear as to whether the vp40 late domains play a role in ebola virus rep ...200516051823
effects of ebola virus glycoproteins on endothelial cell activation and barrier function.ebola virus causes severe hemorrhagic fever with high mortality rates in humans and nonhuman primates. vascular instability and dysregulation are disease-decisive symptoms during severe infection. while the transmembrane glycoprotein gp(1,2) has been shown to cause endothelial cell destruction, the role of the soluble glycoproteins in pathogenesis is largely unknown; however, they are hypothesized to be of biological relevance in terms of target cell activation and/or increase of endothelial per ...200516051836
the ebola virus genomic replication promoter is bipartite and follows the rule of this work we investigated the cis-acting signals involved in replication of ebola virus (ebov) genomic rna. a set of mingenomes with mutant 3' ends were generated and used in a reconstituted replication and transcription system. our results suggest that the ebov genomic replication promoter is bipartite, consisting of a first element located within the leader region of the genome and a second, downstream element separated by a spacer region. while proper spacing of the two promoter elements i ...200516051858
mannose-binding lectin binds to ebola and marburg envelope glycoproteins, resulting in blocking of virus interaction with dc-sign and complement-mediated virus neutralization.mannose-binding lectin (mbl), a serum lectin that mediates innate immune functions including activation of the lectin complement pathway, binds to carbohydrates expressed on some viral glycoproteins. in this study, the ability of mbl to bind to virus particles pseudotyped with ebola and marburg envelope glycoproteins was evaluated. virus particles bearing either ebola (zaire strain) or marburg (musoke strain) envelope glycoproteins bound at significantly higher levels to immobilized mbl compared ...200516099912
the contribution of the endothelium to the development of coagulation disorders that characterize ebola hemorrhagic fever in primates.recently, there have been substantial developments in the understanding of ebola hemorrhagic fever pathogenesis, but there are still major gaps. these infections occur in underdeveloped areas of the world, and much of our knowledge of naturally occurring disease is derived from sporadic outbreaks that occurred decades in the past. recently conducted laboratory animal studies have provided insight into ebola pathogenesis and may help guide clinical investigations of disease using contemporary met ...200516113813
complete genome sequence of an ebola virus (sudan species) responsible for a 2000 outbreak of human disease in uganda.the entire genomic rna of the gulu (uganda 2000) strain of ebola virus was sequenced and compared to the genomes of other filoviruses. this data represents the first comprehensive genetic analysis for a representative isolate of the sudan species of ebola virus. the genome organization of the sudan species is nearly identical to that of the zaire species, but the presence of a gene overlap (between gp and vp30 genes) and a longer trailer sequence distinguish it from that of the reston species. a ...200516139097
rab9 gtpase is required for replication of human immunodeficiency virus type 1, filoviruses, and measles virus.rab proteins and their effectors facilitate vesicular transport by tethering donor vesicles to their respective target membranes. by using gene trap insertional mutagenesis, we identified rab9, which mediates late-endosome-to-trans-golgi-network trafficking, among several candidate host genes whose disruption allowed the survival of marburg virus-infected cells, suggesting that rab9 is utilized in marburg replication. although rab9 has not been implicated in human immunodeficiency virus (hiv) re ...200516140752
using blood glucose data as an indicator for epidemic disease the future, transfer of vital sensor data from patients to the public health care system is likely to become commonplace. systems for automatic transfer of sensor data are now at the prototype stage. as electronic health record (ehr) systems adapt such functionality, widespread use may become an actuality in the foreseeable prevent spreading of diseases, an early detection of infection is important. at the time an outbreak is diagnosed, many people may already be infected due to the ...200516160262
human dendritic cells and macrophages exhibit different intracellular processing pathways for soluble and liposome-encapsulated antigens.the intracellular fates of soluble and liposomal antigens in human macrophages and dendritic cells are not well defined. previous studies using murine macrophages have demonstrated that liposomal antigens can enter the mhc class i pathway. the golgi complex is a major organelle in this pathway. phagocytosis of the antigens is followed by translocation of antigen-derived peptides to the trans-golgi where they can complex with mhc class i molecules. in contrast, soluble antigens are normally proce ...200516164039
inhibiting hiv fusion with a beta-peptide foldamer.linear peptides derived from the hiv gp41 c-terminus (c-peptides), such as the 36-residue fuzeon, are potent hiv fusion inhibitors. these molecules bind to the n-peptide region of gp41 and inhibit an intramolecular protein-protein interaction that powers fusion of the viral and host cell membranes. the n-peptide region contains a surface pocket that is occupied in the post-fusion state by three alpha-helical residues found near the gp41 c-terminus: trp628, trp631, and ile635-the wwi epitope. her ...200516173723
analysis of the expressed heavy chain variable-region genes of macaca fascicularis and isolation of monoclonal antibodies specific for the ebola virus' soluble glycoprotein.the cynomolgus macaque, macaca fascicularis, is frequently used in immunological and other biomedical research as a model for man; understanding it's antibody repertoire is, therefore, of fundamental interest. the expressed variable-region gene repertoire of a single m. fascicularis, which was immune to the ebola virus, was studied. using 5' rapid amplification of cdna ends with immunoglobulin (ig)g-specific primers, we obtained 30 clones encoding full-length variable, diversity, and joining dom ...200516215733
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