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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
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
[viral hemorrhagic fevers--ebola hemorrhagic fever, marburg virus disease, and lassa fever]. 200415624463
containing the threat--don't forget ebola. 200415630468
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 budding.family 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
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 viruses.in 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 six.in 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 outbreaks.in 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 future.to 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
wave-like spread of ebola zaire.in the past decade the zaire strain of ebola virus (zebov) has emerged repeatedly into human populations in central africa and caused massive die-offs of gorillas and chimpanzees. we tested the view that emergence events are independent and caused by zebov variants that have been long resident at each locality. phylogenetic analyses place the earliest known outbreak at yambuku, democratic republic of congo, very near to the root of the zebov tree, suggesting that viruses causing all other known ...200516231972
lewis x component in human milk binds dc-sign and inhibits hiv-1 transfer to cd4+ t lymphocytes.dc-specific icam3-grabbing non-integrin (dc-sign), which is expressed on dcs, can interact with a variety of pathogens such as hiv-1, hepatitis c, ebola, cytomegalovirus, dengue virus, mycobacterium, leishmania, and candida albicans. we demonstrate that human milk can inhibit the dc-sign-mediated transfer of hiv-1 to cd4+ t lymphocytes as well as viral transfer by both immature and mature dcs. the inhibitory factor directly interacted with dc-sign and prevented the hiv-1 gp120 envelope protein f ...200516239964
[human recombinant antibodies to ebola virus: preparation and characteristics].human recombinant antibodies against a purified ebola virus (ev) lysate were selected from a combinatorial library of scfv-antibodies using the phage display technique. nine unique antibodies were identified after sequencing the vh- and vl-genes encoding the selected antibodies. solid-phase enzyme immunoassay (eia) indicated that these antibodies were able to bind both inactivated and native ev. immunoblotting showed that 6 antibodies identified nucleoprotein (np), one antibody did vp24 and anot ...200516250595
protective cytotoxic t-cell responses induced by venezuelan equine encephalitis virus replicons expressing ebola virus proteins.infection with ebola virus causes a severe disease accompanied by high mortality rates, and there are no licensed vaccines or therapies available for human use. filovirus vaccine research efforts still need to determine the roles of humoral and cell-mediated immune responses in protection from ebola virus infection. previous studies indicated that exposure to ebola virus proteins expressed from packaged venezuelan equine encephalitis virus replicons elicited protective immunity in mice and that ...200516254354
predicted inactivation of viruses of relevance to biodefense by solar radiation.uv radiation from the sun is the primary germicide in the environment. the goal of this study was to estimate inactivation of viruses by solar exposure. we reviewed published reports on 254-nm uv inactivation and tabulated the sensitivities of a wide variety of viruses, including those with double-stranded dna, single-stranded dna, double-stranded rna, or single-stranded rna genomes. we calculated d(37) values (fluence producing on average one lethal hit per virion and reducing viable virus to 3 ...200516254359
developing scientist leaders for tumultuous times.leadership is a quality that can be learned. it is a behavior that one practices, and, after lots of practice, it becomes a habit. this is a lesson i learned from my father, who was a career pilot in the us air force and instilled this into me and my siblings from a very early age. it is also something i have learned in observing others. i have frequently asked why some people from certain disciplinary backgrounds seem to have an advantage in the leadership area. think of the backgrounds of our ...200516261495
laboratory diagnosis of ebola and marburg hemorrhagic fever.the control of filovirus outbreaks can be greatly enhanced by timely laboratory confirmation of infection or the identification of alternative disease processes. the status of current laboratory diagnostics for ebola and marburg virus infections is discussed in terms of the assays available and their interpretation. in addition, the role of field-based laboratory support and its limitations and capabilities in an outbreak response setting, especially in regards to real-time pcr and immunofiltrat ...200516267962
ebola virus circulation in africa: a balance between clinical expression and epidemiological silence.nearly thirty years after the first epidemics, ebola virus (ebov) remains hardly described, its transmission unclear and its reservoir elusive. soon after the ebola fever outbreak and virus discovery in 1976 and in order to investigate the distribution of ebov in central africa, several countries including a range of ecological zones were investigated in the early 1980s, using extensive survey: central african republic (car), cameroon, chad, congo, gabon and equatorial guinea. since 1992, elisa ...200516267963
[clinical management of patients and deceased during the ebola outbreak from october to december 2003 in republic of congo].outbreaks of ebola virus hemorrhagic fever (evhf) have been reported since 2001 in the cuvette ouest department, a forested area located in the western north of congo. at the end of october 2003 a new alarm came from this department which was quickly confirmed as being an epidemic of evhf. the outbreak response was organized by the ministry of health with the assistance of an international team under the aegis of who. the case management of suspect cases was done in an isolation ward set up at t ...200516267964
[multiple ebola virus haemorrhagic fever outbreaks in gabon, from october 2001 to april 2002].outbreaks of ebola virus haemorrhagic fever have been reported from 1994 to 1996 in the province of ogooué ivindo, a forest zone situated in the northeast of gabon. each time, the great primates had been identified as the initial source of human infection. end of november 2001 a new alert came from this province, rapidly confirmed as a evhv outbreak. the response was given by the ministry of health with the help of an international team under the aegis of who. an active monitoring system was imp ...200516267965
medical anthropology and ebola in congo: cultural models and humanistic care.seldom have medical anthropologists been involved in efforts to control high mortality diseases such as ebola hemorrhagic fever (ehf) this paper describes the results of two distinct but complementary interventions during the first phases of an outbreak in the republic of congo in 2003. the first approach emphasized understanding local peoples cultural models and political-economic explanations for the disease while the second approach focused on providing more humanitarian care of patients by i ...200516267966
ebola and great apes in central africa: current status and future needs. 200516267967
recent advances in antiviral nucleoside and nucleotide therapeutics.recent developments in nucleoside/nucleotide therapeutics and antiviral drug targets are described covering progress in the development of nucleoside/nucleotide mimetics for the treatment of influenza virus, human immunodeficiency virus type 1, hepatitis b and c virus, herpes virus infections; including herpes simplex virus, cytomegalovirus and varicella zoster virus infections, and the highly pathogenic poxviruses (variola, vaccinia and monkey pox) and filoviruses (ebola and marburg).200516305526
fruit bats as reservoirs of ebola virus.the first recorded human outbreak of ebola virus was in 1976, but the wild reservoir of this virus is still unknown. here we test for ebola in more than a thousand small vertebrates that were collected during ebola outbreaks in humans and great apes between 2001 and 2003 in gabon and the republic of the congo. we find evidence of asymptomatic infection by ebola virus in three species of fruit bat, indicating that these animals may be acting as a reservoir for this deadly virus.200516319873
taking down goliaths: new vaccines may spell the end for ebola, marburg and lassa virus infections. 200516323509
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
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
the role of reverse genetics systems in determining filovirus pathogenicity.the family filoviridae is comprised of two genera: marburgvirus and ebolavirus. to date minigenome systems have been developed for two ebola viruses (reston ebolavirus and zaire ebolavirus [zebov]) as well as for lake victoria marburgvirus, the sole member of the marburgvirus genus. the use of these minigenome systems has helped characterize functions for many viral proteins in both genera and have provided valuable insight towards the development of an infectious clone system in the case of zeb ...200516355872
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
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
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
developments in antiviral drug design, discovery and development in 2004.this article summarizes key aspects of progress made during 2004 toward the design, discovery and development of antiviral agents for clinical use. important developments in the identification, characterization and clinical utility of inhibitors of human immunodeficiency virus; the hepatitis viruses, hepatitis b, hepatitis c; the herpes family of viruses, herpes simplex viruses 1 and 2, varicella zoster virus, epstein-barr virus and human cytomegalovirus; the respiratory viruses, influenza, resp ...200516535860
[isolated case of haemorrhagic fever observed in gabon during the 2002 outbreak of ebola but distant from epidemic zones].during the last outbreak of ebola virus haemorrhagic fever that occurred concurrently in gabon and congo, several primary foci were identified in the ogooue ivindo province (northeast gabon), where previous outbreaks had occurred. a 48-year-old woman living in franceville located 580 km from the epicentre presented fever with haemorrhagic signs. she was evacuated to libreville where ebola infection was suspected. diagnosis was confirmed at the centre international de recherches médicales of fran ...200516548488
john montgomery's legacy: carbocyclic adenosine analogues as sah hydrolase inhibitors with broad-spectrum antiviral activity.ever since the s-adenosylhomocysteine (adohcy, sah) hydrolase was recognized as a pharmacological target for antiviral agents (j. a. montgomery et al., j. med. chem. 25:626-629, 1982), an increasing number of adenosine, acyclic adenosine, and carbocyclic adenosine analogues have been described as potent sah hydrolase inhibitors endowed with broad-spectrum antiviral activity. the antiviral activity spectrum of the sah hydrolase inhibitors include pox-, rhabdo-, filo-, arena-, paramyxo-, reo-, and ...200516438025
[countermeasure against viral hemorrhagic fever at the border in japan].human have struggled against many infectious diseases such as cholera, plague, dysentery and yellow fever for a long time. and we have spent a lot of energy to control these infectious diseases and developed various tool for them. one of these efforts was quarantine system that was established in 14th century in europe. but during recent days, we are suffering from newly emerged diseases. these new infectious diseases are zoonosis and most of them are serious and highly infectious. viral hemorrh ...200516363688
ebola and marburg viruses: pathogenesis and development of countermeasures.ebola and marburg viruses, family filoviridae, are among the best known examples of emerging and re-emerging pathogens. although outbreaks have been sporadic and geographically restricted to areas of central africa, the hemorrhagic fevers caused by these viruses are remarkably severe and are associated with high case fatality rates often exceeding 80 percent. in addition to humans, these viruses have decimated populations of wild apes in central africa. currently, there are no vaccines or effect ...200516375711
interferon: ten stories in one. a short review of some of the highlights in the history of an almost quinquagenarian.this short review article on some pertinent observations in the unfolding story of interferon is dedicated to professor ilona béládi on the occasion of her 80th birthday. this by no means covers the whole story on interferon. it just highlights some of the more striking findings made with interferon (or its inducers) over a time span of almost 50 years since its original discovery (in 1957) by isaacs and lindenmann. these observations concern (i) the induction of interferon by synthetic polyanio ...200516400870
packaging of actin into ebola virus vlps.the actin cytoskeleton has been implicated in playing an important role assembly and budding of several rna virus families including retroviruses and paramyxoviruses. in this report, we sought to determine whether actin is incorporated into ebola vlps, and thus may play a role in assembly and/or budding of ebola virus. our results indicated that actin and ebola virus vp40 strongly co-localized in transfected cells as determined by confocal microscopy. in addition, actin was packaged into budding ...200516367999
[training the trainers seminar and analysis of the ebola virus hemorrhagic fever outbreaks in central africa from 2001 to 2004. (brazzaville, républic of congo, april 6-8, 2004]. 200516267969
therapy and prophylaxis of ebola virus infections.the first cases of ebola hemorrhagic fever were reported from sudan and zaire (now democratic republic of the congo) in 1976, but the virus has only received significant attention since 1995. until recently, the development of therapeutics or vaccines was not considered a priority. the knowledge gained during the past decade on the biology and pathogenesis of ebola virus has led to the development of therapeutic strategies that are currently being investigated. considering the aggressive nature ...200516121689
paramyxovirus mrna editing, the "rule of six" and error catastrophe: a hypothesis.the order mononegavirales includes three virus families that replicate in the cytoplasm: the paramyxoviridae, composed of two subfamilies, the paramyxovirinae and pneumovirinae, the rhabdoviridae and the filoviridae. these viruses, also called non-segmented negative-strand rna viruses (nnv), contain five to ten tandemly linked genes, which are separated by conserved junctional sequences that act as mrna start and poly(a)/stop sites. for the nnv, downstream mrna synthesis depends on termination o ...200515958664
an all-atom model of the pore-like structure of hexameric vp40 from ebola: structural insights into the monomer-hexamer transition.the matrix protein vp40 is an indispensable component of viral assembly and budding by the ebola virus. vp40 is a monomer in solution, but can fold into hexameric and octameric states, two oligomeric conformations that play central roles in the ebola viral life cycle. while the x-ray structures of monomeric and octameric vp40 have been determined, the structure of hexameric vp40 has only been solved by three-dimensional electron microscopy (em) to a resolution of approximately 30 a. in this pape ...200515908231
outbreak of marburg virus hemorrhagic fever--angola, october 1, 2004-march 29, 2005.on march 23, 2005, the world health organization (who) confirmed marburg virus (family filoviridae, which includes ebola virus) as the causative agent of an outbreak of viral hemorrhagic fever (vhf) in uige province in northern angola. testing conducted by cdc's special pathogens branch detected the presence of virus in nine of 12 clinical specimens from patients who died during the outbreak.200515800477
[clinical aspects of viral hemorrhagic fever].viral hemorrhagic fever (vhf) is defined as virus infections that usually cause pyrexia and hemorrhagic symptoms with multiple organ failure. vhf includes following viral infections: ebola hemorrhagic fever (ehf), marburg hemorrhagic fever (mhf), crimean-congo hemorrhagic fever (cchf) and lassa fever. in particular, the causative agents of ehf, mhf, cchf, and lassa fever are ebola, marburg, cchf, lassa viruses, respectively, and regarded as biosafety level-4 pathogens because of their high virul ...200516363689
outbreak of ebola haemorrhagic fever in yambio, south sudan, april - june 2004. 200516285261
providing care and facing death: nursing during ebola outbreaks in central africa.few studies have focused on describing the experiences of health care workers during rapid killing epidemics. in this article, the views and experiences of nurses during three outbreaks of ebola hemorrhagic fever (ehf) in central africa are examined. these three outbreaks occurred in kikwit, democratic republic of congo (drc, 1995); gulu, uganda (2000-2001); and republic of congo (roc, 2003). open-ended and semistructured interviews with individuals and small groups were conducted during the out ...200516160191
[ebola and marburg fever--outbreaks of viral haemorrhagic fever].with an increasing frequency of traveling and tourism to exotic countries, a new threat-import of rare, very dangerous infections-emerges in humane medicine. ebola fever and marburg fever, whose agents come from the same group of filoviridae family, belong among these diseases. the natural reservoir of these viruses has not yet been precisely determined. the pathogenesis of the diseases is not absolutely clear, there is neither a possibility of vaccination, nor an effective treatment. fever and ...200617230375
statistical inference in a stochastic epidemic seir model with control intervention: ebola as a case study.a stochastic discrete-time susceptible-exposed-infectious-recovered (seir) model for infectious diseases is developed with the aim of estimating parameters from daily incidence and mortality time series for an outbreak of ebola in the democratic republic of congo in 1995. the incidence time series exhibit many low integers as well as zero counts requiring an intrinsically stochastic modeling approach. in order to capture the stochastic nature of the transitions between the compartmental populati ...200617156292
a clinical guide to viral haemorrhagic fevers: ebola, marburg and lassa.the viral haemorrhagic fevers are a group of diseases that share many clinical features. ebola, marburg and lassa are diseases that cause a relatively small number of deaths globally, but pose special risks to medical staff due to the ease of transmission, and can have a profound impact to the communities they affect. this article gives a brief overview of diseases caused by the ebola, marburg and lassa viruses. it gives some practical advice to the clinician on the diagnosis and management of t ...200616483416
filovirus assembly and budding.filoviruses belong to the order of negative-stranded non-segmented rna viruses and are classified into two genera, ebola and marburg viruses. they have a characteristic filamentous shape, which is largely determined by the matrix protein vp40. although vp40 is the main driving force for assembly and budding from the host cell, the production of infectious virus involves an intricate interplay between all viral structural proteins in addition to cellular factors, e.g., those that normally functio ...200616364737
[viral haemorrhagic fevers--evolution of the epidemic potential].in this review modern data on dangerous and particularly dangerous viral haemorrhagic fevers caused by a group of viruses belonging to the families of phylo-, arena-, flavi-, bunya- and togaviruses are presented. morbidity rates and epidemics caused by marburg virus, ebola fever virus, lassa fever virus, argentinian and bolivian haemorrhagic fever viruses, dengue haemorrhagic fever virus, crimean haemorrhagic fever virus, hantaviruses are analyzed. mechanisms of the evolution of the epidemic man ...200611949268
new medicines from nature's armamentarium.nature frequently unleashes a barrage of new and frightening diseases against humans--such as hiv, severe acquired respiratory syndrome, ebola virus and avian flu recently--in addition to the seemingly ever-present scourges such as malaria and tuberculosis. fortunately, nature also provides the wherewithal to help conquer the diseases that it sets loose. all that is needed is the human ingenuity to discover, develop and apply the solutions in an optimal fashion. participants at the 9th max tishl ...200616406332
gene-specific countermeasures against ebola virus based on antisense phosphorodiamidate morpholino oligomers.the filoviruses marburg virus and ebola virus (ebov) quickly outpace host immune responses and cause hemorrhagic fever, resulting in case fatality rates as high as 90% in humans and nearly 100% in nonhuman primates. the development of an effective therapeutic for ebov is a daunting public health challenge and is hampered by a paucity of knowledge regarding filovirus pathogenesis. this report describes a successful strategy for interfering with ebov infection using antisense phosphorodiamidate mo ...200616415982
generation of an adenoviral vaccine vector based on simian adenovirus 21.adenoviral vectors can be used to generate potent humoral and cellular immune responses to transgene products. use of adenoviral vectors based on non-human isolates may allow for their utilization in populations harbouring neutralizing antibodies to common human serotypes. a vector chimera was constructed using simian adenovirus 22 (a serotype belonging to the species human adenovirus e) and simian adenovirus 21 (a serotype belonging to the species human adenovirus b) expressing the ebola (zaire ...200616894185
anthrax in western and central african great apes.during the period of december 2004 to january 2005, bacillus anthracis killed three wild chimpanzees (pan troglodytes troglodytes) and one gorilla (gorilla gorilla gorilla) in a tropical forest in cameroon. while this is the second anthrax outbreak in wild chimpanzees, this is the first case of anthrax in gorillas ever reported. the number of great apes in central africa is dramatically declining and the populations are seriously threatened by diseases, mainly ebola. nevertheless, a considerable ...200616900500
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