| analysis of linear b-cell epitopes of the nucleoprotein of ebola virus that distinguish ebola virus subtypes. | ebola virus consists of four genetically distinguishable subtypes. we developed monoclonal antibodies (mabs) to the nucleoprotein (np) of ebola virus zaire subtype and analyzed their cross-reactivities to the reston and sudan subtypes. we further determined the epitopes recognized by these mabs. three mabs reacted with the three major subtypes and recognized a fragment containing 110 amino acids (aa) at the c-terminal extremity. they did not show specific reactivities to any 10-aa short peptides ... | 2003 | 12522044 |
| biochemical and functional characterization of the ebola virus vp24 protein: implications for a role in virus assembly and budding. | the vp24 protein of ebola virus is believed to be a secondary matrix protein and minor component of virions. in contrast, the vp40 protein of ebola virus is the primary matrix protein and the most abundant virion component. the structure and function of vp40 have been well characterized; however, virtually nothing is known regarding the structure and function of vp24. wild-type and mutant forms of vp24 were expressed in mammalian cells to gain a better understanding of the biochemical and functi ... | 2003 | 12525613 |
| overlapping motifs (ptap and ppey) within the ebola virus vp40 protein function independently as late budding domains: involvement of host proteins tsg101 and vps-4. | the vp40 protein of ebola virus can bud from mammalian cells in the form of lipid-bound, virus-like particles (vlps), and late budding domains (l-domains) are conserved motifs (ptap, ppxy, or yxxl; where "x" is any amino acid) that facilitate the budding of vp40-containing vlps. vp40 is unique in that potential overlapping l-domains with the sequences ptap and ppey are present at amino acids 7 to 13 of vp40 (ptappey). l-domains are thought to function by interacting with specific cellular protei ... | 2003 | 12525615 |
| examining unmet needs in infectious disease. | in the past 30 years, more than 30 new aetiological agents of infectious disease have been identified. some of these are responsible for entirely novel and life-threatening disorders, such as aids, ebola fever, hantavirus pulmonary syndrome and nipah virus encephalitis. during the same period, some longstanding infectious diseases (such as tuberculosis) have became resurgent, as a result of a combination of complacency, increased travel and social dislocation, and also increasing drug resistance ... | 2003 | 12546988 |
| ebola virus transcription activator vp30 is a zinc-binding protein. | ebola virus vp30 is an essential activator of viral transcription. in viral particles, vp30 is closely associated with the nucleocapsid complex. a conspicuous structural feature of vp30 is an unconventional zinc-binding cys(3)-his motif comprising amino acids 68 to 95. by using a colorimetric zinc-binding assay we found that the vp30-specific cys(3)-his motif stoichiometrically binds zinc ions in a one-to-one relationship. substitution of the conserved cysteines and the histidine within the moti ... | 2003 | 12584359 |
| imported viral haemorrhagic fever with a potential for person-to-person transmission: review and recommendations for initial management of a suspected case in belgium. | viral haemorrhagic fevers are caused by a wide range of viruses. there are 4 types of viruses well known to spread from person to person and able to cause nosocomial outbreaks with a high case fatality rate: an arenavirus (lassa fever and more exceptionally the junin and machupo virus), a bunyavirus (crimean-congo haemorrhagic fever) and the filoviridae (ebola and marburg viruses). so far there have been only a limited number of imported cases of viral haemorrhagic fever in industrialized countr ... | 2002 | 12534129 |
| ebola virus matrix protein vp40 interaction with human cellular factors tsg101 and nedd4. | the ebola virus matrix protein vp40 is a major viral structural protein and plays a central role in virus assembly and budding at the plasma membrane of infected cells. for efficient budding, a full amino terminus of vp40 is required, which includes a ppxy and a pt/sap motif, both of which have been proposed to interact with cellular proteins. here, we report that ebola vp40 can interact with cellular factors human nedd4 and tsg101 in vitro. we show that ww domain 3 of human nedd4 is necessary a ... | 2003 | 12559917 |
| calcium-dependent conformational changes of membrane-bound ebola fusion peptide drive vesicle fusion. | the fusogenic subdomain of the ebola virus envelope glycoprotein is an internal sequence located ca. 20 residues downstream the n-terminus of the glycoprotein transmembrane subunit. partitioning of the ebola fusion peptide into membranes containing phosphatidylinositol in the absence of ca2+ stabilizes an alpha-helical conformation, and gives rise to vesicle efflux but not vesicle fusion. in the presence of millimolar ca2+ the membrane-bound peptide adopts an extended beta-structure, and induces ... | 2003 | 12560072 |
| historical analysis of the ebola virus: prospective implications for primary care nursing today. | ebola continues to attract worldwide attention as a highly lethal virus of unknown origin that leaves victims bleeding to death and has no known vaccine or cure. the purpose of this historical research was to review and analyze the primary and secondary sources available on ebola for use by primary care nurses in the event of future outbreaks. a rich resource of history has been well documented by some of the original physicians, virologists, and members of international teams, but nothing was f ... | 1998 | 12596837 |
| defense against filoviruses used as biological weapons. | the filoviruses, marburg and ebola, are classified as category a biowarfare agents by the centers for disease control. most known human infections with these viruses have been fatal, and no vaccines or effective therapies are currently available. filoviruses are highly infectious by the airborne route in the laboratory, but investigations of african outbreaks have shown that person-to-person spread requires direct contact with virus-containing material. in consequence, filovirus epidemics can be ... | 2003 | 12615303 |
| polystyrene derivatives substituted with arginine interact with babanki (togaviridae) and kedougou (flaviviridae) viruses. | outbreaks of new or old diseases appear primarily in tropical zones such as africa, south and central america, or asia. among these diseases, those induced by arboviruses (the best known of which are being yellow fever, dengue, ebola, and sindbis) are under intensive observation by the world health organization. rapid isolation and identification of the viral species is the first step in the diagnosis, study, and control of epidemics. one major problem with the isolation of viruses is capturing ... | 2003 | 12601758 |
| [in vitro synthesis of immunoglobulins caused by an inactivated ebola virus]. | an in vitro model ebola infection was used to study the humoral response of human mononuclear cells to stimulation by purified inactivated ebola virus antigen. inactivated ebola virus was cocultivated with human mononuclear cells in the presence or absence of b-cell mitogen lps e. coli: b5. an increase in the rate of synthesis of immunoglobulins (both igg and, to a less extent, other classes) was observed. the ebola virus proteins were suggested to exert no suppression effect on b-cells. the igm ... | 2003 | 12608056 |
| [titration of ebola and marburg viruses by plaque formation under semi liquid agar]. | the method of titration of ebola and marburg viruses using plaque formation under semifluid agar cover is considered. advantages of this method over conventional method of titration of these viruses with the use of hard agar cover are discussed. | 2003 | 12608062 |
| cutting edge: impairment of dendritic cells and adaptive immunity by ebola and lassa viruses. | acute infection of humans with ebola and lassa viruses, two principal etiologic agents of hemorrhagic fevers, often results in a paradoxical pattern of immune responses: early infection, characterized by an outpouring of inflammatory mediators such as tnf-alpha, il-1 beta, and il-6, vs late stage infections, which are associated with poor immune responses. the mechanisms underlying these diverse outcomes are poorly understood. in particular, the role played by cells of the innate immune system, ... | 2003 | 12626527 |
| analysis of the role of predicted rna secondary structures in ebola virus replication. | thermodynamic modeling of ebola viral rna predicts the formation of rna stem-loop structures at the 3' and 5' termini and panhandle structures between the termini of the genomic (or antigenomic) rnas. sequence analysis showed a high degree of identity among ebola zaire, sudan, reston, and cote d'ivoire subtype viruses in their 3' and 5' termini (18 nucleotides in length) and within a second region (internal by approximately 20 nucleotides). while base pairing of the two conserved regions could l ... | 2003 | 12642094 |
| role of escrt-i in retroviral budding. | retroviral late-budding (l) domains are required for the efficient release of nascent virions. the three known types of l domain, designated according to essential tetrapeptide motifs (ptap, ppxy, or ypdl), each bind distinct cellular cofactors. we and others have demonstrated that recruitment of an escrt-i subunit, tsg101, a component of the class e vacuolar protein sorting (vps) machinery, is required for the budding of viruses, such as human immunodeficiency virus type 1 (hiv-1) and ebola vir ... | 2003 | 12663786 |
| therapeutic options for diseases due to potential viral agents of bioterrorism. | the etiologic agents of smallpox and viral hemorrhagic fever have emerged as potential agents of bioterrorism due to their virulence, potential for human to human dissemination and limited strategies for treatment and prevention. cidofovir has shown significant promise in animal models, and limited case reports in humans are encouraging. ribavirin is the treatment of choice for certain hemorrhagic fever viral infections, but has no current application to ebola and marburg infections. current vac ... | 2003 | 12669378 |
| catastrophic ape decline in western equatorial africa. | because rapidly expanding human populations have devastated gorilla (gorilla gorilla) and common chimpanzee (pan troglodytes) habitats in east and west africa, the relatively intact forests of western equatorial africa have been viewed as the last stronghold of african apes. gabon and the republic of congo alone are thought to hold roughly 80% of the world's gorillas and most of the common chimpanzees. here we present survey results conservatively indicating that ape populations in gabon decline ... | 2003 | 12679788 |
| vaccine for aids and ebola virus infection. | ebola virus and hiv present challenges for vaccine development because natural immunity to these viruses is difficult to find, and there are no immune correlates of protection in humans. modern molecular genetic, virologic and immune analyses have been used to rationally identify promising approaches based on animal model and human clinical studies. improved vaccine candidates have been defined for hiv, and a promising ebola vaccine have conferred protection in non-human primates. further evalua ... | 2003 | 12686432 |
| comparison of the protective efficacy of dna and baculovirus-derived protein vaccines for ebola virus in guinea pigs. | the filoviruses ebola virus (ebov) and marburg virus (marv) cause severe hemorrhagic fever in humans for which no vaccines are available. previously, a priming dose of a dna vaccine expressing the glycoprotein (gp) gene of marv followed by boosting with recombinant baculovirus-derived gp protein was found to confer protective immunity to guinea pigs (hevey et al., 2001. vaccine 20, 568-593). to determine whether a similar prime-boost vaccine approach would be effective for ebov, we generated and ... | 2003 | 12686428 |
| ape populations decimated by hunting and ebola virus. | | 2003 | 12686965 |
| ebola virus: immune mechanisms of protection and vaccine development. | vaccination is one of our most powerful antiviral strategies. despite the emergence of deadly viruses such as ebola virus, vaccination efforts have focused mainly on childhood communicable diseases. although ebola virus was once believed to be limited to isolated outbreaks in distant lands, forces of globalization potentiate outbreaks anywhere in the world through incidental transmission. moreover, since this virus has already been transformed into weapon-grade material, the potential exists for ... | 2003 | 12698920 |
| [ebola virus and marburg virus]. | | 2003 | 12718026 |
| conservation biology. ebola, hunting push ape populations to the brink. | | 2003 | 12690159 |
| ebola virus infection inversely correlates with the overall expression levels of promyelocytic leukaemia (pml) protein in cultured cells. | ebola virus causes severe, often fatal hemorrhagic fever in humans. the mechanism of escape from cellular anti-viral mechanisms is not yet fully understood. the promyelocytic leukaemia (pml) associated nuclear body is part of the interferon inducible cellular defense system. several rna viruses have been found to interfere with the anti-viral function of the pml body. the possible interaction between ebola virus and the pml bodies has not yet been explored. | 2003 | 12697055 |
| a current review of ebola virus: pathogenesis, clinical presentation, and diagnostic assessment. | ebola hemorrhagic fever (ehf) is an acute viral syndrome that presents with fever and an ensuing bleeding diathesis that is marked by high mortality in human and nonhuman primates. fatality rates are between 50% and 100%. due to its lethal nature, this filovirus is classified as a biological class 4 pathogen. the natural reservoir of the virus is unknown. as a result, little is understood about how ebola virus is transmitted or how it replicates in its host. although the primary source of infect ... | 2003 | 12698919 |
| cyanovirin-n binds to the viral surface glycoprotein, gp1,2 and inhibits infectivity of ebola virus. | ebola virus (ebo) causes severe hemorrhagic fever and high mortality in humans. there are currently no effective therapies. here, we have explored potential anti-ebo activity of the human immunodeficiency virus (hiv)-inactivating protein cyanovirin-n (cv-n). cv-n is known to potently inhibit the infectivity of a broad spectrum of hiv strains at the level of viral entry. this involves cv-n binding to n-linked high-mannose oligossacharides on the viral glycoprotein gp120. the ebola envelope contai ... | 2003 | 12719006 |
| a fatal attraction: mycobacterium tuberculosis and hiv-1 target dc-sign to escape immune surveillance. | dendritic cells (dcs) are vital in the defense against pathogens. however, it is becoming increasingly clear that some pathogens subvert dc functions to escape immune surveillance. for example, hiv-1 targets the dc-specific c-type lectin dc-sign (dc-specific intercellular-adhesion-molecule-3-grabbing nonintegrin) to hijack dcs for viral dissemination. binding to dc-sign protects hiv-1 from antigen processing and facilitates its transport to lymphoid tissues, where dc-sign promotes hiv-1 infectio ... | 2003 | 12727141 |
| lentivirus vectors pseudotyped with filoviral envelope glycoproteins transduce airway epithelia from the apical surface independently of folate receptor alpha. | the practical application of gene therapy as a treatment for cystic fibrosis is limited by poor gene transfer efficiency with vectors applied to the apical surface of airway epithelia. recently, folate receptor alpha (fr alpha), a glycosylphosphatidylinositol-linked surface protein, was reported to be a cellular receptor for the filoviruses. we found that polarized human airway epithelia expressed abundant fr alpha on their apical surface. in an attempt to target these apical receptors, we pseud ... | 2003 | 12719583 |
| serological reactivity of baculovirus-expressed ebola virus vp35 and nucleoproteins. | ebola virus (ebov) is a member of the family filoviridae and is classified as a biosafety level 4 virus. this classification makes the preparation of antigen and performance of diagnostic assays time-consuming and complicated. the objective of this study was to evaluate the value of ebov immunoassays based on recombinant nucleoprotein (r-np) and recombinant vp35 (r-vp35) using large serum panels of african origin and from primates. furthermore, we investigated whether the results obtained with e ... | 2003 | 12737993 |
| u.s. military officer participation in the centers for disease control and prevention's epidemic intelligence service (1951-2001). | the epidemic intelligence service (eis) was created in 1951 to provide epidemiologists to investigate natural and intentional disease epidemics. from an initial class of 23 u.s. citizens, the program has evolved into a globally recognized, hands-on learning experience, accepting approximately 65 to 75 new officers each year. the first u.s. military epidemic intelligence service officer (eiso) was accepted into the program in 1994. since that time, 12 such officers have completed, or have begun, ... | 2003 | 12775171 |
| vaccine research efforts for filoviruses. | ebola and marburg viruses belong to the family filoviridae, and cause acute, frequently fatal, haemorrhagic fever in humans and non-human primates. no vaccines are available for human use. this review describes the status of research efforts to develop vaccines for these viruses and to identify the immune mechanisms of protection. the vaccine approaches discussed include dna-based vaccines, and subunit vaccines vectored by adenovirus, alphavirus replicons, and vaccinia virus. | 2003 | 12782057 |
| viral hemorrhagic fever--a vascular disease? | the syndrome of "viral hemorrhagic fever" in man caused by certain viruses, such as ebola, lassa, dengue, and crimean-congo hemorrhagic fever viruses, is often associated with a shock syndrome of undetermined pathogenesis. however, the vascular system, particularly the vascular endothelium, seems to be directly and indirectly targeted by all these viruses. here we briefly summarize the current knowledge on marburg and ebola virus infections, the prototype viral hemorrhagic fever agents, and form ... | 2003 | 12783108 |
| changing world, changing doctors, changing education! | future developments in the community will underline the need to provide a community-oriented health care system in which public health doctors collaborate with general practitioners, as the hospital-based health care system that currently exists in many countries will not be able to solve the problems of health care in the future. increasing populations, increasing mobility all over the world, spread of new diseases (aids/hiv and ebola virus for example) will have great impact on our societies a ... | 2003 | 12784489 |
| the crystal structure of the proprotein processing proteinase furin explains its stringent specificity. | in eukaryotes, many essential secreted proteins and peptide hormones are excised from larger precursors by members of a class of calcium-dependent endoproteinases, the prohormone-proprotein convertases (pcs). furin, the best-characterized member of the mammalian pc family, has essential functions in embryogenesis and homeostasis but is also implicated in various pathologies such as tumor metastasis, neurodegeneration and various bacterial and viral diseases caused by such pathogens as anthrax an ... | 2003 | 12794637 |
| ebola haemorrhagic fever among hospitalised children and adolescents in northern uganda: epidemiologic and clinical observations. | a unique feature of previous ebola outbreaks has been the relative sparing of children. for the first time, an out break of an unusual illness-ebola haemorrhagic fever occurred in northern uganda gulu district. | 2001 | 12789118 |
| conservation biology. can great apes be saved from ebola? | | 2003 | 12805515 |
| [analysis of antigenic determinant profiles of the ebola virus vp35 protein n-terminal region using its short recombinant fragments]. | cdna of fragments of gene vp35 of the ebola virus (ev) were expressed in vector pqe30 for the purpose of isolation of recombinant fragments of protein vp35. five short affinity-purified fragments of the ev vp35 protein were analyzed, by using the methods of iea and immunoblotting, with polyclonal antiviral sera (pas) against ev and with hybrid monoclonal antibodies (mabs) ic6 and 6f7 specific to ev vp35 protein. all fragments of protein vp35 with an intact n-terminal region and removed c-termina ... | 2003 | 12800775 |
| antibody-dependent enhancement of ebola virus infection. | most strains of ebola virus cause a rapidly fatal hemorrhagic disease in humans, yet there are still no biologic explanations that adequately account for the extreme virulence of these emerging pathogens. here we show that ebola zaire virus infection in humans induces antibodies that enhance viral infectivity. plasma or serum from convalescing patients enhanced the infection of primate kidney cells by the zaire virus, and this enhancement was mediated by antibodies to the viral glycoprotein and ... | 2003 | 12805454 |
| development, characterization and use of monoclonal vp40-antibodies for the detection of ebola virus. | ebola virus (ebov) causes uncommon but dramatic outbreaks in remote regions of africa, where diagnostic facilities are limited. in order to develop diagnostic tests, which can be handled and distributed easily, monoclonal antibodies (mabs) to ebov, species zaire, were produced from mice immunized with inactivated viral particles. nine stable hybridoma cell lines were obtained producing specific mabs directed against the viral structural protein vp40. these mabs were characterized by enzyme-linke ... | 2003 | 12821193 |
| immunoglobulin g enzyme-linked immunosorbent assay using truncated nucleoproteins of reston ebola virus. | we developed an immunoglobulin g (igg) enzyme-linked immunosorbent assay (elisa), using partial recombinant nucleoproteins (rnp) of reston ebola virus (ebo-r) and zaire ebola virus (ebo-z). we examined the reaction of 10 sera from cynomolgus macaques naturally infected with ebo-r to each of the partial rnp in the igg elisa. all the sera reacted to the c-terminal halves of the rnp of both ebo-r and ebo-z. most of the sera reacted to the rdeltac (amino acid (aa) 360-739), and rdelta6 (aa 451-551) ... | 2003 | 12825739 |
| antigen capture enzyme-linked immunosorbent assay for specific detection of reston ebola virus nucleoprotein. | antigen capture enzyme-linked immunosorbent assay (elisa) is one of the most useful methods to detect ebola virus rapidly. we previously developed an antigen capture elisa using a monoclonal antibody (mab), 3-3d, which reacted not only to the nucleoprotein (np) of zaire ebola virus (ebo-z) but also to the nps of sudan (ebo-s) and reston ebola (ebo-r) viruses. in this study, we developed antigen capture elisas using two novel mabs, res2-6c8 and res2-1d8, specific to the np of ebo-r. res2-6c8 and ... | 2003 | 12853385 |
| the ebola virus vp35 protein inhibits activation of interferon regulatory factor 3. | the ebola virus vp35 protein was previously found to act as an interferon (ifn) antagonist which could complement growth of influenza delns1 virus, a mutant influenza virus lacking the influenza virus ifn antagonist protein, ns1. the ebola virus vp35 could also prevent the virus- or double-stranded rna-mediated transcriptional activation of both the beta ifn (ifn-beta) promoter and the ifn-stimulated isg54 promoter (c. basler et al., proc. natl. acad. sci. usa 97:12289-12294, 2000). we now show ... | 2003 | 12829834 |
| ebola glycoprotein: the key to successful gene therapy? | | 2003 | 12867139 |
| an ebola epidemic simmers in africa: in remote region, outbreak shows staying power. | | 2003 | 12865357 |
| elaboration of laboratory strains of ebola virus and study of pathophysiological reactions of animals inoculated with these strains. | selective passages in animals and cell cultures were used to produce a set of ebola virus (ebo) laboratory strains with changed virulence for some animal genera. comparative study of the genomes of wild-type ebo and selected variants formed the basis for studying the molecular causes of ebo virulence. investigation of pathophysiological reactions of the animals inoculated with these strains allowed some key factors in ebola fever pathogenesis to be determined. | 2003 | 12875925 |
| inactivation of ebola virus with a surfactant nanoemulsion. | hemorrhagic fever caused by ebola virus (ebo) is a highly contagious infection. this necessitates that the contaminated instruments, clothes, and hospital premises must be completely disinfected. nanoemulsions are a new form of disinfectant composed of detergents and vegetable oil suspended in water. the antiviral activity of nanoemulsion atb has been investigated against ebo. the nanoemulsion was tested against two preparations of ebo (strain zaire) obtained from vero cell culture fluid (ebo-zc ... | 2003 | 12875924 |
| pathogens: raft hijackers. | throughout evolution, organisms have developed immune-surveillance networks to protect themselves from potential pathogens. at the cellular level, the signalling events that regulate these defensive responses take place in membrane rafts--dynamic microdomains that are enriched in cholesterol and glycosphingolipids--that facilitate many protein-protein and lipid-protein interactions at the cell surface. pathogens have evolved many strategies to ensure their own survival and to evade the host immu ... | 2003 | 12876558 |
| specific association of glycoprotein b with lipid rafts during herpes simplex virus entry. | herpes simplex virus (hsv) entry requires the interaction of glycoprotein d (gd) with a cellular receptor such as herpesvirus entry mediator (hvem or hvea) or nectin-1 (hvec). however, the fusion mechanism is still not understood. since cholesterol-enriched cell membrane lipid rafts are involved in the entry of other enveloped viruses such as human immunodeficiency virus and ebola virus, we tested whether hsv entry proceeds similarly. vero cells and cells expressing either hvem or nectin-1 were ... | 2003 | 12915568 |
| fast vaccine offers hope in battle with ebola. | | 2003 | 12904747 |
| accelerated vaccination for ebola virus haemorrhagic fever in non-human primates. | containment of highly lethal ebola virus outbreaks poses a serious public health challenge. although an experimental vaccine has successfully protected non-human primates against disease, more than six months was required to complete the immunizations, making it impractical to limit an acute epidemic. here, we report the development of accelerated vaccination against ebola virus in non-human primates. the antibody response to immunization with an adenoviral (adv) vector encoding the ebola glycop ... | 2003 | 12904795 |
| oligomerization of ebola virus vp30 is essential for viral transcription and can be inhibited by a synthetic peptide. | transcription of ebola virus (ebov)-specific mrna is driven by the nucleocapsid proteins np, vp35, and l. this process is further dependent on vp30, an essential ebov-specific transcription factor. the present study addresses the self-assembly of vp30 and the functional significance of this process for viral transcription and propagation. essential for oligomerization of vp30 is a region spanning amino acids 94-112. within this region a cluster of four leucine residues is of critical importance. ... | 2003 | 12912982 |
| ebola virus pathogenesis: implications for vaccines and therapies. | | 2003 | 12941881 |
| nedd4 regulates egress of ebola virus-like particles from host cells. | ebola virus budding is mediated by two proline-rich motifs, ppxy and ptap, within the viral matrix protein vp40. we have previously shown that a nedd4-like protein bul1, but not nedd4, positively regulates budding of type d retrovirus mason-pfizer monkey virus (j. yasuda, e. hunter, m. nakao, and h. shida, embo rep. 3:636-640, 2002). here, we report that the cellular e3 ubiquitin ligase nedd4 regulates budding of vp40-induced virus-like particles (vlps) through interaction with the ppxy motif. m ... | 2003 | 12941909 |
| oligomerization and polymerization of the filovirus matrix protein vp40. | the matrix protein vp40 from ebola virus plays an important role in the assembly process of virus particles by interacting with cellular factors, cellular membranes, and the ribonuclearprotein particle complex. here we show that the n-terminal domain of vp40 folds into a mixture of two different oligomeric states in vitro, namely hexameric and octameric ringlike structures, as detected by gel filtration chromatography, chemical cross-linking, and electron microscopy. octamer formation depends la ... | 2003 | 12919741 |
| protection from lethal infection is determined by innate immune responses in a mouse model of ebola virus infection. | a mouse-adapted strain of ebola zaire virus produces a fatal infection when balb/cj mice are infected intraperitoneally (ip) but subcutaneous (sc) infection with the same virus fails to produce illness and confers long-term protection from lethal ip rechallenge. to identify immune correlates of protection in this model, we compared viral replication and cytokine/chemokine responses to ebola virus in mice infected ip (10 pfu/mouse), or sc (100 pfu/mouse) and sc "immune" mice rechallenged ip (10(6 ... | 2003 | 12919746 |
| comparison of individual and combination dna vaccines for b. anthracis, ebola virus, marburg virus and venezuelan equine encephalitis virus. | multiagent dna vaccines for highly pathogenic organisms offer an attractive approach for preventing naturally occurring or deliberately introduced diseases. few animal studies have compared the feasibility of combining unrelated gene vaccines. here, we demonstrate that dna vaccines to four dissimilar pathogens that are known biowarfare agents, bacillus anthracis, ebola (ebov), marburg (marv), and venezuelan equine encephalitis virus (veev), can elicit protective immunity in relevant animal model ... | 2003 | 12922144 |
| ebola virus: from discovery to vaccine. | ebola virus, being highly pathogenic for humans and non-human primates and the subject of former weapons programmes, is now one of the most feared pathogens worldwide. in addition, the lack of pre- and post-exposure interventions makes the development of rapid diagnostics, new antiviral agents and protective vaccines a priority for many nations. further insight into the ecology, immunology and pathogenesis of ebola virus will promote the delivery of these urgently required tools. | 2003 | 12974482 |
| crystal structure of the measles virus phosphoprotein domain responsible for the induced folding of the c-terminal domain of the nucleoprotein. | measles virus is a negative-sense, single-stranded rna virus belonging to the mononegavirales order which comprises several human pathogens such as ebola, nipah, and hendra viruses. the phosphoprotein of measles virus is a modular protein consisting of an intrinsically disordered n-terminal domain (karlin, d., longhi, s., receveur, v., and canard, b. (2002) virology 296, 251-262) and of a c-terminal moiety (pct) composed of alternating disordered and globular regions. we report the crystal struc ... | 2003 | 12944395 |
| pathogens target dc-sign to influence their fate dc-sign functions as a pathogen receptor with broad specificity. | dendritic cells (dc) are vital in the defense against pathogens. to sense pathogens dc express pathogen recognition receptors such as toll-like receptors (tlr) and c-type lectins that recognize different fragments of pathogens, and subsequently activate or present pathogen fragments to t cells. it is now becoming evident that some pathogens subvert dc functions to escape immune surveillance. hiv-1 targets the dc-specific c-type lectin dc-sign to hijack dc for viral dissemination. hiv-1 binding t ... | 2003 | 12974773 |
| measles virus 1998-2002: progress and controversy. | despite the extensive media exposure that viruses such as west nile, norwalk, and ebola have received lately, and the emerging threat that old pathogens may reappear as new agents of terrorism, measles virus (mv) persists as one of the leading causes of death by infectious agents worldwide, approaching the annual mortality rate of human immunodeficiency virus (hiv)-1. for most mv victims, fatality is indirect: virus-induced transient immunosuppression predisposes the individual to opportunistic ... | 2003 | 14527283 |
| crystal structure of the borna disease virus nucleoprotein. | borna disease virus (bdv) causes an infection of the central nervous system in a wide range of vertebrates, which can fatally progress to an immune-mediated disease, called borna disease. bdv is a member of the mononegavirales, which also includes the highly infectious measles and ebola viruses. the viral nucleoproteins are central to transcription, replication, and packaging of the rna genome. we present the x-ray structure of the bdv nucleoprotein determined at 1.76 a resolution. the structure ... | 2003 | 14527390 |
| a system of protein target sequences for anti-rna-viral chemotherapy by a vitamin b6-derived zinc-chelating trioxa-adamantane-triol. | the synthesis of the structurally unusual heterotricyclic compound 1-[3-hydroxy-5-(hydroxymethyl)-2-methyl-4-pyridinyl]-2,8,9-trioxaadamantane-3,5,7-triol (trivially named bananin, bn) from pyridoxylidenephloroglucinol and a theoretical prospect on possible biological activities of bn are presented in this report. pyridoxylidenephloroglucinol is synthesized by knoevenagel condensation of the vitamin b6 aldehyde pyridoxal with phloroglucinol. pyridoxylidenephloroglucinol rearranges to light-yello ... | 2003 | 14527557 |
| the small ring finger protein z drives arenavirus budding: implications for antiviral strategies. | by using a reverse genetics system that is based on the prototypic arenavirus lymphocytic choriomeningitis virus (lcmv), we have identified the arenavirus small ring finger z protein as the main driving force of virus budding. both lcmv and lassa fever virus (lfv) z proteins exhibited self-budding activity, and both substituted efficiently for the late domain that is present in the gag protein of rous sarcoma virus. lcmv and lfv z proteins contain proline-rich motifs that are characteristic of l ... | 2003 | 14563923 |
| [outbreak of ebola hemorrhagic fever in the republic of the congo, 2003: a new strategy?]. | this article describes the last ebola haemorrhagic fever (ehf) outbreak that occurred in the cuvette ouest region of the republic of congo from january to april 2003. epidemiological study demonstrated that the first patient, in whom diagnosis was made retrospectively, became ill on december 25, 2002. subsequently until may 7, 2003, a total of 143 cases were recorded in the mbomo and kéllé health districts including 129 fatalities. thirteen cases were laboratory confirmed and 130 were epidemiolo ... | 2003 | 14579469 |
| production of monoclonal antibodies and development of an antigen capture elisa directed against the envelope glycoprotein gp of ebola virus. | ebola virus (ebov) causes severe outbreaks of ebola hemorrhagic fever in endemic regions of africa and is considered to be of impact for other parts of the world as an imported viral disease. to develop a new diagnostic test, monoclonal antibodies to ebov were produced from mice immunized with inactivated ebov species zaire. antibodies directed against the viral glycoprotein gp were characterized by elisa, western blot and immunofluorescence analyses. an antigen capture elisa was established, wh ... | 2004 | 14593476 |
| lentiviral vectors pseudotyped with minimal filovirus envelopes increased gene transfer in murine lung. | a human immunodeficiency virus (hiv)-based vector pseudotyped with the ebola zaire (eboz) viral envelope glycoprotein (gp) was recently shown to transduce murine airway epithelia cells in vivo. in this study, the vector was further redesigned to improve gene transfer and also to increase safety. we used mutant eboz envelopes for pseudotyping, which resulted in higher titers and increased transduction of airway cells in vivo compared to vectors pseudotyped with wild-type eboz gp. as these envelop ... | 2003 | 14599811 |
| virology. new vaccine and treatment excite ebola researchers. | | 2003 | 14615510 |
| antibody-dependent enhancement of viral infection: molecular mechanisms and in vivo implications. | besides the common receptor/coreceptor-dependent mechanism of cellular attachment, some viruses rely on antiviral antibodies for their efficient entry into target cells. this mechanism, known as antibody-dependent enhancement (ade) of viral infection, depends on the cross-linking of complexes of virus-antibody or virus-activated complement components through interaction with cellular molecules such as fc receptors or complement receptors, leading to enhanced infection of susceptible cells. recen ... | 2003 | 14625886 |
| pathogenesis of ebola hemorrhagic fever in cynomolgus macaques: evidence that dendritic cells are early and sustained targets of infection. | ebola virus (ebov) infection causes a severe and fatal hemorrhagic disease that in many ways appears to be similar in humans and nonhuman primates; however, little is known about the development of ebov hemorrhagic fever. in the present study, 21 cynomolgus monkeys were experimentally infected with ebov and examined sequentially over a 6-day period to investigate the pathological events of ebov infection that lead to death. importantly, dendritic cells in lymphoid tissues were identified as earl ... | 2003 | 14633608 |
| pathogenesis of ebola hemorrhagic fever in primate models: evidence that hemorrhage is not a direct effect of virus-induced cytolysis of endothelial cells. | ebola virus (ebov) infection causes a severe and often fatal hemorrhagic disease in humans and nonhuman primates. whether infection of endothelial cells is central to the pathogenesis of ebov hemorrhagic fever (hf) remains unknown. to clarify the role of endothelial cells in ebov hf, we examined tissues of 21 ebov-infected cynomolgus monkeys throughout time, and also evaluated ebov infection of primary human umbilical vein endothelial cells and primary human lung-derived microvascular endothelia ... | 2003 | 14633609 |
| folate receptor alpha and caveolae are not required for ebola virus glycoprotein-mediated viral infection. | folate receptor alpha (fralpha) has been described as a factor involved in mediating ebola virus entry into cells (6). furthermore, it was suggested that interaction with fralpha results in internalization and subsequent viral ingress into the cytoplasm via caveolae (9). descriptions of cellular receptors for ebola virus and its entry mechanisms are of fundamental importance, particularly with the advent of vectors bearing ebola virus glycoprotein (gp) being utilized for gene transfer into cell ... | 2003 | 14645601 |
| mannosyl glycodendritic structure inhibits dc-sign-mediated ebola virus infection in cis and in trans. | we have designed a glycodendritic structure, bh30sucman, that blocks the interaction between dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin (dc-sign) and ebola virus (ebov) envelope. bh30sucman inhibits dc-sign-mediated ebov infection at nanomolar concentrations. bh30sucman may counteract important steps of the infective process of ebov and, potentially, of microorganisms shown to exploit dc-sign for cell entry and infection. | 2003 | 14638512 |
| ebola and marburg viruses replicate in monocyte-derived dendritic cells without inducing the production of cytokines and full maturation. | ebola virus (ebov) and marburg virus (marv) cause rapidly progressive hemorrhagic fever with high mortality and may possess specialized mechanisms to evade immune destruction. we postulated that immune evasion could be due to the ability of ebov and marv to interfere with dendritic cells (dcs), which link innate and adaptive immune responses. we demonstrate that ebov and marv infected and replicated in primary human dcs without inducing cytokine secretion. infected dc cultures supported exponent ... | 2003 | 14639532 |
| mechanisms underlying coagulation abnormalities in ebola hemorrhagic fever: overexpression of tissue factor in primate monocytes/macrophages is a key event. | disseminated intravascular coagulation is a prominent manifestation of ebola virus (ebov) infection. here, we report that tissue factor (tf) plays an important role in triggering the hemorrhagic complications that characterize ebov infections. analysis of samples obtained from 25 macaques showed increased levels of tf associated with lymphoid macrophages, whereas analysis of peripheral blood-cell rna showed increased levels of tf transcripts by day 3. plasma from macaques contained increased num ... | 2003 | 14639531 |
| 5'-nor carbocyclic ribavirin. | an efficient synthesis of 5'-nor carbocyclic ribavirin (4) is described in 13 steps from conveniently available (+)-(ir,4s)-4-hydroxy-2-cyclopenten-1-yl acetate (6). compound 4 was evaluated against the following viruses: herpes simplex type 1 and 2, vaccinia, cowpox, smallpox, ebola, hepatitis b, hepatitis c, adenovirus type 1, influenza a (h1n1 and h3n2), influenza b, parainfluenza type 3, pichinde, punta toro a, respiratory syncytial, rhinovirus type 2, venezuelan equine encephalitis, yellow ... | 2003 | 14680022 |
| in vivo oligomerization and raft localization of ebola virus protein vp40 during vesicular budding. | the matrix protein vp40 plays a critical role in ebola virus assembly and budding, a process that utilizes specialized membrane domains known as lipid rafts. previous studies with purified protein suggest a role for oligomerization of vp40 in this process. here, we demonstrate vp40 oligomers in lipid rafts of mammalian cells, virus-like particles, and in the authentic ebola virus. by mutagenesis, we identify several critical c-terminal sequences that regulate oligomerization at the plasma membra ... | 2003 | 14673115 |
| ebola virus-like particles protect from lethal ebola virus infection. | the filovirus ebola causes hemorrhagic fever with 70-80% human mortality. high case-fatality rates, as well as known aerosol infectivity, make ebola virus a potential global health threat and possible biological warfare agent. development of an effective vaccine for use in natural outbreaks, response to biological attack, and protection of laboratory workers is a higher national priority than ever before. coexpression of the ebola virus glycoprotein (gp) and matrix protein (vp40) in mammalian ce ... | 2003 | 14673108 |
| emerging viral infections in a rapidly changing world. | emerging viral infections in both humans and animals have been reported with increased frequency in recent years. recent advances have been made in our knowledge of some of these, including severe acute respiratory syndrome-associated coronavirus, influenza a virus, human metapneumovirus, west nile virus and ebola virus. research efforts to mitigate their effects have concentrated on improved surveillance and diagnostic capabilities, as well as on the development of vaccines and antiviral agents ... | 2003 | 14662395 |
| treatment of ebola virus infection with a recombinant inhibitor of factor viia/tissue factor: a study in rhesus monkeys. | infection with the ebola virus induces overexpression of the procoagulant tissue factor in primate monocytes and macrophages, suggesting that inhibition of the tissue-factor pathway could ameliorate the effects of ebola haemorrhagic fever. here, we tested the notion that blockade of fviia/tissue factor is beneficial after infection with ebola virus. | 2003 | 14683653 |
| containing a haemorrhagic fever epidemic: the ebola experience in uganda (october 2000-january 2001). | introduction: the ebola virus, belonging to the family of filoviruses, was first recognized in 1976 when it caused concurrent outbreaks in yambuku in the democratic republic of congo (drc), and in the town of nzara in sudan. both countries share borders with uganda. a total of 425 cases and 224 deaths attributed to ebola haemorrhagic fever (ehf) were recorded in uganda in 2000/01. although there was delayed detection at the community level, prompt and efficient outbreak investigation led to the ... | 2004 | 14690778 |
| persistent infection with ebola virus under conditions of partial immunity. | ebola hemorrhagic fever in humans is associated with high mortality; however, some infected hosts clear the virus and recover. the mechanisms by which this occurs and the correlates of protective immunity are not well defined. using a mouse model, we determined the role of the immune system in clearance of and protection against ebola virus. all cd8 t-cell-deficient mice succumbed to subcutaneous infection and had high viral antigen titers in tissues, whereas mice deficient in b cells or cd4 t c ... | 2004 | 14694127 |
| production of novel ebola virus-like particles from cdnas: an alternative to ebola virus generation by reverse genetics. | we established a plasmid-based system for generating infectious ebola virus-like particles (vlps), which contain an ebola virus-like minigenome consisting of a negative-sense copy of the green fluorescent protein gene. this system produced nearly 10(3) infectious particles per ml of supernatant, equivalent to the titer of ebola virus generated by a reverse genetics system. interestingly, infectious ebola vlps were generated, even without expression of vp24. transmission and scanning electron mic ... | 2004 | 14694131 |
| towards a vaccine against ebola virus. | ebola virus infection causes hemorrhagic fever with high mortality rates in humans and nonhuman primates. currently, there are no vaccines or therapies approved for human use. outbreaks of ebola virus have been infrequent, largely confined to remote locations in africa and quarantine of sick patients has been effective in controlling epidemics. in the past, this small global market has generated little commercial interest for developing an ebola virus vaccine. however, heightened awareness of bi ... | 2003 | 14711361 |
| risk factors for marburg hemorrhagic fever, democratic republic of the congo. | we conducted two antibody surveys to assess risk factors for marburg hemorrhagic fever in an area of confirmed marburg virus transmission in the democratic republic of the congo. questionnaires were administered and serum samples tested for marburg-specific antibodies by enzyme-linked immunosorbent assay. fifteen (2%) of 912 participants in a general village cross-sectional antibody survey were positive for marburg immunoglobulin g antibody. thirteen (87%) of these 15 were men who worked in the ... | 2003 | 14720391 |
| distribution of hydrophobic residues is crucial for the fusogenic properties of the ebola virus gp2 fusion peptide. | the lipid-destabilizing properties of the n-terminal domain of the gp2 of ebola virus were investigated. our results suggest that the domain of ebola virus needed for fusion is shorter than that previously reported. the fusogenic properties of this domain are related to its oblique orientation at the lipid/water interface owing to an asymmetric distribution of the hydrophobic residues when helical. | 2004 | 14747578 |
| epidemiology. ebola outbreaks may have had independent sources. | | 2004 | 14726565 |
| conference report - i. investigating new vaccines: ebola and hiv: highlights from the viral vaccine meeting; october 25-28, 2003; barcelona, spain. | | 2003 | 14745371 |
| multiple ebola virus transmission events and rapid decline of central african wildlife. | several human and animal ebola outbreaks have occurred over the past 4 years in gabon and the republic of congo. the human outbreaks consisted of multiple simultaneous epidemics caused by different viral strains, and each epidemic resulted from the handling of a distinct gorilla, chimpanzee, or duiker carcass. these animal populations declined markedly during human ebola outbreaks, apparently as a result of ebola infection. recovered carcasses were infected by a variety of ebola strains, suggest ... | 2004 | 14726594 |
| ebola vaccines tested in humans, monkeys. | | 2004 | 14762022 |
| identification of murine t-cell epitopes in ebola virus nucleoprotein. | cd8 t cells play an important role in controlling ebola infection and in mediating vaccine-induced protective immunity, yet little is known about antigenic targets in ebola that are recognized by cd8 t cells. overlapping peptides were used to identify major histocompatibility complex class i-restricted epitopes in mice immunized with vectors encoding ebola nucleoprotein (np). cd8 t-cell responses were mapped to a h-2(d)-restricted epitope (np279-288) and two h-2(b)-restricted epitopes (np44-52 a ... | 2004 | 14972550 |
| transduction of human islets with pseudotyped lentiviral vectors. | type i diabetes is caused by an autoimmune-mediated elimination of insulin-secreting pancreatic islets. genetic modification of islets offers a powerful molecular tool for improving our understanding of islet biology. moreover, efficient genetic engineering of islets could allow for evaluation of new strategies aimed at preventing islet destruction. the present study evaluated the ability of a human immunodeficiency virus (hiv)-based lentiviral vector pseudotyped with various viral envelopes to ... | 2004 | 14975193 |
| prediction of proprotein convertase cleavage sites. | many secretory proteins and peptides are synthesized as inactive precursors that in addition to signal peptide cleavage undergo post-translational processing to become biologically active polypeptides. precursors are usually cleaved at sites composed of single or paired basic amino acid residues by members of the subtilisin/kexin-like proprotein convertase (pc) family. in mammals, seven members have been identified, with furin being the one first discovered and best characterized. recently, the ... | 2004 | 14985543 |
| budding of ppxy-containing rhabdoviruses is not dependent on host proteins tgs101 and vps4a. | viral matrix proteins of several enveloped rna viruses play important roles in virus assembly and budding and are by themselves able to bud from the cell surface in the form of lipid-enveloped, virus-like particles (vlps). three motifs (pt/sap, ppxy, and yxxl) have been identified as late budding domains (l-domains) responsible for efficient budding. l-domains can functionally interact with cellular proteins involved in vacuolar sorting (vps4a and tsg101) and endocytic pathways (nedd4), suggesti ... | 2004 | 14990685 |
| rapid diagnosis of ebola hemorrhagic fever by reverse transcription-pcr in an outbreak setting and assessment of patient viral load as a predictor of outcome. | the largest outbreak on record of ebola hemorrhagic fever (ehf) occurred in uganda from august 2000 to january 2001. the outbreak was centered in the gulu district of northern uganda, with secondary transmission to other districts. after the initial diagnosis of sudan ebolavirus by the national institute for virology in johannesburg, south africa, a temporary diagnostic laboratory was established within the gulu district at st. mary's lacor hospital. the laboratory used antigen capture and rever ... | 2004 | 15047846 |
| human macrophage c-type lectin specific for galactose and n-acetylgalactosamine promotes filovirus entry. | filoviruses cause lethal hemorrhagic disease in humans and nonhuman primates. an initial target of filovirus infection is the mononuclear phagocytic cell. calcium-dependent (c-type) lectins such as dendritic cell- or liver/lymph node-specific icam-3 grabbing nonintegrin (dc-sign or l-sign, respectively), as well as the hepatic asialoglycoprotein receptor, bind to ebola or marburg virus glycoprotein (gp) and enhance the infectivity of these viruses in vitro. here, we demonstrate that a recently i ... | 2004 | 14990712 |
| ebola virus glycoproteins: guidance devices for targeting gene therapy vectors. | replacing the native viral envelope protein on the surface of a retrovirus or lentivirus with the glycoprotein of a foreign enveloped virus, a process called pseudotyping, can expand the set of potential target cells for a viral vector or can restrict entry to specific cells. the ebola virus glycoprotein, because of its evolutionary origins and the route of viral entry promoted by it, possesses distinct advantages in forming the outer shell of such pseudotyped retroviruses for gene therapy appli ... | 2004 | 15006727 |
| 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 ... | 2004 | 15052667 |
| [an effective vaccine against ebola hemorrhagic fever]. | | 2004 | 15049337 |
| l-deaza-5'-noraisteromycin. | (+/-)-1-deazaaristeromycin (4) has been reported to be an inactivator of s-adenosylhomocysteine (adohcy) hydrolase and, as a consequence, to affect s-adenosylmethionine (adomet) mediated macromolecular biomethylations. to extend this to our program focused on 5'-noraristeromycin derivatives as inhibitors of the same hydrolase enzyme as potential antiviral agents, both enantiomers of 1-deaza-5'-noraristeromycin (5 and 20) have been prepared. compounds 5 and 20 were evaluated against the following ... | 2004 | 15043137 |