| generation of biologically contained ebola viruses. | ebola virus (ebov), a public health concern in africa and a potential biological weapon, is classified as a biosafety level-4 agent because of its high mortality rate and the lack of approved vaccines and antivirals. basic research into the mechanisms of ebov pathogenicity and the development of effective countermeasures are restricted by the current biosafety classification of ebovs. we therefore developed biologically contained ebov that express a reporter gene instead of the vp30 gene, which ... | 2008 | 18212124 |
| vaccine to confer to nonhuman primates complete protection against multistrain ebola and marburg virus infections. | filoviruses (ebola and marburg viruses) are among the deadliest viruses known to mankind, with mortality rates nearing 90%. these pathogens are highly infectious through contact with infected body fluids and can be easily aerosolized. additionally, there are currently no licensed vaccines available to prevent filovirus outbreaks. their high mortality rates and infectious capabilities when aerosolized and the lack of licensed vaccines available to prevent such infectious make ebola and marburg vi ... | 2008 | 18216185 |
| [important issues of biological safety]. | the problem of biological security raises alarm due to the real growth of biological threats. biological security includes a wide scope of problems, the solution of which becomes a part of national security as a necessary condition for the constant development of the country. a number of pathogens, such as human immunodeficiency virus, exotic ebola and lassa viruses causing hemorrhagic fever,rotaviruses causing acute intestinal diseases, etc. were first discovered in the last century. terrorist ... | 2007 | 18225506 |
| [medicine and health in the democratic republic of congo: from independence to the third republic]. | the birth and mortality rates in the democratic republic of congo (drc), a former belgian colony, are high, i.e., 48.9/1000 and 17/1000 respectively. the drc also has one of the highest maternal death rates in the world, i.e., 1289/100,000 live births. health conditions have not improved since independence. access to drinking water is limited, living conditions are poor, and food availability in households is low. the mean health services utilization rate in the drc is estimated to be 0.15 visit ... | 2007 | 18225727 |
| the creation of stable cell lines expressing ebola virus glycoproteins and the matrix protein vp40 and generating ebola virus-like particles utilizing an ecdysone inducible mammalian expression system. | ebola virus is a filovirus that causes hemorrhagic fever in humans and is associated with case fatality rates of up to 90%. the lack of therapeutic interventions in combination with the threat of weaponizing this organism has enhanced research investigations. the expression of key viral proteins and the production of virus-like particles in mammalian systems are often pursued for characterization and functional studies. common practice is to express these proteins through transient transfection ... | 2008 | 18242720 |
| viral haemorrhagic fever and vascular alterations. | pathogenesis of viral haemorrhagic fever (vhf) is closely associated with alterations of the vascular system. among the virus families causing vhf, filoviruses (marburg and ebola) are the most fatal, and will be focused on here. after entering the body, ebola primarily targets monocytes/macrophages and dendritic cells. infected dendritic cells are largely impaired in their activation potency, likely contributing to the immune suppression that occurs during filovirus infection. monocytes/macropha ... | 2008 | 18278167 |
| isg15 inhibits nedd4 ubiquitin e3 activity and enhances the innate antiviral response. | interferons regulate diverse immune functions through the transcriptional activation of hundreds of genes involved in anti-viral responses. the interferon-inducible ubiquitin-like protein isg15 is expressed in cells in response to a variety of stress conditions like viral or bacterial infection and is present in its free form or is conjugated to cellular proteins. in addition, protein ubiquitination plays a regulatory role in the immune system. many viruses modulate the ubiquitin (ub) pathway to ... | 2008 | 18287095 |
| global trends in emerging infectious diseases. | emerging infectious diseases (eids) are a significant burden on global economies and public health. their emergence is thought to be driven largely by socio-economic, environmental and ecological factors, but no comparative study has explicitly analysed these linkages to understand global temporal and spatial patterns of eids. here we analyse a database of 335 eid 'events' (origins of eids) between 1940 and 2004, and demonstrate non-random global patterns. eid events have risen significantly ove ... | 2008 | 18288193 |
| isg15 inhibits ebola vp40 vlp budding in an l-domain-dependent manner by blocking nedd4 ligase activity. | ebola virus budding is mediated by the vp40 matrix protein. vp40 can bud from mammalian cells independent of other viral proteins, and efficient release of vp40 virus-like particles (vlps) requires interactions with host proteins such as tsg101 and nedd4, an e3 ubiquitin ligase. ubiquitin itself is thought to be exploited by ebola virus to facilitate efficient virus egress. disruption of vp40 function and thus virus budding remains an attractive target for the development of novel antiviral ther ... | 2008 | 18305167 |
| functional cd8+ t cell responses in lethal ebola virus infection. | ebola virus (ebov) causes highly lethal hemorrhagic fever that leads to death in up to 90% of infected humans. like many other infections, ebov induces massive lymphocyte apoptosis, which is thought to prevent the development of a functional adaptive immune response. in a lethal mouse model of ebov infection, we show that there is an increase in expression of the activation/maturation marker cd44 in cd4(+) and cd8(+) t cells late in infection, preceding a dramatic rebound of lymphocyte numbers i ... | 2008 | 18322215 |
| nonhuman primate quarantine: its evolution and practice. | nonhuman primates (nhps) are imported to the united states for use in research, domestic breeding, and propagation of endangered populations in zoological gardens. during the past 60 years, individuals responsible for nhp importation programs have observed morbidity and mortality typically associated with infectious disease outbreaks. these outbreaks have included infectious agents such as tuberculosis, herpesvirus sp., simian hemorrhagic fever, and filovirus infections such as the ebola and mar ... | 2008 | 18323577 |
| ebola virus matrix protein vp40 uses the copii transport system for its intracellular transport. | the ebola virus matrix protein vp40 plays an important role in virion formation and viral egress from cells. however, the host cell proteins and mechanisms responsible for intracellular transport of vp40 prior to its contribution to virion formation remain to be elucidated. therefore we used coimmunoprecipitation and mass spectrometric analyses to identify host proteins interacting with vp40. we found that sec24c, a component of the host copii vesicular transport system, interacts specifically w ... | 2008 | 18329616 |
| treatment of marburg and ebola hemorrhagic fevers: a strategy for testing new drugs and vaccines under outbreak conditions. | the filoviruses, marburg and ebola, have the dubious distinction of being associated with some of the highest case-fatality rates of any known infectious disease--approaching 90% in many outbreaks. in recent years, laboratory research on the filoviruses has produced treatments and vaccines that are effective in laboratory animals and that could potentially drastically reduce case-fatality rates and curtail outbreaks in humans. however, there are significant challenges in clinical testing of thes ... | 2008 | 18336927 |
| whole-genome expression profiling reveals that inhibition of host innate immune response pathways by ebola virus can be reversed by a single amino acid change in the vp35 protein. | ebola hemorrhagic fever is a rapidly progressing acute febrile illness characterized by high virus replication, severe immunosuppression, and case fatalities of ca. 80%. inhibition of phosphorylation of interferon regulatory factor 3 (irf-3) by the ebola vp35 protein may block the host innate immune response and play an important role in the severity of disease. we used two precisely defined reverse genetics-generated ebola viruses to investigate global host cell responses resulting from the inh ... | 2008 | 18353943 |
| recombinant vesicular stomatitis virus vector mediates postexposure protection against sudan ebola hemorrhagic fever in nonhuman primates. | recombinant vesicular stomatitis virus (vsv) vectors expressing homologous filoviral glycoproteins can completely protect rhesus monkeys against marburg virus when administered after exposure and can partially protect macaques after challenge with zaire ebolavirus. here, we administered a vsv vector expressing the sudan ebolavirus (sebov) glycoprotein to four rhesus macaques shortly after exposure to sebov. all four animals survived sebov challenge, while a control animal that received a nonspec ... | 2008 | 18385248 |
| a filovirus-unique region of ebola virus nucleoprotein confers aberrant migration and mediates its incorporation into virions. | the ebola virus nucleoprotein (np) is an essential component of the nucleocapsid, required for filovirus particle formation and replication. together with virion protein 35 (vp35) and vp24, this gene product gives rise to the filamentous nucleocapsid within transfected cells. ebola virus np migrates aberrantly, with an apparent molecular mass of 115 kda, although it is predicted to encode an approximately 85-kda protein. in this report, we show that two domains of this protein determine this abe ... | 2008 | 18417588 |
| processing of genome 5' termini as a strategy of negative-strand rna viruses to avoid rig-i-dependent interferon induction. | innate immunity is critically dependent on the rapid production of interferon in response to intruding viruses. the intracellular pathogen recognition receptors rig-i and mda5 are essential for interferon induction by viral rnas containing 5' triphosphates or double-stranded structures, respectively. viruses with a negative-stranded rna genome are an important group of pathogens causing emerging and re-emerging diseases. we investigated the ability of genomic rnas from substantial representative ... | 2008 | 18446221 |
| what caused lymphopenia in sars and how reliable is the lymphokine status in glucocorticoid-treated patients? | severe acute respiratory syndrome (sars) outbreak in 2002-03 caused morbidity in over 8000 individuals and mortality in 744 in 29 countries. lymphopenia along with neutrophilia was a feature of sars, as it is in respiratory syncytial virus (rsv) and ebola infections, to name a few. direct infestation of lymphocytes, neutrophils and macrophages by sars coronavirus (cov) has been debated as a cause of lymphopenia, but there is no convincing data. lymphopenia can be caused by glucocorticoids, and t ... | 2008 | 18448259 |
| cell adhesion promotes ebola virus envelope glycoprotein-mediated binding and infection. | ebola virus infects a wide variety of adherent cell types, while nonadherent cells are found to be refractory. to explore this correlation, we compared the ability of pairs of related adherent and nonadherent cells to bind a recombinant ebola virus receptor binding domain (ebov rbd) and to be infected with ebola virus glycoprotein (gp)-pseudotyped particles. both human 293f and thp-1 cells can be propagated as adherent or nonadherent cultures, and in both cases adherent cells were found to be si ... | 2008 | 18448524 |
| hiv-1 assembly: viral glycoproteins segregate quantally to lipid rafts that associate individually with hiv-1 capsids and virions. | hiv-1 assembly depends on its structural protein, gag, which after synthesis on ribosomes, traffics to the late endosome/plasma membrane, associates with hiv env glycoprotein, and forms infectious virions. while env and gag migrate to lipid microdomains, their stoichiometry and specificity of interaction are unknown. pseudotyped viral particles can be made with one viral core surrounded by heterologous envelope proteins. taking advantage of this property, we analyzed the association of hiv env a ... | 2008 | 18474355 |
| the 1995 kikwit ebola outbreak--model of virus properties on system capacity and function: a lesson for future viral epidemics. | the 1995 kikwit ebola outbreak in the democratic republic of the congo is one of the first ebola outbreaks to be treated in a hospital setting and is one of the most well-studied ebola epidemics to have occurred to date. many of the lessons learned from identifying, containing, and treating the epidemic are applicable to future viral outbreaks. this article looks at the characteristics of the ebola virus and health system issues, which affected the healthcare providers' ability to contain and tr ... | 2007 | 18491842 |
| managing potential laboratory exposure to ebola virus by using a patient biocontainment care unit. | in 2004, a scientist from the us army medical research institute of infectious diseases (usamriid) was potentially exposed to a mouse-adapted variant of the zaire species of ebola virus. the circumstances surrounding the case are presented, in addition to an update on historical admissions to the medical containment suite at usamriid. research facilities contemplating work with pathogens requiring biosafety level 4 laboratory precautions should be mindful of the occupational health issues highli ... | 2008 | 18507897 |
| novel astroviruses in insectivorous bats. | bats are increasingly recognized to harbor a wide range of viruses, and in most instances these viruses appear to establish long-term persistence in these animals. they are the reservoir of a number of human zoonotic diseases including nipah, ebola, and severe acute respiratory syndrome. we report the identification of novel groups of astroviruses in apparently healthy insectivorous bats found in hong kong, in particular, bats belonging to the genera miniopterus and myotis. astroviruses are impo ... | 2008 | 18550669 |
| potent in vitro activity of the albumin fusion type 1 interferons (albumin-interferon-alpha and albumin-interferon-beta) against rna viral agents of bioterrorism and the severe acute respiratory syndrome (sars) virus. | the type 1 interferons (inf-alpha and inf-beta) are potent antiviral agents. albumin-inf-alpha and albumin-inf-beta are novel recombinant proteins consisting of ifn-alpha or ifn-beta genetically fused to human albumin. | 2008 | 18560223 |
| a paramyxovirus-vectored intranasal vaccine against ebola virus is immunogenic in vector-immune animals. | ebola virus (ebov) causes outbreaks of a highly lethal hemorrhagic fever in humans. the virus can be transmitted by direct contact as well as by aerosol and is considered a potential bioweapon. because direct immunization of the respiratory tract should be particularly effective against infection of mucosal surfaces, we previously developed an intranasal vaccine based on replication-competent human parainfluenza virus type 3 (hpiv3) expressing ebov glycoprotein gp (hpiv3/ebogp) and showed that i ... | 2008 | 18570964 |
| dc-sign mediates avian h5n1 influenza virus infection in cis and in trans. | dc-sign, a c-type lectin receptor expressed in dendritic cells (dcs), has been identified as a receptor for human immunodeficiency virus type 1, hepatitis c virus, ebola virus, cytomegalovirus, dengue virus, and the sars coronavirus. we used h5n1 pseudotyped and reverse-genetics (rg) virus particles to study their ability to bind with dc-sign. electronic microscopy and functional assay results indicate that pseudotyped viruses containing both ha and na proteins express hemagglutination and are c ... | 2008 | 18593570 |
| molecular ecology and natural history of simian foamy virus infection in wild-living chimpanzees. | identifying microbial pathogens with zoonotic potential in wild-living primates can be important to human health, as evidenced by human immunodeficiency viruses types 1 and 2 (hiv-1 and hiv-2) and ebola virus. simian foamy viruses (sfvs) are ancient retroviruses that infect old and new world monkeys and apes. although not known to cause disease, these viruses are of public health interest because they have the potential to infect humans and thus provide a more general indication of zoonotic expo ... | 2008 | 18604273 |
| structure of the ebola virus glycoprotein bound to an antibody from a human survivor. | ebola virus (ebov) entry requires the surface glycoprotein (gp) to initiate attachment and fusion of viral and host membranes. here we report the crystal structure of ebov gp in its trimeric, pre-fusion conformation (gp1+gp2) bound to a neutralizing antibody, kz52, derived from a human survivor of the 1995 kikwit outbreak. three gp1 viral attachment subunits assemble to form a chalice, cradled by the gp2 fusion subunits, while a novel glycan cap and projected mucin-like domain restrict access to ... | 2008 | 18615077 |
| docking, synthesis, and nmr studies of mannosyl trisaccharide ligands for dc-sign lectin. | dc-sign, a lectin, which presents at the surface of immature dendritic cells, constitutes nowadays a promising target for the design of new antiviral drugs. this lectin recognizes highly glycosylated proteins present at the surface of several pathogens such as hiv, ebola virus, candida albicans, mycobacterium tuberculosis, etc. understanding the binding mode of this lectin is a topic of tremendous interest and will permit a rational design of new and more selective ligands. here, we present comp ... | 2008 | 18633532 |
| [the strategic plan for preparedness and response to bioterrorism in korea]. | following the anthrax bioterrorism attacks in the us in 2001, the korean government established comprehensive countermeasures against bioterrorism. these measures included the government assuming management of all infectious agents that cause diseases, including smallpox, anthrax, plaque, botulism, and the causative agents of viral hemorrhagic fevers (ebola fever, marburg fever, and lassa fever) for national security. in addition, the korean government is reinforcing the ability to prepare and r ... | 2008 | 18664725 |
| ebola images emerge from the cave. | ebola virus causes a lethal hemorrhagic disease for which no therapy or vaccine is currently approved. recently, the crystal structure of the ebola virus glycoprotein in complex with a human neutralizing antibody was illuminated, providing a path from the shadows toward understanding cellular attachment, viral fusion, and immune evasion. | 2008 | 18692765 |
| rna viruses and the mitogenic raf/mek/erk signal transduction cascade. | the raf/mek/erk signal transduction cascade belongs to the mitogen-activated protein kinase (mapk) cascades. raf/mek/erk signaling leads to stimulus-specific changes in gene expression, alterations in cell metabolism or induction of programmed cell death (apoptosis), and thus controls cell differentiation and proliferation. it is induced by extracellular agents, including pathogens such as rna viruses. many dna viruses are known to induce cellular signaling via this pathway. as these pathogens p ... | 2008 | 18713014 |
| adaptive modeling of viral diseases in bats with a focus on rabies. | many emerging and reemerging viruses, such as rabies, sars, marburg, and ebola have bat populations as disease reservoirs. understanding the spillover from bats to humans and other animals, and the associated health risks requires an analysis of the disease dynamics in bat populations. traditional compartmental epizootic models, which are relatively easy to implement and analyze, usually impose unrealistic aggregation assumptions about disease-related structure and depend on parameters that freq ... | 2008 | 18761020 |
| phosphoinositide-3 kinase-akt pathway controls cellular entry of ebola virus. | the phosphoinositide-3 kinase (pi3k) pathway regulates diverse cellular activities related to cell growth, migration, survival, and vesicular trafficking. it is known that ebola virus requires endocytosis to establish an infection. however, the cellular signals that mediate this uptake were unknown for ebola virus as well as many other viruses. here, the involvement of pi3k in ebola virus entry was studied. a novel and critical role of the pi3k signaling pathway was demonstrated in cell entry of ... | 2008 | 18769720 |
| crystal structure and carbohydrate analysis of nipah virus attachment glycoprotein: a template for antiviral and vaccine design. | two members of the paramyxovirus family, nipah virus (niv) and hendra virus (hev), are recent additions to a growing number of agents of emergent diseases which use bats as a natural host. identification of ephrin-b2 and ephrin-b3 as cellular receptors for these viruses has enabled the development of immunotherapeutic reagents which prevent virus attachment and subsequent fusion. here we present the structural analysis of the protein and carbohydrate components of the unbound viral attachment gl ... | 2008 | 18815311 |
| role of ebola virus vp30 in transcription reinitiation. | vp30 is a phosphoprotein essential for the initiation of ebola virus transcription. in this work, we have studied the effect of mutations in vp30 phosphorylation sites on the ebolavirus replication cycle by using a reverse genetics system. we demonstrate that vp30 is involved in reinitiation of gene transcription and that this activity is affected by mutations at the phosphorylation sites. | 2008 | 18829754 |
| biodistribution and toxicological safety of adenovirus type 5 and type 35 vectored vaccines against human immunodeficiency virus-1 (hiv-1), ebola, or marburg are similar despite differing adenovirus serotype vector, manufacturer's construct, or gene inserts. | the vaccine research center has developed vaccine candidates for different diseases/infectious agents (including hiv-1, ebola, and marburg viruses) built on an adenovirus vector platform, based on adenovirus type 5 or 35. to support clinical development of each vaccine candidate, pre-clinical studies were performed in rabbits to determine where in the body they biodistribute and how rapidly they clear, and to screen for potential toxicities (intrinsic and immunotoxicities). the vaccines biodistr ... | 2008 | 18830892 |
| emerging and reemerging diseases: a historical perspective. | summary: between mid-century and 1992, there was a consensus that the battle against infectious diseases had been won, and the surgeon general announced that it was time to close the book. experience with human immunodeficiency virus/acquired immunodeficiency syndrome, the return of cholera to the americas in 1991, the plague outbreak in india in 1994, and the emergence of ebola in zaire in 1995 created awareness of a new vulnerability to epidemics due to population growth, unplanned urbanizatio ... | 2008 | 18837773 |
| next generation of human vaccines: what does the future hold? | the world vaccine congress was held in arlington, va april 21st-24th, 2008. tevi troy, the deputy secretary of the us department of health and human services, set the tone of the meeting during his keynote address. he discussed the government's plan to deliver a strategic outlook and follow a road map for vaccine development. he also emphasized the importance of ongoing cooperation between industry and the government's many departments. in an electrifying keynote address gregory poland, professo ... | 2008 | 18849649 |
| vesicular stomatitis virus-based vaccines protect nonhuman primates against aerosol challenge with ebola and marburg viruses. | considerable progress has been made over the last decade in developing candidate preventive vaccines that can protect nonhuman primates against ebola and marburg viruses. a vaccine based on recombinant vesicular stomatitis virus (vsv) seems to be particularly robust as it can also confer protection when administered as a postexposure treatment. while filoviruses are not thought to be transmitted by aerosol in nature the inhalation route is among the most likely portals of entry in the setting of ... | 2008 | 18930776 |
| nasal delivery of an adenovirus-based vaccine bypasses pre-existing immunity to the vaccine carrier and improves the immune response in mice. | pre-existing immunity to human adenovirus serotype 5 (ad5) is common in the general population. bypassing pre-existing immunity could maximize ad5 vaccine efficacy. vaccination by the intramuscular (i.m.), nasal (i.n.) or oral (p.o.) route with ad5 expressing ebola zaire glycoprotein (ad5-zgp) fully protected naïve mice against lethal challenge with ebola. in the presence of pre-existing immunity, only mice vaccinated i.n. survived. the frequency of ifn-gamma+ cd8+ t cells was reduced by 80% and ... | 2008 | 18958172 |
| detection of viral rna from paraffin-embedded tissues after prolonged formalin fixation. | isolating amplifiable rna from formalin-fixed, paraffin-embedded (ffpe) tissues is more difficult than isolating dna because of rnases, chemical modification of the rna, and cross-linking of nucleic acids and proteins. tissues containing infectious disease agents that require biosafety level (bsl)-3 and -4 necessitate fixation times of 21 and 30 days, respectively. | 2009 | 18977691 |
| stimulation of ebola virus production from persistent infection through activation of the ras/mapk pathway. | human infections with ebola virus (ebov) result in a deadly viral disease known as ebola hemorrhagic fever. up to 90% of infected patients die, and there is no available treatment or vaccine. the sporadic human outbreaks are believed to result when ebov "jumps" from an infected animal to a person and is subsequently transmitted between persons by direct contact with infected blood or body fluids. this study was undertaken to investigate the mechanism by which ebov can persistently infect and the ... | 2008 | 18981410 |
| protection against lethal challenge by ebola virus-like particles produced in insect cells. | ebola virus-like particles (vlps) were produced in insect cells using a recombinant baculovirus expression system and their efficacy for protection against ebola virus infection was investigated. two immunizations with 50 microg ebola vlps (high dose) induced a high level of antibodies against ebola gp that exhibited strong neutralizing activity against gp-mediated virus infection and conferred complete protection of vaccinated mice against lethal challenge by a high dose of mouse-adapted ebola ... | 2009 | 18986663 |
| inhibition of rna virus infections with peptide-conjugated morpholino oligomers. | rna virus infections cause immense human disease burdens globally, and few effective antiviral drugs are available for their treatment. peptide-conjugated phosphorodiamidate morpholino oligomers (ppmo) are nuclease resistant and water-soluble single-stranded-dna-analogues that can enter cells readily and act as steric-blocking antisense agents through stable duplex formation with complementary rna. recently there have been a number of publications documenting sequence-specific and dose-dependent ... | 2008 | 18991679 |
| the yplgvg sequence of the nipah virus matrix protein is required for budding. | nipah virus (niv) is a recently emerged paramyxovirus capable of causing fatal disease in a broad range of mammalian hosts, including humans. together with hendra virus (hev), they comprise the genus henipavirus in the family paramyxoviridae. recombinant expression systems have played a crucial role in studying the cell biology of these biosafety level-4 restricted viruses. henipavirus assembly and budding occurs at the plasma membrane, although the details of this process remain poorly understo ... | 2008 | 19000317 |
| chimeric human parainfluenza virus bearing the ebola virus glycoprotein as the sole surface protein is immunogenic and highly protective against ebola virus challenge. | we generated a new live-attenuated vaccine against ebola virus (ebov) based on a chimeric virus hpiv3/deltaf-hn/ebogp that contains the ebov glycoprotein (gp) as the sole transmembrane envelope protein combined with the internal proteins of human parainfluenza virus type 3 (hpiv3). electron microscopy analysis of the virus particles showed that they have an envelope and surface spikes resembling those of ebov and a particle size and shape resembling those of hpiv3. when hpiv3/deltaf-hn/ebogp was ... | 2009 | 19010509 |
| requirements for cell rounding and surface protein down-regulation by ebola virus glycoprotein. | ebola virus causes an acute hemorrhagic fever that is associated with high morbidity and mortality. the viral glycoprotein is thought to contribute to pathogenesis, though precise mechanisms are unknown. cellular pathogenesis can be modeled in vitro by expression of the ebola viral glycoprotein (gp) in cells, which causes dramatic morphological changes, including cell rounding and surface protein down-regulation. these effects are known to be dependent on the presence of a highly glycosylated re ... | 2009 | 19013626 |
| newly discovered ebola virus associated with hemorrhagic fever outbreak in uganda. | over the past 30 years, zaire and sudan ebolaviruses have been responsible for large hemorrhagic fever (hf) outbreaks with case fatalities ranging from 53% to 90%, while a third species, côte d'ivoire ebolavirus, caused a single non-fatal hf case. in november 2007, hf cases were reported in bundibugyo district, western uganda. laboratory investigation of the initial 29 suspect-case blood specimens by classic methods (antigen capture, igm and igg elisa) and a recently developed random-primed pyro ... | 2008 | 19023410 |
| broad-spectrum inhibition of retroviral and filoviral particle release by tetherin. | the expression of many putative antiviral genes is upregulated when cells encounter type i interferon (ifn), but the actual mechanisms by which many ifn-induced gene products inhibit virus replication are poorly understood. a recently identified ifn-induced antiretroviral protein, termed tetherin (previously known as bst-2 or cd317), blocks the release of nascent human immunodeficiency virus type 1 (hiv-1) particles from infected cells, and an hiv-1 accessory protein, vpu, acts as a viral antago ... | 2009 | 19036818 |
| the ebola virus ribonucleoprotein complex: a novel vp30-l interaction identified. | the ribonucleoprotein (rnp) complex of ebola virus (ebov) is known to be a multiprotein/rna structure, however, knowledge is rather limited regarding the actual protein-protein interactions involved in its formation. here we show that singularly expressed vp35 and vp30 are present throughout the cytoplasm, while np forms prominent cytoplasmic inclusions and l forms smaller perinuclear inclusions. we could demonstrate the existence of np-vp35, np-vp30 and vp35-l interactions, similar to those des ... | 2009 | 19041915 |
| vesicular stomatitis virus-based ebola vaccine is well-tolerated and protects immunocompromised nonhuman primates. | ebola virus (ebov) is a significant human pathogen that presents a public health concern as an emerging/re-emerging virus and as a potential biological weapon. substantial progress has been made over the last decade in developing candidate preventive vaccines that can protect nonhuman primates against ebov. among these prospects, a vaccine based on recombinant vesicular stomatitis virus (vsv) is particularly robust, as it can also confer protection when administered as a postexposure treatment. ... | 2008 | 19043556 |
| structure of the ebola vp35 interferon inhibitory domain. | ebola viruses (ebovs) cause rare but highly fatal outbreaks of viral hemorrhagic fever in humans, and approved treatments for these infections are currently lacking. the ebola vp35 protein is multifunctional, acting as a component of the viral rna polymerase complex, a viral assembly factor, and an inhibitor of host interferon (ifn) production. mutation of select basic residues within the c-terminal half of vp35 abrogates its dsrna-binding activity, impairs vp35-mediated ifn antagonism, and atte ... | 2009 | 19122151 |
| disease modeling for ebola and marburg viruses. | the filoviruses ebola and marburg are zoonotic agents that are classified as both biosafety level 4 and category a list pathogens. these viruses are pathogenic in humans and cause isolated infections or epidemics of viral hemorrhagic fever, mainly in central africa. their natural reservoir has not been definitely identified, but certain species of african bat have been associated with ebola and marburg infections. currently, there are no licensed options available for either treatment or prophyl ... | 2009 | 19132113 |
| [an approach the quantitative determination of the area of glycoprotein spikes at the surface of enveloped viruses]. | the density of distribution of glycoproteins on virion surface seriously influences the virus infectivity and pathogenicity. in the present work a method of quantitative determination of the area occupied by the surface glycoprotein spikes is proposed for influenza virus (strain a/pr/8/34) based on data of tritium bombardment and dynamic light scattering (dls). the method of dls was used for measuring the diameter of the intact virions and the subviral particles (influenza virions lacking glycop ... | 2008 | 19140331 |
| ebola virus protein vp35 impairs the function of interferon regulatory factor-activating kinases ikkepsilon and tbk-1. | the ebola virus (ebov) vp35 protein antagonizes the early antiviral alpha/beta interferon (ifn-alpha/beta) response. we previously demonstrated that vp35 inhibits the virus-induced activation of the ifn-beta promoter by blocking the phosphorylation of ifn-regulatory factor 3 (irf-3), a transcription factor that is crucial for the induction of ifn-alpha/beta expression. furthermore, vp35 blocks ifn-beta promoter activation induced by any of several components of the retinoic acid-inducible gene i ... | 2009 | 19153231 |
| ebola outbreak has experts rooting for answers. | | 2009 | 19158753 |
| emerging infectious diseases. scientists puzzle over ebola-reston virus in pigs. | | 2009 | 19164717 |
| tetherin-mediated restriction of filovirus budding is antagonized by the ebola glycoprotein. | mammalian cells employ numerous innate cellular mechanisms to inhibit viral replication and spread. tetherin, also known as bst-2 or cd317, is a recently identified, ifn-induced, cellular response factor that blocks release of hiv-1 and other retroviruses from infected cells. the means by which tetherin retains retroviruses on the cell surface, as well as the mechanism used by the hiv-1 accessory protein vpu to antagonize tetherin function and promote hiv-1 release, are unknown. here, we documen ... | 2009 | 19179289 |
| [vaccines, biotechnology and their connection with induced abortion]. | diploid cells (wi-38, mrc-5) vaccines have their origin in induced abortions. among these vaccines we fi nd the following: rubella, measles, mumps, rabies, polio, smallpox, hepatitis a, chickenpox, and herpes zoster. nowadays, other abortion tainted vaccines cultivated on transformed cells (293, per.c6) are in the pipeline: flu, respiratory syncytial and parainfluenza viruses, hiv, west nile virus, ebola, marburg and lassa, hepatitis b and c, foot and mouth disease, japanese encephalitis, dengue ... | 2008 | 18611078 |
| expression, purification, crystallization and preliminary x-ray studies of the ebola vp35 interferon inhibitory domain. | ebola vp35 is a multifunctional protein that is important for host immune suppression and pathogenesis. vp35 contains an n-terminal oligomerization domain and a c-terminal interferon inhibitory domain (iid). mutations within the vp35 iid result in loss of host immune suppression. here, efforts to crystallize recombinantly overexpressed vp35 iid that was purified from escherichia coli are described. native and selenomethionine-labeled crystals belonging to the orthorhombic space group p2(1)2(1)2( ... | 2009 | 19194011 |
| ebola reston virus detected pigs in the philippines. | | 2009 | 19215709 |
| outbreak news. ebola reston in pigs and humans, philippines. | | 2009 | 19219963 |
| chemical modifications of antisense morpholino oligomers enhance their efficacy against ebola virus infection. | phosphorodiamidate morpholino oligomers (pmos) are uncharged nucleic acid-like molecules designed to inactivate the expression of specific genes via the antisense-based steric hindrance of mrna translation. pmos have been successful at knocking out viral gene expression and replication in the case of acute viral infections in animal models and have been well tolerated in human clinical trials. we propose that antisense pmos represent a promising class of therapeutic agents that may be useful for ... | 2009 | 19223614 |
| the marburg virus 3' noncoding region structurally and functionally differs from that of ebola virus. | we have previously shown that the first transcription start signal (tss) of zaire ebola virus (zebov) is involved in formation of an rna secondary structure regulating vp30-dependent transcription activation. interestingly, transcription of marburg virus (marv) minigenomes occurs independently of vp30. in this study, we analyzed the structure of the marv 3' noncoding region and its influence on vp30 necessity. secondary structure formation of the tss of the first gene was experimentally determin ... | 2009 | 19225002 |
| purification and functional characterization of the full length recombinant ebola virus vp35 protein expressed in e. coli. | in this work is presented, for the first time, the expression and purification in a prokaryotic system of the functionally active, recombinant full length vp35 protein of ebola virus (ebov). ebov is an enveloped non-segmented negative-stranded rna virus belonging to the filovirus family which causes a severe hemorrhagic fever in humans with mortality rates as high as 90%. several lines of evidence suggest that ebov interferes with host interferon responses and that the lack of these responses al ... | 2009 | 19233284 |
| crystal structure of the borna disease virus matrix protein (bdv-m) reveals ssrna binding properties. | borna disease virus (bdv) is a neurotropic enveloped rna virus that causes a noncytolytic, persistent infection of the central nervous system in mammals. bdv belongs to the order mononegavirales, which also includes the negative-strand rna viruses (nsvs) ebola, marburg, vesicular stomatitis, rabies, mumps, and measles. bdv-m, the matrix protein (m-protein) of bdv, is the smallest m-protein (16.2 kda) among the nsvs. m-proteins play a critical role in virus assembly and budding, mediating the int ... | 2009 | 19237566 |
| potential factors induced by filoviruses that lead to immune supression. | the filoviruses, ebola (ebov) and marburg (marv), are among the deadliest of human pathogens, causing acute diseases typified by rapidly fatal hemorrhagic fevers. upon filoviral infection, innate immune cells become paralyzed and lose the capacity to properly co-stimulate and activate filovirus-specific, t-cell responses. deleterious inflammation and upregulation of co-inhibitory molecules expressed by monocytic lineage cells (e.g., dendritic cells) and their co-inhibitory receptors on t- and b- ... | 2009 | 19275625 |
| drug targets in infections with ebola and marburg viruses. | the development of antiviral drugs for ebola and marburg viruses has been slow. to date, beyond supportive care, no effective treatments, prophylactic measures, therapies, or vaccines are approved to treat or prevent filovirus infections. in this review, we examine the current treatments available to administer care for filovirus infection, the potential therapeutic targets that can be used for filovirus drug development, and the various drug targeting techniques used against filoviruses. | 2009 | 19275706 |
| three-dimensional structure of aaa atpase vps4: advancing structural insights into the mechanisms of endosomal sorting and enveloped virus budding. | vps4 is a aaa atpase that mediates endosomal membrane protein sorting. it is also a host factor hijacked by a diverse set of clinically important viruses, including hiv and ebola, to facilitate viral budding. here we present the three-dimensional structure of the hydrolysis-defective vps4p(e233q) mutant. single-particle analysis, multiangle laser light scattering, and the docking of independently determined atomic models of vps4 monomers reveal a complex with c6 point symmetry, distinguishing be ... | 2009 | 19278657 |
| human ebola outbreak resulting from direct exposure to fruit bats in luebo, democratic republic of congo, 2007. | twelve years after the kikwit ebola outbreak in 1995, ebola virus reemerged in the occidental kasaï province of the democratic republic of congo (drc) between may and november 2007, affecting more than 260 humans and causing 186 deaths. during this latter outbreak we conducted several epidemiological investigations to identify the underlying ecological conditions and animal sources. qualitative social and environmental data were collected through interviews with villagers and by direct observati ... | 2009 | 19323614 |
| correlates of protective immunity for ebola vaccines: implications for regulatory approval by the animal rule. | ebola virus infection is a highly lethal disease for which there are no effective therapeutic or preventive treatments. several vaccines have provided immune protection in laboratory animals, but because outbreaks occur unpredictably and sporadically, vaccine efficacy cannot be proven in human trials, which is required for traditional regulatory approval. the food and drug administration has introduced the 'animal rule', to allow laboratory animal data to be used to show efficacy when human tria ... | 2009 | 19369954 |
| applications of high-throughput genomics to antiviral research: evasion of antiviral responses and activation of inflammation during fulminant rna virus infection. | host responses can contribute to the severity of viral infection, through the failure of innate antiviral mechanisms to recognize and restrict the pathogen, the development of intense systemic inflammation leading to circulatory failure or through tissue injury resulting from overly exuberant cell-mediated immune responses. high-throughput genomics methods are now being used to identify the biochemical pathways underlying ineffective or damaging host responses in a number of acute and chronic vi ... | 2009 | 19375457 |
| single-injection vaccine protects nonhuman primates against infection with marburg virus and three species of ebola virus. | the filoviruses marburg virus and ebola virus cause severe hemorrhagic fever with high mortality in humans and nonhuman primates. among the most promising filovirus vaccines under development is a system based on recombinant vesicular stomatitis virus (vsv) that expresses a single filovirus glycoprotein (gp) in place of the vsv glycoprotein (g). here, we performed a proof-of-concept study in order to determine the potential of having one single-injection vaccine capable of protecting nonhuman pr ... | 2009 | 19386702 |
| enhanced protection against ebola virus mediated by an improved adenovirus-based vaccine. | the ebola virus is transmitted by direct contact with bodily fluids of infected individuals, eliciting death rates as high as 90% among infected humans. currently, replication defective adenovirus-based ebola vaccine is being studied in a phase i clinical trial. another ebola vaccine, based on an attenuated vesicular stomatitis virus has shown efficacy in post-exposure treatment of nonhuman primates to ebola infection. in this report, we modified the common recombinant adenovirus serotype 5-base ... | 2009 | 19390586 |
| generation of vero cells expressing ebola virus glycoprotein. | to establish replication-incompetent ebola virus (ebov) lacking its glycoprotein (gp), we attempted to generate a vero cell line that constitutively expressed gp. we used a retroviral vector to transduce vero cells with the ebov gp gene, resulting in a high expression level of gp on the cell surface. the vero cells expressing ebov gp complemented the replication cycle of vesicular stomatitis virus, which lacks the essential viral glycoprotein. this cell line might be useful for basic research on ... | 2009 | 19420858 |
| mucosal immunization of cynomolgus macaques with the vsvdeltag/zebovgp vaccine stimulates strong ebola gp-specific immune responses. | zaire ebolavirus (zebov) produces a lethal viral hemorrhagic fever in humans and non-human primates. | 2009 | 19440245 |
| non-infectious plasmid engineered to simulate multiple viral threat agents. | the aim of this study was to design and construct a non-virulent simulant to replace several pathogenic viruses in the development of detection and identification methods in biodefense. a non-infectious simulant was designed and engineered to include the nucleic acid signature of veev (venezuelan equine encephalitis virus), influenza virus, rift valley fever virus, machupo virus, lassa virus, yellow fever virus, ebola virus, eastern equine encephalitis virus, junin virus, marburg virus, dengue v ... | 2009 | 19442841 |
| fold prediction of vp24 protein of ebola and marburg viruses using de novo fragment assembly. | virus particle 24 (vp24) is the smallest protein of the ebola and marburg virus genomes. recent experiments show that ebola vp24 blocks binding of tyrosine-phosphorylated stat-1 homodimer (py-stat1) to the npi-1 subfamily of importin alpha, thereby preventing nuclear accumulation of this interferon-promoting transcription factor which, in turn, reduces the innate immune response of the host target. lacking an experimental structure for vp24, we applied de novo protein structure prediction using ... | 2009 | 19447180 |
| emerging infections: a tribute to the one medicine, one health concept. | events in the last decade have taught us that we are now, more than ever, vulnerable to fatal zoonotic diseases such as those caused by haemorrhagic fever viruses, influenza, rabies and bse/vcjd. future research activities should focus on solutions to these problems arising at the interface between animals and humans. a 4-fold classification of emerging zoonoses was proposed: type 1: from wild animals to humans (hanta); type 1 plus: from wild animals to humans with further human-to-human transmi ... | 2009 | 19486315 |
| a charged second-site mutation in the fusion peptide rescues replication of a mutant avian sarcoma and leukosis virus lacking critical cysteine residues flanking the internal fusion domain. | the entry process of the avian sarcoma and leukosis virus (aslv) family of retroviruses requires first a specific interaction between the viral surface (su) glycoproteins and a receptor on the cell surface at a neutral ph, triggering conformational changes in the viral su and transmembrane (tm) glycoproteins, followed by exposure to low ph to complete fusion. the aslv tm glycoprotein has been proposed to adopt a structure similar to that of the ebola virus gp2 protein: each contains an internal ... | 2009 | 19515762 |
| ebola virus vp35 antagonizes pkr activity through its c-terminal interferon inhibitory domain. | ebola virus vp35 contains a c-terminal cluster of basic amino acids required for double-stranded rna (dsrna) binding and inhibition of interferon regulatory factor 3 (irf3). vp35 also blocks protein kinase r (pkr) activation; however, the responsible domain has remained undefined. here we show that the irf inhibitory domain of vp35 mediates the inhibition of pkr and enhances the synthesis of coexpressed proteins. in contrast to dsrna binding and irf inhibition, alanine substitutions of at least ... | 2009 | 19515768 |
| development of a broad-spectrum antiviral with activity against ebola virus. | we report herein the identification of a small molecule therapeutic, fgi-106, which displays potent and broad-spectrum inhibition of lethal viral hemorrhagic fevers pathogens, including ebola, rift valley and dengue fever viruses, in cell-based assays. using mouse models of ebola virus, we further demonstrate that fgi-106 can protect animals from an otherwise lethal infection when used either in a prophylactic or therapeutic setting. a single treatment, administered 1 day after infection, is suf ... | 2009 | 19523489 |
| ebola zaire virus blocks type i interferon production by exploiting the host sumo modification machinery. | ebola zaire virus is highly pathogenic for humans, with case fatality rates approaching 90% in large outbreaks in africa. the virus replicates in macrophages and dendritic cells (dcs), suppressing production of type i interferons (ifns) while inducing the release of large quantities of proinflammatory cytokines. although the viral vp35 protein has been shown to inhibit ifn responses, the mechanism by which it blocks ifn production has not been fully elucidated. we expressed vp35 from a mouse-ada ... | 2009 | 19557165 |
| models of epidemics: when contact repetition and clustering should be included. | the spread of infectious disease is determined by biological factors, e.g. the duration of the infectious period, and social factors, e.g. the arrangement of potentially contagious contacts. repetitiveness and clustering of contacts are known to be relevant factors influencing the transmission of droplet or contact transmitted diseases. however, we do not yet completely know under what conditions repetitiveness and clustering should be included for realistically modelling disease spread. | 2009 | 19563624 |
| discovery of swine as a host for the reston ebolavirus. | since the discovery of the marburg and ebola species of filovirus, seemingly random, sporadic fatal outbreaks of disease in humans and nonhuman primates have given impetus to identification of host tropisms and potential reservoirs. domestic swine in the philippines, experiencing unusually severe outbreaks of porcine reproductive and respiratory disease syndrome, have now been discovered to host reston ebolavirus (rebov). although rebov is the only member of filoviridae that has not been associa ... | 2009 | 19590002 |
| immunoglobulin g in ebola outbreak survivors, gabon. | | 2009 | 19624943 |
| rho gtpases modulate entry of ebola virus and vesicular stomatitis virus pseudotyped vectors. | to explore mechanisms of entry for ebola virus (ebov) glycoprotein (gp) pseudotyped virions, we used comparative gene analysis to identify genes whose expression correlated with viral transduction. candidate genes were identified by using ebov gp pseudotyped virions to transduce human tumor cell lines that had previously been characterized by cdna microarray. transduction profiles for each of these cell lines were generated, and a significant positive correlation was observed between rhoc expres ... | 2009 | 19625394 |
| rig-i activation inhibits ebolavirus replication. | hemorrhagic fever viruses are associated with rapidly progressing severe disease with high case fatality, making them of public health and biothreat importance. effective antivirals are not available for most of the members of this diverse group of viruses. a broad spectrum strategy for antiviral development would be very advantageous. perhaps the most challenging target would be the highly immunosuppressive filoviruses, ebolavirus and marburgvirus, associated with aerosol infectivity and case f ... | 2009 | 19628240 |
| reduced levels of protein tyrosine phosphatase cd45 protect mice from the lethal effects of ebola virus infection. | ebola virus (ebov) infection of humans is a lethal but accidental dead-end event. understanding resistance to ebov in other species may help establish the basis of susceptibility differences among its hosts. although rodents are resistant to ebov, a murine-adapted variant is lethal when injected intraperitoneally into mice. we find that mice expressing reduced levels of the tyrosine phosphatase cd45 are protected against ebov, whereas wild-type, cd45-deficient, or enzymatically inactive cd45-exp ... | 2009 | 19683682 |
| evasion of interferon responses by ebola and marburg viruses. | the filoviruses, ebola virus (ebov) and marburg virus (marv), cause frequently lethal viral hemorrhagic fever. these infections induce potent cytokine production, yet these host responses fail to prevent systemic virus replication. consistent with this, filoviruses have been found to encode proteins vp35 and vp24 that block host interferon (ifn)-alpha/beta production and inhibit signaling downstream of the ifn-alpha/beta and the ifn-gamma receptors, respectively. vp35, which is a component of th ... | 2009 | 19694547 |
| swine ebola. | | 2009 | 19708514 |
| [viruses and bats: rabies and lyssavirus]. | recent emerging zoonoses (hemorrhagic fevers due to ebola or marburg virus, encephalitis due to nipah virus, severe acute respiratory syndrome due to sras virus...) outline the potential of bats as vectors for transmission of infectious disease to humans. such a potential is already known for rabies encephalitis since seven out of the eight genotypes of lyssavirus are transmitted by bats. in addition, phylogenetic reconstructions indicate that lyssavirus have evolved in chiropters before their e ... | 2009 | 19718950 |
| activation of transgene-specific t cells following lentivirus-mediated gene delivery to mouse lung. | integrating lentiviral vectors based on the human immunodeficiency virus type-1 (hiv-1) can transduce quiescent cells, which in lung account for almost 95% of the epithelial cell population. pseudotyping lentiviral vectors with the envelope glycoprotein from the ebola zaire virus, the lymphocytic choriomeningitis virus (lcmv), the mokola virus, and the vesicular stomatitis virus (vsv-g) resulted in transduction of mouse alveolar epithelium, but gene expression in the lung of c57bl/6 and balb/c m ... | 2010 | 19724265 |
| zaire ebola virus entry into human dendritic cells is insensitive to cathepsin l inhibition. | cathepsins b and l contribute to ebola virus (ebov) entry into vero cells and mouse embryonic fibroblasts. however, the role of cathepsins in ebov-infection of human dendritic cells (dcs), important targets of infection in vivo, remains undefined. here, ebov-like particles containing a beta-lactamase-vp40 fusion reporter and ebola virus were used to demonstrate the cathepsin dependence of ebov entry into human monocyte-derived dcs. however, while dc infection is blocked by cathepsin b inhibitor, ... | 2010 | 19775255 |
| large serological survey showing cocirculation of ebola and marburg viruses in gabonese bat populations, and a high seroprevalence of both viruses in rousettus aegyptiacus. | ebola and marburg viruses cause highly lethal hemorrhagic fevers in humans. recently, bats of multiple species have been identified as possible natural hosts of zaire ebolavirus (zebov) in gabon and republic of congo, and also of marburgvirus (marv) in gabon and democratic republic of congo. | 2009 | 19785757 |
| regulation of marburg virus (marv) budding by nedd4.1: a different ww domain of nedd4.1 is critical for binding to marv and ebola virus vp40. | the vp40 matrix protein of marburg virus (marv) has been shown to be the driving force behind marv budding, a process in which the pppy l-domain motif of vp40 plays a critical role. here, we report that vps4b and nedd4.1 play critical roles in marv vp40-mediated budding. we showed that unidentified activities of the nedd4.1 hect domain, along with its e3 ubiquitin ligase activity, may be required for marv budding. moreover, we showed that the first ww domain of nedd4.1, ww1, is critical for bind ... | 2010 | 19812267 |
| the vp35 protein of ebola virus impairs dendritic cell maturation induced by virus and lipopolysaccharide. | ebola virus causes rapidly progressive haemorrhagic fever, which is associated with severe immuosuppression. in infected dendritic cells (dcs), ebola virus replicates efficiently and inhibits dc maturation without inducing cytokine expression, leading to impaired t-cell proliferation. however, the underlying mechanism remains unclear. in this study, we report that ebola virus vp35 impairs the maturation of mouse dcs. when expressed in mouse immature dcs, ebola virus vp35 prevents virus-stimulate ... | 2010 | 19828757 |
| interaction between ebola virus glycoprotein and host toll-like receptor 4 leads to induction of proinflammatory cytokines and socs1. | ebola virus initially targets monocytes and macrophages, which can lead to the release of proinflammatory cytokines and chemokines. these inflammatory cytokines are thought to contribute to the development of circulatory shock seen in fatal ebola virus infections. here we report that host toll-like receptor 4 (tlr4) is a sensor for ebola virus glycoprotein (gp) on virus-like particles (vlps) and that resultant tlr4 signaling pathways lead to the production of proinflammatory cytokines and suppre ... | 2010 | 19846529 |
| an enzymatic virus-like particle assay for sensitive detection of virus entry. | a viral entry assay where a beta-lactamase reporter protein fused to the influenza matrix protein-1 (blam1) is packaged as a structural component into influenza virus-like particles (vlps) is described. the bla reporter is released upon fusion with target cells and can be detected in live cells by flow cytometry, microscopy, or fluorometric plate reader for utility in high-throughput screening approaches. the production of blam1 vlps and subsequent transfer of bla activity to target cells requir ... | 2010 | 19879300 |