Publications

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
[ebola--haemorrhagic fever].	this review presents the latest findings on ebola. ebola presents one of the highest case-fatality rates of all infectious diseases, and in 2007 outbreaks were observed first in the democratic republic of congo and later in uganda with a new subtype. accumulating evidence suggests that fruit bats are a likely reservoir for the ebola virus. the frequency of filovirus outbreaks in central africa is increasing and the potential for introduction and patient care in denmark is evaluated.	2008	19087734
no exit: targeting the budding process to inhibit filovirus replication.	the filoviruses, ebola and marburg, cause severe hemorrhagic fever in humans and nonhuman primates, with high mortality rates. although the filovirus replication pathway is now understood in considerable detail, no antiviral drugs have yet been developed that directly inhibit steps in the replication cycle. one potential target is the filovirus vp40 matrix protein, the key viral protein that drives the budding process, in part by mediating specific virus-host interactions to facilitate the effic ...	2009	19114059
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
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
experimental vaccine may have saved hamburg scientist from ebola fever.		2009	19307268
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
fibroblastic reticular cells and their role in viral hemorrhagic fevers.	viral hemorrhagic fevers (vhfs) caused by ebola, marburg and lassa viruses often manifest as multiple organ dysfunction and hemorrhagic shock with high mortality. these viruses target numerous cell types, including monocytes and dendritic cells, which are primary early targets that mediate critical pathogenetic processes. this review focuses on fibroblastic reticular cells (frcs), another prevalent infected cell type that is known as a key regulator of circulatory and immune functions. viral inf ...	2009	19400762
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
optimal treatment of an sir epidemic model with time delay.	in this paper the optimal control strategies of an sir (susceptible-infected-recovered) epidemic model with time delay are introduced. in order to do this, we consider an optimally controlled sir epidemic model with time delay where a control means treatment for infectious hosts. we use optimal control approach to minimize the probability that the infected individuals spread and to maximize the total number of susceptible and recovered individuals. we first derive the basic reproduction number a ...	2009	19464340
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
design and synthesis of an antigenic mimic of the ebola glycoprotein.	an antigenic mimic of the ebola glycoprotein was synthesized and tested for its ability to be recognized by an anti-ebola glycoprotein antibody. epitope-mapping procedures yielded a suitable epitope that, when presented on the surface of a nanoparticle, forms a structure that is recognized by an antibody specific for the native protein. this mimic-antibody interaction has been quantitated through elisa and qcm-based methods and yielded an affinity (k(d) = 12 × 10(-6) m) within two orders of magn ...	2008	19609372
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
report of the international conference on risk communication strategies for bsl-4 laboratories, tokyo, october 3-5, 2007.	working with highly pathogenic agents such as ebola or marburg virus in the context of infection control or biodefense research requires high-biocontainment laboratories of the biosafety level 4 (bsl-4) to protect researchers and laboratory staff from infection and to prevent the unintentional release of harmful agents. the public perception of research on highly pathogenic agents and the operation of high-containment facilities is often ambivalent: while the output of the biomedical research is ...	2009	19635008
testing and validation of high density resequencing microarray for broad range biothreat agents detection.	rapid and effective detection and identification of emerging microbiological threats and potential biowarfare agents is very challenging when using traditional culture-based methods. contemporary molecular techniques, relying upon reverse transcription and/or polymerase chain reaction (rt-pcr/pcr) provide a rapid and effective alternative, however, such assays are generally designed and optimized to detect only a limited number of targets, and seldom are capable of differentiation among variants ...	2009	19668365
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
infection control during filoviral hemorrhagic fever outbreaks: preferences of community members and health workers in masindi, uganda.	interviews were conducted with health workers and community members in masindi, uganda on improving the acceptability of infection control measures used during an ebola outbreak. measures that promote cultural sensitivity and transparency of control activities were preferred and should be employed in future control efforts. we suggest assessing the practicality of body bags with viewing windows, and face shields with or without chin protectors, in future outbreaks.	2010	19783269
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
[electron microscopic analysis of viral assembly and budding].	viruses show ultrastructural changes during viral assembly and budding processes in which viral genome and proteins are systemically assembled. electron microscopy is the only way that enables us to observe such ultrastructural changes. we have investigated the mechanisms of ebola and influenza virion formation by electron microscopy. we have elucidated the roles of each ebola virus protein in viral assembly and budding as well as the mechanisms of genome packaging of influenza a viruses.	2009	19927994
antiviral activity of the interferon-induced cellular protein bst-2/tetherin.	pathogenic microorganisms encode proteins that antagonize specific aspects of innate or adaptive immunity. just as the study of the hiv-1 accessory protein vif led to the identification of cellular cytidine deaminases as host defense proteins, the study of hiv-1 vpu recently led to the discovery of the interferon-induced transmembrane protein bst-2 (cd317; tetherin) as a novel component of the innate defense against enveloped viruses. bst-2 is an unusually structured protein that restricts the r ...	2009	19929170
dna vaccines for biodefense.	an ideal biodefense vaccine platform would allow for the quick formulation of novel vaccines in response to emerging or engineered pathogens. the resultant vaccine should elicit protective immune responses in one to three doses and be unaffected by pre-existing immunity to vaccine components. in addition, it should be amenable to combination and multi-agent formulation, and should be safe for all populations and the environment. dna vaccines can potentially meet all of these requirements; thus, ...	2009	19943766
fgi-104: a broad-spectrum small molecule inhibitor of viral infection.	the treatment of viral diseases remains an intractable problem facing the medical community. conventional antivirals focus upon selective targeting of virus-encoded targets. however, the plasticity of viral nucleic acid mutation, coupled with the large number of progeny that can emerge from a single infected cells, often conspire to render conventional antivirals ineffective as resistant variants emerge. compounding this, new viral pathogens are increasingly recognized and it is highly improbabl ...	2009	19966942
establishment, immortalisation and characterisation of pteropid bat cell lines.	bats are the suspected natural reservoir hosts for a number of new and emerging zoonotic viruses including nipah virus, hendra virus, severe acute respiratory syndrome coronavirus and ebola virus. since the discovery of sars-like coronaviruses in chinese horseshoe bats, attempts to isolate a sl-cov from bats have failed and attempts to isolate other bat-borne viruses in various mammalian cell lines have been similarly unsuccessful. new stable bat cell lines are needed to help with these investig ...	2009	20011515
how ebola impacts genetics of western lowland gorilla populations.	emerging infectious diseases in wildlife are major threats for both human health and biodiversity conservation. infectious diseases can have serious consequences for the genetic diversity of populations, which could enhance the species' extinction probability. the ebola epizootic in western and central africa induced more than 90% mortality in western lowland gorilla population. although mortality rates are very high, the impacts of ebola on genetic diversity of western lowland gorilla have neve ...	2009	20020045
conserved motifs within ebola and marburg virus vp40 proteins are important for stability, localization, and subsequent budding of virus-like particles.	the filovirus vp40 protein is capable of budding from mammalian cells in the form of virus-like particles (vlps) that are morphologically indistinguishable from infectious virions. ebola virus vp40 (evp40) contains well-characterized overlapping l domains, which play a key role in mediating efficient virus egress. l domains represent only one component required for efficient budding and, therefore, there is a need to identify and characterize additional domains important for vp40 function. we de ...	2010	20032189
role of surfactant protein a and d (sp-a and sp-d) in human antiviral host defense.	sp-a and sp-d contribute to host defense against respiratory viral infection. the most extensive body of evidence relates to influenza a viruses (iav), and evidence from gene-deleted mice also indicate a role for surfactant collectins in defense against respiratory syncytial virus (rsv) and adenovirus. some important respiratory pathogens including rhinovirus and metapneumovirus have not yet been examined. viral pathogens that enter the body via the respiratory tract (e.g., ebola virus), replica ...	2010	20036966
metabolic investigation of host/pathogen interaction using ms2-infected escherichia coli.	rna viruses are responsible for a variety of illnesses among people, including but not limited to the common cold, the flu, hiv, and ebola. developing new drugs and new strategies for treating diseases caused by these viruses can be an expensive and time-consuming process. mathematical modeling may be used to elucidate host-pathogen interactions and highlight potential targets for drug development, as well providing the basis for optimizing patient treatment strategies. the purpose of this work ...	2009	20042079
high-level rapid production of full-size monoclonal antibodies in plants by a single-vector dna replicon system.	plant viral vectors have great potential in rapid production of important pharmaceutical proteins. however, high-yield production of hetero-oligomeric proteins that require the expression and assembly of two or more protein subunits often suffers problems due to the "competing" nature of viral vectors derived from the same virus. previously we reported that a bean yellow dwarf virus (beydv)-derived, three-component dna replicon system allows rapid production of single recombinant proteins in pla ...	2010	20047189
biochemical and structural characterization of cathepsin l-processed ebola virus glycoprotein: implications for viral entry and immunogenicity.	ebola virus (ebov) cellular attachment and entry is initiated by the envelope glycoprotein (gp) on the virion surface. entry of this virus is ph dependent and associated with the cleavage of gp by proteases, including cathepsin l (catl) and/or catb, in the endosome or cell membrane. here, we characterize the product of catl cleavage of zaire ebov gp (zebov-gp) and evaluate its relevance to entry. a stabilized recombinant form of the ebov gp trimer was generated using a trimerization domain linke ...	2010	20053739
mutations abrogating vp35 interaction with double-stranded rna render ebola virus avirulent in guinea pigs.	ebola virus (ebov) protein vp35 is a double-stranded rna (dsrna) binding inhibitor of host interferon (ifn)-alpha/beta responses that also functions as a viral polymerase cofactor. recent structural studies identified key features, including a central basic patch, required for vp35 dsrna binding activity. to address the functional significance of these vp35 structural features for ebov replication and pathogenesis, two point mutations, k319a/r322a, that abrogate vp35 dsrna binding activity and s ...	2010	20071589
structural basis for dsrna recognition and interferon antagonism by ebola vp35.	ebola viral protein 35 (vp35), encoded by the highly pathogenic ebola virus, facilitates host immune evasion by antagonizing antiviral signaling pathways, including those initiated by rig-i-like receptors. here we report the crystal structure of the ebola vp35 interferon inhibitory domain (iid) bound to short double-stranded rna (dsrna), which together with in vivo results reveals how vp35-dsrna interactions contribute to immune evasion. conserved basic residues in vp35 iid recognize the dsrna b ...	2010	20081868
marburg virus evades interferon responses by a mechanism distinct from ebola virus.	previous studies have demonstrated that marburg viruses (marv) and ebola viruses (ebov) inhibit interferon (ifn)-alpha/beta signaling but utilize different mechanisms. ebov inhibits ifn signaling via its vp24 protein which blocks the nuclear accumulation of tyrosine phosphorylated stat1. in contrast, marv infection inhibits ifnalpha/beta induced tyrosine phosphorylation of stat1 and stat2. marv infection is now demonstrated to inhibit not only ifnalpha/beta but also ifngamma-induced stat phospho ...	2010	20084112
case definition for ebola and marburg haemorrhagic fevers: a complex challenge for epidemiologists and clinicians.	viral haemorrhagic fevers (vhfs) represent a challenge for public health because of their epidemic potential, and their possible use as bioterrorism agents poses particular concern. in 1999 the world health organization (who) proposed a case definition for vhfs, subsequently adopted by other international institutions with the aim of early detection of initial cases/outbreaks in western countries. we applied this case definition to reports of ebola and marburg virus infections to estimate its se ...	2009	20128442
mucosal parainfluenza virus-vectored vaccine against ebola virus replicates in the respiratory tract of vector-immune monkeys and is immunogenic.	we previously used human parainfluenza virus type 3 (hpiv3) as a vector to express the ebola virus (ebov) gp glycoprotein. the resulting hpiv3/ebogp vaccine was immunogenic and protective against ebov challenge in a non-human primate model. however, it remained unclear whether the vaccine would be effective in adults due to preexisting immunity to hpiv3. here, the immunogenicity of hpiv3/ebogp was compared in hpiv3-naive and hpiv3-immune rhesus monkeys. after a single dose of hpiv3/ebogp, the ti ...	2010	20129638
identification of n-glycans from ebola virus glycoproteins by matrix-assisted laser desorption/ionisation time-of-flight and negative ion electrospray tandem mass spectrometry.	the larger fragment of the transmembrane glycoprotein (gp1) and the soluble glycoprotein (sgp) of ebola virus were expressed in human embryonic kidney cells and the secreted products were purified from the supernatant for carbohydrate analysis. the n-glycans were released with pngase f from within sodium dodecyl sulphate/polyacrylamide gel electrophoresis (sds-page) gels. identification of the glycans was made with normal-phase high-performance liquid chromatography (hplc), matrix-assisted laser ...	2010	20131323
a broad-spectrum antiviral targeting entry of enveloped viruses.	we describe an antiviral small molecule, lj001, effective against numerous enveloped viruses including influenza a, filoviruses, poxviruses, arenaviruses, bunyaviruses, paramyxoviruses, flaviviruses, and hiv-1. in sharp contrast, the compound had no effect on the infection of nonenveloped viruses. in vitro and in vivo assays showed no overt toxicity. lj001 specifically intercalated into viral membranes, irreversibly inactivated virions while leaving functionally intact envelope proteins, and inh ...	2010	20133606
histidine-mediated rna transfer to gdp for unique mrna capping by vesicular stomatitis virus rna polymerase.	the rna-dependent rna polymerase l protein of vesicular stomatitis virus, a prototype of nonsegmented negative-strand (nns) rna viruses, forms a covalent complex with a 5'-phosphorylated viral mrna-start sequence (l-prna), a putative intermediate in the unconventional mrna capping reaction catalyzed by the rna:gdp polyribonucleotidyltransferase (prntase) activity. here, we directly demonstrate that the purified l-prna complex transfers prna to gdp to produce the capped rna (gpp-prna), indicating ...	2010	20142503
characterization of the ebola virus nucleoprotein-rna complex.	when ebola virus nucleoprotein (np) is expressed in mammalian cells, it assembles into helical structures. here, the recombinant np helix purified from cells expressing np was characterized biochemically and morphologically. we found that the recombinant np helix is associated with non-viral rna, which is not protected from rnase digestion and that the morphology of the helix changes depending on the environmental salt concentration. the n-terminal 450 aa residues of np are sufficient for these ...	2010	20164259
protection of nonhuman primates against two species of ebola virus infection with a single complex adenovirus vector.	ebola viruses are highly pathogenic viruses that cause outbreaks of hemorrhagic fever in humans and other primates. to meet the need for a vaccine against the several types of ebola viruses that cause human diseases, we developed a multivalent vaccine candidate (ebo7) that expresses the glycoproteins of zaire ebolavirus (zebov) and sudan ebolavirus (sebov) in a single complex adenovirus-based vector (cadvax). we evaluated our vaccine in nonhuman primates against the parenteral and aerosol routes ...	2010	20181765
ebola virus uses clathrin-mediated endocytosis as an entry pathway.	ebola virus (ebov) infects several cell types and while viral entry is known to be ph-dependent, the exact entry pathway(s) remains unknown. to gain insights into ebov entry, the role of several inhibitors of clathrin-mediated endocytosis in blocking infection mediated by hiv pseudotyped with the ebov envelope glycoprotein (ebgp) was examined. wild type hiv and envelope-minus hiv pseudotyped with vesicular stomatitis virus glycoprotein (vsvg) were used as controls to assess cell viability after ...	2010	20202662
identification of sars-like coronaviruses in horseshoe bats (rhinolophus hipposideros) in slovenia.	bats have been identified as a natural reservoir for an increasing number of emerging zoonotic viruses, such as hendra virus, nipah virus, ebola virus, marburg virus, rabies and other lyssaviruses. recently, a large number of viruses closely related to members of the genus coronavirus have been associated with severe acute respiratory syndrome (sars) and detected in bat species. in this study, samples were collected from 106 live bats of seven different bat species from 27 different locations in ...	2010	20217155
simultaneous detection of cdc category "a" dna and rna bioterrorism agents by use of multiplex pcr & rt-pcr enzyme hybridization assays.	assays to simultaneously detect multiple potential agents of bioterrorism are limited. two multiplex pcr and rt-pcr enzyme hybridization assays (mpcr-eha, mrt-pcr-eha) were developed to simultaneously detect many of the cdc category "a" bioterrorism agents. the "bio t" dna assay was developed to detect: variola major (vm), bacillus anthracis (ba), yersinia pestis (yp), francisella tularensis (ft) and varicella zoster virus (vzv). the "bio t" rna assay (mrt-pcr-eha) was developed to detect: ebola ...	2009	20224751
cross-species pathogen transmission and disease emergence in primates.	many of the most virulent emerging infectious diseases in humans, e.g., aids and ebola, are zoonotic, having shifted from wildlife populations. critical questions for predicting disease emergence are: (1) what determines when and where a disease will first cross from one species to another, and (2) which factors facilitate emergence after a successful host shift. in wild primates, infectious diseases most often are shared between species that are closely related and inhabit the same geographic r ...	2010	20232229
personal protection during resuscitation of casualties contaminated with chemical or biological warfare agents--a survey of medical first responders.	the threat of mass casualties caused by an unconventional terrorist attack is a challenge for the public health system, with special implications for emergency medicine, anesthesia, and intensive care. advanced life support of patients injured by chemical or biological warfare agents requires an adequate level of personal protection. the aim of this study was to evaluate the personal protection knowledge of emergency physicians and anesthetists who would be at the frontline of the initial health ...	2009	20301071