Publications

rescue of recombinant marburg virus from cdna is dependent on nucleocapsid protein vp30.	here we report recovery of infectious marburg virus (marv) from a full-length cdna clone. compared to the wild-type virus, recombinant marv showed no difference in terms of morphology of virus particles, intracellular distribution in infected cells, and growth kinetics. the nucleocapsid protein vp30 of marv and ebola virus (ebov) contains a zn-binding motif which is important for the function of vp30 as a transcriptional activator in ebov, whereas its role for marv is unclear. it has been report ...	2006	16379005
[bats, reserves of the ebola virus: the mystery is dissipated].		2006	16386226
internalizing antibodies to the c-type lectins, l-sign and dc-sign, inhibit viral glycoprotein binding and deliver antigen to human dendritic cells for the induction of t cell responses.	the c-type lectin l-sign is expressed on liver and lymph node endothelial cells, where it serves as a receptor for a variety of carbohydrate ligands, including icam-3, ebola, and hiv. to consider targeting liver/lymph node-specific icam-3-grabbing nonintegrin (l-sign) for therapeutic purposes in autoimmunity and infectious disease, we isolated and characterized fabs that bind strongly to l-sign, but to a lesser degree or not at all to dendritic cell-specific icam-grabbing nonintegrin (dc-sign). ...	2006	16365436
time- and temperature-dependent activation of hepatitis c virus for low-ph-triggered entry.	hepatitis c virus (hcv) is an important human pathogen associated with chronic liver disease. recently, based on a genotype 2a isolate, tissue culture systems supporting complete replication and infectious virus production have been developed. in this study, we used cell culture-produced infectious hcv to analyze the viral entry pathway into huh-7.5 cells. bafilomycin a1 and concanamycin a, inhibitors of vacuolar atpases, prevented hcv entry when they were present prior to infection and had mini ...	2006	16439530
development of human monoclonal antibodies against diseases caused by emerging and biodefense-related viruses.	polyclonal antibodies have a century-old history of being effective against some viruses; recently, monoclonal antibodies (mabs) have also shown success. the humanized mab synagis (palivizumab), which is still the only mab against a viral disease approved by the us fda, has been widely used as a prophylactic measure against respiratory syncytial virus infections in neonates and immunocompromised individuals. the first fully human mabs against two other paramyxoviruses, hendra and nipah virus, wh ...	2006	16441209
development of treatment strategies to combat ebola and marburg viruses.	ebola and marburg viruses are emerging/re-emerging pathogens that pose a significant threat to human health. these naturally occurring viral infections frequently cause a lethal hemorrhagic fever in humans and nonhuman primates. the disastrous consequences of infection with these viruses have been pursued as potential biological weapons. to date, there are no therapeutic options available for the prophylaxis or treatment of infected individuals. the recognition that ebola and marburg viruses may ...	2006	16441210
[scientific progress and new biological weapons].	the biological weapons are different from conventional weapons, because living germs hold an extraordinary and predictable potential for multiplication, propagation and genetic variation during their dissemination in a susceptible population. only natural pathogens (1rst generation weapons) have been used in the past (smallpox virus, plague, anthrax, toxins...). however, new threats are emerging, due to the rapid progress of scientific knowledge and its exponential worldwide diffusion. it is pos ...	2006	16457765
a single intranasal inoculation with a paramyxovirus-vectored vaccine protects guinea pigs against a lethal-dose ebola virus challenge.	to determine whether intranasal inoculation with a paramyxovirus-vectored vaccine can induce protective immunity against ebola virus (ev), recombinant human parainfluenza virus type 3 (hpiv3) was modified to express either the ev structural glycoprotein (gp) by itself (hpiv3/ebogp) or together with the ev nucleoprotein (np) (hpiv3/ebogp-np). expression of ev gp by these recombinant viruses resulted in its efficient incorporation into virus particles and increased cytopathic effect in vero cells. ...	2006	16474134
vp35 knockdown inhibits ebola virus amplification and protects against lethal infection in mice.	phosphorodiamidate morpholino oligomers (pmo) are a class of uncharged single-stranded dna analogs modified such that each subunit includes a phosphorodiamidate linkage and morpholine ring. pmo antisense agents have been reported to effectively interfere with the replication of several positive-strand rna viruses in cell culture. the filoviruses, marburg virus and ebola virus (ebov), are negative-strand rna viruses that cause up to 90% lethality in human outbreaks. there is currently no commerci ...	2006	16495261
development of a cadvax-based bivalent ebola virus vaccine that induces immune responses against both the sudan and zaire species of ebola virus.	ebola virus (ebov) causes a severe hemorrhagic fever for which there are currently no vaccines or effective treatments. while lethal human outbreaks have so far been restricted to sub-saharan africa, the potential exploitation of ebov as a biological weapon cannot be ignored. two species of ebov, sudan ebolavirus (sebov) and zaire ebolavirus (zebov), have been responsible for all of the deadly human outbreaks resulting from this virus. therefore, it is important to develop a vaccine that can pre ...	2006	16501083
detection of cell-cell fusion mediated by ebola virus glycoproteins.	ebola viruses (ebov) are enveloped rna viruses infecting cells by a ph-dependent process mediated by viral glycoproteins (gp) involving endocytosis of virions and their routing into acidic endosomes. as with well-characterized ph-dependent viral entry proteins, in particular influenza virus hemagglutinin, it is thought that ebov gp require activation by low ph in order to mediate fusion of the viral envelope with the membrane of endosomes. however, it has not yet been possible to confirm the dir ...	2006	16501090
global suppression of the host antiviral response by ebola- and marburgviruses: increased antagonism of the type i interferon response is associated with enhanced virulence.	we studied the effect of filovirus infection on host cell gene expression by characterizing the regulation of gene expression responses in human liver cells infected with zaire ebolavirus (zebov), reston ebolavirus (rebov), and marburgvirus (marv), using transcriptional profiling and bioinformatics. expression microarray analysis demonstrated that filovirus infection resulted in the up-regulation of immune-related genes and the down-regulation of many coagulation and acute-phase proteins. these ...	2006	16501110
de novo syntheses of marburg virus antigens from adenovirus vectors induce potent humoral and cellular immune responses.	marburg virus (marv) is an african filovirus that causes a deadly hemorrhagic fever in humans, with up to 90% mortality. currently, there are no marv vaccines or therapies approved for human use. we hypothesized that developing a vaccine that induces a de novo synthesis of marv antigens in vivo will lead to strong induction of both a humoral and cell-mediated immune response against marv. here, we develop and characterize three novel gene-based vaccine candidates which express the viral glycopro ...	2006	16530297
emergency medicine and the public's health: emerging infectious diseases.	in recent years, multiple global forces have contributed to the emergence and widespread distribution of previously unknown disease entities. this article discusses ebola virus, west nile virus, and hantavirus as representative emerging infectious diseases. smallpox is discussed along with concerns about the safety of the smallpox vaccine, given the uncertain risk of bioterrorism and smallpox exposure. ed physicians must become familiar with the presentation, management, and public health impact ...	2006	16982350
a dna vaccine for ebola virus is safe and immunogenic in a phase i clinical trial.	ebola viruses represent a class of filoviruses that causes severe hemorrhagic fever with high mortality. recognized first in 1976 in the democratic republic of congo, outbreaks continue to occur in equatorial africa. a safe and effective ebola virus vaccine is needed because of its continued emergence and its potential for use for biodefense. we report the safety and immunogenicity of an ebola virus vaccine in its first phase i human study. a three-plasmid dna vaccine encoding the envelope glyco ...	2006	16988008
mutation of ymyl in the nipah virus matrix protein abrogates budding and alters subcellular localization.	matrix (m) proteins reportedly direct the budding of paramyxoviruses from infected cells. in order to begin to characterize the assembly process for the highly lethal, emerging paramyxovirus nipah virus (niv), we have examined the budding of niv m. we demonstrated that expression of the niv m protein is sufficient to produce budding virus-like particles (vlps) that are physically and morphologically similar to niv. we identified in niv m a sequence, ymyl, with similarity to the ypdl late domain ...	2006	17005661
tyro3 family-mediated cell entry of ebola and marburg viruses.	filoviruses, represented by the genera ebolavirus and marburgvirus, cause a lethal hemorrhagic fever in humans and in nonhuman primates. although filovirus can replicate in various tissues or cell types in these animals, the molecular mechanisms of its broad tropism remain poorly understood. here we show the involvement of members of the tyro3 receptor tyrosine kinase family-axl, dtk, and mer-in cell entry of filoviruses. ectopic expression of these family members in lymphoid cells, which otherw ...	2006	17005688
bile salt-stimulated lipase from human milk binds dc-sign and inhibits human immunodeficiency virus type 1 transfer to cd4+ t cells.	a wide range of pathogens, including human immunodeficiency virus type 1 (hiv-1), hepatitis c virus, ebola virus, cytomegalovirus, dengue virus, mycobacterium, leishmania, and helicobacter pylori, can interact with dendritic cell (dc)-specific icam3-grabbing nonintegrin (dc-sign), expressed on dcs and a subset of b cells. more specifically, the interaction of the gp120 envelope protein of hiv-1 with dc-sign can facilitate the transfer of virus to cd4+ t lymphocytes in trans and enhance infection ...	2006	17005819
evaluation of promed-mail as an electronic early warning system for emerging animal diseases: 1996 to 2004.	to identify emerging animal and zoonotic diseases and associated geographic distribution, disease agents, animal hosts, and seasonality of reporting in the program for monitoring emerging diseases (promed)-mail electronic early warning system.	2006	17014355
implication of a retrovirus-like glycoprotein peptide in the immunopathogenesis of ebola and marburg viruses.	ebola and marburg viruses can cause hemorrhagic fever (hf) outbreaks with high mortality in primates. whereas marburg (marv), ebola zaire (zebov), and ebola sudan (sebov) viruses are pathogenic in humans, apes, and monkeys, ebola reston (rebov) is pathogenic only in monkeys. early immunosuppression may contribute to pathogenesis by facilitating viral replication. lymphocyte depletion, intravascular apoptosis, and cytokine dysregulation are prominent in fatal cases. here we functionally character ...	2006	17023517
[properties of the ebola virus glycoprotein].	in central and west africa, ebola virus, a member of the filovirus group, has produced sporadic outbreaks of lethal disease. this virus causes hemorrhagic fever in humans and nonhuman primates, resulting in mortality rates of up to 90%. although there are no satisfactory biologic explanations for this extreme virulence, it has been suggested that functions of the envelope glycoprotein are likely to play important roles in the pathogenicity of ebola virus.	2006	17038820
zoonotic viral diseases and the frontier of early diagnosis, control and prevention.	public awareness of the human health risks of zoonotic infections has grown in recent years. currently, concern of h5n1 flu transmission from migratory bird populations has increased with foci of fatal human cases. this comes on the heels of other major zoonotic viral epidemics in the last decade. these include other acute emerging or re-emerging viral diseases such as severe acute respiratory syndrome (sars), west-nile virus, ebola virus, monkeypox, as well as the more inapparent insidious slow ...	2006	17040245
recent common ancestry of ebola zaire virus found in a bat reservoir.		2006	17069458
[hemorrhagic (marburg, ebola, lassa, and bolivian) fevers: epidemiology, clinical pictures, and treatment].	the evaluation of the biological and epidemiological properties of ebola, marburg, lassa, and machupo viruses suggests that they are of social importance for health care authorities. the studies have created prerequisites to the development of reliable biosafety means against these pathogens. particular emphasis is laid on the methods for infection diagnosis and on the studies to design specific protective agents--immunoglobulins and inactivated vaccines.	2006	17087059
progress towards the treatment of ebola haemorrhagic fever.	being highly pathogenic for human and nonhuman primates and the subject of former weapon programmes makes ebola virus one of the most feared pathogens worldwide today. due to a lack of licensed pre- and postexposure intervention, the current response depends on rapid diagnostics, proper isolation procedures and supportive care of case patients. consequently, the development of more specific countermeasures is of high priority for the preparedness of many nations. over the past years, enhanced re ...	2006	17107278
toxicological safety evaluation of dna plasmid vaccines against hiv-1, ebola, severe acute respiratory syndrome, or west nile virus is similar despite differing plasmid backbones or gene-inserts.	the vaccine research center has developed a number of vaccine candidates for different diseases/infectious agents (hiv-1, severe acute respiratory syndrome virus, west nile virus, and ebola virus, plus a plasmid cytokine adjuvant-il-2/ig) based on a dna plasmid vaccine platform. to support the clinical development of each of these vaccine candidates, preclinical studies were performed to screen for potential toxicities (intrinsic and immunotoxicities). all treatment-related toxicities identified ...	2006	16569728
biodistribution of dna plasmid vaccines against hiv-1, ebola, severe acute respiratory syndrome, or west nile virus is similar, without integration, despite differing plasmid backbones or gene inserts.	the vaccine research center has developed a number of vaccine candidates for different diseases/infectious agents (hiv-1, severe acute respiratory syndrome virus, west nile virus, and ebola virus, plus a plasmid cytokine adjuvant-il-2/ig) based on a dna plasmid vaccine platform. to support the clinical development of each of these vaccine candidates, preclinical studies have been performed in mice or rabbits to determine where in the body these plasmid vaccines would biodistribute and how rapidl ...	2006	16569729
functional mapping of the nucleoprotein of ebola virus.	at 739 amino acids, the nucleoprotein (np) of ebola virus is the largest nucleoprotein of the nonsegmented negative-stranded rna viruses, and like the nps of other viruses, it plays a central role in virus replication. huang et al. (y. huang, l. xu, y. sun, and g. j. nabel, mol. cell 10:307-316, 2002) previously demonstrated that np, together with the minor matrix protein vp24 and polymerase cofactor vp35, is necessary and sufficient for the formation of nucleocapsid-like structures that are mor ...	2006	16571791
role of endosomal cathepsins in entry mediated by the ebola virus glycoprotein.	using chemical inhibitors and small interfering rna (sirna), we have confirmed roles for cathepsin b (catb) and cathepsin l (catl) in ebola virus glycoprotein (gp)-mediated infection. treatment of ebola virus gp pseudovirions with catb and catl converts gp1 from a 130-kda to a 19-kda species. virus with 19-kda gp1 displays significantly enhanced infection and is largely resistant to the effects of the catb inhibitor and sirna, but it still requires a low-ph-dependent endosomal/lysosomal function ...	2006	16571833
[ebola and marburg viruses: the humans strike back].	ebola and marburg viruses are the causative agents of rapidly progressive hemorrhagic fevers with high mortality rates. pre- or post-exposure treatments against the diseases are currently not available for human use. in the field, establishment of strict quarantine measures preventing further virus transmission are still the only way to fight the infections. however, our knowledge of ebola and marburg viruses has markedly increased as a result of two recent discoveries discussed in this review. ...	2006	16597410
[sphingolipids, vehicle for pathogenic agents and cause of genetic diseases].	sphingolipids are present in all eukaryotic cells and share a sphingoid base : sphingosine. they were first discovered in 1884 and for a long time they were thought to participate to membrane structure only. recently it has been established that they are mainly located in particular areas of the membrane called rafts which are signalling platforms. it has also been demonstrated that sphingolipids are receptors and second messengers. they play a crucial role in cellular functioning and are necess ...	2006	16597411
ebola virus glycoprotein gp is not cytotoxic when expressed constitutively at a moderate level.	transient expression of ebola virus (ebov) glycoprotein gp causes downregulation of surface proteins, cell rounding and detachment, a phenomenon believed to play a central role in the pathogenicity of the virus. in this study, evidence that moderate expression of gp does not result in such morphological changes was provided. it was shown that gp continuously produced in 293t cells from the kunjin virus replicon was correctly processed and transported to the plasma membrane without affecting the ...	2006	16603527
laboratory diagnostic systems for ebola and marburg hemorrhagic fevers developed with recombinant proteins.		2006	16603611
antisense treatments for biothreat agents.	antisense oligomers (asos) represent a promising technology to treat viral and bacterial infections, and have already been shown to be successful against a variety of pathogens in cell culture studies and nonhuman primate models of infection. for these reasons, antisense technologies are being pursued as treatments against biothreat agents such as ebola virus, dengue virus and bacillus anthracis. several generations of modified oligonucleotides have been developed to maximize nuclease resistance ...	2006	16610760
ebola virus: unravelling pathogenesis to combat a deadly disease.	ebola virus (ebov) causes severe haemorrhagic fever leading to up to 90% lethality. increasingly frequent outbreaks and the placement of ebov in the category a list of potential biothreat agents have boosted interest in this virus. furthermore, development of new technologies (e.g. reverse genetics systems) and extensive studies on ebola haemorrhagic fever (ehf) in animal models have substantially expanded the knowledge on the pathogenic mechanisms that underlie this disease. two major factors i ...	2006	16616875
emerging infectious diseases at the beginning of the 21st century.	the emergence and re-emergence of infectious diseases involves many interrelated factors. global interconnectedness continues to increase with international travel and trade; economic, political, and cultural interactions; and human-to-human and animal-to-human interactions. these interactions include the accidental and deliberate sharing of microbial agents and antimicrobial resistance and allow the emergence of new and unrecognized microbial disease agents. as the 21st century begins, already ...	2006	16629503
detection of ebola virus in oral fluid specimens during outbreaks of ebola virus hemorrhagic fever in the republic of congo.	patients who have refused to provide blood samples has meant that there have been significant delays in confirming outbreaks of ebola virus hemorrhagic fever (evhf). during the 2 evhf outbreaks in the republic of congo in 2003, we assessed the use of oral fluid specimens versus serum samples for laboratory confirmation of cases of evhf.	2006	16652308
ebola virus-like particles produced in insect cells exhibit dendritic cell stimulating activity and induce neutralizing antibodies.	recombinant baculoviruses (rbv) expressing ebola virus vp40 (rbv-vp40) or gp (rbv-gp) proteins were generated. infection of sf9 insect cells by rbv-vp40 led to assembly and budding of filamentous particles from the cell surface as shown by electron microscopy. ebola virus-like particles (vlps) were produced by coinfection of sf9 cells with rbv-vp40 and rbv-gp, and incorporation of ebola gp into vlps was demonstrated by sds-page and western blot analysis. recombinant baculovirus infection of inse ...	2006	16678231
immune protection of nonhuman primates against ebola virus with single low-dose adenovirus vectors encoding modified gps.	ebola virus causes a hemorrhagic fever syndrome that is associated with high mortality in humans. in the absence of effective therapies for ebola virus infection, the development of a vaccine becomes an important strategy to contain outbreaks. immunization with dna and/or replication-defective adenoviral vectors (rad) encoding the ebola glycoprotein (gp) and nucleoprotein (np) has been previously shown to confer specific protective immunity in nonhuman primates. gp can exert cytopathic effects o ...	2006	16683867
ebola virus vp35-vp40 interaction is sufficient for packaging 3e-5e minigenome rna into virus-like particles.	the packaging of viral genomic rna into nucleocapsids and subsequently into virions is not completely understood. phosphoprotein (p) and nucleoprotein (np) interactions link np-rna complexes with p-l (polymerase) complexes to form viral nucleocapsids. the nucleocapsid then interacts with the viral matrix protein, leading to specific packaging of the nucleocapsid into the virion. a mammalian two-hybrid assay and confocal microscopy were used to demonstrate that ebola virus vp35 and vp40 interact ...	2006	16698994
ebola virus vp24 binds karyopherin alpha1 and blocks stat1 nuclear accumulation.	ebola virus (ebov) infection blocks cellular production of alpha/beta interferon (ifn-alpha/beta) and the ability of cells to respond to ifn-alpha/beta or ifn-gamma. the ebov vp35 protein has previously been identified as an ebov-encoded inhibitor of ifn-alpha/beta production. however, the mechanism by which ebov infection inhibits responses to ifns has not previously been defined. here we demonstrate that the ebov vp24 protein functions as an inhibitor of ifn-alpha/beta and ifn-gamma signaling. ...	2006	16698996
ebola virus vp35 protein binds double-stranded rna and inhibits alpha/beta interferon production induced by rig-i signaling.	the ebola virus (ebov) vp35 protein blocks the virus-induced phosphorylation and activation of interferon regulatory factor 3 (irf-3), a transcription factor critical for the induction of alpha/beta interferon (ifn-alpha/beta) expression. however, the mechanism(s) by which this blockage occurs remains incompletely defined. we now provide evidence that vp35 possesses double-stranded rna (dsrna)-binding activity. specifically, vp35 bound to poly(ri) . poly(rc)-coated sepharose beads but not contro ...	2006	16698997
postexposure protection of guinea pigs against a lethal ebola virus challenge is conferred by rna interference.	ebola virus (ebov) infection causes a frequently fatal hemorrhagic fever (hf) that is refractory to treatment with currently available antiviral therapeutics. rna interference represents a powerful, naturally occurring biological strategy for the inhibition of gene expression and has demonstrated utility in the inhibition of viral replication. here, we describe the development of a potential therapy for ebov infection that is based on small interfering rnas (sirnas).	2006	16703508
functional expression of mouse relaxin and mouse relaxin-3 in the lung from an ebola virus glycoprotein-pseudotyped lentivirus via tracheal delivery.	the peptide hormone relaxin is a known modulator of connective tissue and the extracellular matrix by virtue of its ability to regulate matrix metalloproteinases (mmps). relaxin knockout mice exhibit age-related pulmonary fibrosis, and delivery of recombinant human h2 relaxin ameliorates fibrotic-like conditions in the mouse lung. we investigated whether lentiviral vectors (lvs) engineering the expression of murine relaxins could induce mmp activity in the mouse lung. mouse relaxin and mouse rel ...	2006	16709614
effect of ebola virus proteins gp, np and vp35 on vp40 vlp morphology.	recently we described a role for ebola virus proteins, np, gp, and vp35 in enhancement of vp40 vlp budding. to explore the possibility that vlp structure was altered by co-expression of ebov proteins leading to the observed enhancement of vp40 vlp budding, we performed density gradient analysis as well as electron microscopy studies. our data suggest that vp40 is the major determinant of vlp morphology, as co-expression of np, gp and vp35 did not significantly change vlp density, length, and dia ...	2006	16719918
interaction of amsh with escrt-iii and deubiquitination of endosomal cargo.	the "class e" vacuolar protein sorting (vps) pathway mediates sorting of ubiquitinated cargo into the forming vesicles of the multivesicular bodies (mvb), and it is essential for down-regulation of signaling by growth factors and budding of enveloped viruses such as ebola and hiv-1. work in yeast has identified doa4 as a gene that is recruited by the class e machinery to remove ubiquitin from the endosomal cargo before it is incorporated into mvb vesicles, but the identity of the mammalian count ...	2006	16760479
reverse genetic generation of recombinant zaire ebola viruses containing disrupted irf-3 inhibitory domains results in attenuated virus growth in vitro and higher levels of irf-3 activation without inhibiting viral transcription or replication.	the vp35 protein of zaire ebola virus is an essential component of the viral rna polymerase complex and also functions to antagonize the cellular type i interferon (ifn) response by blocking activation of the transcription factor irf-3. we previously mapped the irf-3 inhibitory domain within the c terminus of vp35. in the present study, we show that mutations that disrupt the irf-3 inhibitory function of vp35 do not disrupt viral transcription/replication, suggesting that the two functions of vp ...	2006	16775331
[chiroptera and zoonosis: an emerging problem on all five continents].	zoonosis is the cause of the vast majority of emerging diseases. bats that occupy the second place in the mammal class play an important role. whether they belong to the microchiroptera suborder or to the megachiroptera suborder, bats on all five continents have been implicated in transmission of numerous pathogens including not only viruses such as lyssavirus (e.g. rabies), hepanivirus (e.g. hendra and nipah virus) and recently coronavirus (e.g. sars-like coronavirus and ebola virus) but also f ...	2006	16775933
viral haemorrhagic fevers caused by lassa, ebola and marburg viruses.		2006	16802617
activation of triggering receptor expressed on myeloid cells-1 on human neutrophils by marburg and ebola viruses.	marburg virus (marv) and ebola virus (ebov), members of the viral family filoviridae, cause fatal hemorrhagic fevers in humans and nonhuman primates. high viral burden is coincident with inadequate adaptive immune responses and robust inflammatory responses, and virus-mediated dysregulation of early host defenses has been proposed. recently, a novel class of innate receptors called the triggering receptors expressed in myeloid cells (trem) has been discovered and shown to play an important role ...	2006	16809329
infection of naive target cells with virus-like particles: implications for the function of ebola virus vp24.	infectious virus-like particle (ivlp) systems have recently been established for several negative-strand rna viruses, including the highly pathogenic zaire ebolavirus (zebov), and allow study of the viral life cycle under biosafety level 2 conditions. however, current systems depend on the expression of viral helper nucleocapsid proteins in target cells, thus making it impossible to determine whether ribonucleoprotein complexes transferred by ivlps are able to facilitate initial transcription, a ...	2006	16809331
complex adenovirus-vectored vaccine protects guinea pigs from three strains of marburg virus challenges.	the marburg virus (marv), an african filovirus closely related to the ebola virus, causes a deadly hemorrhagic fever in humans, with up to 90% mortality. currently, treatment of disease is only supportive, and no vaccines are available to prevent spread of marv infections. in order to address this need, we have developed and characterized a novel recombinant vaccine that utilizes a single complex adenovirus-vectored vaccine (cadvax) to overexpress a marv glycoprotein (gp) fusion protein derived ...	2006	16820184
gorilla susceptibility to ebola virus: the cost of sociality.		2006	16824905
a luciferase-based budding assay for ebola virus.	the vp40 matrix protein of ebola virus (ebov) is capable of budding from mammalian cells as a virus-like particle (vlp) and is the major protein involved in virus egress. a functional budding assay has been developed based upon this characteristic of vp40 to assess the contributions of vp40 sequences as well as host proteins to the budding process. this well-defined assay has been modified for potential use in a high-throughput format in which the detection and quantification of firefly lucifera ...	2006	16837071
identification of two amino acid residues on ebola virus glycoprotein 1 critical for cell entry.	using site-directed mutagenesis and retroviral vector pseudotyping of the wild type or mutated glycoprotein of zaire ebolavirus (zebov), we analyzed 15 conserved residues in the n-terminus of the filovirus glycoprotein 1 (gp1) in order to identify residues critical for cell entry. results from infectivity assays and western blot analyses identified two phenylalanine residues at positions 88 and 159 that appear to be critical for zebov entry in vitro. we extended this observation by introduction ...	2006	16839637
peptides derived from hiv-1, hiv-2, ebola virus, sars coronavirus and coronavirus 229e exhibit high affinity binding to the formyl peptide receptor.	peptides derived from the membrane proximal region of fusion proteins of human immunodeficiency viruses 1 and 2, coronavirus 229 e, severe acute respiratory syndrome coronavirus and ebola virus were all potent antagonists of the formyl peptide receptor expressed in chinese hamster ovary cells. binding of viral peptides was affected by the naturally occurring polymorphisms at residues 190 and 192, which are located at second extracellular loop-transmembrane helix 5 interface. substitution of r190 ...	2006	16842982
molecular determinants of ebola virus virulence in mice.	zaire ebolavirus (zebov) causes severe hemorrhagic fever in humans and nonhuman primates, with fatality rates in humans of up to 90%. the molecular basis for the extreme virulence of zebov remains elusive. while adult mice resist zebov infection, the mayinga strain of the virus has been adapted to cause lethal infection in these animals. to understand the pathogenesis underlying the extreme virulence of ebola virus (ebov), here we identified the mutations responsible for the acquisition of the h ...	2006	16848640
detection of ebola virus envelope using monoclonal and polyclonal antibodies in elisa, surface plasmon resonance and a quartz crystal microbalance immunosensor.	ebola virus (ebov) zaire, sudan, as well as ivory coast are virulent human ebov species. both polyclonal and monoclonal antibodies (mabs) were developed against soluble ebov envelope glycoprotein (gp) for the study of ebov envelope diversity and development of diagnostic reagents. three ebov sudan-gulu gp peptides, from the n-terminus, mid-gp, and c-terminus regions were used to immunize rabbits for the generation of anti-ebov polyclonal antibodies. polyclonal antisera raised against the c-termi ...	2006	16857271
[hematological and immunological parameters during ebola virus passages in guinea-pigs].	the trend in hematological and immunological parameters during ebola virus passages in guinea-pigs indicated that pathophysiological changes occurred just during the second passage and further became stronger. the increase of some parameters and their correlation with the occurrence of fatal outcomes allowed the authors to reveal the most significant changes as increased juvenile platelets, whole blood virus appearance, higher echinocytes, a rise in the pro mil of blast cells and megakaryocytes ...	2006	16929596
structure-function analysis of the soluble glycoprotein, sgp, of ebola virus.	in addition to the transmembrane protein, gp(1,2), the ebola virus glycoprotein gene encodes the soluble glycoproteins sgp and delta-peptide. two more soluble proteins, gp(1) and gp(1,2deltatm), are generated from gp(1,2) as a result of disulfide-bond instability and proteolytic cleavage, respectively, and are shed from the surface of infected cells. the sgp glycoprotein is secreted as a disulfide-linked homodimer, but there have been conflicting reports on whether it is arranged in a parallel o ...	2006	16977667
structural studies of algal lectins with anti-hiv activity.	a number of antiviral lectins, small proteins that bind carbohydrates found on viral envelopes, are currently in pre-clinical trials as potential drugs for prevention of transmission of human immunodeficiency virus (hiv) and other enveloped viruses, such as the ebola virus and the coronavirus responsible for severe acute respiratory syndrome (sars). lectins of algal origin whose antiviral properties make them candidate agents for prevention of viral transmission through topical applications incl ...	2006	17128290
[emerging viral diseases].	emerging and re-emerging infectious diseases have again entered the public arena in recent years. this is due to factors such as evolving lifestyles, ecological and socio-political upheavals, and recent diagnostic advances. numerous pathogens, including viruses like west nile, chikungunya and japanese encephalitis on the one hand, and hemorrhagic fever viruses like ebola and maburg, are particular concerns. recently, the corona virus responsible for sars, which caused an epidemic sufficiently wo ...	2006	17140098
ebola outbreak killed 5000 gorillas.	over the past decade, the zaire strain of ebola virus (zebov) has repeatedly emerged in gabon and congo. each human outbreak has been accompanied by reports of gorilla and chimpanzee carcasses in neighboring forests, but both the extent of ape mortality and the causal role of zebov have been hotly debated. here, we present data suggesting that in 2002 and 2003 zebov killed about 5000 gorillas in our study area. the lag between neighboring gorilla groups in mortality onset was close to the zebov ...	2006	17158318
antiviral properties of deazaadenine nucleoside derivatives.	viral infections have menaced human beings since time immemorial, and even today new viral strains that cause lethal diseases are being discovered with alarming frequency. one major example is hiv, the etiological agent of aids, which spread up in the last two decades. very recently, other virus based diseases such as avian flu have spread fear around the world, and hemorrhagic fevers from central africa serious threaten human health because of their very deadly effects. new antiviral agents are ...	2006	17168721
public health awareness of emerging zoonotic viruses of bats: a european perspective.	bats classified in the order chiroptera are the most abundant and widely distributed non-human mammalian species in the world. several bat species are reservoir hosts of zoonotic viruses and therefore can be a public health hazard. lyssaviruses of different genotypes have emerged from bats in america (genotype 1 rabies virus; rabv), europe (european bat lyssavirus; eblv), and australia (australian bat lyssavirus; ablv), whereas nipah virus is the most important recent zoonosis of bat origin in a ...	2006	17187565
[the properties of ebola virus proteins].	the paper describes the structure and functions of ebola virus properties. it also presents information on the role of structural (np, vp40, vp35, gp, vp30, vp24, and l) and secreted (sgp, delta-peptide, gp1, gp(1,2delta), ssgp) proteins in the viral replication cycle and in the pathogenesis of ebola hemorrhagic fever.	2006	17214074
[detection of anti-lassa antibodies in the western forest area of the ivory coast].	lassa fever is an african viral hemorrhagic fever (vhf) known to be endemic in a number of west african countries including nigeria, sierra leone, liberia and guinea. despite having common borders with liberia and guinea, côte d'ivoire has never reported any cases of lassa fever. in march 2000, as part of a research project on vhf--mainly yellow fever, lassa fever and ebola fever--in guinea and cote d'ivoire, an exploratory survey was conducted to assess knowledge about vhf and immunological sta ...	2006	17201291
filoviruses and the balance of innate, adaptive, and inflammatory responses.	the filoviruses marburg virus and ebola virus are among the deadliest of human pathogens, causing fulminant hemorrhagic fevers typified by overmatched specific immune responses and profuse inflammatory responses. keys to both vaccination and treatment may reside, first, in the understanding of immune dysfunctions that parallel filoviral disease and, second, in devising ways to redirect and restore normal immune function as well as to mitigate inflammation. here, we describe how filoviral infecti ...	2006	17201655
[the primordial reservoir in the infectious contagion cicle. the avian influenza model].	an update of the role of the primordial reservoir in the biological cycle of the process of infection and contagion is made, using diseases of very frequent incidence at the present moment in the mediterranean area and the iberian peninsula. these diseases are, amongst others severe and acute respiratory syndrome (sars), rabies, lyme disease, african horse sickness, blue tongue, african swine fever, ebola hemorrhagic fever, hantavirosis, and avian influenza. the zoonoses classification proposed ...	2006	17451102
chimpanzee adenovirus vaccine protects against zaire ebola virus.	this study evaluated the use of a chimpanzee-based adenovirus vaccine in mouse and guinea pigs models of zaire ebola virus (zebov) infection. vaccine vector expressing the envelope glycoprotein of zebov was created from the molecular clone of chimpanzee adenovirus pan7 (adc7). adc7 vaccine stimulated robust t and b cell responses to zebov in naïve mice inducing complete protection to an otherwise lethal challenge of zebov. complete protection to zaire ebola virus was also observed in guinea pigs ...	2006	16356525
nonstructural protein 3 of bluetongue virus assists virus release by recruiting escrt-i protein tsg101.	the release of bluetongue virus (btv) and other members of the orbivirus genus from infected host cells occurs predominantly by cell lysis, and in some cases, by budding from the plasma membrane. two nonstructural proteins, ns3 and ns3a, have been implicated in this process. here we show that both proteins bind to human tsg101 and its ortholog from drosophila melanogaster with similar strengths in vitro. this interaction is mediated by a conserved psap motif in ns3 and appears to play a role in ...	2006	16352570
development of a novel one-tube isothermal reverse transcription thermophilic helicase-dependent amplification platform for rapid rna detection.	the high complexity and cost of polymerase chain reaction-based molecular diagnostics sometimes limits their use in the clinical diagnostics setting. a new helicase-based isothermal amplification method offers an alternative to standard polymerase chain reaction, allowing amplification and detection of specific dna sequences at a constant reaction temperature without thermocycling equipment. herein, we describe the development of a novel one-tube isothermal reverse transcription-thermophilic hel ...	2007	17975029
crystal structure of the c-terminal domain of ebola virus vp30 reveals a role in transcription and nucleocapsid association.	transcription of the highly pathogenic ebola virus depends on vp30, a nucleocapsid-associated ebola virus-specific transcription factor. the transcription activator vp30 was shown to play an essential role in ebola virus replication, most likely by stabilizing nascent mrna. here we present the crystal structure of the c-terminal domain (ctd) of vp30 (vp30(ctd)) at 2.0-a resolution. vp30(ctd) folds independently into a dimeric helical assembly. the vp30(ctd) dimers assemble into hexamers that are ...	2007	17202263
[bad bats?].	for many centuries, man is fascinated by bats, the only flying mammals. probably because of their particular immune system, bats can be considered an important reservoir for new emerging viral diseases like sars-coronavirus, marburg fever, ebola fever and nipah virus encephalitis. during closer contact, they can transmit rabies and probably other nonviral infectious diseases. bats get closer to man due to ecological modifications like deforestation, so that transmission of new infectious agents ...	2007	17985603
an interferon-alpha-induced tethering mechanism inhibits hiv-1 and ebola virus particle release but is counteracted by the hiv-1 vpu protein.	type 1 interferon (ifn) inhibits the release of hiv-1 virus particles via poorly defined mechanisms. here, we show that ifnalpha induces retention of viral particles on the surface of fibroblasts, t cells, or primary lymphocytes infected with hiv-1 lacking the vpu protein. retained particles are tethered to cell surfaces, can be endocytosed, appear fully assembled, exhibit mature morphology, and can be detached by protease. strikingly, expression of the hiv-1 vpu protein attenuates the ability o ...	2007	18005734
[feline immunodeficiency virus tropism].	feline immunodeficiency virus (fiv) induces a disease similar to acquired immunodeficiency syndrome (aids) in cats, yet in contrast to human immunodeficiency virus (hiv), cd4 is not the viral receptor. we identified a primary receptor for fiv as cd134 (ox40), a t cell activation antigen and costimulatory molecule. cd134 expression promotes viral binding and renders cells permissive for viral entry, productive infection, and syncytium formation. infection is cxcr4-dependent, analogous to infectio ...	2007	18040157
ebola outbreak in uganda "atypical", say experts.		2007	18161067
[recombinant full-size human antibody to ebola virus].	a full-size human antibody to ebola virus was constructed by joining genes encoding the constant domains of the heavy and light chains of human immunoglobulin with the corresponding dna fragments encoding variable domains of the single-chain antibody 4d1 specific to ebola virus, which was chosen from a combinatorial phage display library of single-strand human antibodies. two expression plasmids. pch1 and pcl1, containing the artificial genes encoding the light and heavy chains of human immunogl ...	2007	18173122
[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 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
unconventional mechanism of mrna capping by the rna-dependent rna polymerase of vesicular stomatitis virus.	all known eukaryotic and some viral mrna capping enzymes (ces) transfer a gmp moiety of gtp to the 5'-diphosphate end of the acceptor rna via a covalent enzyme-gmp intermediate to generate the cap structure. in striking contrast, the putative ce of vesicular stomatitis virus (vsv), a prototype of nonsegmented negative-strand (nns) rna viruses including rabies, measles, and ebola, incorporates the gdp moiety of gtp into the cap structure of transcribing mrnas. here, we report that the rna-depende ...	2007	17218273
mapping of the vp40-binding regions of the nucleoprotein of ebola virus.	expression of ebola virus nucleoprotein (np) in mammalian cells leads to the formation of helical structures, which serve as a scaffold for the nucleocapsid. we recently found that np binding with the matrix protein vp40 is important for nucleocapsid incorporation into virions (t. noda, h. ebihara, y. muramoto, k. fujii, a. takada, h. sagara, j. h. kim, h. kida, h. feldmann, and y. kawaoka, plos pathog. 2:e99, 2006). to identify the region(s) on the np molecule required for vp40 binding, we exam ...	2007	17229682
proteolytic processing of the ebola virus glycoprotein is not critical for ebola virus replication in nonhuman primates.	enveloped viruses often require cleavage of a surface glycoprotein by a cellular endoprotease such as furin for infectivity and virulence. previously, we showed that ebola virus glycoprotein does not require the furin cleavage motif for virus replication in cell culture. here, we show that there are no appreciable differences in disease progression, hematology, serum biochemistry, virus titers, or lethality in nonhuman primates infected with an ebola virus lacking the furin recognition sequence ...	2007	17229700
effective post-exposure treatment of ebola infection.	ebola viruses are highly lethal human pathogens that have received considerable attention in recent years due to an increasing re-emergence in central africa and a potential for use as a biological weapon. there is no vaccine or treatment licensed for human use. in the past, however, important advances have been made in developing preventive vaccines that are protective in animal models. in this regard, we showed that a single injection of a live-attenuated recombinant vesicular stomatitis virus ...	2007	17238284
neutralizing antibody fails to impact the course of ebola virus infection in monkeys.	prophylaxis with high doses of neutralizing antibody typically offers protection against challenge with viruses producing acute infections. in this study, we have investigated the ability of the neutralizing human monoclonal antibody, kz52, to protect against ebola virus in rhesus macaques. this antibody was previously shown to fully protect guinea pigs from infection. four rhesus macaques were given 50 mg/kg of neutralizing human monoclonal antibody kz52 intravenously 1 d before challenge with ...	2007	17238286
status and challenges of filovirus vaccines.	vaccines that could protect humans against the highly lethal marburg and ebola viruses have eluded scientists for decades. classical approaches have been generally unsuccessful for marburg and ebola viruses and pose enormous safety concerns as well. modern approaches, in particular those using vector-based approaches have met with success in nonhuman primate models although success against ebola has been more difficult to achieve than marburg. despite these successes, more work remains to be don ...	2007	17241710
rift valley fever outbreak--kenya, november 2006-january 2007.	in mid-december 2006, several unexplained fatalities associated with fever and generalized bleeding were reported to the kenya ministry of health (kmoh) from garissa district in north eastern province (nep). by december 20, a total of 11 deaths had been reported. of serum samples collected from the first 19 patients, rift valley fever (rvf) virus rna or immunoglobulin m (igm) antibodies against rvf virus were found in samples from 10 patients; all serum specimens were negative for yellow fever, ...	2007	17268404
gene transfer in human skin with different pseudotyped hiv-based vectors.	pseudotyping lentiviral vector with other viral surface proteins could be applied for treating genetic anomalies in human skin. in this study, the modification of hiv vector tropism by pseudotyping with the envelope glycoprotein from vesicular stomatitis virus (vsv), the zaire ebola (eboz) virus, murine leukemia virus (mulv), lymphocytic choriomeningitis virus (lcmv), rabies or the rabies-related mokola virus encoding lacz as a reporter gene was evaluated qualitatively and quantitatively in huma ...	2007	17268532
development of vaccines for marburg hemorrhagic fever.	marburg (marv) and ebola viruses (ebov) emerged from the rainforests of central africa more than 30 years ago causing outbreaks of severe and, usually, fatal hemorrhagic fever. ebov has garnered the lion's share of the attention, fueled by the higher frequency of ebov outbreaks, high mortality rates and importation into the usa, documented in such popular works as the best-selling novel 'the hot zone'. however, recent large outbreaks of hundreds of cases of marv infection in the democratic repub ...	2007	17280479
interaction of tsg101 with marburg virus vp40 depends on the pppy motif, but not the pt/sap motif as in the case of ebola virus, and tsg101 plays a critical role in the budding of marburg virus-like particles induced by vp40, np, and gp.	marburg virus (marv) vp40 is a matrix protein that can be released from mammalian cells in the form of virus-like particles (vlps) and contains the pppy sequence, which is an l-domain motif. here, we demonstrate that the pppy motif is important for vp40-induced vlp budding and that vlp production is significantly enhanced by coexpression of np and gp. we show that tsg101 interacts with vp40 depending on the presence of the pppy motif, but not the pt/sap motif as in the case of ebola virus, and p ...	2007	17301151
identification of inhibitors using a cell-based assay for monitoring golgi-resident protease activity.	noninvasive real-time quantification of cellular protease activity allows monitoring of enzymatic activity and identification of activity modulators within the protease's natural milieu. we developed a protease activity assay based on differential localization of a recombinant reporter consisting of a golgi retention signal and a protease cleavage sequence fused to alkaline phosphatase (ap). when expressed in mammalian cells, this protein localizes to golgi bodies and, on protease-mediated cleav ...	2007	17316541
mechanism of ad5 vaccine immunity and toxicity: fiber shaft targeting of dendritic cells.	recombinant adenoviral (rad) vectors elicit potent cellular and humoral immune responses and show promise as vaccines for hiv-1, ebola virus, tuberculosis, malaria, and other infections. these vectors are now widely used and have been generally well tolerated in vaccine and gene therapy clinical trials, with many thousands of people exposed. at the same time, dose-limiting adverse responses have been observed, including transient low-grade fevers and a prior human gene therapy fatality, after sy ...	2007	17319743
[molecular mechanisms of ebola virus reproduction].	the review presents recent data on the molecular mechanisms of the stages of an ebola virus replication cycle, on the interaction of viral and cellular components at each stage, as well as on the mechanisms responsible for he realization of viral genetic information in the infected cell.	2007	17338228
the dc-sign-related lectin lsectin mediates antigen capture and pathogen binding by human myeloid cells.	liver and lymph node sinusoidal endothelial cell c-type lectin (lsectin [clec4g]) is a c-type lectin encoded within the liver/lymph node-specific intercellular adhesion molecule-3-grabbing nonintegrin (l-sign)/dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (dc-sign)/cd23 gene cluster. lsectin expression has been previously described as restricted to sinusoidal endothelial cells of the liver and lymph node. we now report lsectin expression in human peripheral blood ...	2007	17339424
viral exanthems in the tropics.	viral exanthems are a common problem in tropical regions, particularly affecting children. most exanthems are transient and harmless, but some are potentially very dangerous. pregnant women and malnourished or immunocompromised infants carry the greatest risk of adverse outcome. in this article, parvovirus b19; dengue and yellow fever; west nile, barmah forest, marburg, and ebola viruses, and human herpesviruses; asymmetric periflexural exanthema of childhood; measles; rubella; enteroviruses; la ...	2007	17350501
production and characterization of monoclonal antibodies against different epitopes of ebola virus antigens.	ebola virus (ebov) causes hemorrhagic fever in humans and nonhuman primates with up to 90% mortality rate. in this study, ebola virus like particles (evlps) and the aglycosyl subfragment of glycoprotein (gp(1) subfragment d) were used to generate monoclonal antibodies (mabs) against different epitopes of the viral antigens. such mabs could be useful in diagnostics and potential therapeutics of viral infection and its hemorrhagic symptoms. hybridoma cell fusion technology was used for production ...	2007	17368819
nkp30-dependent cytolysis of filovirus-infected human dendritic cells.	understanding how protective innate immune responses are generated is crucial to defeating highly lethal emerging pathogens. accumulating evidence suggests that potent innate immune responses are tightly linked to control of ebola and marburg filoviral infections. here, we report that unlike authentic or inactivated ebola and marburg, filovirus-derived virus-like particles directly activated human natural killer (nk) cells in vitro, evidenced by pro-inflammatory cytokine production and enhanced ...	2007	17381429
differential expression of the ebola virus gp(1,2) protein and its fragments in e. coli.	bacterial expression platforms are frequently used for the expression and production of different recombinant proteins. the full length ebola virus (ebov) gp(1,2) gene and subfragments of the gp(1) gene were cloned in a bacterial expression vector as a c-terminal his(6) fusion protein. surprisingly, the full length ebov gp(1,2) gene could not be expressed in escherichia coli. the subfragments of gp(1) were only expressed in small amounts with the exception of one small fragment (subfragment d) w ...	2007	17383893
ebola virus infection of human pbmcs causes massive death of macrophages, cd4 and cd8 t cell sub-populations in vitro.	ebola virus causes an often fatal disease characterized by poor immune response and high inflammatory reaction in the patients. one of the causes for poor immunity is virus-mediated apoptosis of lymphocytes in the host. in this study, we infected human pbmcs with ebola zaire virus and study apoptosis of different cell types using flow cytometry. we have shown that ebola virus causes bystander death of cd4 and cd8 t cells. cells infected with virus had 30-40% active caspase 3(+), annexin-v(+) and ...	2007	17391724