PMID(sorted ascending)
transduction of the choroid plexus and ependyma in neonatal mouse brain by vesicular stomatitis virus glycoprotein-pseudotyped lentivirus and adeno-associated virus type 5 vectors.evaluation of gene transfer into the developing mouse brain has shown that when adeno-associated virus serotype 1 (aav1) or aav2 vectors are injected into the cerebral lateral ventricles at birth, widespread parenchymal transduction occurs. lentiviral vectors have not been tested by this route. in this study, we found that injection of lentiviral vectors pseudotyped with vesicular stomatitis virus glycoprotein (vsv-g) resulted in targeted transduction of the ependymal cells lining the ventricula ...200515703488
low seroprevalence of igg antibodies to ebola virus in an epidemic zone: ogooué-ivindo region, northeastern gabon, 1997.a population-based serosurvey was performed to determine the seroprevalence of antibodies to ebola virus (ebo) in a region that has experienced multiple epidemics of ebo hemorrhagic fever. of 2533 residents in 8 villages, serum samples from 979 (38.6%) were tested by enzyme-linked immunosorbent assay for immunoglobulin (ig) g and igm antibodies to ebola-zaire (ebo-z) virus. fourteen samples (1.4%) were found positive for igg antibodies, and 4 of these (.4%) were samples from survivors of an epid ...200515717273
wild animal mortality monitoring and human ebola outbreaks, gabon and republic of congo, 2001-2003.all human ebola virus outbreaks during 2001-2003 in the forest zone between gabon and republic of congo resulted from handling infected wild animal carcasses. after the first outbreak, we created an animal mortality monitoring network in collaboration with the gabonese and congolese ministries of forestry and environment and wildlife organizations (wildlife conservation society and programme de conservation et utilisation rationnelle des ecosystemes forestiers en afrique centrale) to predict and ...200515752448
ebola virus antibody prevalence in dogs and human risk.during the 2001-2002 outbreak in gabon, we observed that several dogs were highly exposed to ebola virus by eating infected dead animals. to examine whether these animals became infected with ebola virus, we sampled 439 dogs and screened them by ebola virus-specific immunoglobulin (ig) g assay, antigen detection, and viral polymerase chain reaction amplification. seven (8.9%) of 79 samples from the 2 main towns, 15 (15.2%) of 99 samples from mekambo, and 40 (25.2%) of 159 samples from villages i ...200515757552
rna polymerase i-driven minigenome system for ebola general, ebola viruses are well known for their ability to cause severe hemorrhagic fever in both human and nonhuman primates. however, despite substantial sequence homology to other members of the family filoviridae, reston ebolavirus displays reduced pathogenicity for nonhuman primates and has never been demonstrated to cause clinical disease in humans, despite its ability to cause infection. in order to develop a tool to explore potential roles for transcription and replication in the redu ...200515767442
cd8-mediated protection against ebola virus infection is perforin dependent.cd8 t cells have been shown to play an important role in the clearance and protection against fatal ebola virus infection. in this study, we examined the mechanisms by which cd8 t cells mediate this protection. our data demonstrate that all normal mice infected s.c. with a mouse-adapted ebola virus survived the infection, as did 100% of mice deficient in fas and 90% of those deficient in ifn-gamma. in contrast, perforin-deficient mice uniformly died after s.c. challenge. perforin-deficient mice ...200515778381
association of ebola virus matrix protein vp40 with microtubules.viruses exploit a variety of cellular components to complete their life cycles, and it has become increasingly clear that use of host cell microtubules is a vital part of the infection process for many viruses. a variety of viral proteins have been identified that interact with microtubules, either directly or via a microtubule-associated motor protein. here, we report that ebola virus associates with microtubules via the matrix protein vp40. when transfected into mammalian cells, a fraction of ...200515795257
comprehensive analysis of ebola virus gp1 in viral entry.ebola virus infection is initiated by interactions between the viral glycoprotein gp1 and its cognate receptor(s), but little is known about the structure and function of gp1 in viral entry, partly due to the concern about safety when working with the live ebola virus and the difficulty of manipulating the rna genome of ebola virus. in this study, we have used a human immunodeficiency virus-based pseudotyped virus as a surrogate system to dissect the role of ebola virus gp1 in viral entry. analy ...200515795265
outbreak of marburg virus hemorrhagic fever--angola, october 1, 2004-march 29, 2005.on march 23, 2005, the world health organization (who) confirmed marburg virus (family filoviridae, which includes ebola virus) as the causative agent of an outbreak of viral hemorrhagic fever (vhf) in uige province in northern angola. testing conducted by cdc's special pathogens branch detected the presence of virus in nine of 12 clinical specimens from patients who died during the outbreak.200515800477
nucleocapsid-like structures of ebola virus reconstructed using electron tomography.electron tomography (et) is a new technique for high resolution, three-dimensional (3d) reconstruction of pleiomorphic macromolecular complexes, such as virus components. by employing this technique, we resolved the 3d structure of ebola virus nucleocapsid-like (nc-like) structures in the cytoplasm of cells expressing np, vp24, and vp35: the minimum components required to form these nc-like structures. reconstruction of these tubular nc-like structures of ebola virus showed them to be composed o ...200515805739
virus-like particles exhibit potential as a pan-filovirus vaccine for both ebola and marburg viral infections.a safe and effective pan-filovirus vaccine is highly desirable since the filoviruses ebola virus (ebov) and marburg virus (marv) cause highly lethal disease typified by unimpeded viral replication and severe hemorrhagic fever. previously, we showed that expression of the homologous glycoprotein (gp) and matrix protein vp40 from a single filovirus, either ebov or marv, resulted in formation of wild-type virus-like particles (vlps) in mammalian cells. when used as a vaccine, the wild-type vlps pro ...200515811650
endosomal proteolysis of the ebola virus glycoprotein is necessary for infection.ebola virus (ebov) causes rapidly fatal hemorrhagic fever in humans and there is currently no effective treatment. we found that the infection of african green monkey kidney (vero) cells by vesicular stomatitis viruses bearing the ebov glycoprotein (gp) requires the activity of endosomal cysteine proteases. using selective protease inhibitors and protease-deficient cell lines, we identified an essential role for cathepsin b (catb) and an accessory role for cathepsin l (catl) in ebov gp-dependent ...200515831716
functional characterization of ebola virus l-domains using vsv recombinants.vsv recombinants containing the overlapping l-domain sequences from ebola virus vp40 (ptappey) were recovered by reverse-genetics. replication kinetics of m40-wt, m40-p24l, and m40-y30a were indistinguishable from vsv-wt in bhk-21 cells, whereas the double mutant (m40-p2728a) was defective in budding. insertion of the ebola l-domain region into vsv m protein was sufficient to alter the dependence on host proteins for efficient budding. indeed, m40 recombinants containing a functional ptap motif ...200515892969
analysis of ebola virus and vlp release using an immunocapture assay.ebola virus (ebov), an emerging pathogen, is the causative agent of a rapidly progressive hemorrhagic fever with high mortality rates. there are currently no approved vaccines or treatments available for ebola hemorrhagic fever. standard plaque assays are currently the only reliable techniques for enumerating the virus. effective drug-discovery screening as well as target identification and validation require simple and more rapid detection methods. this report describes the development of a rap ...200515893559
ebola virus: the role of macrophages and dendritic cells in the pathogenesis of ebola hemorrhagic fever.ebola hemorrhagic fever is a severe viral infection characterized by fever, shock and coagulation defects. recent studies in macaques show that major features of illness are caused by effects of viral replication on macrophages and dendritic cells. infected macrophages produce proinflammatory cytokines, chemokines and tissue factor, attracting additional target cells and inducing vasodilatation, increased vascular permeability and disseminated intravascular coagulation. however, they cannot rest ...200515896665
an all-atom model of the pore-like structure of hexameric vp40 from ebola: structural insights into the monomer-hexamer transition.the matrix protein vp40 is an indispensable component of viral assembly and budding by the ebola virus. vp40 is a monomer in solution, but can fold into hexameric and octameric states, two oligomeric conformations that play central roles in the ebola viral life cycle. while the x-ray structures of monomeric and octameric vp40 have been determined, the structure of hexameric vp40 has only been solved by three-dimensional electron microscopy (em) to a resolution of approximately 30 a. in this pape ...200515908231
particulate delivery systems for biodefense subunit vaccines.expanding identification of potentially protective subunit antigens and correlates of protection has provided a basis for the introduction of safer vaccines. despite encouraging results in animal models, the significant potential of particulate delivery systems in vaccine design has not yet translated into effective vaccines available for use in humans. this review article will focus on the current status of the development of particulate vaccines, mainly liposomes and bio-degradable polymers, a ...200515935873
live attenuated recombinant vaccine protects nonhuman primates against ebola and marburg viruses.vaccines and therapies are urgently needed to address public health needs stemming from emerging pathogens and biological threat agents such as the filoviruses ebola virus (ebov) and marburg virus (marv). here, we developed replication-competent vaccines against ebov and marv based on attenuated recombinant vesicular stomatitis virus vectors expressing either the ebov glycoprotein or marv glycoprotein. a single intramuscular injection of the ebov or marv vaccine elicited completely protective im ...200515937495
paramyxovirus mrna editing, the "rule of six" and error catastrophe: a hypothesis.the order mononegavirales includes three virus families that replicate in the cytoplasm: the paramyxoviridae, composed of two subfamilies, the paramyxovirinae and pneumovirinae, the rhabdoviridae and the filoviridae. these viruses, also called non-segmented negative-strand rna viruses (nnv), contain five to ten tandemly linked genes, which are separated by conserved junctional sequences that act as mrna start and poly(a)/stop sites. for the nnv, downstream mrna synthesis depends on termination o ...200515958664
novel innate immune functions for galectin-1: galectin-1 inhibits cell fusion by nipah virus envelope glycoproteins and augments dendritic cell secretion of proinflammatory cytokines.galectin-1 (gal-1), an endogenous lectin secreted by a variety of cell types, has pleiotropic immunomodulatory functions, including regulation of lymphocyte survival and cytokine secretion in autoimmune, transplant disease, and parasitic infection models. however, the role of gal-1 in viral infections is unknown. nipah virus (niv) is an emerging pathogen that causes severe, often fatal, febrile encephalitis. the primary targets of niv are endothelial cells. niv infection of endothelial cells res ...200515972675
marburg and ebola--arming ourselves against the deadly filoviruses. 200515972860
how ebola virus infects cells. 200515972874
the natural history of ebola virus in africa.several countries spanning the equatorial forest regions of africa have had outbreaks of ebola hemorrhagic fever over the last three decades. this article is an overview of the many published investigations of how ebola virus circulates in its natural environment, focusing on the viral reservoir, susceptible animal species, environmental conditions favoring inter-species transmission, and how the infection is transmitted to humans. major breakthroughs have been made in recent years but many outs ...200516002313
induction of humoral and cd8+ t cell responses are required for protection against lethal ebola virus infection.ebola virus (ebov)-like particles (evlp), composed of the ebov glycoprotein and matrix viral protein (vp)40 with a lipid membrane, are a highly efficacious method of immunization against ebov infection. the exact requirements for immunity against ebov infection are poorly defined at this time. the goal of this work was to determine the requirements for ebov immunity following evlp vaccination. vaccination of balb/c or c57bl/6 mice with evlps in conjunction with qs-21 adjuvant resulted in mixed i ...200516002721
vaccines against ebola and marburg viruses show promise in primate studies. 200516014579
a single shot against ebola and marburg virus. 200516015361
filovirus-like particles as vaccines and discovery tools.ebola and marburg viruses are members of the family filoviridae, which cause severe hemorrhagic fevers in humans. filovirus outbreaks have been sporadic, with mortality rates currently ranging from 30 to 90%. unfortunately, there is no efficacious human therapy or vaccine available to treat disease caused by either ebola or marburg virus infection. expression of the filovirus matrix protein, vp40, is sufficient to drive spontaneous production and release of virus-like particles (vlps) that resem ...200516026254
the intrinsically disordered c-terminal domain of the measles virus nucleoprotein interacts with the c-terminal domain of the phosphoprotein via two distinct sites and remains predominantly unfolded.measles virus is a negative-sense, single-stranded rna virus within the mononegavirales order,which includes several human pathogens, including rabies, ebola, nipah, and hendra viruses. the measles virus nucleoprotein consists of a structured n-terminal domain, and of an intrinsically disordered c-terminal domain, n(tail) (aa 401-525), which undergoes induced folding in the presence of the c-terminal domain (xd, aa 459-507) of the viral phosphoprotein. with in n(tail), an alpha-helical molecular ...200516046624
ebola virus vp40 late domains are not essential for viral replication in cell culture.ebola virus particle formation and budding are mediated by the vp40 protein, which possesses overlapping ptap and ppxy late domain motifs (7-ptappxy-13). these late domain motifs have also been found in the gag proteins of retroviruses and the matrix proteins of rhabdo- and arenaviruses. while in vitro studies suggest a critical role for late domain motifs in the budding of these viruses, including ebola virus, it remains unclear as to whether the vp40 late domains play a role in ebola virus rep ...200516051823
effects of ebola virus glycoproteins on endothelial cell activation and barrier function.ebola virus causes severe hemorrhagic fever with high mortality rates in humans and nonhuman primates. vascular instability and dysregulation are disease-decisive symptoms during severe infection. while the transmembrane glycoprotein gp(1,2) has been shown to cause endothelial cell destruction, the role of the soluble glycoproteins in pathogenesis is largely unknown; however, they are hypothesized to be of biological relevance in terms of target cell activation and/or increase of endothelial per ...200516051836
the ebola virus genomic replication promoter is bipartite and follows the rule of this work we investigated the cis-acting signals involved in replication of ebola virus (ebov) genomic rna. a set of mingenomes with mutant 3' ends were generated and used in a reconstituted replication and transcription system. our results suggest that the ebov genomic replication promoter is bipartite, consisting of a first element located within the leader region of the genome and a second, downstream element separated by a spacer region. while proper spacing of the two promoter elements i ...200516051858
mannose-binding lectin binds to ebola and marburg envelope glycoproteins, resulting in blocking of virus interaction with dc-sign and complement-mediated virus neutralization.mannose-binding lectin (mbl), a serum lectin that mediates innate immune functions including activation of the lectin complement pathway, binds to carbohydrates expressed on some viral glycoproteins. in this study, the ability of mbl to bind to virus particles pseudotyped with ebola and marburg envelope glycoproteins was evaluated. virus particles bearing either ebola (zaire strain) or marburg (musoke strain) envelope glycoproteins bound at significantly higher levels to immobilized mbl compared ...200516099912
the contribution of the endothelium to the development of coagulation disorders that characterize ebola hemorrhagic fever in primates.recently, there have been substantial developments in the understanding of ebola hemorrhagic fever pathogenesis, but there are still major gaps. these infections occur in underdeveloped areas of the world, and much of our knowledge of naturally occurring disease is derived from sporadic outbreaks that occurred decades in the past. recently conducted laboratory animal studies have provided insight into ebola pathogenesis and may help guide clinical investigations of disease using contemporary met ...200516113813
therapy and prophylaxis of ebola virus infections.the first cases of ebola hemorrhagic fever were reported from sudan and zaire (now democratic republic of the congo) in 1976, but the virus has only received significant attention since 1995. until recently, the development of therapeutics or vaccines was not considered a priority. the knowledge gained during the past decade on the biology and pathogenesis of ebola virus has led to the development of therapeutic strategies that are currently being investigated. considering the aggressive nature ...200516121689
complete genome sequence of an ebola virus (sudan species) responsible for a 2000 outbreak of human disease in uganda.the entire genomic rna of the gulu (uganda 2000) strain of ebola virus was sequenced and compared to the genomes of other filoviruses. this data represents the first comprehensive genetic analysis for a representative isolate of the sudan species of ebola virus. the genome organization of the sudan species is nearly identical to that of the zaire species, but the presence of a gene overlap (between gp and vp30 genes) and a longer trailer sequence distinguish it from that of the reston species. a ...200516139097
rab9 gtpase is required for replication of human immunodeficiency virus type 1, filoviruses, and measles virus.rab proteins and their effectors facilitate vesicular transport by tethering donor vesicles to their respective target membranes. by using gene trap insertional mutagenesis, we identified rab9, which mediates late-endosome-to-trans-golgi-network trafficking, among several candidate host genes whose disruption allowed the survival of marburg virus-infected cells, suggesting that rab9 is utilized in marburg replication. although rab9 has not been implicated in human immunodeficiency virus (hiv) re ...200516140752
providing care and facing death: nursing during ebola outbreaks in central africa.few studies have focused on describing the experiences of health care workers during rapid killing epidemics. in this article, the views and experiences of nurses during three outbreaks of ebola hemorrhagic fever (ehf) in central africa are examined. these three outbreaks occurred in kikwit, democratic republic of congo (drc, 1995); gulu, uganda (2000-2001); and republic of congo (roc, 2003). open-ended and semistructured interviews with individuals and small groups were conducted during the out ...200516160191
using blood glucose data as an indicator for epidemic disease the future, transfer of vital sensor data from patients to the public health care system is likely to become commonplace. systems for automatic transfer of sensor data are now at the prototype stage. as electronic health record (ehr) systems adapt such functionality, widespread use may become an actuality in the foreseeable prevent spreading of diseases, an early detection of infection is important. at the time an outbreak is diagnosed, many people may already be infected due to the ...200516160262
human dendritic cells and macrophages exhibit different intracellular processing pathways for soluble and liposome-encapsulated antigens.the intracellular fates of soluble and liposomal antigens in human macrophages and dendritic cells are not well defined. previous studies using murine macrophages have demonstrated that liposomal antigens can enter the mhc class i pathway. the golgi complex is a major organelle in this pathway. phagocytosis of the antigens is followed by translocation of antigen-derived peptides to the trans-golgi where they can complex with mhc class i molecules. in contrast, soluble antigens are normally proce ...200516164039
inhibiting hiv fusion with a beta-peptide foldamer.linear peptides derived from the hiv gp41 c-terminus (c-peptides), such as the 36-residue fuzeon, are potent hiv fusion inhibitors. these molecules bind to the n-peptide region of gp41 and inhibit an intramolecular protein-protein interaction that powers fusion of the viral and host cell membranes. the n-peptide region contains a surface pocket that is occupied in the post-fusion state by three alpha-helical residues found near the gp41 c-terminus: trp628, trp631, and ile635-the wwi epitope. her ...200516173723
analysis of the expressed heavy chain variable-region genes of macaca fascicularis and isolation of monoclonal antibodies specific for the ebola virus' soluble glycoprotein.the cynomolgus macaque, macaca fascicularis, is frequently used in immunological and other biomedical research as a model for man; understanding it's antibody repertoire is, therefore, of fundamental interest. the expressed variable-region gene repertoire of a single m. fascicularis, which was immune to the ebola virus, was studied. using 5' rapid amplification of cdna ends with immunoglobulin (ig)g-specific primers, we obtained 30 clones encoding full-length variable, diversity, and joining dom ...200516215733
wave-like spread of ebola the past decade the zaire strain of ebola virus (zebov) has emerged repeatedly into human populations in central africa and caused massive die-offs of gorillas and chimpanzees. we tested the view that emergence events are independent and caused by zebov variants that have been long resident at each locality. phylogenetic analyses place the earliest known outbreak at yambuku, democratic republic of congo, very near to the root of the zebov tree, suggesting that viruses causing all other known ...200516231972
lewis x component in human milk binds dc-sign and inhibits hiv-1 transfer to cd4+ t lymphocytes.dc-specific icam3-grabbing non-integrin (dc-sign), which is expressed on dcs, can interact with a variety of pathogens such as hiv-1, hepatitis c, ebola, cytomegalovirus, dengue virus, mycobacterium, leishmania, and candida albicans. we demonstrate that human milk can inhibit the dc-sign-mediated transfer of hiv-1 to cd4+ t lymphocytes as well as viral transfer by both immature and mature dcs. the inhibitory factor directly interacted with dc-sign and prevented the hiv-1 gp120 envelope protein f ...200516239964
[human recombinant antibodies to ebola virus: preparation and characteristics].human recombinant antibodies against a purified ebola virus (ev) lysate were selected from a combinatorial library of scfv-antibodies using the phage display technique. nine unique antibodies were identified after sequencing the vh- and vl-genes encoding the selected antibodies. solid-phase enzyme immunoassay (eia) indicated that these antibodies were able to bind both inactivated and native ev. immunoblotting showed that 6 antibodies identified nucleoprotein (np), one antibody did vp24 and anot ...200516250595
protective cytotoxic t-cell responses induced by venezuelan equine encephalitis virus replicons expressing ebola virus proteins.infection with ebola virus causes a severe disease accompanied by high mortality rates, and there are no licensed vaccines or therapies available for human use. filovirus vaccine research efforts still need to determine the roles of humoral and cell-mediated immune responses in protection from ebola virus infection. previous studies indicated that exposure to ebola virus proteins expressed from packaged venezuelan equine encephalitis virus replicons elicited protective immunity in mice and that ...200516254354
predicted inactivation of viruses of relevance to biodefense by solar radiation.uv radiation from the sun is the primary germicide in the environment. the goal of this study was to estimate inactivation of viruses by solar exposure. we reviewed published reports on 254-nm uv inactivation and tabulated the sensitivities of a wide variety of viruses, including those with double-stranded dna, single-stranded dna, double-stranded rna, or single-stranded rna genomes. we calculated d(37) values (fluence producing on average one lethal hit per virion and reducing viable virus to 3 ...200516254359
developing scientist leaders for tumultuous times.leadership is a quality that can be learned. it is a behavior that one practices, and, after lots of practice, it becomes a habit. this is a lesson i learned from my father, who was a career pilot in the us air force and instilled this into me and my siblings from a very early age. it is also something i have learned in observing others. i have frequently asked why some people from certain disciplinary backgrounds seem to have an advantage in the leadership area. think of the backgrounds of our ...200516261495
laboratory diagnosis of ebola and marburg hemorrhagic fever.the control of filovirus outbreaks can be greatly enhanced by timely laboratory confirmation of infection or the identification of alternative disease processes. the status of current laboratory diagnostics for ebola and marburg virus infections is discussed in terms of the assays available and their interpretation. in addition, the role of field-based laboratory support and its limitations and capabilities in an outbreak response setting, especially in regards to real-time pcr and immunofiltrat ...200516267962
ebola virus circulation in africa: a balance between clinical expression and epidemiological silence.nearly thirty years after the first epidemics, ebola virus (ebov) remains hardly described, its transmission unclear and its reservoir elusive. soon after the ebola fever outbreak and virus discovery in 1976 and in order to investigate the distribution of ebov in central africa, several countries including a range of ecological zones were investigated in the early 1980s, using extensive survey: central african republic (car), cameroon, chad, congo, gabon and equatorial guinea. since 1992, elisa ...200516267963
[clinical management of patients and deceased during the ebola outbreak from october to december 2003 in republic of congo].outbreaks of ebola virus hemorrhagic fever (evhf) have been reported since 2001 in the cuvette ouest department, a forested area located in the western north of congo. at the end of october 2003 a new alarm came from this department which was quickly confirmed as being an epidemic of evhf. the outbreak response was organized by the ministry of health with the assistance of an international team under the aegis of who. the case management of suspect cases was done in an isolation ward set up at t ...200516267964
[multiple ebola virus haemorrhagic fever outbreaks in gabon, from october 2001 to april 2002].outbreaks of ebola virus haemorrhagic fever have been reported from 1994 to 1996 in the province of ogooué ivindo, a forest zone situated in the northeast of gabon. each time, the great primates had been identified as the initial source of human infection. end of november 2001 a new alert came from this province, rapidly confirmed as a evhv outbreak. the response was given by the ministry of health with the help of an international team under the aegis of who. an active monitoring system was imp ...200516267965
medical anthropology and ebola in congo: cultural models and humanistic care.seldom have medical anthropologists been involved in efforts to control high mortality diseases such as ebola hemorrhagic fever (ehf) this paper describes the results of two distinct but complementary interventions during the first phases of an outbreak in the republic of congo in 2003. the first approach emphasized understanding local peoples cultural models and political-economic explanations for the disease while the second approach focused on providing more humanitarian care of patients by i ...200516267966
ebola and great apes in central africa: current status and future needs. 200516267967
[training the trainers seminar and analysis of the ebola virus hemorrhagic fever outbreaks in central africa from 2001 to 2004. (brazzaville, républic of congo, april 6-8, 2004]. 200516267969
outbreak of ebola haemorrhagic fever in yambio, south sudan, april - june 2004. 200516285261
recent advances in antiviral nucleoside and nucleotide therapeutics.recent developments in nucleoside/nucleotide therapeutics and antiviral drug targets are described covering progress in the development of nucleoside/nucleotide mimetics for the treatment of influenza virus, human immunodeficiency virus type 1, hepatitis b and c virus, herpes virus infections; including herpes simplex virus, cytomegalovirus and varicella zoster virus infections, and the highly pathogenic poxviruses (variola, vaccinia and monkey pox) and filoviruses (ebola and marburg).200516305526
fruit bats as reservoirs of ebola virus.the first recorded human outbreak of ebola virus was in 1976, but the wild reservoir of this virus is still unknown. here we test for ebola in more than a thousand small vertebrates that were collected during ebola outbreaks in humans and great apes between 2001 and 2003 in gabon and the republic of the congo. we find evidence of asymptomatic infection by ebola virus in three species of fruit bat, indicating that these animals may be acting as a reservoir for this deadly virus.200516319873
taking down goliaths: new vaccines may spell the end for ebola, marburg and lassa virus infections. 200516323509
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 ...200616352570
the role of reverse genetics systems in determining filovirus pathogenicity.the family filoviridae is comprised of two genera: marburgvirus and ebolavirus. to date minigenome systems have been developed for two ebola viruses (reston ebolavirus and zaire ebolavirus [zebov]) as well as for lake victoria marburgvirus, the sole member of the marburgvirus genus. the use of these minigenome systems has helped characterize functions for many viral proteins in both genera and have provided valuable insight towards the development of an infectious clone system in the case of zeb ...200516355872
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 ...200616356525
[countermeasure against viral hemorrhagic fever at the border in japan].human have struggled against many infectious diseases such as cholera, plague, dysentery and yellow fever for a long time. and we have spent a lot of energy to control these infectious diseases and developed various tool for them. one of these efforts was quarantine system that was established in 14th century in europe. but during recent days, we are suffering from newly emerged diseases. these new infectious diseases are zoonosis and most of them are serious and highly infectious. viral hemorrh ...200516363688
[clinical aspects of viral hemorrhagic fever].viral hemorrhagic fever (vhf) is defined as virus infections that usually cause pyrexia and hemorrhagic symptoms with multiple organ failure. vhf includes following viral infections: ebola hemorrhagic fever (ehf), marburg hemorrhagic fever (mhf), crimean-congo hemorrhagic fever (cchf) and lassa fever. in particular, the causative agents of ehf, mhf, cchf, and lassa fever are ebola, marburg, cchf, lassa viruses, respectively, and regarded as biosafety level-4 pathogens because of their high virul ...200516363689
filovirus assembly and budding.filoviruses belong to the order of negative-stranded non-segmented rna viruses and are classified into two genera, ebola and marburg viruses. they have a characteristic filamentous shape, which is largely determined by the matrix protein vp40. although vp40 is the main driving force for assembly and budding from the host cell, the production of infectious virus involves an intricate interplay between all viral structural proteins in addition to cellular factors, e.g., those that normally functio ...200616364737
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). ...200616365436
packaging of actin into ebola virus vlps.the actin cytoskeleton has been implicated in playing an important role assembly and budding of several rna virus families including retroviruses and paramyxoviruses. in this report, we sought to determine whether actin is incorporated into ebola vlps, and thus may play a role in assembly and/or budding of ebola virus. our results indicated that actin and ebola virus vp40 strongly co-localized in transfected cells as determined by confocal microscopy. in addition, actin was packaged into budding ...200516367999
ebola and marburg viruses: pathogenesis and development of countermeasures.ebola and marburg viruses, family filoviridae, are among the best known examples of emerging and re-emerging pathogens. although outbreaks have been sporadic and geographically restricted to areas of central africa, the hemorrhagic fevers caused by these viruses are remarkably severe and are associated with high case fatality rates often exceeding 80 percent. in addition to humans, these viruses have decimated populations of wild apes in central africa. currently, there are no vaccines or effect ...200516375711
rescue of recombinant marburg virus from cdna is dependent on nucleocapsid protein 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 ...200616379005
[bats, reserves of the ebola virus: the mystery is dissipated]. 200616386226
interferon: ten stories in one. a short review of some of the highlights in the history of an almost quinquagenarian.this short review article on some pertinent observations in the unfolding story of interferon is dedicated to professor ilona béládi on the occasion of her 80th birthday. this by no means covers the whole story on interferon. it just highlights some of the more striking findings made with interferon (or its inducers) over a time span of almost 50 years since its original discovery (in 1957) by isaacs and lindenmann. these observations concern (i) the induction of interferon by synthetic polyanio ...200516400870
new medicines from nature's armamentarium.nature frequently unleashes a barrage of new and frightening diseases against humans--such as hiv, severe acquired respiratory syndrome, ebola virus and avian flu recently--in addition to the seemingly ever-present scourges such as malaria and tuberculosis. fortunately, nature also provides the wherewithal to help conquer the diseases that it sets loose. all that is needed is the human ingenuity to discover, develop and apply the solutions in an optimal fashion. participants at the 9th max tishl ...200616406332
gene-specific countermeasures against ebola virus based on antisense phosphorodiamidate morpholino oligomers.the filoviruses marburg virus and ebola virus (ebov) quickly outpace host immune responses and cause hemorrhagic fever, resulting in case fatality rates as high as 90% in humans and nearly 100% in nonhuman primates. the development of an effective therapeutic for ebov is a daunting public health challenge and is hampered by a paucity of knowledge regarding filovirus pathogenesis. this report describes a successful strategy for interfering with ebov infection using antisense phosphorodiamidate mo ...200616415982
john montgomery's legacy: carbocyclic adenosine analogues as sah hydrolase inhibitors with broad-spectrum antiviral activity.ever since the s-adenosylhomocysteine (adohcy, sah) hydrolase was recognized as a pharmacological target for antiviral agents (j. a. montgomery et al., j. med. chem. 25:626-629, 1982), an increasing number of adenosine, acyclic adenosine, and carbocyclic adenosine analogues have been described as potent sah hydrolase inhibitors endowed with broad-spectrum antiviral activity. the antiviral activity spectrum of the sah hydrolase inhibitors include pox-, rhabdo-, filo-, arena-, paramyxo-, reo-, and ...200516438025
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 ...200616439530
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 ...200616441209
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 ...200616441210
[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 ...200616457765
a single intranasal inoculation with a paramyxovirus-vectored vaccine protects guinea pigs against a lethal-dose ebola virus 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. ...200616474134
a clinical guide to viral haemorrhagic fevers: ebola, marburg and lassa.the viral haemorrhagic fevers are a group of diseases that share many clinical features. ebola, marburg and lassa are diseases that cause a relatively small number of deaths globally, but pose special risks to medical staff due to the ease of transmission, and can have a profound impact to the communities they affect. this article gives a brief overview of diseases caused by the ebola, marburg and lassa viruses. it gives some practical advice to the clinician on the diagnosis and management of t ...200616483416
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 ...200616495261
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 ...200616501083
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 ...200616501090
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 ...200616501110
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 ...200616530297
developments in antiviral drug design, discovery and development in 2004.this article summarizes key aspects of progress made during 2004 toward the design, discovery and development of antiviral agents for clinical use. important developments in the identification, characterization and clinical utility of inhibitors of human immunodeficiency virus; the hepatitis viruses, hepatitis b, hepatitis c; the herpes family of viruses, herpes simplex viruses 1 and 2, varicella zoster virus, epstein-barr virus and human cytomegalovirus; the respiratory viruses, influenza, resp ...200516535860
[isolated case of haemorrhagic fever observed in gabon during the 2002 outbreak of ebola but distant from epidemic zones].during the last outbreak of ebola virus haemorrhagic fever that occurred concurrently in gabon and congo, several primary foci were identified in the ogooue ivindo province (northeast gabon), where previous outbreaks had occurred. a 48-year-old woman living in franceville located 580 km from the epicentre presented fever with haemorrhagic signs. she was evacuated to libreville where ebola infection was suspected. diagnosis was confirmed at the centre international de recherches médicales of fran ...200516548488
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 ...200616569728
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 ...200616569729
functional mapping of the nucleoprotein of ebola 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 ...200616571791
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 ...200616571833
[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. ...200616597410
[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 ...200616597411
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 ...200616603527
laboratory diagnostic systems for ebola and marburg hemorrhagic fevers developed with recombinant proteins. 200616603611
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 ...200616610760
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 ...200616616875
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 ...200616629503
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.200616652308
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 ...200616678231
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 ...200616683867
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