Publications

TitleAbstractYear
Filter
PMID
Filter
[antigenic differences in wild-type and guinea pig-adapted ebola virus strains].the splenocytes isolated from the mice immunized with wild-type or guinea pig-adapted ebola virus strains were used to obtain hybridoma collections. investigation of the monoclonal antibodies (mab) obtained to one of the strains to another revealed antigenic interstrain differences in nucleoprotein and vp40. it is interesting that the differences were found in the hydridoma collection obtained against the wild-type strain. the mabs produced by hydridomas to the adapted strain were found to equal ...201021381339
a new ebola virus nonstructural glycoprotein expressed through rna editing.ebola virus (ebov), an enveloped, single-stranded, negative-sense rna virus, causes severe hemorrhagic fever in humans and nonhuman primates. the ebov glycoprotein (gp) gene encodes the nonstructural soluble glycoprotein (sgp) but also produces the transmembrane glycoprotein (gp1,2) through transcriptional editing. a third gp gene product, a small soluble glycoprotein (ssgp), has long been postulated to be produced also as a result of transcriptional editing. to identify and characterize the exp ...201121411529
lessons learned during active epidemiological surveillance of ebola and marburg viral hemorrhagic fever epidemics in africa.to review epidemiological surveillance approaches used during ebola and marburg hemorrhagic fever epidemics in africa in the past fifteen years. overall, 26 hemorrhagic epidemic outbreaks have been registered in 12 countries; 18 caused by the ebola virus and eight by the marburg virus. about 2551 cases have been reported, among which 268 were health workers (9,3%).201021413569
[study of the functional role of mutation in the guinea pig-adapted ebola virus genome on a drosophila melanogaster model].ebola virus virulence in guinea pigs, which appears through virus adaptation to this animal host, correlates with substitutions in the gene encoding vp24 protein. in particular, the substitution his-->tyr186 was found when obtaining strain 8 ms. an attempt was made to clarify the functional role of this substitution in a transgenic fruit fly model. using the drosophila transformation technique provided transgenic strains that contained genomic insertions of wild-type ebola virus vp24 gene and th ...201121427954
inhibition of ebola virus entry by a c-peptide targeted to endosomes.ebola virus (ebov) and marburg virus (marv) (filoviruses) are the causative agents of severe hemorrhagic fever. infection begins with uptake of particles into cellular endosomes, where the viral envelope glycoprotein (gp) catalyzes fusion between the viral and host cell membranes. this fusion event is thought to involve conformational rearrangements of the transmembrane subunit (gp2) of the envelope spike that ultimately result in formation of a six-helix bundle by the n- and c-terminal heptad r ...201121454542
laboratory detection and diagnosis of filoviruses.ebola virus (ebov) and marburg virus (marv), belonging to the filoviridae family, emerged four decades ago and caused severe viral hemorrhagic fever in human and other primates. as high as 50-90% mortality, filoviruses can cause significant threats to public health. however, so far no specific and efficient vaccine has been available, nor have other treatment methods proved to be effective. it is of great importance to detect these pathogens specific, rapidly and sensitively in order to control ...201121468930
development and characterization of rabbit and mouse antibodies against ebolavirus envelope glycoproteins.ebolaviruses are the etiologic agents of severe viral hemorrhagic fevers in primates, including humans, and could be misused for the development of biological weapons. the ability to rapidly detect and differentiate these viruses is therefore crucial. antibodies that can detect reliably the ebolavirus surface envelope glycoprotein gp(1,2) or a truncated variant that is secreted from infected cells (sgp) are required for advanced development of diagnostic assays such as sandwich elisas or western ...201121513741
european risk assessment guidance for infectious diseases transmitted on aircraft - the ragida project. 201121527131
from the cover: t-cell immunoglobulin and mucin domain 1 (tim-1) is a receptor for zaire ebolavirus and lake victoria marburgvirus.the glycoproteins (gp) of enveloped viruses facilitate entry into the host cell by interacting with specific cellular receptors. despite extensive study, a cellular receptor for the deadly filoviruses ebolavirus and marburgvirus has yet to be identified and characterized. here, we show that t-cell ig and mucin domain 1 (tim-1) binds to the receptor binding domain of the zaire ebola virus (ebov) glycoprotein, and ectopic tim-1 expression in poorly permissive cells enhances ebov infection by 10- t ...201121536871
detection of viruses in used ventilation filters from two large public buildings.background: viral and bacterial pathogens may be present in the air after being released from infected individuals and animals. filters are installed in the heating, ventilation, and air-conditioning (hvac) systems of buildings to protect ventilation equipment and maintain healthy indoor air quality. these filters process enormous volumes of air. this study was undertaken to determine the utility of sampling used ventilation filters to assess the types and concentrations of virus aerosols presen ...201121549446
ebola virus as a foodborne pathogen? cause for consideration, but not panic. 201121571727
replication, pathogenicity, shedding, and transmission of zaire ebolavirus in pigs.background. reston ebolavirus was recently detected in pigs in the philippines. specific antibodies were found in pig farmers, indicating exposure to the virus. this important observation raises the possibility that pigs may be susceptible to ebola virus infection, including from other species, such as zaire ebolavirus (zebov), and can transmit to other susceptible hosts. methods. this study investigated whether zebov, a species commonly reemerging in central africa, can replicate and induce dis ...201121571728
protocol for recombinant rbd-based sars vaccines: protein preparation, animal vaccination and neutralization detection.based on their safety profile and ability to induce potent immune responses against infections, subunit vaccines have been used as candidates for a wide variety of pathogens (1-3). since the mammalian cell system is capable of post-translational modification, thus forming properly folded and glycosylated proteins, recombinant proteins expressed in mammalian cells have shown the greatest potential to maintain high antigenicity and immunogenicity (4-6). although no new cases of sars have been repo ...201121587153
a limited outbreak of ebola haemorrhagic fever in etoumbi, republic of congo, 2005.ebolavirus has caused highly lethal outbreaks of haemorrhagic fever in the congo basin. the 2005 outbreak in the republic of congo occurred in the etoumbi district of cuvette ouest department between april and may. the two index cases were infected while poaching. the sanitary response consisted of active surveillance and contact tracing, public awareness campaigns and community mobilization, case management and safe burial practices, and laboratory confirmation. twelve cases and ten deaths were ...201121605882
depletion of gtp pool is not the predominant mechanism by which ribavirin exerts its antiviral effect on lassa virus.ribavirin (1-β-d-ribofuranosyl-1,2,4-triazole-3-carboxamide) is the standard treatment for lassa fever, though its mode of action is unknown. one possibility is depletion of the intracellular gtp pool via inhibition of the cellular enzyme inosine monophosphate dehydrogenase (impdh). this study compared the anti-arenaviral effect of ribavirin with that of two other impdh inhibitors, mycophenolic acid (mpa) and 5-ethynyl-1-β-d-ribofuranosylimidazole-4-carboxamide (eicar). all three compounds were ...201121616094
comparative virology and aids (review).the scientific debate between pros and cons of the hiv criminal theory of aids still remains unsettled. the purpose of this review is to promote resolution of the problem by extracting a common principle of the host-virus relation using data resources for each of 4 viruses as follows: a) polyoma virus, b) marek's disease virus, c) ebola virus, d) korean hemorrhagic fever virus. conclusions drawn from this study are given as follows: i) environment emerged as the cardinal factor to modify the pro ...199621594370
pseudosaccharide functionalized dendrimers as potent inhibitors of dc-sign dependent ebola pseudotyped viral infection.the development of compounds with strong affinity for the receptor dc-sign is a topic of remarkable interest due to the role that this lectin plays in several pathogen infection processes and in the modulation of the immune response. dc-sign recognizes mannosylated and fucosylated oligosaccharides in a multivalent manner. therefore, multivalent carbohydrate systems are required to interact in an efficient manner with this receptor and compete with the natural ligands. we have previously demonstr ...201121650462
jaagsiekte sheep retrovirus pseudotyped lentiviral vector-mediated gene transfer to fetal ovine lung.viral vector-mediated gene transfer to the postnatal respiratory epithelium has, in general, been of low efficiency due to physical and immunological barriers, non-apical location of cellular receptors critical for viral uptake and limited transduction of resident stem/progenitor cells. these obstacles may be overcome using a prenatal strategy. in this study, hiv-1-based lentiviral vectors (lvs) pseudotyped with the envelope glycoproteins of jaagsiekte sheep retrovirus (jsrv-lv), baculovirus gp6 ...201121654824
un-"escrt"-ed budding.in their recent publication, rossman et al. [1] describe how the inherent budding capability of its m2 protein allows influenza a virus to bypass recruitment of the cellular escrt machinery enlisted by several other enveloped rna and dna viruses, including hiv, ebola, rabies, herpes simplex type 1 and hepatitis b. studies from the same laboratory [2] and other laboratories [3-6] indicate that budding of plasmid-derived virus-like particles can be mediated by the influenza virus hemagglutinin and ...201121666754
serologic cross-reactivity of human igm and igg antibodies to five species of ebola virus.five species of ebola virus (ebov) have been identified, with nucleotide differences of 30-45% between species. four of these species have been shown to cause ebola hemorrhagic fever (ehf) in humans and a fifth species (reston ebolavirus) is capable of causing a similar disease in non-human primates. while examining potential serologic cross-reactivity between ebov species is important for diagnostic assays as well as putative vaccines, the nature of cross-reactive antibodies following ebov infe ...201121666792
characterization of the receptor-binding domain of ebola glycoprotein in viral entry.ebola virus infection causes severe hemorrhagic fever in human and non-human primates with high mortality. viral entry/infection is initiated by binding of glycoprotein gp protein on ebola virion to host cells, followed by fusion of virus-cell membrane also mediated by gp. using an human immunodeficiency virus (hiv)-based pseudotyping system, the roles of 41 ebola gp1 residues in the receptor-binding domain in viral entry were studied by alanine scanning substitutions. we identified that four re ...201121667336
usa focuses on ebola vaccine but research gaps remain. 201121809495
the fusogenic tilted peptide (67-78) of a-synuclein is a cholesterol binding domain.parkinson's disease-associated a-synuclein is an amyloidogenic protein not only expressed in the cytoplasm of neurons, but also secreted in the extracellular space and internalized into glial cells through a lipid raft-dependent process. we previously showed that a-synuclein interacts with raft glycosphingolipids through a structural motif common to various viral and amyloidogenic proteins. here we report that a-synuclein also interacts with cholesterol, as assessed by surface pressure measureme ...201121756873
[indications for pcr in travel medicine].the use of pcr-based molecular diagnosis in travel medicine remains limited to specific indications such as clinical suspicion of some of the viral hemorrhagic fevers (e.g. ebola, marburg), differential diagnosis between entamoeba histolytica (pathogen) and e. dispar (non pathogen) in the stools, and parasitological diagnosis of cutaneous leishmaniasis. the scope of indications is likely to expand in the coming years with the development of techniques (e.g. multiplex pcr) able to identify severa ...201121692311
current perspectives on the phylogeny of filoviridae.sporadic fatal outbreaks of disease in humans and non-human primates caused by ebola or marburg viruses have driven research into the characterization of these viruses with the hopes of identifying host tropisms and potential reservoirs. such an understanding of the relatedness of newly discovered filoviruses may help to predict risk factors for outbreaks of hemorrhagic disease in humans and/or non-human primates. recent discoveries such as three distinct genotypes of reston ebolavirus, unexpect ...201121742058
functional genomics reveals the induction of inflammatory response and metalloproteinase gene expression during lethal ebola virus infection.ebola virus is the etiologic agent of a lethal hemorrhagic fever in humans and nonhuman primates with mortality rates of up to 90%. previous studies with zaire ebola virus (zebov), mouse-adapted virus (ma-zebov), and mutant viruses (zebov-np(ma), zebov-vp24(ma), and zebov-np/vp24(ma)) allowed us to identify the mutations in viral protein 24 (vp24) and nucleoprotein (np) responsible for acquisition of high virulence in mice. to elucidate specific molecular signatures associated with lethality, we ...201121734050
[ebola and marburg hemorrhagic fever viruses: update on filoviruses].the ebola and marburg viruses are the sole members of the filoviridae family of viruses. they are characterized by a long filamentous form that is unique in the viral world. filoviruses are among the most virulent pathogens currently known to infect humans. they cause fulminating disease characterized by acute fever followed by generalized hemorrhagic syndrome that is associated with 90% mortality in the most severe forms. epidemic outbreaks of marburg and ebola viruses have taken a heavy toll o ...201121695865
an enzymatic assay for detection of viral entry.this unit describes a viral entry assay where a beta-lactamase reporter protein fused to the matrix protein of either influenza (blam1) or ebola virus (blavp40) is packaged as a structural component into virus-like particles (vlps). the bla reporter is released upon fusion with target cells and can be detected in live cells by flow cytometry, microscopy, or a fluorometric plate reader for utility in high-throughput screening approaches. the transfer of bla to a target cell by blam1 or blavp40 vl ...201121688257
ebolavirus {delta}-peptide immunoadhesins inhibit marburgvirus and ebolavirus cell entry.with the exception of reston and lloviu viruses, filoviruses (marburgviruses, ebolaviruses, and "cuevaviruses") cause severe viral hemorrhagic fevers in humans. filoviruses use a class i fusion protein, gp(1,2), to bind to an unknown, but shared, cell surface receptor to initiate virus-cell fusion. in addition to gp(1,2), ebolaviruses and cuevaviruses, but not marburgviruses, express two secreted glycoproteins, soluble gp (sgp) and small soluble gp (ssgp). all three glycoproteins have identical ...201121697477
ebola and marburg haemorrhagic fever viruses: major scientific advances, but a relatively minor public health threat for africa.ebola and marburg viruses are the only members of the filoviridae family (order mononegavirales), a group of viruses characterized by a linear, non-segmented, single-strand negative rna genome. they are among the most virulent pathogens for humans and great apes, causing acute haemorrhagic fever and death within a matter of days. since their discovery 50 years ago, filoviruses have caused only a few outbreaks, with 2317 clinical cases and 1671 confirmed deaths, which is negligible compared with ...201121722250
[Antiviral drugs].It is 50 years since the first antiviral drug--JUDR for the local herpes keratitis was introduced and over 25 years since HIV/AIDS was isolated and the Noble Prize in Medicine and Physiology was given to its discovers. Now, there are 50 antiviral drugs, in which 25 are for HIV, the others are for herpes virus, shingles, cytomegalovirus, hepatitis virus and influenza A virus. Drugs for hemorrhagic fever Ebola and Marbourg as well as Denga fever are under way In the paper the current knowledge on ...201121675143
reston ebolavirus in humans and animals in the philippines: a review.the 2008 reston ebolavirus infection event in domestic pigs has triggered continuing epidemiologic investigations among philippine health and veterinary agencies in collaboration with international filovirus experts. prior to this, there were only 3 known and documented reston ebolavirus outbreaks in nonhuman primates in the world, all traced back to a single geographic source in the philippines in a monkey breeding/export facility. the first one in 1989 was the first-ever ebola virus that emerg ...201121987747
inactivated or live-attenuated bivalent vaccines that confer protection against rabies and ebola viruses.the search for a safe and efficacious vaccine for ebola virus continues, as no current vaccine candidate is nearing licensure. we have developed (i) replication-competent, (ii) replication-deficient, and (iii) chemically inactivated rabies virus (rabv) vaccines expressing zaire ebola virus (zebov) glycoprotein (gp) by a reverse genetics system based on the sad b19 rabv wildlife vaccine. zebov gp is efficiently expressed by these vaccine candidates and is incorporated into virions. the vaccine ca ...201121849459
Emergence of divergent Zaire ebola virus strains in Democratic Republic of the Congo in 2007 and 2008.Zaire ebolavirus was responsible for 2 outbreaks in Democratic Republic of the Congo (DRC), in 1976 and 1995. The virus reemerged in DRC 12 years later, causing 2 successive outbreaks in the Luebo region, Kasai Occidental province, in 2007 and 2008.201121987750
Recombinant vesicular stomatitis virus-based vaccines against Ebola and Marburg virus infections.The filoviruses, Marburg virus and Ebola virus, cause severe hemorrhagic fever with a high mortality rate in humans and nonhuman primates. Among the most-promising filovirus vaccines under development is a system based on recombinant vesicular stomatitis virus (rVSV) that expresses a single filovirus glycoprotein (GP) in place of the VSV glycoprotein (G). Importantly, a single injection of blended rVSV-based filovirus vaccines was shown to completely protect nonhuman primates against Marburg vir ...201121987744
Contribution of Sec61a to the life cycle of Ebola virus.Similar to other viruses, the viral proteins of Ebola virus (EBOV) interact with a variety of host proteins for its replication. Of the 7 structural proteins encoded in the EBOV genome, VP24 is the smallest and is multifunctional.201121987770
cd59 incorporation protects hepatitis c virus against complement-mediated destruction.several enveloped viruses including human immunodeficiency virus type 1 (hiv-1), cytomegalovirus (cmv), herpes simplex virus 1 (hsv-1), ebola virus, vaccinia virus, and influenza virus have been found to incorporate host regulators of complement activation (rca) into their viral envelopes and, as a result, escape antibody-dependent complement-mediated lysis (adcml). hepatitis c virus (hcv) is an enveloped virus of the family flaviviridae and incorporates more than 10 host lipoproteins. patients ...201121932413
an unconventional pathway of mrna cap formation by vesiculoviruses.mrnas of vesicular stomatitis virus (vsv), a prototype of nonsegmented negative strand (nns) rna viruses (e.g., rabies, measles, mumps, ebola, and borna disease viruses), possess the 5'-terminal cap structure identical to that of eukaryotic mrnas, but the mechanism of mrna cap formation is distinctly different from the latter. the elucidation of the unconventional capping of vsv mrna remained elusive for three decades since the discovery of the cap structure in some viral and eukaryotic mrnas in ...201121945214
the ebola virus glycoprotein mediates entry via a non-classical dynamin-dependent macropinocytic pathway.ebola virus (ebov) has been reported to enter cultured cell lines via a dynamin-2-independent macropinocytic pathway or clathrin-mediated endocytosis. the route(s) of productive ebov internalization into physiologically relevant cell types remain unexplored, and viral-host requirements for this process are incompletely understood. here, we use electron microscopy and complementary chemical and genetic approaches to demonstrate that the viral glycoprotein, gp, induces macropinocytic uptake of vir ...201121907381
genomic rna editing and its impact on ebola virus adaptation during serial passages in cell culture and infection of guinea pigs.synthesis of the structural, surface glycoprotein (gp) of ebola virus (ebov) is dependent on transcriptional rna editing phenomenon. editing results in the insertion of an extra adenosine by viral polymerase at the editing site (7 consecutive template uridines) during transcription of gp gene of the wild-type virus (ebov/7u). in this study, we demonstrate that passage of ebov/7u in vero e6 cells results in the appearance and rapid accumulation of a variant (ebov/8u) containing an additional urid ...201121987773
development of an antiviral screening protocol: one-stone-two-birds.as prophylactic therapies and vaccines against viral infections continue to improve, drug resistant strains are continuing to arise; therefore it is imperative to develop new therapeutics against these diseases. for highly pathogenic viruses, such as ebola and h5n1 influenza virus, the need for antivirals is even more urgent due to limited therapeutics against these viruses. furthermore, the high pathogenicity of such viruses often makes it difficult to work with such agents. in this report, we ...201122140608
Progress in recombinant DNA-derived vaccines for Lassa virus and filoviruses.Developing vaccines for highly pathogenic viruses such as those causing Lassa, Ebola, and Marburg hemorrhagic fevers is a daunting task due to both scientific and logistical constraints. Scientific hurdles to overcome include poorly defined relationships between pathogenicity and protective immune responses, genetic diversity of viruses, and safety in a target population that includes a large number of individuals with compromised immune systems. Logistical obstacles include the requirement for ...201121925552
antibody-dependent enhancement of marburg virus infection.marburg virus (marv) and ebola virus (ebov) cause severe hemorrhagic fever in primates. earlier studies demonstrated that antibodies to particular epitopes on the glycoprotein (gp) of ebov enhanced virus infectivity in vitro.201121987779
real-time monitoring of cardiovascular function in rhesus macaques infected with zaire ebolavirus.nine rhesus macaques were implanted with multisensor telemetry devices and internal jugular vein catheters before being infected with zaire ebolavirus. all animals developed viremia, fever, a hemorrhagic rash, and typical changes of ebola hemorrhagic fever in clinical laboratory tests. three macaques unexpectedly survived this usually lethal disease, making it possible to compare physiological parameters in lethally challenged animals and survivors. after the onset of fever, lethal illness was c ...201121987736
impact of systemic or mucosal immunity to adenovirus on ad-based ebola virus vaccine efficacy in guinea pigs.approximately 35% of the north american population and an estimated 90% of the sub-saharan african population have antibodies against adenovirus serotype 5 (adhu5) that are capable of neutralizing adhu5-based vaccines. in mice, intranasal delivery of adhu5 expressing the zaire ebolavirus glycoprotein human adenovirus serotype 5 (ad) containing the genes for the zaire ebolavirus glycoprotein (zgp) under the expressional control of a cytomegalovirus immediate early promoter (cmv)) can bypass syste ...201121987739
Ebola virus enters host cells by macropinocytosis and clathrin-mediated endocytosis.Virus entry into host cells is the first step of infection and a crucial determinant of pathogenicity. Here we show that Ebola virus-like particles (EBOV-VLPs) composed of the glycoprotein GP(1,2) and the matrix protein VP40 use macropinocytosis and clathrin-mediated endocytosis to enter cells. EBOV-VLPs applied to host cells induced actin-driven ruffling and enhanced FITC-dextran uptake, which indicated macropinocytosis as the main entry mechanism. This was further supported by inhibition of en ...201121987776
unconventional secretion of ebola virus matrix protein vp40.the ebola virus matrix protein vp40 plays an essential role in virus assembly and budding. in this study we reveal that transient vp40 expression results in the release into the culture medium of substantial amounts of soluble monomeric vp40 in addition to the release of virus-like particles containing an oligomeric form of this protein as previously described. we show that vp40 secretion is endoplasmic reticulum/golgi-independent and is not associated with cell death. soluble vp40 was observed ...201121987759
using next generation sequencing to identify yellow fever virus in uganda.in october and november 2010, hospitals in northern uganda reported patients with suspected hemorrhagic fevers. initial tests for ebola viruses, marburg virus, rift valley fever virus, and crimean congo hemorrhagic fever virus were negative. unbiased pcr amplification of total rna extracted directly from patient sera and next generation sequencing resulted in detection of yellow fever virus and generation of 98% of the virus genome sequence. this finding demonstrated the utility of next generati ...201221962764
infection of xc cells by mlvs and ebola virus is endosome-dependent but acidification-independent.inhibitors of endosome acidification or cathepsin proteases attenuated infections mediated by envelope proteins of xenotropic murine leukemia virus-related virus (xmrv) and ebola virus, as well as ecotropic, amphotropic, polytropic, and xenotropic murine leukemia viruses (mlvs), indicating that infections by these viruses occur through acidic endosomes and require cathepsin proteases in the susceptible cells such as te671 cells. however, as previously shown, the endosome acidification inhibitors ...201122022555
Clinical aspects of Marburg hemorrhagic fever.Marburg virus belongs to the genus Marburgvirus in the family Filoviridae and causes a severe hemorrhagic fever, known as Marburg hemorrhagic fever (MHF), in both humans and nonhuman primates. Similar to the more widely known Ebola hemorrhagic fever, MHF is characterized by systemic viral replication, immunosuppression and abnormal inflammatory responses. These pathological features of the disease contribute to a number of systemic dysfunctions including hemorrhages, edema, coagulation abnormali ...201122046196
Conserved proline-rich region of Ebola virus matrix protein VP40 is essential for plasma membrane targeting and virus-like particle release.The matrix protein VP40 is essential for Ebola virus (EBOV) and Marburg virus assembly and budding at the plasma membrane. In this study we have investigated the effect of single amino acid substitutions in a conserved proline-rich region of the EBOV VP40 located in the carboxy-terminal part of the protein. We demonstrate that substitutions within this region result in an alteration of intracellular VP40 localization and also cause a reduction or a complete block of virus-like particle budding, ...201121987765
single immunization with a monovalent vesicular stomatitis virus-based vaccine protects nonhuman primates against heterologous challenge with bundibugyo ebolavirus.the recombinant vesicular stomatitis virus (rvsv) vector-based monovalent vaccine platform expressing a filovirus glycoprotein has been demonstrated to provide protection from lethal challenge with ebola (ebov) and marburg (marv) viruses both prophylactically and after exposure. this platform provides protection between heterologous strains within a species; however, protection from lethal challenge between species has been largely unsuccessful. to determine whether the rvsv-ebov vaccines have t ...201121987745
filovirus outbreak detection and surveillance: lessons from bundibugyo.the first outbreak of ebola hemorrhagic fever (ehf) due to bundibugyo ebolavirus occurred in uganda from august to december 2007. during outbreak response and assessment, we identified 131 ehf cases (44 suspect, 31 probable, and 56 confirmed). consistent with previous large filovirus outbreaks, a long temporal lag (approximately 3 months) occurred between initial ehf cases and the subsequent identification of ebola virus and outbreak response, which allowed for prolonged person-to-person transmi ...201121987748
differential requirements for clathrin endocytic pathway components in cellular entry by ebola and marburg glycoprotein pseudovirions.clathrin-mediated endocytosis was previously implicated as one of the cellular pathways involved in filoviral glycoprotein mediated viral entry into target cells. here we have further dissected the requirements for different components of this pathway in ebola versus marburg virus glycoprotein (gp) mediated viral infection. although a number of these components were involved in both cases; ebola gp-dependent viral entry specifically required the cargo recognition proteins eps15 and dab2 as well ...201121855102
a single sublingual dose of an adenovirus-based vaccine protects against lethal ebola challenge in mice and guinea pigs.sublingual (sl) delivery, a noninvasive immunization method that bypasses the intestinal tract for direct entry into the circulation, was evaluated with an adenovirus (ad5)-based vaccine for ebola. mice and guinea pigs were immunized via the intramuscular (im), nasal (in), oral (po) and sl routes. sl immunization elicited strong transgene expression in and attracted cd11c(+) antigen presenting cells to the mucosa. a sl dose of 1 × 10(8) infectious particles induced ebola zaire glycoprotein (zgp) ...201122149096
the ebola virus vp24 protein prevents hnrnp c1/c2 binding to karyopherin α1 and partially alters its nuclear import.the ebola virus (ebov) protein vp24 inhibits type i and ii interferon (ifn) signaling by binding to npi-1 subfamily karyopherin α (kpna) nuclear import proteins, preventing their interaction with tyrosine-phosphorylated stat1 (phospho-stat1). this inhibits phospho-stat1 nuclear import. a biochemical screen now identifies heterogeneous nuclear ribonuclear protein complex c1/c2 (hnrnp c1/c2) nuclear import as an additional target of vp24. co-immunoprecipitation studies demonstrate that hnrnp c1/c2 ...201121987768
identification of an antioxidant small-molecule with broad-spectrum antiviral activity.the highly lethal filoviruses, ebola and marburg cause severe hemorrhagic fever in humans and non-human primates. to date there are no licensed vaccines or therapeutics to counter these infections. identifying novel pathways and host targets that play an essential role during infection will provide potential targets to develop therapeutics. small molecule chemical screening for ebola virus inhibitors resulted in identification of a compound nsc 62914. the compound was found to exhibit anti-filov ...201222027648
characterization of filovirus protein-protein interactions in mammalian cells using bimolecular complementation.the virion protein 40 (vp40) and nucleoprotein (np) of ebola (ebov) and marburg viruses (marv) play key roles during virion assembly and egress. the ability to detect interactions between vp40-vp40, vp40-np, and np-np and follow these complexes as they traffic through mammalian cells would enhance our understanding of the molecular events leading to filovirus assembly and budding, and provide new insights into filovirus replication and pathogenesis. here, we successfully employed a bimolecular c ...201121987757
management of accidental exposure to ebola virus in the biosafety level 4 laboratory, hamburg, germany.a needlestick injury occurred during an animal experiment in the biosafety level 4 laboratory in hamburg, germany, in march 2009. the syringe contained zaire ebolavirus (zebov) mixed with freund's adjuvant. neither an approved treatment nor a postexposure prophylaxis (pep) exists for ebola hemorrhagic fever. following a risk-benefit assessment, it was recommended the exposed person take an experimental vaccine that had shown pep efficacy in zebov-infected nonhuman primates (nhps) [12]. the vacci ...201121987751
enhanced potency of a fucose-free monoclonal antibody being developed as an ebola virus immunoprotectant.no countermeasures currently exist for the prevention or treatment of the severe sequelae of filovirus (such as ebola virus; ebov) infection. to overcome this limitation in our biodefense preparedness, we have designed monoclonal antibodies (mabs) which could be used in humans as immunoprotectants for ebov, starting with a murine mab (13f6) that recognizes the heavily glycosylated mucin-like domain of the virion-attached glycoprotein (gp). point mutations were introduced into the variable region ...201122143789
high-throughput screening of viral entry inhibitors using pseudotyped virus.virus entry into a host cell is an attractive target for therapy because propagation of virus can be blocked at an early stage, minimizing chances for the virus to acquire drug resistance. anti-infective drug discovery for bsl-4 viruses like ebola or lassa hemorrhagic fever virus presents challenges due to the requirement for a bsl-4 laboratory containment facility. pseudotyped viruses provide a surrogate model in which the native envelope glycoprotein of a bsl-2 level virus (e.g., vesicular sto ...201021935898
therapeutics of ebola hemorrhagic fever: whole-genome transcriptional analysis of successful disease mitigation.the mechanisms of ebola (ebov) pathogenesis are only partially understood, but the dysregulation of normal host immune responses (including destruction of lymphocytes, increases in circulating cytokine levels, and development of coagulation abnormalities) is thought to play a major role. accumulating evidence suggests that much of the observed pathology is not the direct result of virus-induced structural damage but rather is due to the release of soluble immune mediators from ebov-infected cell ...201121987740
vp24 is a molecular determinant of ebola virus virulence in guinea pigs.in sharp contrast to human and nonhuman primates, guinea pigs and some other mammals resist ebola virus (ebov) replication and do not develop illness upon virus inoculation. however, serial passaging of ebov in guinea pigs results in a selection of variants with high pathogenicity. in this report, using a reverse genetics approach, we demonstrate that this dramatic increase in ebov pathogenicity is associated with amino acid substitutions in the structural protein vp24. we show that although rep ...201121987737
filovirus infection of stat-1 knockout mice.we evaluated the susceptibility to ebola and marburg virus infection of mice that cannot respond to interferon (ifn)-α/β and ifn-γ because of deletion of the stat-1 gene. a mouse-adapted zaire ebolavirus (zebov) caused rapidly lethal disease; wild-type zebov and sudan ebolavirus and 4 different marburg virus strains produced severe, but more slowly progressive illness; and reston ebolavirus caused mild disease that was late in onset. the virulence of each agent was mirrored by the pace and sever ...201121987780
vesicular stomatitis virus-based ebola vaccines with improved cross-protective efficacy.for ebola virus (ebov), 4 different species are known: zaire, sudan, côte d'ivoire, and reston ebolavirus. the newly discovered bundibugyo ebolavirus has been proposed as a 5th species. so far, no cross-neutralization among ebov species has been described, aggravating progress toward cross-species protective vaccines. with the use of recombinant vesicular stomatitis virus (rvsv)-based vaccines, guinea pigs could be protected against zaire ebolavirus (zebov) infection only when immunized with a v ...201121987743
Plasmid DNA production for therapeutic applications.Plasmid DNA (pDNA) is the base for promising DNA vaccines and gene therapies against many infectious, acquired, and genetic diseases, including HIV-AIDS, Ebola, Malaria, and different types of cancer, enteric pathogens, and influenza. Compared to conventional vaccines, DNA vaccines have many advantages such as high stability, not being infectious, focusing the immune response to only those antigens desired for immunization and long-term persistence of the vaccine protection. Especially in develo ...201222160904
ebola virus entry requires the cholesterol transporter niemann-pick c1.infections by the ebola and marburg filoviruses cause a rapidly fatal haemorrhagic fever in humans for which no approved antivirals are available. filovirus entry is mediated by the viral spike glycoprotein (gp), which attaches viral particles to the cell surface, delivers them to endosomes and catalyses fusion between viral and endosomal membranes. additional host factors in the endosomal compartment are probably required for viral membrane fusion; however, despite considerable efforts, these c ...201121866103
bimolecular complementation to visualize filovirus vp40-host complexes in live mammalian cells: toward the identification of budding inhibitors.virus-host interactions play key roles in promoting efficient egress of many rna viruses, including ebola virus (ebov or "e") and marburg virus (marv or "m"). late- (l-) domains conserved in viral matrix proteins recruit specific host proteins, such as tsg101 and nedd4, to facilitate the budding process. these interactions serve as attractive targets for the development of broad-spectrum budding inhibitors. a major gap still exists in our understanding of the mechanism of filovirus budding due t ...201122102845
rapid high yield production of different glycoforms of ebola virus monoclonal antibody.fc-glycosylation of monoclonal antibodies (mabs) has profound implications on the fc-mediated effector functions. alteration of this glycosylation may affect the efficiency of an antibody. however, difficulties in the production of mabs with homogeneous n-glycosylation profiles in sufficient amounts hamper investigations of the potential biological impact of different glycan residues.201122039433
A replicating cytomegalovirus-based vaccine encoding a single Ebola virus nucleoprotein CTL epitope confers protection against Ebola virus.Human outbreaks of Ebola virus (EBOV) are a serious human health concern in Central Africa. Great apes (gorillas/chimpanzees) are an important source of EBOV transmission to humans due to increased hunting of wildlife including the 'bush-meat' trade. Cytomegalovirus (CMV) is an highly immunogenic virus that has shown recent utility as a vaccine platform. CMV-based vaccines also have the unique potential to re-infect and disseminate through target populations regardless of prior CMV immunity, whi ...201121858240
evasion of the interferon-mediated antiviral response by filoviruses.the members of the filoviruses are recognized as some of the most lethal viruses affecting human and non-human primates. the only two genera of the filoviridae family, marburg virus (marv) and ebola virus (ebov), comprise the main etiologic agents of severe hemorrhagic fever outbreaks in central africa, with case fatality rates ranging from 25 to 90%. fatal outcomes have been associated with a late and dysregulated immune response to infection, very likely due to the virus targeting key host imm ...201021994610
BST2/Tetherin enhances entry of human cytomegalovirus.Interferon-induced BST2/Tetherin prevents budding of vpu-deficient HIV-1 by tethering mature viral particles to the plasma membrane. BST2 also inhibits release of other enveloped viruses including Ebola virus and Kaposi's sarcoma associated herpesvirus (KSHV), indicating that BST2 is a broadly acting antiviral host protein. Unexpectedly however, recovery of human cytomegalovirus (HCMV) from supernatants of BST2-expressing human fibroblasts was increased rather than decreased. Furthermore, BST2 s ...201122072961
Role of VP30 phosphorylation in the Ebola virus replication cycle.Ebola virus (EBOV) transcription is dependent on the phosphoprotein VP30, a component of the viral nucleocapsid. VP30 is phosphorylated at 2 serine residue clusters located at the N-terminal part of the protein. In this report, we have investigated the role of VP30 phosphorylation in EBOV replication using a reverse genetics approach. In effect, recombinant EBOVs with the VP30 serine clusters substituted either by nonphosphorylatable alanines or phosphorylation-mimicking aspartates were generate ...201121987772
drbp76 associates with ebola virus vp35 and suppresses viral polymerase function.the zaire ebola virus (ebov) protein vp35 is multifunctional; it inhibits ifn-α/β production and functions as a cofactor of the viral rna polymerase. mass spectrometry identified the double stranded rna binding protein 76 (drbp76/nfar-1/nf90) as a cellular factor that associates with the vp35 c-terminal interferon inhibitory domain (iid). drbp76 is described to regulate host cell protein synthesis and play an important role in host defense. the vp35-iid-drbp76 interaction required the addition o ...201121987769
inhibition of lassa virus and ebola virus infection in host cells treated with the kinase inhibitors genistein and tyrphostin.arenaviruses and filoviruses are capable of causing hemorrhagic fever syndrome in humans. limited therapeutic and/or prophylactic options are available for humans suffering from viral hemorrhagic fever. in this report, we demonstrate that pre-treatment of host cells with the kinase inhibitors genistein and tyrphostin ag1478 leads to inhibition of infection or transduction in cells infected with ebola virus, marburg virus, and lassa virus. in all, the results demonstrate that a kinase inhibitor c ...201121947546
Knockdown of Ebola virus VP24 impairs viral nucleocapsid assembly and prevents virus replication.The structural protein VP24 of Ebola virus (EBOV) is a determinant of virulence in rodent models and possesses an interferon antagonist function. In this study, we investigate the role of VP24 in EBOV replication using RNA interference by small interfering RNA to knock down the expression of this protein in virus-infected cells. We reveal that VP24 is required for assembly of viral nucleocapsids and that silencing of VP24 expression prevents the release of EBOV.201121987766
Crystal structure of swine major histocompatibility complex class I SLA-1 0401 and identification of 2009 pandemic swine-origin influenza A H1N1 virus cytotoxic T lymphocyte epitope peptides.The presentation of viral epitopes to cytotoxic T lymphocytes (CTLs) by swine leukocyte antigen class I (SLA I) is crucial for swine immunity. To illustrate the structural basis of swine CTL epitope presentation, the first SLA crystal structures, SLA-1 0401, complexed with peptides derived from either 2009 pandemic H1N1 (pH1N1) swine-origin influenza A virus (S-OIV(NW9); NSDTVGWSW) or Ebola virus (Ebola(AY9); ATAAATEAY) were determined in this study. The overall peptide-SLA-1 0401 structures res ...201121900158
protective efficacy of a bivalent recombinant vesicular stomatitis virus vaccine in the syrian hamster model of lethal ebola virus infection.outbreaks of filoviral hemorrhagic fever occur sporadically and unpredictably across wide regions in central africa and overlap with the occurrence of other infectious diseases of public health importance.201121987746
Robust production of virus-like particles and monoclonal antibodies with geminiviral replicon vectors in lettuce.Pharmaceutical protein production in plants has been greatly promoted by the development of viral-based vectors and transient expression systems. Tobacco and related Nicotiana species are currently the most common host plants for the generation of plant-made pharmaceutical proteins (PMPs). Downstream processing of target PMPs from these plants, however, is hindered by potential technical and regulatory difficulties owing to the presence of high levels of phenolics and toxic alkaloids. Here, we e ...201221883868
ebola reston virus infection of pigs: clinical significance and transmission potential.in 2008, reston ebolavirus (rebov) was isolated from pigs during a disease investigation in the philippines. porcine reproductive and respiratory syndrome virus (prrsv) and porcine circovirus type 2 (pcv-2) infections were also confirmed in affected herds and the contribution of rebov to the disease outbreak remains uncertain. we have conducted experimental challenge studies in 5-week-old pigs, with exposure of animals to 10(6) tcid(50) of a 2008 swine isolate of rebov via either the oronasal or ...201121987755
sensing carbohydrate-protein interactions at picomolar concentrations using cantilever arrays.carbohydrates are important mediators of many biological processes that underlie cellular communication and disease mechanisms. therapeutic agents include carbohydrate-based vaccines and the potent anti-viral protein cyanovirin-n (cv-n). cv-n acts by specifically binding the carbohydrate structures decorating the cell surface of deadly viruses including human immunodeficiency virus (hi-v) or ebola. in search for new carbohydrate-binding proteins and the development of sensors that exploit carboh ...201122022717
pathogenesis of marburg hemorrhagic fever in cynomolgus macaques.marburg virus (marv) infection causes a severe and often fatal hemorrhagic disease in primates; however, little is known about the development of marv hemorrhagic fever. in this study we evaluated the progression of marv infection in nonhuman primates.201121987738
Ebola virus glycoprotein needs an additional trigger, beyond proteolytic priming for membrane fusion.Ebolavirus belongs to the family filoviridae and causes severe hemorrhagic fever in humans with 50-90% lethality. Detailed understanding of how the viruses attach to and enter new host cells is critical to development of medical interventions. The virus displays a trimeric glycoprotein (GP(1,2)) on its surface that is solely responsible for membrane attachment, virus internalization and fusion. GP(1,2) is expressed as a single peptide and is cleaved by furin in the host cells to yield two disulp ...201122102923
Host response dynamics following lethal infection of rhesus macaques with Zaire ebolavirus.To gain further insight into the interdependent pathogenic processes in Ebola hemorrhagic fever (EHF), we have examined the dynamics of host responses in individual rhesus macaques infected with Zaire ebolavirus over the entire disease course. Examination of coagulation parameters revealed that decreased coagulation inhibitor activity triggered severe coagulopathy as indicated by prolonged coagulation times and decreased fibrinogen levels. This has been proposed as one of the significant mechani ...201121987781
Ebola virion attachment and entry into human macrophages profoundly effects early cellular gene expression.Zaire ebolavirus (ZEBOV) infections are associated with high lethality in primates. ZEBOV primarily targets mononuclear phagocytes, which are activated upon infection and secrete mediators believed to trigger initial stages of pathogenesis. The characterization of the responses of target cells to ZEBOV infection may therefore not only further understanding of pathogenesis but also suggest possible points of therapeutic intervention. Gene expression profiles of primary human macrophages exposed t ...201122028943
Ebola virus failure to stimulate plasmacytoid dendritic cell interferon responses correlates with impaired cellular entry.We examined the ability of the Ebola virus to elicit an antiviral response from plasmacytoid dendritic cells (pDCs). Exposure of pDCs to Ebola virus did not result in significantly higher levels of interferon-a production than the levels in mock-infected cells. After inoculation with Ebola virus under the same conditions, conventional dendritic cells expressed viral proteins whereas pDCs did not, suggesting that the latter cells were not infected. Assessment of the entry of Ebola virus-like part ...201121987778
Advances in virus-like particle vaccines for filoviruses.Ebola virus (EBOV) and Marburg virus (MARV) are among the deadliest human pathogens, with no vaccines or therapeutics available. Multiple vaccine platforms have been tested for efficacy as prophylactic pretreatments or therapeutics for prevention of filovirus hemorrhagic fever. Most successful vaccines are based on a virus-vectored approach expressing the protective glycoprotein (GP); protein-based subunit and DNA vaccines have been tested with moderate success. Virus-like particle (VLP) vaccine ...201121987741
impact of ebola mucin-like domain on antiglycoprotein antibody responses induced by ebola virus-like particles.ebola virus (ebov) glycoprotein (gp), responsible for mediating host-cell attachment and membrane fusion, contains a heavily glycosylated mucin-like domain hypothesized to shield gp from neutralizing antibodies. to test whether the mucin-like domain inhibits the production and function of anti-gp antibodies, we vaccinated mice with ebola virus-like particles (vlps) that express vesicular stomatitis virus g, wild-type ebov gp (ebgp), ebov gp without its mucin-like domain (δmucgp), or ebov gp with ...201121987758
simian hemorrhagic fever virus infection of rhesus macaques as a model of viral hemorrhagic fever: clinical characterization and risk factors for severe disease.simian hemorrhagic fever virus (shfv) has caused sporadic outbreaks of hemorrhagic fevers in macaques at primate research facilities. shfv is a bsl-2 pathogen that has not been linked to human disease; as such, investigation of shfv pathogenesis in non-human primates (nhps) could serve as a model for hemorrhagic fever viruses such as ebola, marburg, and lassa viruses. here we describe the pathogenesis of shfv in rhesus macaques inoculated with doses ranging from 50 pfu to 500,000 pfu. disease se ...201122014505
Small molecule inhibitors reveal Niemann-Pick C1 is essential for Ebola virus infection.Ebola virus (EboV) is a highly pathogenic enveloped virus that causes outbreaks of zoonotic infection in Africa. The clinical symptoms are manifestations of the massive production of pro-inflammatory cytokines in response to infection and in many outbreaks, mortality exceeds 75%. The unpredictable onset, ease of transmission, rapid progression of disease, high mortality and lack of effective vaccine or therapy have created a high level of public concern about EboV. Here we report the identificat ...201121866101
The importance of the NP: VP35 ratio in Ebola virus nucleocapsid formation.Ebola virus VP35 is a cofactor of the viral RNA polymerase complex and, together with NP and VP24, is an essential component for nucleocapsid formation. In the present study, we examined the interactions between VP35 and NP and found that VP35 interacts with helical NP-RNA complexes through the C-terminus of NP. We also found that coexpression of excess VP35 with NP reduced the yields of NP-RNA complexes purified by CsCl gradient ultracentrifugation and inhibited the formation of the NP-induced ...201121987764
One health: zoonoses in the exotic animal practice.Zoonoses make up approximately ¾ of today’s emerging infectious diseases; many of these zoonoses come from exotic pets and wildlife. Recent outbreaks in humans associated with nondomestic animals include Sudden Acute Respiratory Syndrome, Ebola virus, salmonellosis, and monkeypox. Expanding human populations, increased exotic pet ownership and changes in climate may contribute to increased incidence of zoonoses. Education and preventive medicine practices can be applied by veterinarians and othe ...201121872779
a nonreplicating subunit vaccine protects mice against lethal ebola virus challenge.ebola hemorrhagic fever is an acute and often deadly disease caused by ebola virus (ebov). the possible intentional use of this virus against human populations has led to design of vaccines that could be incorporated into a national stockpile for biological threat reduction. we have evaluated the immunogenicity and efficacy of an ebov vaccine candidate in which the viral surface glycoprotein is biomanufactured as a fusion to a monoclonal antibody that recognizes an epitope in glycoprotein, resul ...201122143779
the ebola virus glycoprotein and hiv-1 vpu employ different strategies to counteract the antiviral factor tetherin.the antiviral protein tetherin/bst2/cd317/hm1.24 restricts cellular egress of human immunodeficiency virus (hiv) and of particles mimicking the ebola virus (ebov), a hemorrhagic fever virus. the hiv-1 viral protein u (vpu) and the ebov-glycoprotein (ebov-gp) both inhibit tetherin. here, we compared tetherin counteraction by ebov-gp and vpu. we found that ebov-gp but not vpu counteracted tetherin from different primate species, indicating that ebov-gp and vpu target tetherin differentially. tethe ...201121987761
biophysical characterization and conformational stability of ebola and marburg virus-like particles.the filoviruses, ebola virus and marburg virus, cause severe hemorrhagic fever with up to 90% human mortality. virus-like particles of ebov (evlps) and marv (mvlps) are attractive vaccine candidates. for the development of stable vaccines, the conformational stability of these two enveloped vlps produced in insect cells was characterized by various spectroscopic techniques over a wide ph and temperature range. temperature-induced aggregation of the vlps at various ph values was monitored by ligh ...201121858822
sgp serves as a structural protein in ebola virus infection.sgp, which is perceived as nonstructural, secretory glycoprotein, shares 295 amino acids at its n-terminal with gp(1,2), which include the specific residue necessary to interact with gp(2). in the present study, we tested whether the sgp protein of zaire ebolavirus (zebov) could substitute for gp(1) and form a complex with gp(2), thus serving as a structural protein.201121987767
kunjin virus replicon-based vaccines expressing ebola virus glycoprotein gp protect the guinea pig against lethal ebola virus infection.pre- or postexposure treatments against the filoviral hemorrhagic fevers are currently not available for human use. we evaluated, in a guinea pig model, the immunogenic potential of kunjin virus (kun)-derived replicons as a vaccine candidate against ebola virus (ebov). virus like particles (vlps) containing kun replicons expressing ebov wild-type glycoprotein gp, membrane anchor-truncated gp (gp/ctr), and mutated gp (d637l) with enhanced shedding capacity were generated and assayed for their pro ...201121987742
Tumor biomarker glycoproteins in the seminal plasma of healthy human males are endogenous ligands for DC-SIGN.DC-SIGN is an immune C-type lectin that is expressed on both immature and mature dendritic cells associated with peripheral and lymphoid tissues in humans. It is a pattern recognition receptor that binds to several pathogens including HIV-1, Ebola virus, Mycobacterium tuberculosis, Candida albicans, Helicobacter pylori, and Schistosoma mansoni. Evidence is now mounting that DC-SIGN also recognizes endogenous glycoproteins, and that such interactions play a major role in maintaining immune homeo ...201121986992
The Ebola virus soluble glycoprotein (sGP) does not affect lymphocyte apoptosis and adhesion to activated endothelium.Ebola virus infection is associated with the release of a soluble glycoprotein (sGP) from infected cells. The sGP has been proposed to modulate Ebola virus pathogenesis in primates but little is known about the role of this protein during infection and disease manifestation. So far sGP has been shown to revert the effect of tumor necrosis factor a (TNF-a) on endothelial permeability, indicating that the function of sGP might be antiinflammatory. Since bystander apoptosis of lymphocytes has been ...201121987774
Comparative analysis of Ebola virus glycoprotein interactions with human and bat cells.Infection with Ebola virus (EBOV) causes hemorrhagic fever in humans with high case-fatality rates. The EBOV-glycoprotein (EBOV-GP) facilitates viral entry and promotes viral release from human cells. African fruit bats are believed not to develop disease upon EBOV infection and have been proposed as a natural reservoir of EBOV. We compared EBOV-GP interactions with human cells and cells from African fruit bats. We found that susceptibility to EBOV-GP-dependent infection was not limited to bat c ...201121987760
Displaying items 1101 - 1200 of 7763