Publications
| Title | Abstract | Year Filter | PMID(sorted ascending) Filter |
|---|
| whole-genome expression profiling reveals that inhibition of host innate immune response pathways by ebola virus can be reversed by a single amino acid change in the vp35 protein. | ebola hemorrhagic fever is a rapidly progressing acute febrile illness characterized by high virus replication, severe immunosuppression, and case fatalities of ca. 80%. inhibition of phosphorylation of interferon regulatory factor 3 (irf-3) by the ebola vp35 protein may block the host innate immune response and play an important role in the severity of disease. we used two precisely defined reverse genetics-generated ebola viruses to investigate global host cell responses resulting from the inh ... | 2008 | 18353943 |
| recombinant vesicular stomatitis virus vector mediates postexposure protection against sudan ebola hemorrhagic fever in nonhuman primates. | recombinant vesicular stomatitis virus (vsv) vectors expressing homologous filoviral glycoproteins can completely protect rhesus monkeys against marburg virus when administered after exposure and can partially protect macaques after challenge with zaire ebolavirus. here, we administered a vsv vector expressing the sudan ebolavirus (sebov) glycoprotein to four rhesus macaques shortly after exposure to sebov. all four animals survived sebov challenge, while a control animal that received a nonspec ... | 2008 | 18385248 |
| a filovirus-unique region of ebola virus nucleoprotein confers aberrant migration and mediates its incorporation into virions. | the ebola virus nucleoprotein (np) is an essential component of the nucleocapsid, required for filovirus particle formation and replication. together with virion protein 35 (vp35) and vp24, this gene product gives rise to the filamentous nucleocapsid within transfected cells. ebola virus np migrates aberrantly, with an apparent molecular mass of 115 kda, although it is predicted to encode an approximately 85-kda protein. in this report, we show that two domains of this protein determine this abe ... | 2008 | 18417588 |
| rapid bio-barcode assay for multiplex dna detection based on capillary dna analyzer. | the detection of virus at low copy number is important for clinical diagnosis. in this study, a rapid bio-barcode assay was developed and it could detect short sequences of four types of virus dna simultaneously at the concentration as low as 5p mol/l in 40 min with capillary 3730 dna analyzer. the background of the assay using high salt concentration prepared nanogold particle probes was five times less than that of the assay using conventionally prepared probes. with further optimization, the ... | 2008 | 18440653 |
| cell adhesion promotes ebola virus envelope glycoprotein-mediated binding and infection. | ebola virus infects a wide variety of adherent cell types, while nonadherent cells are found to be refractory. to explore this correlation, we compared the ability of pairs of related adherent and nonadherent cells to bind a recombinant ebola virus receptor binding domain (ebov rbd) and to be infected with ebola virus glycoprotein (gp)-pseudotyped particles. both human 293f and thp-1 cells can be propagated as adherent or nonadherent cultures, and in both cases adherent cells were found to be si ... | 2008 | 18448524 |
| the 1995 kikwit ebola outbreak--model of virus properties on system capacity and function: a lesson for future viral epidemics. | the 1995 kikwit ebola outbreak in the democratic republic of the congo is one of the first ebola outbreaks to be treated in a hospital setting and is one of the most well-studied ebola epidemics to have occurred to date. many of the lessons learned from identifying, containing, and treating the epidemic are applicable to future viral outbreaks. this article looks at the characteristics of the ebola virus and health system issues, which affected the healthcare providers' ability to contain and tr ... | 2007 | 18491842 |
| managing potential laboratory exposure to ebola virus by using a patient biocontainment care unit. | in 2004, a scientist from the us army medical research institute of infectious diseases (usamriid) was potentially exposed to a mouse-adapted variant of the zaire species of ebola virus. the circumstances surrounding the case are presented, in addition to an update on historical admissions to the medical containment suite at usamriid. research facilities contemplating work with pathogens requiring biosafety level 4 laboratory precautions should be mindful of the occupational health issues highli ... | 2008 | 18507897 |
| potent in vitro activity of the albumin fusion type 1 interferons (albumin-interferon-alpha and albumin-interferon-beta) against rna viral agents of bioterrorism and the severe acute respiratory syndrome (sars) virus. | the type 1 interferons (inf-alpha and inf-beta) are potent antiviral agents. albumin-inf-alpha and albumin-inf-beta are novel recombinant proteins consisting of ifn-alpha or ifn-beta genetically fused to human albumin. | 2008 | 18560223 |
| a paramyxovirus-vectored intranasal vaccine against ebola virus is immunogenic in vector-immune animals. | ebola virus (ebov) causes outbreaks of a highly lethal hemorrhagic fever in humans. the virus can be transmitted by direct contact as well as by aerosol and is considered a potential bioweapon. because direct immunization of the respiratory tract should be particularly effective against infection of mucosal surfaces, we previously developed an intranasal vaccine based on replication-competent human parainfluenza virus type 3 (hpiv3) expressing ebov glycoprotein gp (hpiv3/ebogp) and showed that i ... | 2008 | 18570964 |
| action needed to prevent extinctions caused by disease. | 2008 | 18615062 | |
| structure of the ebola virus glycoprotein bound to an antibody from a human survivor. | ebola virus (ebov) entry requires the surface glycoprotein (gp) to initiate attachment and fusion of viral and host membranes. here we report the crystal structure of ebov gp in its trimeric, pre-fusion conformation (gp1+gp2) bound to a neutralizing antibody, kz52, derived from a human survivor of the 1995 kikwit outbreak. three gp1 viral attachment subunits assemble to form a chalice, cradled by the gp2 fusion subunits, while a novel glycan cap and projected mucin-like domain restrict access to ... | 2008 | 18615077 |
| ebola images emerge from the cave. | ebola virus causes a lethal hemorrhagic disease for which no therapy or vaccine is currently approved. recently, the crystal structure of the ebola virus glycoprotein in complex with a human neutralizing antibody was illuminated, providing a path from the shadows toward understanding cellular attachment, viral fusion, and immune evasion. | 2008 | 18692765 |
| sensitive and selective viral dna detection assay via microbead-based rolling circle amplification. | we report a sensitive and efficient magnetic bead-based assay for viral dna identification using isothermal amplification of a reporting probe. | 2008 | 18694640 |
| phosphoinositide-3 kinase-akt pathway controls cellular entry of ebola virus. | the phosphoinositide-3 kinase (pi3k) pathway regulates diverse cellular activities related to cell growth, migration, survival, and vesicular trafficking. it is known that ebola virus requires endocytosis to establish an infection. however, the cellular signals that mediate this uptake were unknown for ebola virus as well as many other viruses. here, the involvement of pi3k in ebola virus entry was studied. a novel and critical role of the pi3k signaling pathway was demonstrated in cell entry of ... | 2008 | 18769720 |
| role of ebola virus vp30 in transcription reinitiation. | vp30 is a phosphoprotein essential for the initiation of ebola virus transcription. in this work, we have studied the effect of mutations in vp30 phosphorylation sites on the ebolavirus replication cycle by using a reverse genetics system. we demonstrate that vp30 is involved in reinitiation of gene transcription and that this activity is affected by mutations at the phosphorylation sites. | 2008 | 18829754 |
| biodistribution and toxicological safety of adenovirus type 5 and type 35 vectored vaccines against human immunodeficiency virus-1 (hiv-1), ebola, or marburg are similar despite differing adenovirus serotype vector, manufacturer's construct, or gene inserts. | the vaccine research center has developed vaccine candidates for different diseases/infectious agents (including hiv-1, ebola, and marburg viruses) built on an adenovirus vector platform, based on adenovirus type 5 or 35. to support clinical development of each vaccine candidate, pre-clinical studies were performed in rabbits to determine where in the body they biodistribute and how rapidly they clear, and to screen for potential toxicities (intrinsic and immunotoxicities). the vaccines biodistr ... | 2008 | 18830892 |
| vesicular stomatitis virus-based vaccines protect nonhuman primates against aerosol challenge with ebola and marburg viruses. | considerable progress has been made over the last decade in developing candidate preventive vaccines that can protect nonhuman primates against ebola and marburg viruses. a vaccine based on recombinant vesicular stomatitis virus (vsv) seems to be particularly robust as it can also confer protection when administered as a postexposure treatment. while filoviruses are not thought to be transmitted by aerosol in nature the inhalation route is among the most likely portals of entry in the setting of ... | 2008 | 18930776 |
| nasal delivery of an adenovirus-based vaccine bypasses pre-existing immunity to the vaccine carrier and improves the immune response in mice. | pre-existing immunity to human adenovirus serotype 5 (ad5) is common in the general population. bypassing pre-existing immunity could maximize ad5 vaccine efficacy. vaccination by the intramuscular (i.m.), nasal (i.n.) or oral (p.o.) route with ad5 expressing ebola zaire glycoprotein (ad5-zgp) fully protected naïve mice against lethal challenge with ebola. in the presence of pre-existing immunity, only mice vaccinated i.n. survived. the frequency of ifn-gamma+ cd8+ t cells was reduced by 80% and ... | 2008 | 18958172 |
| detection of viral rna from paraffin-embedded tissues after prolonged formalin fixation. | isolating amplifiable rna from formalin-fixed, paraffin-embedded (ffpe) tissues is more difficult than isolating dna because of rnases, chemical modification of the rna, and cross-linking of nucleic acids and proteins. tissues containing infectious disease agents that require biosafety level (bsl)-3 and -4 necessitate fixation times of 21 and 30 days, respectively. | 2009 | 18977691 |
| stimulation of ebola virus production from persistent infection through activation of the ras/mapk pathway. | human infections with ebola virus (ebov) result in a deadly viral disease known as ebola hemorrhagic fever. up to 90% of infected patients die, and there is no available treatment or vaccine. the sporadic human outbreaks are believed to result when ebov "jumps" from an infected animal to a person and is subsequently transmitted between persons by direct contact with infected blood or body fluids. this study was undertaken to investigate the mechanism by which ebov can persistently infect and the ... | 2008 | 18981410 |
| protection against lethal challenge by ebola virus-like particles produced in insect cells. | ebola virus-like particles (vlps) were produced in insect cells using a recombinant baculovirus expression system and their efficacy for protection against ebola virus infection was investigated. two immunizations with 50 microg ebola vlps (high dose) induced a high level of antibodies against ebola gp that exhibited strong neutralizing activity against gp-mediated virus infection and conferred complete protection of vaccinated mice against lethal challenge by a high dose of mouse-adapted ebola ... | 2009 | 18986663 |
| requirements for cell rounding and surface protein down-regulation by ebola virus glycoprotein. | ebola virus causes an acute hemorrhagic fever that is associated with high morbidity and mortality. the viral glycoprotein is thought to contribute to pathogenesis, though precise mechanisms are unknown. cellular pathogenesis can be modeled in vitro by expression of the ebola viral glycoprotein (gp) in cells, which causes dramatic morphological changes, including cell rounding and surface protein down-regulation. these effects are known to be dependent on the presence of a highly glycosylated re ... | 2009 | 19013626 |
| newly discovered ebola virus associated with hemorrhagic fever outbreak in uganda. | over the past 30 years, zaire and sudan ebolaviruses have been responsible for large hemorrhagic fever (hf) outbreaks with case fatalities ranging from 53% to 90%, while a third species, côte d'ivoire ebolavirus, caused a single non-fatal hf case. in november 2007, hf cases were reported in bundibugyo district, western uganda. laboratory investigation of the initial 29 suspect-case blood specimens by classic methods (antigen capture, igm and igg elisa) and a recently developed random-primed pyro ... | 2008 | 19023410 |
| the ebola virus ribonucleoprotein complex: a novel vp30-l interaction identified. | the ribonucleoprotein (rnp) complex of ebola virus (ebov) is known to be a multiprotein/rna structure, however, knowledge is rather limited regarding the actual protein-protein interactions involved in its formation. here we show that singularly expressed vp35 and vp30 are present throughout the cytoplasm, while np forms prominent cytoplasmic inclusions and l forms smaller perinuclear inclusions. we could demonstrate the existence of np-vp35, np-vp30 and vp35-l interactions, similar to those des ... | 2009 | 19041915 |
| vesicular stomatitis virus-based ebola vaccine is well-tolerated and protects immunocompromised nonhuman primates. | ebola virus (ebov) is a significant human pathogen that presents a public health concern as an emerging/re-emerging virus and as a potential biological weapon. substantial progress has been made over the last decade in developing candidate preventive vaccines that can protect nonhuman primates against ebov. among these prospects, a vaccine based on recombinant vesicular stomatitis virus (vsv) is particularly robust, as it can also confer protection when administered as a postexposure treatment. ... | 2008 | 19043556 |
| the pathogen receptor liver and lymph node sinusoidal endotelial cell c-type lectin is expressed in human kupffer cells and regulated by pu.1. | human lsectin (liver and lymph node sinusoidal endothelial cell c-type lectin, clec4g) is a c-type lectin encoded within the l-sign/dc-sign/cd23 gene cluster. lsectin acts as a pathogen attachment factor for ebolavirus and the sars coronavirus, and its expression can be induced by interleukin-4 on monocytes and macrophages. although reported as a liver and lymph node sinusoidal endothelial cell-specific molecule, lsectin could be detected in the mutz-3 dendritic-like cell line at the messenger r ... | 2009 | 19111020 |
| structure of the ebola vp35 interferon inhibitory domain. | ebola viruses (ebovs) cause rare but highly fatal outbreaks of viral hemorrhagic fever in humans, and approved treatments for these infections are currently lacking. the ebola vp35 protein is multifunctional, acting as a component of the viral rna polymerase complex, a viral assembly factor, and an inhibitor of host interferon (ifn) production. mutation of select basic residues within the c-terminal half of vp35 abrogates its dsrna-binding activity, impairs vp35-mediated ifn antagonism, and atte ... | 2009 | 19122151 |
| disease modeling for ebola and marburg viruses. | the filoviruses ebola and marburg are zoonotic agents that are classified as both biosafety level 4 and category a list pathogens. these viruses are pathogenic in humans and cause isolated infections or epidemics of viral hemorrhagic fever, mainly in central africa. their natural reservoir has not been definitely identified, but certain species of african bat have been associated with ebola and marburg infections. currently, there are no licensed options available for either treatment or prophyl ... | 2009 | 19132113 |
| the primed ebolavirus glycoprotein (19-kilodalton gp1,2): sequence and residues critical for host cell binding. | entry of ebolavirus (ebov) into cells is mediated by its glycoprotein (gp(1,2)), a class i fusion protein whose structure was recently determined (j. e. lee et al., nature 454:177-182, 2008). here we confirmed two major predictions of the structural analysis, namely, the residues in gp(1) and gp(2) that remain after gp(1,2) is proteolytically primed by endosomal cathepsins for fusion and residues in gp(1) that are critical for binding to host cells. mass spectroscopic analysis indicated that pri ... | 2009 | 19144707 |
| ebola virus protein vp35 impairs the function of interferon regulatory factor-activating kinases ikkepsilon and tbk-1. | the ebola virus (ebov) vp35 protein antagonizes the early antiviral alpha/beta interferon (ifn-alpha/beta) response. we previously demonstrated that vp35 inhibits the virus-induced activation of the ifn-beta promoter by blocking the phosphorylation of ifn-regulatory factor 3 (irf-3), a transcription factor that is crucial for the induction of ifn-alpha/beta expression. furthermore, vp35 blocks ifn-beta promoter activation induced by any of several components of the retinoic acid-inducible gene i ... | 2009 | 19153231 |
| ebola outbreak has experts rooting for answers. | 2009 | 19158753 | |
| emerging infectious diseases. scientists puzzle over ebola-reston virus in pigs. | 2009 | 19164717 | |
| tetherin-mediated restriction of filovirus budding is antagonized by the ebola glycoprotein. | mammalian cells employ numerous innate cellular mechanisms to inhibit viral replication and spread. tetherin, also known as bst-2 or cd317, is a recently identified, ifn-induced, cellular response factor that blocks release of hiv-1 and other retroviruses from infected cells. the means by which tetherin retains retroviruses on the cell surface, as well as the mechanism used by the hiv-1 accessory protein vpu to antagonize tetherin function and promote hiv-1 release, are unknown. here, we documen ... | 2009 | 19179289 |
| expression, purification, crystallization and preliminary x-ray studies of the ebola vp35 interferon inhibitory domain. | ebola vp35 is a multifunctional protein that is important for host immune suppression and pathogenesis. vp35 contains an n-terminal oligomerization domain and a c-terminal interferon inhibitory domain (iid). mutations within the vp35 iid result in loss of host immune suppression. here, efforts to crystallize recombinantly overexpressed vp35 iid that was purified from escherichia coli are described. native and selenomethionine-labeled crystals belonging to the orthorhombic space group p2(1)2(1)2( ... | 2009 | 19194011 |
| replication-deficient ebolavirus as a vaccine candidate. | ebolavirus causes severe hemorrhagic fever, with case fatality rates as high as 90%. currently, no licensed vaccine is available against ebolavirus. we previously generated a replication-deficient, biologically contained ebolavirus, eboladeltavp30, which lacks the essential vp30 gene, grows only in cells stably expressing this gene product, and is genetically stable. here, we evaluated the vaccine potential of eboladeltavp30. first, we demonstrated its safety in stat-1-knockout mice, a susceptib ... | 2009 | 19211761 |
| ebola reston virus detected pigs in the philippines. | 2009 | 19215709 | |
| chemical modifications of antisense morpholino oligomers enhance their efficacy against ebola virus infection. | phosphorodiamidate morpholino oligomers (pmos) are uncharged nucleic acid-like molecules designed to inactivate the expression of specific genes via the antisense-based steric hindrance of mrna translation. pmos have been successful at knocking out viral gene expression and replication in the case of acute viral infections in animal models and have been well tolerated in human clinical trials. we propose that antisense pmos represent a promising class of therapeutic agents that may be useful for ... | 2009 | 19223614 |
| the marburg virus 3' noncoding region structurally and functionally differs from that of ebola virus. | we have previously shown that the first transcription start signal (tss) of zaire ebola virus (zebov) is involved in formation of an rna secondary structure regulating vp30-dependent transcription activation. interestingly, transcription of marburg virus (marv) minigenomes occurs independently of vp30. in this study, we analyzed the structure of the marv 3' noncoding region and its influence on vp30 necessity. secondary structure formation of the tss of the first gene was experimentally determin ... | 2009 | 19225002 |
| drug targets in infections with ebola and marburg viruses. | the development of antiviral drugs for ebola and marburg viruses has been slow. to date, beyond supportive care, no effective treatments, prophylactic measures, therapies, or vaccines are approved to treat or prevent filovirus infections. in this review, we examine the current treatments available to administer care for filovirus infection, the potential therapeutic targets that can be used for filovirus drug development, and the various drug targeting techniques used against filoviruses. | 2009 | 19275706 |
| human ebola outbreak resulting from direct exposure to fruit bats in luebo, democratic republic of congo, 2007. | twelve years after the kikwit ebola outbreak in 1995, ebola virus reemerged in the occidental kasaï province of the democratic republic of congo (drc) between may and november 2007, affecting more than 260 humans and causing 186 deaths. during this latter outbreak we conducted several epidemiological investigations to identify the underlying ecological conditions and animal sources. qualitative social and environmental data were collected through interviews with villagers and by direct observati ... | 2009 | 19323614 |
| development and characterization of a mouse model for marburg hemorrhagic fever. | the lack of a mouse model has hampered an understanding of the pathogenesis and immunity of marburg hemorrhagic fever (mhf), the disease caused by marburgvirus (marv), and has created a bottleneck in the development of antiviral therapeutics. primary isolates of the filoviruses, i.e., ebolavirus (ebov) and marv, are not lethal to immunocompetent adult mice. previously, pathological, virologic, and immunologic evaluation of a mouse-adapted ebov, developed by sequential passages in suckling mice, ... | 2009 | 19369350 |
| applications of high-throughput genomics to antiviral research: evasion of antiviral responses and activation of inflammation during fulminant rna virus infection. | host responses can contribute to the severity of viral infection, through the failure of innate antiviral mechanisms to recognize and restrict the pathogen, the development of intense systemic inflammation leading to circulatory failure or through tissue injury resulting from overly exuberant cell-mediated immune responses. high-throughput genomics methods are now being used to identify the biochemical pathways underlying ineffective or damaging host responses in a number of acute and chronic vi ... | 2009 | 19375457 |
| single-injection vaccine protects nonhuman primates against infection with marburg virus and three species of ebola virus. | the filoviruses marburg virus and ebola virus cause severe hemorrhagic fever with high mortality in humans and nonhuman primates. among the most promising filovirus vaccines under development is a system based on recombinant vesicular stomatitis virus (vsv) that expresses a single filovirus glycoprotein (gp) in place of the vsv glycoprotein (g). here, we performed a proof-of-concept study in order to determine the potential of having one single-injection vaccine capable of protecting nonhuman pr ... | 2009 | 19386702 |
| enhanced protection against ebola virus mediated by an improved adenovirus-based vaccine. | the ebola virus is transmitted by direct contact with bodily fluids of infected individuals, eliciting death rates as high as 90% among infected humans. currently, replication defective adenovirus-based ebola vaccine is being studied in a phase i clinical trial. another ebola vaccine, based on an attenuated vesicular stomatitis virus has shown efficacy in post-exposure treatment of nonhuman primates to ebola infection. in this report, we modified the common recombinant adenovirus serotype 5-base ... | 2009 | 19390586 |
| ebolavirus vp35 interacts with the cytoplasmic dynein light chain 8. | the viral protein vp35 of ebolavirus (ebov) is implicated to have diverse roles in the viral life cycle. we employed a yeast two-hybrid screen to search for vp35 binding partners and identified the cytoplasmic dynein light chain (dlc8) as a protein that interacts with vp35. mapping analysis unraveled a consensus motif, sqtqt, within vp35 through which vp35 binds to dlc8. the disruption of dlc8 binding does not affect the ability of vp35 to inhibit type i ifn production. given that vp35 from vari ... | 2009 | 19403681 |
| alpha5beta1-integrin controls ebolavirus entry by regulating endosomal cathepsins. | integrins are involved in the binding and internalization of both enveloped and nonenveloped viruses. by using 3 distinct cell systems-cho cells lacking expression of alpha(5)beta(1)-integrin, hela cells treated with sirna to alpha(5)-integrin, and mouse beta(1)-integrin knockout fibroblasts, we show that alpha(5)beta(1)-integrin is required for efficient infection by pseudovirions bearing the ebolavirus glycoprotein (gp). these integrins are necessary for viral entry but not for binding or inte ... | 2009 | 19416892 |
| generation of vero cells expressing ebola virus glycoprotein. | to establish replication-incompetent ebola virus (ebov) lacking its glycoprotein (gp), we attempted to generate a vero cell line that constitutively expressed gp. we used a retroviral vector to transduce vero cells with the ebov gp gene, resulting in a high expression level of gp on the cell surface. the vero cells expressing ebov gp complemented the replication cycle of vesicular stomatitis virus, which lacks the essential viral glycoprotein. this cell line might be useful for basic research on ... | 2009 | 19420858 |
| mucosal immunization of cynomolgus macaques with the vsvdeltag/zebovgp vaccine stimulates strong ebola gp-specific immune responses. | zaire ebolavirus (zebov) produces a lethal viral hemorrhagic fever in humans and non-human primates. | 2009 | 19440245 |
| non-infectious plasmid engineered to simulate multiple viral threat agents. | the aim of this study was to design and construct a non-virulent simulant to replace several pathogenic viruses in the development of detection and identification methods in biodefense. a non-infectious simulant was designed and engineered to include the nucleic acid signature of veev (venezuelan equine encephalitis virus), influenza virus, rift valley fever virus, machupo virus, lassa virus, yellow fever virus, ebola virus, eastern equine encephalitis virus, junin virus, marburg virus, dengue v ... | 2009 | 19442841 |
| fold prediction of vp24 protein of ebola and marburg viruses using de novo fragment assembly. | virus particle 24 (vp24) is the smallest protein of the ebola and marburg virus genomes. recent experiments show that ebola vp24 blocks binding of tyrosine-phosphorylated stat-1 homodimer (py-stat1) to the npi-1 subfamily of importin alpha, thereby preventing nuclear accumulation of this interferon-promoting transcription factor which, in turn, reduces the innate immune response of the host target. lacking an experimental structure for vp24, we applied de novo protein structure prediction using ... | 2009 | 19447180 |
| characterization of ebolavirus regulatory genomic regions. | for filoviruses, such as ebolavirus and the closely related marburgvirus, transcriptional regulation is poorly understood. the open reading frames (orfs) that encode the viral proteins are separated by regulatory regions composed of the 3' nontranslated region (ntr) of the upstream gene, highly conserved transcription stop and start signals, and the 5'ntr of the downstream gene. the conserved transcription stop and start signals either overlap, or they are separated by intergenic regions (igrs) ... | 2009 | 19481829 |
| expression of ebolavirus glycoprotein on the target cells enhances viral entry. | entry of ebolavirus to the target cells is mediated by the viral glycoprotein gp. the native gp exists as a homotrimer on the virions and contains two subunits, a surface subunit (gp1) that is involved in receptor binding and a transmembrane subunit (gp2) that mediates the virus-host membrane fusion. previously we showed that over-expression of gp on the target cells blocks gp-mediated viral entry, which is mostly likely due to receptor interference by gp1. | 2009 | 19505320 |
| ebola virus vp35 antagonizes pkr activity through its c-terminal interferon inhibitory domain. | ebola virus vp35 contains a c-terminal cluster of basic amino acids required for double-stranded rna (dsrna) binding and inhibition of interferon regulatory factor 3 (irf3). vp35 also blocks protein kinase r (pkr) activation; however, the responsible domain has remained undefined. here we show that the irf inhibitory domain of vp35 mediates the inhibition of pkr and enhances the synthesis of coexpressed proteins. in contrast to dsrna binding and irf inhibition, alanine substitutions of at least ... | 2009 | 19515768 |
| development of a broad-spectrum antiviral with activity against ebola virus. | we report herein the identification of a small molecule therapeutic, fgi-106, which displays potent and broad-spectrum inhibition of lethal viral hemorrhagic fevers pathogens, including ebola, rift valley and dengue fever viruses, in cell-based assays. using mouse models of ebola virus, we further demonstrate that fgi-106 can protect animals from an otherwise lethal infection when used either in a prophylactic or therapeutic setting. a single treatment, administered 1 day after infection, is suf ... | 2009 | 19523489 |
| ebola zaire virus blocks type i interferon production by exploiting the host sumo modification machinery. | ebola zaire virus is highly pathogenic for humans, with case fatality rates approaching 90% in large outbreaks in africa. the virus replicates in macrophages and dendritic cells (dcs), suppressing production of type i interferons (ifns) while inducing the release of large quantities of proinflammatory cytokines. although the viral vp35 protein has been shown to inhibit ifn responses, the mechanism by which it blocks ifn production has not been fully elucidated. we expressed vp35 from a mouse-ada ... | 2009 | 19557165 |
| neutralizing ebolavirus: structural insights into the envelope glycoprotein and antibodies targeted against it. | the ebolavirus (ebov) envelope glycoprotein (gp) is solely responsible for viral attachment to, fusion with, and entry of new host cells, and consequently is a major target of vaccine design efforts. recently determined crystal structures of key antibodies in complex with their ebov epitopes have provided insights into the molecular architecture of gp and defined likely hotspots for viral neutralization. in this review, we discuss the structural basis for antibody-mediated neutralization of ebol ... | 2009 | 19559599 |
| multifunctional nanoarchitectures from dna-based abc monomers. | the ability to attach different functional moieties to a molecular building block could lead to applications in nanoelectronics, nanophotonics, intelligent sensing and drug delivery. the building unit needs to be both multivalent and anisotropic, and although many anisotropic building blocks have been created, these have not been universally applicable. recently, dna has been used to generate various nanostructures or hybrid systems, and as a generic building block for various applications. here ... | 2009 | 19581895 |
| ebolavirus glycoprotein gp masks both its own epitopes and the presence of cellular surface proteins. | ebolavirus (ebov) is the etiological agent of a severe hemorrhagic fever with a high mortality rate. the spike glycoprotein (gp) is believed to be one of the major determinants of virus pathogenicity. in this study, we demonstrated the molecular mechanism responsible for the downregulation of surface markers caused by ebov gp expression. we showed that expression of mature gp on the plasma membrane results in the masking of cellular surface proteins, including major histocompatibility complex cl ... | 2009 | 19587051 |
| discovery of swine as a host for the reston ebolavirus. | since the discovery of the marburg and ebola species of filovirus, seemingly random, sporadic fatal outbreaks of disease in humans and nonhuman primates have given impetus to identification of host tropisms and potential reservoirs. domestic swine in the philippines, experiencing unusually severe outbreaks of porcine reproductive and respiratory disease syndrome, have now been discovered to host reston ebolavirus (rebov). although rebov is the only member of filoviridae that has not been associa ... | 2009 | 19590002 |
| rho gtpases modulate entry of ebola virus and vesicular stomatitis virus pseudotyped vectors. | to explore mechanisms of entry for ebola virus (ebov) glycoprotein (gp) pseudotyped virions, we used comparative gene analysis to identify genes whose expression correlated with viral transduction. candidate genes were identified by using ebov gp pseudotyped virions to transduce human tumor cell lines that had previously been characterized by cdna microarray. transduction profiles for each of these cell lines were generated, and a significant positive correlation was observed between rhoc expres ... | 2009 | 19625394 |
| rig-i activation inhibits ebolavirus replication. | hemorrhagic fever viruses are associated with rapidly progressing severe disease with high case fatality, making them of public health and biothreat importance. effective antivirals are not available for most of the members of this diverse group of viruses. a broad spectrum strategy for antiviral development would be very advantageous. perhaps the most challenging target would be the highly immunosuppressive filoviruses, ebolavirus and marburgvirus, associated with aerosol infectivity and case f ... | 2009 | 19628240 |
| reduced levels of protein tyrosine phosphatase cd45 protect mice from the lethal effects of ebola virus infection. | ebola virus (ebov) infection of humans is a lethal but accidental dead-end event. understanding resistance to ebov in other species may help establish the basis of susceptibility differences among its hosts. although rodents are resistant to ebov, a murine-adapted variant is lethal when injected intraperitoneally into mice. we find that mice expressing reduced levels of the tyrosine phosphatase cd45 are protected against ebov, whereas wild-type, cd45-deficient, or enzymatically inactive cd45-exp ... | 2009 | 19683682 |
| evasion of interferon responses by ebola and marburg viruses. | the filoviruses, ebola virus (ebov) and marburg virus (marv), cause frequently lethal viral hemorrhagic fever. these infections induce potent cytokine production, yet these host responses fail to prevent systemic virus replication. consistent with this, filoviruses have been found to encode proteins vp35 and vp24 that block host interferon (ifn)-alpha/beta production and inhibit signaling downstream of the ifn-alpha/beta and the ifn-gamma receptors, respectively. vp35, which is a component of th ... | 2009 | 19694547 |
| swine ebola. | 2009 | 19708514 | |
| american chemical society fall meeting, 16-20 august, washington, d.c. sugary achilles' heel raises hope for broad-acting antiviral drugs. | 2009 | 19729635 | |
| zaire ebola virus entry into human dendritic cells is insensitive to cathepsin l inhibition. | cathepsins b and l contribute to ebola virus (ebov) entry into vero cells and mouse embryonic fibroblasts. however, the role of cathepsins in ebov-infection of human dendritic cells (dcs), important targets of infection in vivo, remains undefined. here, ebov-like particles containing a beta-lactamase-vp40 fusion reporter and ebola virus were used to demonstrate the cathepsin dependence of ebov entry into human monocyte-derived dcs. however, while dc infection is blocked by cathepsin b inhibitor, ... | 2010 | 19775255 |
| large serological survey showing cocirculation of ebola and marburg viruses in gabonese bat populations, and a high seroprevalence of both viruses in rousettus aegyptiacus. | ebola and marburg viruses cause highly lethal hemorrhagic fevers in humans. recently, bats of multiple species have been identified as possible natural hosts of zaire ebolavirus (zebov) in gabon and republic of congo, and also of marburgvirus (marv) in gabon and democratic republic of congo. | 2009 | 19785757 |
| the vp35 protein of ebola virus impairs dendritic cell maturation induced by virus and lipopolysaccharide. | ebola virus causes rapidly progressive haemorrhagic fever, which is associated with severe immuosuppression. in infected dendritic cells (dcs), ebola virus replicates efficiently and inhibits dc maturation without inducing cytokine expression, leading to impaired t-cell proliferation. however, the underlying mechanism remains unclear. in this study, we report that ebola virus vp35 impairs the maturation of mouse dcs. when expressed in mouse immature dcs, ebola virus vp35 prevents virus-stimulate ... | 2010 | 19828757 |
| interaction between ebola virus glycoprotein and host toll-like receptor 4 leads to induction of proinflammatory cytokines and socs1. | ebola virus initially targets monocytes and macrophages, which can lead to the release of proinflammatory cytokines and chemokines. these inflammatory cytokines are thought to contribute to the development of circulatory shock seen in fatal ebola virus infections. here we report that host toll-like receptor 4 (tlr4) is a sensor for ebola virus glycoprotein (gp) on virus-like particles (vlps) and that resultant tlr4 signaling pathways lead to the production of proinflammatory cytokines and suppre ... | 2010 | 19846529 |
| a forward genetic strategy reveals destabilizing mutations in the ebolavirus glycoprotein that alter its protease dependence during cell entry. | ebolavirus (ebov) entry into cells requires proteolytic disassembly of the viral glycoprotein, gp. this proteolytic processing, unusually extensive for an enveloped virus entry protein, is mediated by cysteine cathepsins, a family of endosomal/lysosomal proteases. previous work has shown that cleavage of gp by cathepsin b (catb) is specifically required to generate a critical entry intermediate. the functions of this intermediate are not well understood. we used a forward genetic strategy to inv ... | 2010 | 19846533 |
| an enzymatic virus-like particle assay for sensitive detection of virus entry. | a viral entry assay where a beta-lactamase reporter protein fused to the influenza matrix protein-1 (blam1) is packaged as a structural component into influenza virus-like particles (vlps) is described. the bla reporter is released upon fusion with target cells and can be detected in live cells by flow cytometry, microscopy, or fluorometric plate reader for utility in high-throughput screening approaches. the production of blam1 vlps and subsequent transfer of bla activity to target cells requir ... | 2010 | 19879300 |
| tetherin inhibits hiv-1 release by directly tethering virions to cells. | tetherin is an interferon-induced protein whose expression blocks the release of hiv-1 and other enveloped viral particles. the underlying mechanism by which tetherin functions and whether it directly or indirectly causes virion retention are unknown. here, we elucidate the mechanism by which tetherin exerts its antiviral activity. we demonstrate, through mutational analyses and domain replacement experiments, that tetherin configuration rather than primary sequence is critical for antiviral act ... | 2009 | 19879838 |
| ebolavirus vp24 binding to karyopherins is required for inhibition of interferon signaling. | the ebolavirus vp24 protein counteracts alpha/beta interferon (ifn-alpha/beta) and ifn-gamma signaling by blocking the nuclear accumulation of tyrosine-phosphorylated stat1 (py-stat1). according to the proposed model, vp24 binding to members of the npi-1 subfamily of karyopherin alpha (kpnalpha) nuclear localization signal receptors prevents their binding to py-stat1, thereby preventing py-stat1 nuclear accumulation. this study now identifies two domains of vp24 required for inhibition of ifn-be ... | 2010 | 19889762 |
| phenylalanines at positions 88 and 159 of ebolavirus envelope glycoprotein differentially impact envelope function. | the envelope glycoprotein (gp) of ebolavirus (ebov) mediates viral entry into host cells. through mutagenesis, we and other groups reported that two phenylalanines at positions 88 and 159 of gp are critical for viral entry. however, it remains elusive which steps of viral entry are impaired by f88 or f159 mutations and how. in this study, we further characterized these two phenylalanines through mutagenesis and examined the impact on gp expression, function, and structure. our data suggest that ... | 2010 | 19906395 |
| techniques and tactics used in determining the structure of the trimeric ebolavirus glycoprotein. | the trimeric membrane-anchored ebolavirus envelope glycoprotein (gp) is responsible for viral attachment, fusion and entry. knowledge of its structure is important both for understanding ebolavirus entry and for the development of medical interventions. crystal structures of viral glycoproteins, especially those in their metastable prefusion oligomeric states, can be difficult to achieve given the challenges in production, purification, crystallization and diffraction that are inherent in the he ... | 2009 | 19923712 |
| [electron microscopic analysis of viral assembly and budding]. | viruses show ultrastructural changes during viral assembly and budding processes in which viral genome and proteins are systemically assembled. electron microscopy is the only way that enables us to observe such ultrastructural changes. we have investigated the mechanisms of ebola and influenza virion formation by electron microscopy. we have elucidated the roles of each ebola virus protein in viral assembly and budding as well as the mechanisms of genome packaging of influenza a viruses. | 2009 | 19927994 |
| dna vaccines for biodefense. | an ideal biodefense vaccine platform would allow for the quick formulation of novel vaccines in response to emerging or engineered pathogens. the resultant vaccine should elicit protective immune responses in one to three doses and be unaffected by pre-existing immunity to vaccine components. in addition, it should be amenable to combination and multi-agent formulation, and should be safe for all populations and the environment. dna vaccines can potentially meet all of these requirements; thus, ... | 2009 | 19943766 |
| ebolavirus vp35 uses a bimodal strategy to bind dsrna for innate immune suppression. | ebolavirus causes a severe hemorrhagic fever and is divided into five distinct species, of which reston ebolavirus is uniquely nonpathogenic to humans. disease caused by ebolavirus is marked by early immunosuppression of innate immune signaling events, involving silencing and sequestration of double-stranded rna (dsrna) by the viral protein vp35. here we present unbound and dsrna-bound crystal structures of the dsrna-binding domain of reston ebolavirus vp35. the structures show that vp35 forms a ... | 2010 | 20018665 |
| mechanisms and consequences of ebolavirus-induced lymphocyte apoptosis. | ebolavirus (ebov) is a member of the filovirus family and causes severe hemorrhagic fever, resulting in death in up to 90% of infected humans. ebov infection induces massive bystander lymphocyte apoptosis; however, neither the cellular apoptotic pathway(s) nor the systemic implications of lymphocyte apoptosis in ebov infection are known. in this study, we show data suggesting that ebov-induced lymphocyte apoptosis in vivo occurs via both the death receptor (extrinsic) and mitochondrial (intrinsi ... | 2010 | 20028660 |
| conserved motifs within ebola and marburg virus vp40 proteins are important for stability, localization, and subsequent budding of virus-like particles. | the filovirus vp40 protein is capable of budding from mammalian cells in the form of virus-like particles (vlps) that are morphologically indistinguishable from infectious virions. ebola virus vp40 (evp40) contains well-characterized overlapping l domains, which play a key role in mediating efficient virus egress. l domains represent only one component required for efficient budding and, therefore, there is a need to identify and characterize additional domains important for vp40 function. we de ... | 2010 | 20032189 |
| biochemical and structural characterization of cathepsin l-processed ebola virus glycoprotein: implications for viral entry and immunogenicity. | ebola virus (ebov) cellular attachment and entry is initiated by the envelope glycoprotein (gp) on the virion surface. entry of this virus is ph dependent and associated with the cleavage of gp by proteases, including cathepsin l (catl) and/or catb, in the endosome or cell membrane. here, we characterize the product of catl cleavage of zaire ebov gp (zebov-gp) and evaluate its relevance to entry. a stabilized recombinant form of the ebov gp trimer was generated using a trimerization domain linke ... | 2010 | 20053739 |
| mutations abrogating vp35 interaction with double-stranded rna render ebola virus avirulent in guinea pigs. | ebola virus (ebov) protein vp35 is a double-stranded rna (dsrna) binding inhibitor of host interferon (ifn)-alpha/beta responses that also functions as a viral polymerase cofactor. recent structural studies identified key features, including a central basic patch, required for vp35 dsrna binding activity. to address the functional significance of these vp35 structural features for ebov replication and pathogenesis, two point mutations, k319a/r322a, that abrogate vp35 dsrna binding activity and s ... | 2010 | 20071589 |
| structural basis for dsrna recognition and interferon antagonism by ebola vp35. | ebola viral protein 35 (vp35), encoded by the highly pathogenic ebola virus, facilitates host immune evasion by antagonizing antiviral signaling pathways, including those initiated by rig-i-like receptors. here we report the crystal structure of the ebola vp35 interferon inhibitory domain (iid) bound to short double-stranded rna (dsrna), which together with in vivo results reveals how vp35-dsrna interactions contribute to immune evasion. conserved basic residues in vp35 iid recognize the dsrna b ... | 2010 | 20081868 |
| marburg virus evades interferon responses by a mechanism distinct from ebola virus. | previous studies have demonstrated that marburg viruses (marv) and ebola viruses (ebov) inhibit interferon (ifn)-alpha/beta signaling but utilize different mechanisms. ebov inhibits ifn signaling via its vp24 protein which blocks the nuclear accumulation of tyrosine phosphorylated stat1. in contrast, marv infection inhibits ifnalpha/beta induced tyrosine phosphorylation of stat1 and stat2. marv infection is now demonstrated to inhibit not only ifnalpha/beta but also ifngamma-induced stat phospho ... | 2010 | 20084112 |
| challenges in biodefense research and the role of us army veterinary pathologists. | for years the nation's development of medical countermeasures to biowarfare agents has primarily existed as the domain of the united states military, but it has taken on increased urgency in the last few years. the realization that the civilian population is also at risk from biological agents has resulted in the institution of new biodefense programs at a variety of nonmilitary organizations. usamriid, a long-time leader in the nation's biodefense effort, will soon be joined by other us governm ... | 2007 | 20088227 |
| mucosal parainfluenza virus-vectored vaccine against ebola virus replicates in the respiratory tract of vector-immune monkeys and is immunogenic. | we previously used human parainfluenza virus type 3 (hpiv3) as a vector to express the ebola virus (ebov) gp glycoprotein. the resulting hpiv3/ebogp vaccine was immunogenic and protective against ebov challenge in a non-human primate model. however, it remained unclear whether the vaccine would be effective in adults due to preexisting immunity to hpiv3. here, the immunogenicity of hpiv3/ebogp was compared in hpiv3-naive and hpiv3-immune rhesus monkeys. after a single dose of hpiv3/ebogp, the ti ... | 2010 | 20129638 |
| measles virus m protein-driven particle production does not involve the endosomal sorting complex required for transport (escrt) system. | assembly and budding of enveloped rna viruses rely on viral matrix (m) proteins and host proteins involved in sorting and vesiculation of cellular cargoes, such as the endosomal sorting complex required for transport (escrt). the measles virus (mv) m protein promotes virus-like particle (vlp) production, and we now show that it shares association with detergent-resistant or tetraspanin-enriched membrane microdomains with ebolavirus vp40 protein, yet accumulates less efficiently at the plasma mem ... | 2010 | 20130136 |
| identification of n-glycans from ebola virus glycoproteins by matrix-assisted laser desorption/ionisation time-of-flight and negative ion electrospray tandem mass spectrometry. | the larger fragment of the transmembrane glycoprotein (gp1) and the soluble glycoprotein (sgp) of ebola virus were expressed in human embryonic kidney cells and the secreted products were purified from the supernatant for carbohydrate analysis. the n-glycans were released with pngase f from within sodium dodecyl sulphate/polyacrylamide gel electrophoresis (sds-page) gels. identification of the glycans was made with normal-phase high-performance liquid chromatography (hplc), matrix-assisted laser ... | 2010 | 20131323 |
| high prevalence of both humoral and cellular immunity to zaire ebolavirus among rural populations in gabon. | to better understand zaire ebolavirus (zebov) circulation and transmission to humans, we conducted a large serological survey of rural populations in gabon, a country characterized by both epidemic and non epidemic regions. the survey lasted three years and covered 4,349 individuals from 220 randomly selected villages, representing 10.7% of all villages in gabon. using a sensitive and specific elisa method, we found a zebov-specific igg seroprevalence of 15.3% overall, the highest ever reported. ... | 2010 | 20161740 |
| role of the gtpase rab1b in ebolavirus particle formation. | the ebolavirus matrix protein vp40 is essential for virion assembly and egress. recently, we reported that the coat protein complex ii (copii) transport system plays an important role in the transport of vp40 to the plasma membrane. here, we show that dominant-negative mutants of the gtpase rab1b interfere with vp40-mediated particle formation. rab1b activates gbf1 (golgi-specific bfa [brefeldin a] resistance factor 1), a critical factor in the assembly of copi vesicles. activated gbf1 stimulate ... | 2010 | 20164217 |
| characterization of the ebola virus nucleoprotein-rna complex. | when ebola virus nucleoprotein (np) is expressed in mammalian cells, it assembles into helical structures. here, the recombinant np helix purified from cells expressing np was characterized biochemically and morphologically. we found that the recombinant np helix is associated with non-viral rna, which is not protected from rnase digestion and that the morphology of the helix changes depending on the environmental salt concentration. the n-terminal 450 aa residues of np are sufficient for these ... | 2010 | 20164259 |
| protection of nonhuman primates against two species of ebola virus infection with a single complex adenovirus vector. | ebola viruses are highly pathogenic viruses that cause outbreaks of hemorrhagic fever in humans and other primates. to meet the need for a vaccine against the several types of ebola viruses that cause human diseases, we developed a multivalent vaccine candidate (ebo7) that expresses the glycoproteins of zaire ebolavirus (zebov) and sudan ebolavirus (sebov) in a single complex adenovirus-based vector (cadvax). we evaluated our vaccine in nonhuman primates against the parenteral and aerosol routes ... | 2010 | 20181765 |
| ebolavirus glycoprotein structure and mechanism of entry. | ebolavirus (ebov) is a highly virulent pathogen capable of causing a severe hemorrhagic fever with 50-90% lethality. the ebov glycoprotein (gp) is the only virally expressed protein on the virion surface and is critical for attachment to host cells and catalysis of membrane fusion. hence, the ebov gp is a critical component of vaccines as well as a target of neutralizing antibodies and inhibitors of attachment and fusion. the crystal structure of the zaire ebolavirus gp in its trimeric, prefusio ... | 2009 | 20198110 |
| ebola virus uses clathrin-mediated endocytosis as an entry pathway. | ebola virus (ebov) infects several cell types and while viral entry is known to be ph-dependent, the exact entry pathway(s) remains unknown. to gain insights into ebov entry, the role of several inhibitors of clathrin-mediated endocytosis in blocking infection mediated by hiv pseudotyped with the ebov envelope glycoprotein (ebgp) was examined. wild type hiv and envelope-minus hiv pseudotyped with vesicular stomatitis virus glycoprotein (vsvg) were used as controls to assess cell viability after ... | 2010 | 20202662 |
| antiviral activity of a small-molecule inhibitor of filovirus infection. | there exists an urgent need to develop licensed drugs and vaccines for the treatment or prevention of filovirus infections. fgi-103 is a low-molecular-weight compound that was discovered through an in vitro screening assay utilizing a variant of zaire ebolavirus (zebov) that expresses green fluorescent protein. in vitro analyses demonstrated that fgi-103 also exhibits antiviral activity against wild-type zebov and sudan ebolavirus, as well as marburgvirus (marv) strains ci67 and ravn. in vivo ad ... | 2010 | 20211898 |
| antibody-mediated neutralization of ebola virus can occur by two distinct mechanisms. | human ebola virus causes severe hemorrhagic fever disease with high mortality and there is no vaccine or treatment. antibodies in survivors occur early, are sustained, and can delay infection when transferred into nonhuman primates. monoclonal antibodies (mabs) from survivors exhibit potent neutralizing activity in vitro and are protective in rodents. to better understand targets and mechanisms of neutralization, we investigated a panel of mabs shown previously to react with the envelope glycopr ... | 2010 | 20304456 |
| studies of the "chain reversal regions" of the avian sarcoma/leukosis virus (aslv) and ebolavirus fusion proteins: analogous residues are important, and a his residue unique to enva affects the ph dependence of aslv entry. | most class i fusion proteins exist as trimers of dimers composed of a receptor binding and a fusion subunit. in their postfusion forms, the three fusion subunits form trimers of hairpins consisting of a central coiled coil (formed by the n-terminal helices), an intervening sequence, and a region containing the c helix (and flanking strands) that runs antiparallel to and packs in the grooves of the n-terminal coiled coil. for filoviruses and most retroviruses, the intervening sequence includes a ... | 2010 | 20335266 |
| [stabilization of peroxidase conjugates used in enzyme immunoassay systems to detect ebola and marburg virus antigens]. | the time course of changes in the activity of solutions of horseradish peroxidase conjugates with immunoglobulins against ebola and marburg fevers was studied in the presence of different components. the series of the conjugates of elisa kits for the detection of ebola and marburg virus antigens, which were prepared on the basis of the designed stabilizing solution, preserved at less than 90% of its baseline activity during 10 months at a storage temperature of 2 to 8 degrees c. | 2010 | 20364672 |
| reduced virus replication, proinflammatory cytokine production, and delayed macrophage cell death in human pbmcs infected with the newly discovered bundibugyo ebolavirus relative to zaire ebolavirus. | bundibugyo ebolavirus is a newly identified ebolavirus species. the virus was responsible for a recent hemorrhagic fever outbreak in uganda with an approximate 30% case fatality rate. in this study, we compared the pathogenesis of bundibugyo with highly lethal zaire ebolavirus by using in vitro human pbmcs. we found that pbmcs infected with bundibugyo ebolaviruses resulted in 1 to 2 log lower virus yields compared to zaire ebolavirus and produced 2- to 10-fold lower levels of tnf-alpha, mcp-1, i ... | 2010 | 20394957 |
| structural and functional characterization of reston ebola virus vp35 interferon inhibitory domain. | ebolaviruses are causative agents of lethal hemorrhagic fever in humans and nonhuman primates. among the filoviruses characterized thus far, reston ebola virus (rebov) is the only ebola virus that is nonpathogenic to humans despite the fact that rebov can cause lethal disease in nonhuman primates. previous studies also suggest that rebov is less effective at inhibiting host innate immune responses than zaire ebola virus (zebov) or marburg virus. virally encoded vp35 protein is critical for immun ... | 2010 | 20399790 |