| 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 |
| 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 |
| 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 |
| 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 |
| regulation of marburg virus (marv) budding by nedd4.1: a different ww domain of nedd4.1 is critical for binding to marv and ebola virus vp40. | the vp40 matrix protein of marburg virus (marv) has been shown to be the driving force behind marv budding, a process in which the pppy l-domain motif of vp40 plays a critical role. here, we report that vps4b and nedd4.1 play critical roles in marv vp40-mediated budding. we showed that unidentified activities of the nedd4.1 hect domain, along with its e3 ubiquitin ligase activity, may be required for marv budding. moreover, we showed that the first ww domain of nedd4.1, ww1, is critical for bind ... | 2010 | 19812267 |
| discovery of common marburgvirus protective epitopes in a balb/c mouse model. | marburg virus (marv) causes acute hemorrhagic fever that is often lethal, and no licensed vaccines are available for preventing this deadly viral infection. the immune mechanisms for protection against marv are poorly understood, but previous studies suggest that both antibodies and t cells are required. in our study, we infected balb/c mice with plaque-purified, nonlethal marv and used overlapping peptides to map h2d-restricted cd8+ t-cell epitopes. | 2009 | 19712478 |
| 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 |
| dimerization of tetherin is not essential for its antiviral activity against lassa and marburg viruses. | tetherin (also known as bst2, cd317 or hm1.24) has recently been reported to inhibit a wide range of viruses. however, the antiviral mechanism of action of tetherin has not been determined. both ends of the tetherin molecule are associated with the plasma membrane and it forms a homodimer. therefore, a model in which progeny virions are retained on the cell surface by dimer formation between tetherin molecules on the viral envelope and plasma membrane has been proposed as the antiviral mechanism ... | 2009 | 19742323 |
| monovalent virus-like particle vaccine protects guinea pigs and nonhuman primates against infection with multiple marburg viruses. | virus-like particle (vlp)-based vaccines have the advantage of being morphologically and antigenically similar to the live virus from which they are derived. expression of the glycoprotein and vp40 matrix protein from lake victoria marburgvirus (marv) results in spontaneous production of vlps in mammalian cells. guinea pigs vaccinated with marburg virus vlps (mvlps) or inactivated marv (imarv) develop homologous humoral and t-cell responses and are completely protected from a lethal homologous m ... | 2008 | 18444889 |
| 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 |
| different potential of c-type lectin-mediated entry between marburg virus strains. | the glycoproteins (gps) of filoviruses are responsible for virus entry into cells. it is known that gp interacts with cellular c-type lectins for virus attachment to cells. since primary target cells of filoviruses express c-type lectins, c-type lectin-mediated entry is thought to be a possible determinant of virus tropism and pathogenesis. we compared the efficiency of c-type lectin-mediated entry between marburg virus strains angola and musoke by using a vesicular stomatitis virus (vsv) pseudo ... | 2010 | 20219911 |
| [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 |
| development and evaluation of a simple assay for marburg virus detection using a reverse transcription-loop-mediated isothermal amplification method. | marburg virus (marv) causes a severe hemorrhagic fever in humans with a high mortality rate. the rapid and accurate identification of the virus is required to appropriately provide infection control and outbreak management. here, we developed and evaluated a one-step reverse transcription-loop-mediated isothermal amplification (rt-lamp) assay for the rapid and simple detection of marv. by combining two sets of primers specific for the musoke and ravn genetic lineages, a multiple rt-lamp assay de ... | 2010 | 20421440 |
| factors associated with marburg hemorrhagic fever: analysis of patient data from uige, angola. | reliable on-site polymerase chain reaction (pcr) testing for marburg hemorrhagic fever (mhf) is not always available. therefore, clinicians triage patients on the basis of presenting symptoms and contact history. using patient data collected in uige, angola, in 2005, we assessed the sensitivity and specificity of these factors to evaluate the validity of world health organization (who)-recommended case definitions for mhf. | 2010 | 20441515 |
| marburg virus in fruit bat, kenya. | | 2010 | 20113584 |
| 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 |
| filoviruses are ancient and integrated into mammalian genomes. | hemorrhagic diseases from ebolavirus and marburgvirus (filoviridae) infections can be dangerous to humans because of high fatality rates and a lack of effective treatments or vaccine. although there is evidence that wild mammals are infected by filoviruses, the biology of host-filovirus systems is notoriously poorly understood. specifically, identifying potential reservoir species with the expected long-term coevolutionary history of filovirus infections has been intractable. integrated elements ... | 2010 | 20569424 |
| establishment and application of an infectious virus-like particle system for marburg virus. | the highly pathogenic marburg virus (marv) can only be investigated in high containment laboratories, which is time consuming and expensive. to investigate the marv life cycle under normal laboratory conditions, an infectious virus-like particle (vlp) system was developed. the infectious vlp system is based on the t7-polymerase driven synthesis of a marv-specific minigenome that encodes luciferase and is transcribed and replicated by the simultaneously expressed marv nucleocapsid proteins np, vp ... | 2010 | 20071483 |
| prospects for immunisation against marburg and ebola viruses. | for more than 30 years the filoviruses, marburg virus and ebola virus, have been associated with periodic outbreaks of hemorrhagic fever that produce severe and often fatal disease. the filoviruses are endemic primarily in resource-poor regions in central africa and are also potential agents of bioterrorism. although no vaccines or antiviral drugs for marburg or ebola are currently available, remarkable progress has been made over the last decade in developing candidate preventive vaccines again ... | 2010 | 20658513 |
| the survival of filoviruses in liquids, on solid substrates and in a dynamic aerosol. | filoviruses are associated with high morbidity and lethality rates in humans, are capable of human-to-human transmission, via infected material such as blood, and are believed to have low infectious doses for humans. filoviruses are able to infect via the respiratory route and are lethal at very low doses in experimental animal models, but there is minimal information on how well the filoviruses survive within aerosol particles. there is also little known about how well filoviruses survive in li ... | 2010 | 20553340 |
| tsg101 is recruited by a late domain of the nucleocapsid protein to support budding of marburg virus-like particles. | the nucleoprotein np of marburg virus (marv) is the major component of the viral nucleocapsid, which also consists of the viral proteins vp35, l, and vp30, as well as the viral genome. during virus assembly at the plasma membrane, the nucleocapsids are enwrapped by the major matrix protein vp40 and the viral envelope, which contains the transmembrane glycoprotein gp. upon recombinant expression, vp40 alone is able to induce the formation and release of virus-like particles (vlps) that closely re ... | 2010 | 20504928 |
| unexpected inheritance: multiple integrations of ancient bornavirus and ebolavirus/marburgvirus sequences in vertebrate genomes. | vertebrate genomes contain numerous copies of retroviral sequences, acquired over the course of evolution. until recently they were thought to be the only type of rna viruses to be so represented, because integration of a dna copy of their genome is required for their replication. in this study, an extensive sequence comparison was conducted in which 5,666 viral genes from all known non-retroviral families with single-stranded rna genomes were matched against the germline genomes of 48 vertebrat ... | 2010 | 20686665 |
| infectious lassa virus, but not filoviruses, is restricted by bst-2/tetherin. | bone marrow stromal antigen 2 (bst-2/tetherin) is a cellular membrane protein that inhibits the release of hiv-1. we show for the first time, using infectious viruses, that bst-2 also inhibits egress of arenaviruses but has no effect on filovirus replication and spread. specifically, infectious lassa virus (lasv) release significantly decreased or increased in human cells in which bst-2 was either stably expressed or knocked down, respectively. in contrast, replication and spread of infectious z ... | 2010 | 20686043 |
| development of high-content imaging assays for lethal viral pathogens. | filoviruses such as ebola (ebov) and marburg (marv) are single-stranded negative sense rna viruses that cause acute hemorrhagic fever with high mortality rates. currently, there are no licensed vaccines or therapeutics to counter filovirus infections in humans. the development of higher throughput/high-content primary screening assays followed by validation using the low-throughput traditional plaque or real-time pcr assays will greatly aid efforts toward the discovery of novel antiviral therape ... | 2010 | 20639507 |
| vector choice determines immunogenicity and potency of genetic vaccines against angola marburg virus in nonhuman primates. | the immunogenicity and durability of genetic vaccines are influenced by the composition of gene inserts and choice of delivery vector. dna vectors are a promising vaccine approach showing efficacy when combined in prime-boost regimens with recombinant protein or viral vectors, but they have shown limited comparative efficacy as a stand-alone platform in primates, due possibly to suboptimal gene expression or cell targeting. here, regimens using dna plasmids modified for optimal antigen expressio ... | 2010 | 20660192 |
| 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 |
| imported case of marburg hemorrhagic fever - colorado, 2008. | marburg hemorrhagic fever (mhf) is a rare, viral hemorrhagic fever (vhf); the causative agent is an rna virus in the family filoviridae, and growing evidence demonstrates that fruit bats are the natural reservoir of marburg virus (marv). on january 9, 2008, an infectious disease physician notified the colorado department of public health and environment (cdphe) of a case of unexplained febrile illness requiring hospitalization in a woman who had returned from travel in uganda. testing of early c ... | 2009 | 20019654 |
| 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 |
| detection of all known filovirus species by reverse transcription-polymerase chain reaction using a primer set specific for the viral nucleoprotein gene. | the filoviruses, marburg virus (marv) and ebola virus (ebov), are causative agents of severe hemorrhagic fever with high mortality rates in humans and non-human primates. sporadic outbreaks of filovirus infection have occurred in central africa and parts of asia. identification of the natural reservoir animals that are unknown yet and epidemiological investigations are current challenges to forestall outbreaks of filovirus diseases. the filovirus species identified currently include one in the m ... | 2010 | 21093485 |
| advanced antisense therapies for postexposure protection against lethal filovirus infections. | currently, no vaccines or therapeutics are licensed to counter ebola or marburg viruses, highly pathogenic filoviruses that are causative agents of viral hemorrhagic fever. here we show that administration of positively charged phosphorodiamidate morpholino oligomers (pmoplus), delivered by various dosing strategies initiated 30-60 min after infection, protects>60% of rhesus monkeys against lethal zaire ebola virus (zebov) and 100% of cynomolgus monkeys against lake victoria marburg virus (marv) ... | 2010 | 20729866 |
| identification of essential filovirion-associated host factors by serial proteomic analysis and rnai screen. | an assessment of the total protein composition of filovirus (ebolavirus and marburgvirus) virions is currently lacking. in this study, liquid chromatography-linked tandem mass spectrometry of purified ebola and marburg virions was performed to identify associated cellular proteins. host proteins involved in cell adhesion, cytoskeleton, cell signaling, intracellular trafficking, membrane organization, and chaperones were identified. significant overlap exists between this data set and proteomic s ... | 2010 | 20702783 |
| one more piece in the vacv ecological puzzle: could peridomestic rodents be the link between wildlife and bovine vaccinia outbreaks in brazil? | despite the fact that smallpox eradication was declared by the world health organization (who) in 1980, other poxviruses have emerged and re-emerged, with significant public health and economic impacts. vaccinia virus (vacv), a poxvirus used during the who smallpox vaccination campaign, has been involved in zoonotic infections in brazilian rural areas (bovine vaccinia outbreaks - bv), affecting dairy cattle and milkers. little is known about vacv's natural hosts and its epidemiological and ecolo ... | 2009 | 19838293 |
| distinct patterns of ifitm-mediated restriction of filoviruses, sars coronavirus, and influenza a virus. | interferon-inducible transmembrane proteins 1, 2, and 3 (ifitm1, 2, and 3) are recently identified viral restriction factors that inhibit infection mediated by the influenza a virus (iav) hemagglutinin (ha) protein. here we show that ifitm proteins restricted infection mediated by the entry glycoproteins (gp(1,2)) of marburg and ebola filoviruses (marv, ebov). consistent with these observations, interferon-β specifically restricted filovirus and iav entry processes. ifitm proteins also inhibited ... | 2011 | 21253575 |
| progress in filovirus vaccine development: evaluating the potential for clinical use. | marburg and ebola viruses cause severe hemorrhagic fever in humans and nonhuman primates. currently, there are no effective treatments and no licensed vaccines; although a number of vaccine platforms have proven successful in animal models. the ideal filovirus vaccine candidate should be able to provide rapid protection following a single immunization, have the potential to work postexposure and be cross-reactive or multivalent against all marburg virus strains and all relevant ebola virus speci ... | 2011 | 21162622 |
| key genomic changes necessary for an in vivo lethal mouse marburgvirus variant selection process. | marburgvirus (marv) infections are generally lethal in humans and nonhuman primates but require in vivo lethal mouse variant selection by the serial transfer (passage) of the nonlethal virus into naïve mice to propagate a lethal infection. the passage of progenitor (wild-type) marv or ravn virus (ravv) from infected scid balb/c mouse liver homogenates into immunocompetent balb/c mice results in the selection of lethal mouse viruses from within the quasispecies sufficient to establish lethality i ... | 2011 | 21289122 |
| 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 ... | 2011 | 21987745 |
| alkylated porphyrins have broad antiviral activity against hepadnaviruses, flaviviruses, filoviruses, and arenaviruses. | we screened ∼2,200 compounds known to be safe in people for the ability to reduce the amount of virion-associated hepatitis b virus (hbv) dna in the culture medium of producer cells. these efforts led to the discovery of an alkylated porphyrin, chlorophyllide, as the compound that achieved the greatest reduction in signal. here we report that chlorophyllide directly and quantitatively disrupted hbv virions at micromolar concentrations, resulting in the loss of all detectable virion dna, without ... | 2010 | 21135183 |
| identification of a small-molecule entry inhibitor for filoviruses. | ebola virus (ebov) causes severe hemorrhagic fever, for which therapeutic options are not available. preventing the entry of ebov into host cells is an attractive antiviral strategy, which has been validated for hiv by the fda approval of the anti-hiv drug enfuvirtide. to identify inhibitors of ebov entry, the ebov envelope glycoprotein (ebov-gp) gene was used to generate pseudotype viruses for screening of chemical libraries. a benzodiazepine derivative (compound 7) was identified from a high-t ... | 2011 | 21270170 |
| marburg virus vp40 antagonizes interferon signaling in a species-specific manner. | marburgviruses are zoonotic pathogens that cause lethal hemorrhagic fever in humans and nonhuman primates. however, they do not cause lethal disease in immunocompetent mice unless they are adapted to this species. the adaptation process can therefore provide insight into the specific virus-host interactions that determine virulence. in primate cells, the lake victoria marburgvirus musoke strain (marv) vp40 matrix protein antagonizes alpha/beta interferon (ifn-a/ß) and ifn-? signaling by inhibiti ... | 2011 | 21325424 |
| 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 ... | 2011 | 21536871 |
| 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%). | 2010 | 21413569 |
| 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 ... | 2011 | 21454542 |
| the cytoplasmic domain of marburg virus gp modulates early steps of viral infection. | marburg virus infection is mediated by the only viral surface protein, gp, a trimeric type i transmembrane protein. while its ectodomain mediates receptor binding and fusion of viral and cellular membranes and its transmembrane domain is essential for the recruitment of gp into budding particles by the matrix protein vp40, the role of the short cytoplasmic domain has remained enigmatic. here we show that a missing cytoplasmic domain did not impair trimerization, intracellular transport, or incor ... | 2011 | 21680524 |
| the use of a mobile laboratory unit in support of patient management and epidemiological surveillance during the 2005 marburg outbreak in angola. | marburg virus (marv), a zoonotic pathogen causing severe hemorrhagic fever in man, has emerged in angola resulting in the largest outbreak of marburg hemorrhagic fever (mhf) with the highest case fatality rate to date. | 2011 | 21629730 |
| 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 ... | 2011 | 21697477 |
| an alternative method of measuring aerosol survival using spiders' webs and its use for the filoviruses. | understanding the ability to survive in an aerosol leads to better understanding of the hazard posed by pathogenic organisms and can inform decisions related to the control and management of disease outbreaks. this basic survival information is sometimes lacking for high priority select agents such as the filoviruses which cause severe disease with high case fatality rates and can be acquired through the aerosol route. microthreads in the form of spiders' webs were used to capture aerosolised fi ... | 2011 | 21762730 |
| 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 ... | 2011 | 21468930 |
| 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 ... | 2011 | 21722250 |
| [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 ... | 2011 | 21695865 |
| aerosol exposure to the angola strain of marburg virus causes lethal viral hemorrhagic fever in cynomolgus macaques. | cynomolgus macaques were exposed to the angola strain of lake victoria marburg virus (marv) by aerosol to examine disease course and lethality. macaques became febrile 4 to 7 days postexposure; the peak febrile response was delayed 1 to 2 days in animals that received a lower dose; viremia coincided with the onset of fever. all 6 macaques succumbed to the infection, with the 3 macaques in the low-dose group becoming moribund on day 9, a day later than the macaques in the high-dose group. gross p ... | 2010 | 20807825 |
| 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 ... | 2011 | 22046196 |
| establishment of fruit bat cells (rousettus aegyptiacus) as a model system for the investigation of filoviral infection. | the fruit bat species rousettus aegyptiacus was identified as a potential reservoir for the highly pathogenic filovirus marburg virus. to establish a basis for a molecular understanding of the biology of filoviruses in the reservoir host, we have adapted a set of molecular tools for investigation of filovirus replication in a recently developed cell line, r06e, derived from the species rousettus aegyptiacus. | 2010 | 20808767 |
| 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 ... | 2011 | 21855102 |
| enzyme-linked immunosorbent assay for detection of filovirus species-specific antibodies. | several enzyme-linked immunosorbent assays (elisas) for the detection of filovirus-specific antibodies have been developed. however, diagnostic methods to distinguish antibodies specific to the respective species of filoviruses, which provide the basis for serological classification, are not readily available. we established an elisa using his-tagged secreted forms of the transmembrane glycoproteins (gps) of five different ebola virus (ebov) species and one marburg virus (marv) strain as antigen ... | 2010 | 20861331 |
| proposal for a revised taxonomy of the family filoviridae: classification, names of taxa and viruses, and virus abbreviations. | the taxonomy of the family filoviridae (marburgviruses and ebolaviruses) has changed several times since the discovery of its members, resulting in a plethora of species and virus names and abbreviations. the current taxonomy has only been partially accepted by most laboratory virologists. confusion likely arose for several reasons: species names that consist of several words or which (should) contain diacritical marks, the current orthographic identity of species and virus names, and the simila ... | 2010 | 21046175 |
| phosphorylation of marburg virus np region ii modulates viral rna synthesis. | phosphorylation of the marburg virus nucleoprotein np is distributed over 7 regions (i-vii) in its c-terminus. the exact localization of phosphorylated amino acids and function of np phosphorylation are unknown. here, we show that the major phosphate acceptor sites in np region ii are serine 446 and serines 453-455; the latter are located in a cluster of 6 serine residues (aa 450-455). the function of phosphorylation in region ii was tested using an infectious virus-like particle assay. phosphor ... | 2011 | 21987771 |
| evolutionary maintenance of filovirus-like genes in bat genomes. | little is known of the biological significance and evolutionary maintenance of integrated non-retroviral rna virus genes in eukaryotic host genomes. here, we isolated novel filovirus-like genes from bat genomes and tested for evolutionary maintenance. we also estimated the age of filovirus vp35-like gene integrations and tested the phylogenetic hypotheses that there is a eutherian mammal clade and a marsupial/ebolavirus/marburgvirus dichotomy for filoviruses. | 2011 | 22093762 |
| 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 ... | 2011 | 21987780 |
| 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 ... | 2011 | 21987757 |
| recombinant marburg virus expressing egfp allows rapid screening of virus growth and real-time visualization of virus spread. | the generation of recombinant enhanced green fluorescent protein (egfp)-expressing viruses has significantly improved the study of their life cycle and opened up the possibility for the rapid screening of antiviral drugs. here we report rescue of a recombinant marburg virus (marv) expressing egfp from an additional transcription unit (atu). the atu was inserted between the second and third genes, encoding vp35 and vp40, respectively. live-cell imaging was used to follow virus spread in real time ... | 2011 | 21987762 |
| is marburg virus enzootic in gabon? | marburg virus (marv) nucleic acid was detected in rousettus aegyptiacus bats in 2005 and 2006 in the midwest and southeast of gabon. in this study we used marv-specific real-time reverse-transcription polymerase chain reaction (rt-pcr) and marv-specific nested rt-pcr assay to screen 1257 bats caught during july 2009, december 2009, and june 2010 in 3 caves situated in northern gabon. nine specimens tested positive by the real-time assay, with cycle threshold values ranging from 35 to 39, of whic ... | 2011 | 21987754 |
| Identification of amino acids in Marburg virus VP40 that are important for virus-like particle budding. | The matrix protein VP40 of Marburg virus promotes the formation and release of virus-like particles (VLPs). Marburg virus VP40 interacts with cellular Tsg101 via its L domain motif; however, mutation of this motif does not affect VLP budding or the accumulation of VP40 in multivesicular bodies (MVBs), which are platforms for virus particle formation. To identify regions of Marburg virus VP40 that are important for VLP budding, we examined deletion mutants and alanine-scanning mutants at the N- a ... | 2011 | 21987763 |
| 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 ... | 2011 | 21866103 |
| 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 ... | 2011 | 22102845 |
| Genus-specific recruitment of filovirus ribonucleoprotein complexes into budding particles. | The filoviral matrix protein VP40 orchestrates virus morphogenesis and budding. To do this it interacts with both the glycoprotein (GP1,2) and the ribonucleoprotein (RNP) complex components; however, these interactions are still not well understood. Here we show that for efficient VP40-driven formation of transcription and replication-competent virus-like particles (trVLPs), which contain both an RNP complex and GP1,2, the RNP components and VP40, but not GP1,2 and VP40, must be from the same ge ... | 2011 | 21900424 |
| Lethality and pathogenesis of airborne infection with filoviruses in A129 a/ß -/- interferon receptor-deficient mice. | Normal immunocompetent mice are not susceptible to non-adapted filoviruses. There are therefore two strategies available to establish a murine model of filovirus infection: adaptation of the virus to the host or the use of genetically modified mice that are susceptible to the virus. A number of knockout (KO) strains of mice with defects in either their adaptive or innate immunity are susceptible to non-adapted filoviruses. In this study, A129 a/ß -/- interferon receptor-deficient KO mice, strain ... | 2012 | 21852521 |
| 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 ... | 2011 | 21987741 |
| 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 ... | 2011 | 21987761 |
| phosphorylation of marburg virus matrix protein vp40 triggers assembly of nucleocapsids with the viral envelope at the plasma membrane. | marburg virus (marv) matrix protein vp40 plays a key role in virus assembly, recruiting nucleocapsids and the surface protein gp to filopodia, the sites of viral budding. in addition, vp40 is the only marv protein able to induce the release of filamentous virus-like particles (vlps) indicating its function in marv budding. here, we demonstrated that vp40 is phosphorylated and that tyrosine residues at positions 7, 10, 13 and 19 represent major phosphorylation acceptor sites. mutagenesis of these ... | 2011 | 21981045 |
| 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 ... | 2011 | 21987744 |
| 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. | 2011 | 21987779 |
| 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 ... | 2010 | 21994610 |
| 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. | 2011 | 21987738 |
| Filoviral immune evasion mechanisms. | The Filoviridae family of viruses, which includes the genera Ebolavirus (EBOV) and Marburgvirus (MARV), causes severe and often times lethal hemorrhagic fever in humans. Filoviral infections are associated with ineffective innate antiviral responses as a result of virally encoded immune antagonists, which render the host incapable of mounting effective innate or adaptive immune responses. The Type I interferon (IFN) response is critical for establishing an antiviral state in the host cell and su ... | 2011 | 21994800 |
| protective role of cytotoxic t lymphocytes in filovirus hemorrhagic fever. | infection with many emerging viruses, such as the hemorrhagic fever disease caused by the filoviruses, marburg (marv), and ebola virus (ebov), leaves the host with a short timeframe in which to mouse a protective immune response. in lethal cases, uncontrolled viral replication and virus-induced immune dysregulation are too severe to overcome, and mortality is generally associated with a lack of notable immune responses. vaccination studies in animals have demonstrated an association of igg and n ... | 2011 | 22253531 |
| generation and epitope mapping of a monoclonal antibody against nucleoprotein of ebola virus. | ebola virus (ebov) causes highly lethal hemorrhagic fever in humans and nonhuman primates and has a significant impact on public health. the nucleoprotein (np) of ebov (ebov-np) plays a central role in virus replication and has been used as a target molecule for disease diagnosis. in this study, we generated a monoclonal antibody (mab) against ebov-np and mapped the epitope motif required for recognition by the mab. the mab generated via immunization of mice with prokaryotically expressed recomb ... | 2012 | 23457784 |
| a small nonhuman primate model for filovirus-induced disease. | ebolavirus and marburgvirus are members of the filovirus family and induce a fatal hemorrhagic disease in humans and nonhuman primates with 90% case fatality. to develop a small nonhuman primate model for filovirus disease, common marmosets (callithrix jacchus) were intramuscularly inoculated with wild type marburgvirus musoke or ebolavirus zaire. the infection resulted in a systemic fatal disease with clinical and morphological features closely resembling human infection. animals experienced we ... | 2011 | 21959017 |
| 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 ... | 2011 | 21858822 |