Publications
| Title | Abstract | Year Filter | PMID(sorted ascending) Filter |
|---|
| suppression of pact-induced type i interferon production by herpes simplex virus 1 us11 protein. | herpes simplex virus 1 (hsv-1) us11 protein is a double-stranded rna-binding protein that suppresses type i interferon production through the inhibition of the cytoplasmic rna sensor rig-i. whether additional cellular mediators are involved in this suppression remains to be determined. in this study, we report on the requirement of cellular double-stranded rna-binding protein pact for us11-mediated perturbation of type i interferon production. us11 associates with pact tightly to prevent it from ... | 2013 | 24067967 |
| a fusion-inhibiting peptide against rift valley fever virus inhibits multiple, diverse viruses. | for enveloped viruses, fusion of the viral envelope with a cellular membrane is critical for a productive infection to occur. this fusion process is mediated by at least three classes of fusion proteins (class i, ii, and iii) based on the protein sequence and structure. for rift valley fever virus (rvfv), the glycoprotein gc (class ii fusion protein) mediates this fusion event following entry into the endocytic pathway, allowing the viral genome access to the cell cytoplasm. here, we show that p ... | 2013 | 24069485 |
| hospital-based surveillance for viral hemorrhagic fevers and hepatitides in ghana. | viral hemorrhagic fevers (vhf) are acute diseases associated with bleeding, organ failure, and shock. vhf may hardly be distinguished clinically from other diseases in the african hospital, including viral hepatitis. this study was conducted to determine if vhf and viral hepatitis contribute to hospital morbidity in the central and northern parts of ghana. | 2013 | 24069490 |
| differential potential for envelope glycoprotein-mediated steric shielding of host cell surface proteins among filoviruses. | the viral envelope glycoprotein (gp) is thought to play important roles in the pathogenesis of filovirus infection. it is known that gp expressed on the cell surface forms a steric shield over host proteins such as major histocompatibility complex class i and integrin β1, which may result in the disorder of cell-to-cell contacts and/or inhibition of the immune response. however, it is not clarified whether this phenomenon contributes to the pathogenicity of filoviruses. in this study, we found t ... | 2013 | 24074577 |
| ifitms restrict the replication of multiple pathogenic viruses. | the interferon-inducible transmembrane protein (ifitm) family inhibits a growing number of pathogenic viruses, among them influenza a virus, dengue virus, hepatitis c virus, and ebola virus. this review covers recent developments in our understanding of the ifitm's molecular determinants, potential mechanisms of action, and impact on pathogenesis. | 2013 | 24076421 |
| malaria vaccine, ebola therapy promising in early studies. | 2013 | 24084902 | |
| filovirus replication and transcription. | the highly pathogenic filoviruses, marburg and ebola virus, belong to the nonsegmented negative-sense rna viruses of the order mononegavirales. the mode of replication and transcription is similar for these viruses. on one hand, the negative-sense rna genome serves as a template for replication, to generate progeny genomes, and, on the other hand, for transcription, to produce mrnas. despite the similarities in the replication/transcription strategy, filoviruses have evolved structural and funct ... | 2007 | 24093048 |
| ebola virus-like particles stimulate type i interferons and proinflammatory cytokine expression through the toll-like receptor and interferon signaling pathways. | ebola viruses (ebov) can cause severe hemorrhagic disease with high case fatality rates. currently, no vaccines or therapeutics are approved for use in humans. ebola virus-like particles (evlp) comprising of virus protein (vp40), glycoprotein, and nucleoprotein protect rodents and nonhuman primates from lethal ebov infection, representing as a candidate vaccine for ebov infection. previous reports have shown that evlp stimulate the expression of proinflammatory cytokines in dendritic cells (dcs) ... | 2014 | 24102579 |
| the cytoprotective enzyme heme oxygenase-1 suppresses ebola virus replication. | ebola virus (ebov) is the causative agent of a severe hemorrhagic fever in humans with reported case fatality rates as high as 90%. there are currently no licensed vaccines or antiviral therapeutics to combat ebov infections. heme oxygenase-1 (ho-1), an enzyme that catalyzes the rate-limiting step in heme degradation, has antioxidative properties and protects cells from various stresses. activated ho-1 was recently shown to have antiviral activity, potently inhibiting the replication of viruses ... | 2013 | 24109237 |
| strategies of highly pathogenic rna viruses to block dsrna detection by rig-i-like receptors: hide, mask, hit. | double-stranded rna (dsrna) is synthesized during the course of infection by rna viruses as a byproduct of replication and transcription and acts as a potent trigger of the host innate antiviral response. in the cytoplasm of the infected cell, recognition of the presence of viral dsrna as a signature of "non-self" nucleic acid is carried out by rig-i-like receptors (rlrs), a set of dedicated helicases whose activation leads to the production of type i interferon α/β (ifn-α/β). to overcome the in ... | 2013 | 24129118 |
| mabs and ad-vectored ifn-α therapy rescue ebola-infected nonhuman primates when administered after the detection of viremia and symptoms. | zmab is a promising treatment against ebola virus (ebov) disease that has been shown to protect 50% (two of four) of nonhuman primates (nhps) when administered 2 days post-infection (dpi). to extend the treatment window and improve protection, we combined zmab with adenovirus-vectored interferon-α (ad-ifn) and evaluated efficacy in ebov-infected nhps. seventy-five percent (three of four) and 100% (four of four) of cynomolgus and rhesus macaques survived, respectively, when treatment was initiate ... | 2013 | 24132638 |
| activity of and effect of subcutaneous treatment with the broad-spectrum antiviral lectin griffithsin in two laboratory rodent models. | griffithsin (grft) is a red-alga-derived lectin that binds the terminal mannose residues of n-linked glycans found on the surface of human immunodeficiency virus type 1 (hiv-1), hiv-2, and other enveloped viruses, including hepatitis c virus (hcv), severe acute respiratory syndrome coronavirus (sars-cov), and ebola virus. grft displays no human t-cell mitogenic activity and does not induce production of proinflammatory cytokines in treated human cell lines. however, despite the growing evidence ... | 2013 | 24145548 |
| ebola virus rna editing depends on the primary editing site sequence and an upstream secondary structure. | ebolavirus (ebov), the causative agent of a severe hemorrhagic fever and a biosafety level 4 pathogen, increases its genome coding capacity by producing multiple transcripts encoding for structural and nonstructural glycoproteins from a single gene. this is achieved through rna editing, during which non-template adenosine residues are incorporated into the ebov mrnas at an editing site encoding for 7 adenosine residues. however, the mechanism of ebov rna editing is currently not understood. in t ... | 2013 | 24146620 |
| [filoviruses]. | filoviruses (ebola and marburg viruses) cause severe hemorrhagic fever in humans and nonhuman primates. no effective prophylaxis or treatment for filovirus diseases is yet commercially available. recent studies have advanced our knowledge of filovirus protein functions and interaction between viral and host factors in the replication cycle. current findings on the ecology of filoviruses (i.e., natural infection of nonprimate animals and discovery of a new member of filoviruses in europe) have al ... | 2012 | 24153230 |
| incubation period of ebola hemorrhagic virus subtype zaire. | ebola hemorrhagic fever has killed over 1300 people, mostly in equatorial africa. there is still uncertainty about the natural reservoir of the virus and about some of the factors involved in disease transmission. until now, a maximum incubation period of 21 days has been assumed. | 2011 | 24159443 |
| an update on the use of antibodies against the filoviruses. | multiple recent, independent studies have confirmed that passively administered antibodies can provide effective postexposure therapy in nonhuman primates after exposure to an otherwise lethal dose of ebola virus or marburg virus. in this article, we review composition and performance of the antibody cocktails tested thus far, what is known about antibody epitopes on the viral glycoprotein target and ongoing research questions in further development of such cocktails for pre-exposure or emergenc ... | 0 | 24188676 |
| virus nomenclature below the species level: a standardized nomenclature for filovirus strains and variants rescued from cdna. | specific alterations (mutations, deletions, insertions) of virus genomes are crucial for the functional characterization of their regulatory elements and their expression products, as well as a prerequisite for the creation of attenuated viruses that could serve as vaccine candidates. virus genome tailoring can be performed either by using traditionally cloned genomes as starting materials, followed by site-directed mutagenesis, or by de novo synthesis of modified virus genomes or parts thereof. ... | 2014 | 24190508 |
| recombinant lentogenic newcastle disease virus expressing ebola virus gp infects cells independently of exogenous trypsin and uses macropinocytosis as the major pathway for cell entry. | using reverse genetics, we generated a recombinant low-pathogenic lasota strain newcastle disease virus (ndv) expressing the glycoprotein (gp) of ebola virus (ebov), designated rla-ebovgp, and evaluated its biological characteristic in vivo and in vitro. | 2013 | 24209904 |
| could the ebola virus matrix protein vp40 be a drug target? | filoviruses are filamentous lipid-enveloped viruses and include ebola (ebov) and marburg, which are morphologically identical but antigenically distinct. these viruses can be very deadly with outbreaks of ebov having clinical fatality as high as 90%. in 2012 there were two separate ebola outbreaks in the democratic republic of congo and uganda that resulted in 25 and 4 fatalities, respectively. the lack of preventive vaccines and fda-approved therapeutics has struck fear that the ebov could beco ... | 2014 | 24283270 |
| sustained protection against ebola virus infection following treatment of infected nonhuman primates with zmab. | ebola virus (ebov) is one of the most lethal filoviruses, with mortality rates of up to 90% in humans. previously, we demonstrated 100% and 50% survival of ebov-infected cynomologus macaques with a combination of 3 ebov-gp-specific monoclonal antibodies (zmab) administered at 24 or 48 hours post-exposure, respectively. the survivors demonstrated ebov-gp-specific humoral and cell-mediated immune responses. in order to evaluate whether the immune response induced in nhps during the zmab treatment ... | 2013 | 24284388 |
| structural characterization of the glycoprotein gp2 core domain from the cas virus, a novel arenavirus-like species. | fusion of the viral and host cell membranes is a necessary first step for infection by enveloped viruses and is mediated by the envelope glycoprotein. the transmembrane subunits from the structurally defined "class i" glycoproteins adopt an α-helical "trimer-of-hairpins" conformation during the fusion pathway. here, we present our studies on the envelope glycoprotein transmembrane subunit, gp2, of the cas virus (casv). casv was recently identified from annulated tree boas (corallus annulatus) wi ... | 2014 | 24333483 |
| vesicular stomatitis virus-based vaccines protect nonhuman primates against bundibugyo ebolavirus. | ebola virus (ebov) causes severe and often fatal hemorrhagic fever in humans and nonhuman primates (nhps). currently, there are no licensed vaccines or therapeutics for human use. recombinant vesicular stomatitis virus (rvsv)-based vaccine vectors, which encode an ebov glycoprotein in place of the vsv glycoprotein, have shown 100% efficacy against homologous sudan ebolavirus (sebov) or zaire ebolavirus (zebov) challenge in nhps. in addition, a single injection of a blend of three rvsv vectors co ... | 2013 | 24367715 |
| feline immunodeficiency virus envelope glycoproteins antagonize tetherin through a distinctive mechanism that requires virion incorporation. | bst2/tetherin inhibits the release of enveloped viruses from cells. primate lentiviruses have evolved specific antagonists (vpu, nef, and env). here we characterized tetherin proteins of species representing both branches of the order carnivora. comparison of tiger and cat (feliformia) to dog and ferret (caniformia) genes demonstrated that the tiger and cat share a start codon mutation that truncated most of the tetherin cytoplasmic tail early in the feliformia lineage (19 of 27 amino acids, inc ... | 2014 | 24390322 |
| vaccination with recombinant adenoviruses expressing ebola virus glycoprotein elicits protection in the interferon alpha/beta receptor knock-out mouse. | the resistance of adult immunocompetent mice to infection with ebolaviruses has led to the development of alternative small animal models that utilise immunodeficient mice, for example the interferon α/β receptor knock-out mouse (ifnr(-/-)). ifnr(-/-) mice have been shown to be susceptible to infection with ebolaviruses by multiple routes but it is not known if this murine model is suitable for testing therapeutics that rely on the generation of an immune response for efficacy. we have tested re ... | 2014 | 24461913 |
| post-exposure efficacy of oral t-705 (favipiravir) against inhalational ebola virus infection in a mouse model. | filoviruses cause disease with high case fatality rates and are considered biological threat agents. licensed post-exposure therapies that can be administered by the oral route are desired for safe and rapid distribution and uptake in the event of exposure or outbreaks. favipiravir or t-705 has broad antiviral activity and has already undergone phase ii and is undergoing phase iii clinical trials for influenza. here we report the first use of t-705 against ebola virus. t-705 gave 100% protection ... | 2014 | 24462697 |
| comprehensive functional analysis of n-linked glycans on ebola virus gp1. | ebola virus (ebov) entry requires the virion surface-associated glycoprotein (gp) that is composed of a trimer of heterodimers (gp1/gp2). the gp1 subunit contains two heavily glycosylated domains, the glycan cap and the mucin-like domain (mld). the glycan cap contains only n-linked glycans, whereas the mld contains both n- and o-linked glycans. site-directed mutagenesis was performed on ebov gp1 to systematically disrupt n-linked glycan sites to gain an understanding of their role in gp structur ... | 2014 | 24473128 |
| role of phosphatidylserine receptors in enveloped virus infection. | we recently demonstrated that a soluble protein, gas6, can facilitate viral entry by bridging viral envelope phosphatidylserine to axl, a receptor tyrosine kinase expressed on target cells. the interaction between phosphatidylserine, gas6, and axl was originally shown to be a molecular mechanism through which phagocytes recognize phosphatidylserine exposed on dead cells. since our initial report, several groups have confirmed that axl/gas6, as well as other phosphatidylserine receptors, facilita ... | 2014 | 24478428 |
| in silico derived small molecules bind the filovirus vp35 protein and inhibit its polymerase cofactor activity. | the ebola virus (ebov) genome only encodes a single viral polypeptide with enzymatic activity, the viral large (l) rna-dependent rna polymerase protein. however, currently, there is limited information about the l protein, which has hampered the development of antivirals. therefore, antifiloviral therapeutic efforts must include additional targets such as protein-protein interfaces. viral protein 35 (vp35) is multifunctional and plays important roles in viral pathogenesis, including viral mrna s ... | 2014 | 24495995 |
| identification of a broad-spectrum antiviral small molecule against severe acute respiratory syndrome coronavirus and ebola, hendra, and nipah viruses by using a novel high-throughput screening assay. | severe acute respiratory syndrome coronavirus (sars-cov) and ebola, hendra, and nipah viruses are members of different viral families and are known causative agents of fatal viral diseases. these viruses depend on cathepsin l for entry into their target cells. the viral glycoproteins need to be primed by protease cleavage, rendering them active for fusion with the host cell membrane. in this study, we developed a novel high-throughput screening assay based on peptides, derived from the glycoprot ... | 2014 | 24501399 |
| antibody therapy for ebola: is the tide turning around? | ebola viruses can cause severe hemorrhagic fever in humans and nonhuman primates with fatality rates up to 90%, and are identified as biosafety level 4 pathogens and cdc category a agents of bioterrorism. to date, there are no approved therapies and vaccines available to treat these infections. antibody therapy was estimated to be an effective and powerful treatment strategy against infectious pathogens in the late 19th, early 20th centuries but has fallen short to meet expectations to widely co ... | 2014 | 24503566 |
| emerging filoviral disease in uganda: proposed explanations and research directions. | outbreaks of ebola and marburg virus diseases have recently increased in frequency in uganda. this increase is probably caused by a combination of improved surveillance and laboratory capacity, increased contact between humans and the natural reservoir of the viruses, and fluctuations in viral load and prevalence within this reservoir. the roles of these proposed explanations must be investigated in order to guide appropriate responses to the changing epidemiological profile. other african setti ... | 2014 | 24515940 |
| middle east respiratory syndrome coronavirus 4a protein is a double-stranded rna-binding protein that suppresses pact-induced activation of rig-i and mda5 in the innate antiviral response. | middle east respiratory syndrome coronavirus (mers-cov) is an emerging pathogen that causes severe disease in human. mers-cov is closely related to bat coronaviruses hku4 and hku5. evasion of the innate antiviral response might contribute significantly to mers-cov pathogenesis, but the mechanism is poorly understood. in this study, we characterized mers-cov 4a protein as a novel immunosuppressive factor that antagonizes type i interferon production. mers-cov 4a protein contains a double-stranded ... | 2014 | 24522921 |
| a host-oriented inhibitor of junin argentine hemorrhagic fever virus egress. | there are currently no u.s. food and drug administration (fda)-approved vaccines or therapeutics to prevent or treat argentine hemorrhagic fever (ahf). the causative agent of ahf is junin virus (junv); a new world arenavirus classified as a national institute of allergy and infectious disease/centers for disease control and prevention category a priority pathogen. the ptap late (l) domain motif within junv z protein facilitates virion egress and transmission by recruiting host tsg101 and other e ... | 2014 | 24522922 |
| ebola hemorrhagic fever: novel biomarker correlates of clinical outcome. | ebola hemorrhagic fever (ehf) outbreaks occur sporadically in africa and result in high rates of death. the 2000-2001 outbreak of sudan virus-associated ehf in the gulu district of uganda led to 425 cases, of which 216 were laboratory confirmed, making it the largest ehf outbreak on record. serum specimens from this outbreak had been preserved in liquid nitrogen from the time of collection and were available for analysis. | 2014 | 24526742 |
| clinical documentation and data transfer from ebola and marburg virus disease wards in outbreak settings: health care workers' experiences and preferences. | understanding human filovirus hemorrhagic fever (fhf) clinical manifestations and evaluating treatment strategies require the collection of clinical data in outbreak settings, where clinical documentation has been limited. currently, no consensus among filovirus outbreak-response organisations guides best practice for clinical documentation and data transfer. semi-structured interviews were conducted with health care workers (hcws) involved in fhf outbreaks in sub-saharan africa, and with hcws e ... | 2014 | 24556792 |
| ebola virus vaccines: an overview of current approaches. | ebola hemorrhagic fever is one of the most fatal viral diseases worldwide affecting humans and nonhuman primates. although infections only occur frequently in central africa, the virus has the potential to spread globally and is classified as a category a pathogen that could be misused as a bioterrorism agent. as of today there is no vaccine or treatment licensed to counteract ebola virus infections. dna, subunit and several viral vector approaches, replicating and non-replicating, have been tes ... | 2014 | 24575870 |
| successful treatment of advanced ebola virus infection with t-705 (favipiravir) in a small animal model. | outbreaks of ebola hemorrhagic fever in sub-saharan africa are associated with case fatality rates of up to 90%. currently, neither a vaccine nor an effective antiviral treatment is available for use in humans. here, we evaluated the efficacy of the pyrazinecarboxamide derivative t-705 (favipiravir) against zaire ebola virus (ebov) in vitro and in vivo. t-705 suppressed replication of zaire ebov in cell culture by 4log units with an ic90 of 110μm. mice lacking the type i interferon receptor (ifn ... | 2014 | 24583123 |
| toll-like receptor agonist augments virus-like particle-mediated protection from ebola virus with transient immune activation. | identifying safe and effective adjuvants is critical for the advanced development of protein-based vaccines. pattern recognition receptor (prr) agonists are increasingly being explored as potential adjuvants, but there is concern that the efficacy of these molecules may be dependent on potentially dangerous levels of non-specific immune activation. the filovirus virus-like particle (vlp) vaccine protects mice, guinea pigs, and nonhuman primates from viral challenge. in this study, we explored th ... | 2014 | 24586996 |
| protection against filovirus diseases by a novel broad-spectrum nucleoside analogue bcx4430. | filoviruses are emerging pathogens and causative agents of viral haemorrhagic fever. case fatality rates of filovirus disease outbreaks are among the highest reported for any human pathogen, exceeding 90% (ref. 1). licensed therapeutic or vaccine products are not available to treat filovirus diseases. candidate therapeutics previously shown to be efficacious in non-human primate disease models are based on virus-specific designs and have limited broad-spectrum antiviral potential. here we show t ... | 2014 | 24590073 |
| multiple roles of the coagulation protease cascade during virus infection. | the coagulation cascade is activated during viral infections. this response may be part of the host defense system to limit spread of the pathogen. however, excessive activation of the coagulation cascade can be deleterious. in fact, inhibition of the tissue factor/factor viia complex reduced mortality in a monkey model of ebola hemorrhagic fever. other studies showed that incorporation of tissue factor into the envelope of herpes simplex virus increases infection of endothelial cells and mice. ... | 2014 | 24632711 |
| expression, purification, crystallization and preliminary x-ray analysis of full-length human rig-i. | the human innate immune system can detect invasion by microbial pathogens through pattern-recognition receptors that recognize structurally conserved pathogen-associated molecular patterns. retinoic acid-inducible gene i (rig-i)-like helicases (rlhs) are one of the two major families of pattern-recognition receptors that can detect viral rna. rig-i, belonging to the rlh family, is capable of recognizing intracellular viral rna from rna viruses, including influenza virus and ebola virus. here, fu ... | 2014 | 24637767 |
| induced il-10 splice altering approach to antiviral drug discovery. | ebola virus causes an acute hemorrhagic fever lethal in primates and rodents. the contribution of host immune factors to pathogenesis has yet to be determined and may reveal efficacious targets for potential treatment. in this study, we show that the interleukin (il)-10 signaling pathway modulates ebola pathogenesis. il-10(-/-) mice and wild-type mice receiving antisense targeting il-10 signaling via disrupting expression through aberrant splice altering were resistant to ebola virus infection. ... | 2014 | 24655055 |
| fullerene sugar balls: a new class of biologically active fullerene derivatives. | among the large variety of bioactive c60 derivatives, fullerene derivatives substituted with sugar residues, that is, glycofullerenes, are of particular interest. the sugar residues are not only solubilizing groups; their intrinsic biological properties also provide additional appealing features to the conjugates. the most recent advances in the synthesis and the biological applications of glycofullerenes are summarized in the present review article with special emphasis on globular glycofullere ... | 2014 | 24678063 |
| ebola outbreak claims more than 60 lives. | 2014 | 24687456 | |
| characterizing functional domains for tim-mediated enveloped virus entry. | t-cell immunoglobulin and mucin domain 1 (tim-1) and other tim family members were recently identified as phosphatidylserine (ptdser)-mediated virus entry-enhancing receptors (pveers). these proteins enhance entry of ebola virus (ebov) and other viruses by binding ptdser on the viral envelope, concentrating virus on the cell surface, and promoting subsequent internalization. the ptdser-binding activity of the immunoglobulin-like variable (igv) domain is essential for both virus binding and inter ... | 2014 | 24696470 |
| structure of the reston ebolavirus vp30 c-terminal domain. | the ebolaviruses can cause severe hemorrhagic fever. essential to the ebolavirus life cycle is the protein vp30, which serves as a transcriptional cofactor. here, the crystal structure of the c-terminal, np-binding domain of vp30 from reston ebolavirus is presented. reston vp30 and ebola vp30 both form homodimers, but the dimeric interfaces are rotated relative to each other, suggesting subtle inherent differences or flexibility in the dimeric interface. | 2014 | 24699737 |
| diverse viral glycoproteins as well as cd4 co-package into the same human immunodeficiency virus (hiv-1) particles. | retroviruses can acquire not only their own glycoproteins as they bud from the cellular membrane, but also some cellular and foreign viral glycoproteins. many of these non-native glycoproteins are actively recruited to budding virions, particularly other viral glycoproteins. this observation suggests that there may be a conserved mechanism underlying the recruitment of glycoproteins into viruses. if a conserved mechanism is used, diverse glycoproteins should localize to a single budding retrovir ... | 2014 | 24708808 |
| the clinically approved drugs amiodarone, dronedarone and verapamil inhibit filovirus cell entry. | filoviruses such as ebola virus and marburg virus cause a severe haemorrhagic fever syndrome in humans for which there is no specific treatment. since filoviruses use a complex route of cell entry that depends on numerous cellular factors, we hypothesized that there may be drugs already approved for human use for other indications that interfere with signal transduction or other cellular processes required for their entry and hence have anti-filoviral properties. | 2014 | 24710028 |
| west africa struggles to contain ebola outbreak. | 2014 | 24712029 | |
| high-throughput, luciferase-based reverse genetics systems for identifying inhibitors of marburg and ebola viruses. | marburg virus (marv) and ebola virus (ebov), members of the family filoviridae, represent a significant challenge to global public health. currently, no licensed therapies exist to treat filovirus infections, which cause up to 90% mortality in human cases. to facilitate development of antivirals against these viruses, we established two distinct screening platforms based on marv and ebov reverse genetics systems that express secreted gaussia luciferase (gluc). the first platform is a mini-genome ... | 2014 | 24713118 |
| fear spreads as number of ebola cases in guinea rises. | 2014 | 24714448 | |
| analysis of determinants in filovirus glycoproteins required for tetherin antagonism. | the host cell protein tetherin can restrict the release of enveloped viruses from infected cells. the hiv-1 protein vpu counteracts tetherin by removing it from the site of viral budding, the plasma membrane, and this process depends on specific interactions between the transmembrane domains of vpu and tetherin. in contrast, the glycoproteins (gps) of two filoviruses, ebola and marburg virus, antagonize tetherin without reducing surface expression, and the domains in gp required for tetherin cou ... | 2014 | 24721789 |
| infectious disease. are bats spreading ebola across sub-saharan africa? | 2014 | 24723589 | |
| possible leap ahead in filovirus therapeutics. | in a recent study published in nature, warren et al. describe the generation of a novel synthetic adenosine analogue, bcx4430, a synthetic drug-like small molecule that provides protection from ebola and marburg virus infection in animal models. | 2014 | 24732011 |
| a bsl-4 high-throughput screen identifies sulfonamide inhibitors of nipah virus. | nipah virus is a biosafety level 4 (bsl-4) pathogen that causes severe respiratory illness and encephalitis in humans. to identify novel small molecules that target nipah virus replication as potential therapeutics, southern research institute and galveston national laboratory jointly developed an automated high-throughput screening platform that is capable of testing 10,000 compounds per day within bsl-4 biocontainment. using this platform, we screened a 10,080-compound library using a cell-bas ... | 0 | 24735442 |
| emergence of zaire ebola virus disease in guinea. | in march 2014, the world health organization was notified of an outbreak of a communicable disease characterized by fever, severe diarrhea, vomiting, and a high fatality rate in guinea. virologic investigation identified zaire ebolavirus (ebov) as the causative agent. full-length genome sequencing and phylogenetic analysis showed that ebov from guinea forms a separate clade in relationship to the known ebov strains from the democratic republic of congo and gabon. epidemiologic investigation link ... | 2014 | 24738640 |
| small-molecule probes targeting the viral ppxy-host nedd4 interface block egress of a broad range of rna viruses. | budding of filoviruses, arenaviruses, and rhabdoviruses is facilitated by subversion of host proteins, such as nedd4 e3 ubiquitin ligase, by viral ppxy late (l) budding domains expressed within the matrix proteins of these rna viruses. as l domains are important for budding and are highly conserved in a wide array of rna viruses, they represent potential broad-spectrum targets for the development of antiviral drugs. to identify potential competitive blockers, we used the known nedd4 ww domain-pp ... | 2014 | 24741084 |
| characterization of host immune responses in ebola virus infections. | ebola causes highly lethal hemorrhagic fever in humans with no licensed countermeasures. its virulence can be attributed to several immunoevasion mechanisms: an early inhibition of innate immunity started by the downregulation of type i interferon, epitope masking and subversion of the adaptive humoural immunity by secreting a truncated form of the viral glycoprotein. deficiencies in specific and non-specific antiviral responses result in unrestricted viral replication and dissemination in the h ... | 2014 | 24742338 |
| bat flight and zoonotic viruses. | bats are sources of high viral diversity and high-profile zoonotic viruses worldwide. although apparently not pathogenic in their reservoir hosts, some viruses from bats severely affect other mammals, including humans. examples include severe acute respiratory syndrome coronaviruses, ebola and marburg viruses, and nipah and hendra viruses. factors underlying high viral diversity in bats are the subject of speculation. we hypothesize that flight, a factor common to all bats but to no other mammal ... | 2014 | 24750692 |
| material proximities and hotspots: toward an anthropology of viral hemorrhagic fevers. | this article outlines a research program for an anthropology of viral hemorrhagic fevers (collectively known as vhfs). it begins by reviewing the social science literature on ebola, marburg, and lassa fevers and charting areas for future ethnographic attention. we theoretically elaborate the hotspot as a way of integrating analysis of the two routes of vhf infection: from animal reservoirs to humans and between humans. drawing together recent anthropological investigations of human-animal entang ... | 2014 | 24752909 |
| durability of a vesicular stomatitis virus-based marburg virus vaccine in nonhuman primates. | the filoviruses, marburg virus (marv) and ebola virus, causes severe hemorrhagic fever with high mortality in humans and nonhuman primates. a promising filovirus vaccine under development is based on a recombinant vesicular stomatitis virus (rvsv) that expresses individual filovirus glycoproteins (gps) in place of the vsv glycoprotein (g). these vaccines have shown 100% efficacy against filovirus infection in nonhuman primates when challenge occurs 28-35 days after a single injection immunizatio ... | 2014 | 24759889 |
| [why does the ebola virus (which is prevalent in guinea today) not scare us?]. | 2014 | 24791431 | |
| post-exposure therapy of filovirus infections. | filovirus infections cause fatal hemorrhagic fever characterized by the initial onset of general symptoms before rapid progression to severe disease; the most virulent species can cause death to susceptible hosts within 10 days after the appearance of symptoms. before the advent of monoclonal antibody (mab) therapy, infection of nonhuman primates (nhps) with the most virulent filovirus species was fatal if interventions were not administered within minutes. a novel nucleoside analogue, bcx4430, ... | 2014 | 24794572 |
| the 2014 ebola virus disease outbreak in west africa. | on 23 march 2014, the world health organization issued its first communiqué on a new outbreak of ebola virus disease (evd), which began in december 2013 in guinée forestière (forested guinea), the eastern sector of the republic of guinea. located on the atlantic coast of west africa, guinea is the first country in this geographical region in which an outbreak of evd has occurred, leaving aside the single case reported in ivory coast in 1994. cases have now also been confirmed across guinea as we ... | 2014 | 24795448 |
| ebola--a growing threat? | 2014 | 24805988 | |
| assessment and improvement of indian-origin rhesus macaque and mauritian-origin cynomolgus macaque genome annotations using deep transcriptome sequencing data. | the genome annotations of rhesus (macaca mulatta) and cynomolgus (macaca fascicularis) macaques, two of the most common non-human primate animal models, are limited. | 2014 | 24810475 |
| pyridinyl imidazole inhibitors of p38 map kinase impair viral entry and reduce cytokine induction by zaire ebolavirus in human dendritic cells. | antigen presenting cells (apcs), including macrophages and dendritic cells, are early and sustained targets of ebola virus (ebov) infection in vivo. because ebov activates mitogen-activated protein kinase (mapk) signaling upon infection of apcs, we evaluated the effect of pyridinyl imidazole inhibitors of p38 mapk on ebov infection of human apcs and ebov mediated cytokine production from human dcs. the p38 mapk inhibitors reduced viral replication in pma-differentiated macrophage-like human thp- ... | 2014 | 24815087 |
| digital sensing and sizing of vesicular stomatitis virus pseudotypes in complex media: a model for ebola and marburg detection. | rapid, sensitive, and direct label-free capture and characterization of nanoparticles from complex media such as blood or serum will broadly impact medicine and the life sciences. we demonstrate identification of virus particles in complex samples for replication-competent wild-type vesicular stomatitis virus (vsv), defective vsv, and ebola- and marburg-pseudotyped vsv with high sensitivity and specificity. size discrimination of the imaged nanoparticles (virions) allows differentiation between ... | 2014 | 24840765 |
| ethical dilemmas in protecting individual rights versus public protection in the case of infectious diseases. | infectious diseases-including emerging and re-emerging diseases such as ebola and tuberculosis-continue to be important causes of morbidity and mortality in the globalizing, contemporary world. this article discusses the ethical issues associated with protecting the rights of individuals versus the protection of the health of populations in the case of infectious diseases. the discussion uses the traditional medical ethics approach together with the public health approach presented by faden and ... | 2013 | 24847171 |
| outbreak news. ebola virus disease, west africa. | 2014 | 24864345 | |
| ebola haemorrhagic fever in west africa. | 2014 | 24877203 | |
| viral proteins that bind double-stranded rna: countermeasures against host antiviral responses. | several animal viruses encode proteins that bind double-stranded rna (dsrna) to counteract host dsrna-dependent antiviral responses. this article discusses the structure and function of the dsrna-binding proteins of influenza a virus and ebola viruses (ebovs). | 2014 | 24905203 |
| ebola in west africa: gaining community trust and confidence. | 2014 | 24910220 | |
| vaccinating captive chimpanzees to save wild chimpanzees. | infectious disease has only recently been recognized as a major threat to the survival of endangered chimpanzees and critically endangered gorillas in the wild. one potentially powerful tool, vaccination, has not been deployed in fighting this disease threat, in good part because of fears about vaccine safety. here we report on what is, to our knowledge, the first trial in which captive chimpanzees were used to test a vaccine intended for use on wild apes rather than humans. we tested a virus-li ... | 2014 | 24912183 |
| identification of continuous human b-cell epitopes in the vp35, vp40, nucleoprotein and glycoprotein of ebola virus. | ebola virus (ebov) is a highly virulent human pathogen. recovery of infected patients is associated with efficient ebov-specific immunoglobulin g (igg) responses, whereas fatal outcome is associated with defective humoral immunity. as b-cell epitopes on ebov are poorly defined, we sought to identify specific epitopes in four ebov proteins (glycoprotein (gp), nucleoprotein (np), and matrix viral protein (vp)40 and vp35). for the first time, we tested ebov igg+ sera from asymptomatic individuals a ... | 2014 | 24914933 |
| evolutionary origins of human herpes simplex viruses 1 and 2. | herpesviruses have been infecting and codiverging with their vertebrate hosts for hundreds of millions of years. the primate simplex viruses exemplify this pattern of virus-host codivergence, at a minimum, as far back as the most recent common ancestor of new world monkeys, old world monkeys, and apes. humans are the only primate species known to be infected with two distinct herpes simplex viruses: hsv-1 and hsv-2. human herpes simplex viruses are ubiquitous, with over two-thirds of the human p ... | 2014 | 24916030 |
| a highly immunogenic fragment derived from zaire ebola virus glycoprotein elicits effective neutralizing antibody. | in order to produce polyvalent vaccines based on single rvsv vector, we investigated the immunogenicity, antibody neutralizing activity, and antigenic determinant domain of zaire ebola's fragment mfl (aa 393-556) that contains furin site and internal fusion loop. both the recombinant protein and the recombinant plasmid of fragment mfl elicited high levels of antibody, similar to those of zaire ebola gp (zgp). the mfl fragment of zgp also elicited high levels of neutralizing antibody and induced ... | 2014 | 24930448 |
| role of protein phosphatase 1 in dephosphorylation of ebola virus vp30 protein and its targeting for the inhibition of viral transcription. | the filovirus ebola (ebov) causes the most severe hemorrhagic fever known. the ebov rna-dependent polymerase complex includes a filovirus-specific vp30, which is critical for the transcriptional but not replication activity of ebov polymerase; to support transcription, vp30 must be in a dephosphorylated form. here we show that ebov vp30 is phosphorylated not only at the n-terminal serine clusters identified previously but also at the threonine residues at positions 143 and 146. we also show that ... | 2014 | 24936058 |
| ebola virus modulates transforming growth factor β signaling and cellular markers of mesenchyme-like transition in hepatocytes. | ebola virus (ebov) causes a severe hemorrhagic disease in humans and nonhuman primates, with a median case fatality rate of 78.4%. although ebov is considered a public health concern, there is a relative paucity of information regarding the modulation of the functional host response during infection. we employed temporal kinome analysis to investigate the relative early, intermediate, and late host kinome responses to ebov infection in human hepatocytes. pathway overrepresentation analysis and f ... | 2014 | 24942569 |
| undiagnosed acute viral febrile illnesses, sierra leone. | sierra leone in west africa is in a lassa fever-hyperendemic region that also includes guinea and liberia. each year, suspected lassa fever cases result in submission of ≈500-700 samples to the kenema government hospital lassa diagnostic laboratory in eastern sierra leone. generally only 30%-40% of samples tested are positive for lassa virus (lasv) antigen and/or lasv-specific igm; thus, 60%-70% of these patients have acute diseases of unknown origin. to investigate what other arthropod-borne an ... | 0 | 24959946 |
| ebola viral disease outbreak--west africa, 2014. | on march 21, 2014, the guinea ministry of health reported the outbreak of an illness characterized by fever, severe diarrhea, vomiting, and a high case-fatality rate (59%) among 49 persons. specimens from 15 of 20 persons tested at institut pasteur in lyon, france, were positive for an ebola virus by polymerase chain reaction. viral sequencing identified ebola virus (species zaïre ebolavirus), one of five viruses in the genus ebolavirus, as the cause. cases of ebola viral disease (evd) were init ... | 2014 | 24964881 |
| a novel life cycle modeling system for ebola virus shows a genome length-dependent role of vp24 in virus infectivity. | work with infectious ebola viruses is restricted to biosafety level 4 (bsl4) laboratories, presenting a significant barrier for studying these viruses. life cycle modeling systems, including minigenome systems and transcription- and replication-competent virus-like particle (trvlp) systems, allow modeling of the virus life cycle under bsl2 conditions; however, all current systems model only certain aspects of the virus life cycle, rely on plasmid-based viral protein expression, and have been use ... | 2014 | 24965473 |
| membrane binding and bending in ebola vp40 assembly and egress. | lipid-enveloped viruses contain a lipid bilayer coat that protects their genome and helps to facilitate entry into the host cell. filoviruses are lipid-enveloped viruses that have up to 90% clinical fatality and include marbug (marv) and ebola (ebov). these pleomorphic filamentous viruses enter the host cell through their membrane-embedded glycoprotein and then replicate using just seven genes encoded in their negative-sense rna genome. ebov budding occurs from the inner leaflet of the plasma me ... | 2014 | 24995005 |
| how ebola impacts social dynamics in gorillas: a multistate modelling approach. | emerging infectious diseases can induce rapid changes in population dynamics and threaten population persistence. in socially structured populations, the transfers of individuals between social units, for example, from breeding groups to non-breeding groups, shape population dynamics. we suggest that diseases may affect these crucial transfers. we aimed to determine how disturbance by an emerging disease affects demographic rates of gorillas, especially transfer rates within populations and immi ... | 2015 | 24995485 |
| ebola in west africa: a familiar pattern? | 2014 | 24999980 | |
| health ministers in west africa hold crisis talks on ebola virus. | 2014 | 25000938 | |
| ebola in sierra leone: a call for action. | 2014 | 25002177 | |
| ebola outbreak response; experience and development of screening tools for viral haemorrhagic fever (vhf) in a hiv center of excellence near to vhf epicentres. | there have been 3 outbreaks of viral hemorrhagic fever (vhf) in uganda in the last 2 years. vhf often starts with non-specific symptoms prior to the onset of haemorrhagic signs. hiv clinics in vhf outbreak countries such as uganda see large numbers of patients with hiv 1/2 infection presenting with non-specific symptoms every day. whilst there are good screening tools for general health care facilities expecting vhf suspects, we were unable to find tools for use in hiv or other non-acute clinics ... | 2014 | 25007269 |
| spatial localization of the ebola virus glycoprotein mucin-like domain determined by cryo-electron tomography. | the ebola virus glycoprotein mucin-like domain (mld) is implicated in ebola virus cell entry and immune evasion. using cryo-electron tomography of ebola virus-like particles, we determined a three-dimensional structure for the full-length glycoprotein in a near-native state and compared it to that of a glycoprotein lacking the mld. our results, which show that the mld is located at the apex and the sides of each glycoprotein monomer, provide a structural template for analysis of mld function. | 2014 | 25008940 |
| [a first outbreak of ebola virus in west africa]. | 2014 | 25014459 | |
| hspa5 is an essential host factor for ebola virus infection. | development of novel strategies targeting the highly virulent ebolaviruses is urgently required. a proteomic study identified the er chaperone hspa5 as an ebolavirus-associated host protein. here, we show using the hspa5 inhibitor (-)- epigallocatechin gallate (egcg) that the chaperone is essential for virus infection, thereby demonstrating a functional significance for the association. furthermore, in vitro and in vivo gene targeting impaired viral replication and protected animals in a lethal ... | 2014 | 25017472 |
| ebola emergency meeting establishes new control centre. | 2014 | 25025099 | |
| ebola and marburg virus diseases in africa: increased risk of outbreaks in previously unaffected areas? | filoviral hemorrhagic fever (fhf) is caused by ebolaviruses and marburgviruses, which both belong to the family filoviridae. egyptian fruit bats (rousettus aegyptiacus) are the most likely natural reservoir for marburgviruses and entry into caves and mines that they stay in has often been associated with outbreaks of mvd. on the other hand, the natural reservoir for ebola viruses remains elusive; however, handling of wild animal carcasses has been associated with some outbreaks of evd. in the la ... | 2014 | 25040642 |
| visual displays that directly interface and provide read-outs of molecular states via molecular graphics processing units. | the monitoring of molecular systems usually requires sophisticated technologies to interpret nanoscale events into electronic-decipherable signals. we demonstrate a new method for obtaining read-outs of molecular states that uses graphics processing units made from molecular circuits. because they are made from molecules, the units are able to directly interact with molecular systems. we developed deoxyribozyme-based graphics processing units able to monitor nucleic acids and output alphanumeric ... | 2014 | 25044570 |
| [ebola vigilance]. | 2014 | 25055582 | |
| evaluation of transmission risks associated with in vivo replication of several high containment pathogens in a biosafety level 4 laboratory. | containment level 4 (cl4) laboratories studying biosafety level 4 viruses are under strict regulations to conduct nonhuman primate (nhp) studies in compliance of both animal welfare and biosafety requirements. nhps housed in open-barred cages raise concerns about cross-contamination between animals, and accidental exposure of personnel to infectious materials. to address these concerns, two nhp experiments were performed. one examined the simultaneous infection of 6 groups of nhps with 6 differe ... | 2014 | 25059478 |
| infectious diseases. ebola drugs still stuck in lab. | 2014 | 25061181 | |
| two doctors die from ebola and lives of others under threat in west africa. | 2014 | 25073968 | |
| a new approach to determining whole viral genomic sequences including termini using a single deep sequencing run. | next-generation sequencing is now commonly used for a variety of applications in virology including virus discovery, investigation of quasispecies, viral evolution, metagenomics, and analyses of antiviral resistance. however, there are limitations with the current sample preparation methods used for deep sequencing of viral genomes, especially during de novo sequencing. for example, current methods are unable to capture the terminal sequences of viral genomes in an efficient and effective manner ... | 2014 | 25075935 |
| outbreak of ebola virus disease in guinea: where ecology meets economy. | 2014 | 25079231 |