| venezuelan equine encephalitis virus replicon particle vaccine protects nonhuman primates from intramuscular and aerosol challenge with ebolavirus. | there are no vaccines or therapeutics currently approved for the prevention or treatment of ebolavirus infection. previously, a replicon vaccine based on venezuelan equine encephalitis virus (veev) demonstrated protective efficacy against marburg virus in nonhuman primates. here, we report the protective efficacy of sudan virus (sudv)- and ebola virus (ebov)-specific veev replicon particle (vrp) vaccines in nonhuman primates. vrp vaccines were developed to express the glycoprotein (gp) of either ... | 2013 | 23408633 |
| ebolavirus nucleoprotein c-termini potently attract single domain antibodies enabling monoclonal affinity reagent sandwich assay (marsa) formulation. | antigen detection assays can play an important part in environmental surveillance and diagnostics for emerging threats. we are interested in accelerating assay formulation; targeting the agents themselves to bypass requirements for a priori genome information or surrogates. previously, using in vitro affinity reagent selection on marburg virus we rapidly established monoclonal affinity reagent sandwich assay (marsa) where one recombinant antibody clone was both captor and tracer for polyvalent n ... | 2013 | 23577211 |
| use of the syrian hamster as a new model of ebola virus disease and other viral hemorrhagic fevers. | historically, mice and guinea pigs have been the rodent models of choice for therapeutic and prophylactic countermeasure testing against ebola virus disease (evd). recently, hamsters have emerged as a novel animal model for the in vivo study of evd. in this review, we discuss the history of the hamster as a research laboratory animal, as well as current benefits and challenges of this model. availability of immunological reagents is addressed. salient features of evd in hamsters, including relev ... | 2012 | 23242370 |
| immune parameters correlate with protection against ebola virus infection in rodents and nonhuman primates. | ebola virus causes severe hemorrhagic fever in susceptible hosts. currently, no licensed vaccines or treatments are available; however, several experimental vaccines have been successful in protecting rodents and nonhuman primates (nhps) from the lethal zaire ebolavirus (zebov) infection. the objective of this study was to evaluate immune responses correlating with survival in these animals after lethal challenge with zebov. knockout mice with impaired ability to generate normal t and/or b cell ... | 0 | 23115355 |
| mouse models for filovirus infections. | the filoviruses marburg- and ebolaviruses can cause severe hemorrhagic fever (hf) in humans and nonhuman primates. because many cases have occurred in geographical areas lacking a medical research infrastructure, most studies of the pathogenesis of filoviral hf, and all efforts to develop drugs and vaccines, have been carried out in biocontainment laboratories in non-endemic countries, using nonhuman primates (nhps), guinea pigs and mice as animal models. nhps appear to closely mirror filoviral ... | 2012 | 23170168 |
| prediction and identification of mouse cytotoxic t lymphocyte epitopes in ebola virus glycoproteins. | ebola viruses (ebovs) cause severe hemorrhagic fever with a high mortality rate. at present, there are no licensed vaccines or efficient therapies to combat ebov infection. previous studies have shown that both humoral and cellular immune responses are crucial for controlling ebola infection. cd8+ t cells play an important role in mediating vaccine-induced protective immunity. the objective of this study was to identify h-2d-specific t cell epitopes in ebov glycoproteins (gps). | 2012 | 22695180 |
| current ebola vaccines. | ebolaviruses cause severe viral hemorrhagic fever in humans and non-human primates (nhps), with case fatality rates of up to 90%. currently, neither a specific treatment nor a vaccine licensed for use in humans is available. however, a number of vaccine candidates have been developed in the last decade that are highly protective in nhps, the gold standard animal model for ebola hemorrhagic fever. | 2012 | 22559078 |
| illustrating and homology modeling the proteins of the zika virus. | the zika virus (zikv) is a flavivirus of the family flaviviridae, which is similar to dengue virus, yellow fever and west nile virus. recent outbreaks in south america, latin america, the caribbean and in particular brazil have led to concern for the spread of the disease and potential to cause guillain-barré syndrome and microcephaly. although zikv has been known of for over 60 years there is very little in the way of knowledge of the virus with few publications and no crystal structures. no an ... | 2016 | 27746901 |
| filovirus research in gabon and equatorial africa: the experience of a research center in the heart of africa. | health research programs targeting the population of gabon and equatorial africa at the international center for medical research in franceville (cirmf), gabon, have evolved during the years since its inception in 1979 in accordance with emerging diseases. since the reemergence of ebola virus in central africa, the cirmf "emerging viral disease unit" developed diagnostic tools and epidemiologic strategies and transfers of such technology to support the response of the national public health syst ... | 2012 | 23170174 |
| zika virus: the latest newcomer. | since the beginning of this century, humanity has been facing a new emerging, or re-emerging, virus threat almost every year: west nile, influenza a, avian flu, dengue, chikungunya, sars, mers, ebola, and now zika, the latest newcomer. zika virus (zikv), a flavivirus transmitted by aedes mosquitoes, was identified in 1947 in a sentinel monkey in uganda, and later on in humans in nigeria. the virus was mainly confined to the african continent until it was detected in south-east asia the 1980's, t ... | 2016 | 27148186 |
| identify-isolate-inform: a tool for initial detection and management of zika virus patients in the emergency department. | first isolated in 1947 from a monkey in the zika forest in uganda, and from mosquitoes in the same forest the following year, zika virus has gained international attention due to concerns for infection in pregnant women potentially causing fetal microcephaly. more than one million people have been infected since the appearance of the virus in brazil in 2015. approximately 80% of infected patients are asymptomatic. an association with microcephaly and other birth defects as well as guillain-barre ... | 2016 | 27330653 |
| induction of the pro-inflammatory nf-kb-sensitive mirna-146a by human neurotrophic viruses. | | 2015 | 25691883 |
| the immune gene repertoire of an important viral reservoir, the australian black flying fox. | bats are the natural reservoir host for a range of emerging and re-emerging viruses, including sars-like coronaviruses, ebola viruses, henipaviruses and rabies viruses. however, the mechanisms responsible for the control of viral replication in bats are not understood and there is little information available on any aspect of antiviral immunity in bats. massively parallel sequencing of the bat transcriptome provides the opportunity for rapid gene discovery. although the genomes of one megabat an ... | 2012 | 22716473 |
| small molecule inhibitors of er α-glucosidases are active against multiple hemorrhagic fever viruses. | host cellular endoplasmic reticulum α-glucosidases i and ii are essential for the maturation of viral glycosylated envelope proteins that use the calnexin mediated folding pathway. inhibition of these glycan processing enzymes leads to the misfolding and degradation of these viral glycoproteins and subsequent reduction in virion secretion. we previously reported that, cm-10-18, an imino sugar α-glucosidase inhibitor, efficiently protected the lethality of dengue virus infection of mice. in the c ... | 2013 | 23578725 |
| structural analysis of monomeric rna-dependent polymerases: evolutionary and therapeutic implications. | the crystal structures of monomeric rna-dependent rna polymerases and reverse transcriptases of more than 20 different viruses are available in the protein data bank. they all share the characteristic right-hand shape of dna- and rna polymerases formed by the fingers, palm and thumb subdomains, and, in many cases, "fingertips" that extend from the fingers towards the thumb subdomain, giving the viral enzyme a closed right-hand appearance. six conserved structural motifs that contain key residues ... | 2015 | 26397100 |
| 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 |
| 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 |
| the ebola virus interferon antagonist vp24 directly binds stat1 and has a novel, pyramidal fold. | ebolaviruses cause hemorrhagic fever with up to 90% lethality and in fatal cases, are characterized by early suppression of the host innate immune system. one of the proteins likely responsible for this effect is vp24. vp24 is known to antagonize interferon signaling by binding host karyopherin α proteins, thereby preventing them from transporting the tyrosine-phosphorylated transcription factor stat1 to the nucleus. here, we report that vp24 binds stat1 directly, suggesting that vp24 can suppre ... | 2012 | 22383882 |
| open drug discovery for the zika virus. | the zika virus (zikv) outbreak in the americas has caused global concern that we may be on the brink of a healthcare crisis. the lack of research on zikv in the over 60 years that we have known about it has left us with little in the way of starting points for drug discovery. our response can build on previous efforts with virus outbreaks and lean heavily on work done on other flaviviruses such as dengue virus. we provide some suggestions of what might be possible and propose an open drug discov ... | 2016 | 27134728 |
| mrprimerv: a database of pcr primers for rna virus detection. | many infectious diseases are caused by viral infections, and in particular by rna viruses such as mers, ebola and zika. to understand viral disease, detection and identification of these viruses are essential. although pcr is widely used for rapid virus identification due to its low cost and high sensitivity and specificity, very few online database resources have compiled pcr primers for rna viruses. to effectively detect viruses, the mrprimerv database (http://mrprimerv.com) contains 152 380 2 ... | 2016 | 27899620 |
| febrile illness diagnostics and the malaria-industrial complex: a socio-environmental perspective. | global prioritization of single-disease eradication programs over improvements to basic diagnostic capacity in the global south have left the world unprepared for epidemics of chikungunya, ebola, zika, and whatever lies on the horizon. the medical establishment is slowly realizing that in many parts of sub-saharan africa (ssa), particularly urban areas, up to a third of patients suffering from acute fever do not receive a correct diagnosis of their infection. | 2016 | 27855644 |
| evaluation of realstar reverse transcription-polymerase chain reaction kits for filovirus detection in the laboratory and field. | diagnosis of ebola virus (ebov) disease (evd) requires laboratory testing. | 2016 | 27549586 |
| one-step reverse-transcription fret-pcr for differential detection of five ebolavirus species. | ebola is an emerging infectious disease caused by a deadly virus belonging to the family filoviridae, genus ebolavirus. based on their geographical distribution, ebolavirus has been classified into total five species so far, mainly zaire, sudan, taï forest, bundibugyo and reston. it is important to be able to differentiate the ebolavirus species as they significantly differ in pathogenicity and more than one species can be present in an area. we have developed a one-step step-down rt-pcr detecti ... | 2015 | 26017916 |
| ebola vp40 in exosomes can cause immune cell dysfunction. | ebola virus (ebov) is an enveloped, ssrna virus from the family filoviridae capable of causing severe hemorrhagic fever with up to 80-90% mortality rates. the most recent outbreak of ebov in west africa starting in 2014 resulted in over 11,300 deaths; however, long-lasting persistence and recurrence in survivors has been documented, potentially leading to further transmission of the virus. we have previously shown that exosomes from cells infected with hiv-1, htlv-1 and rift valley fever virus a ... | 2016 | 27872619 |
| highly conserved regions in ebola virus rna dependent rna polymerase may be act as a universal novel peptide vaccine target: a computational approach. | ebola virus (ebov) is such kind of virus which is responsible for 23,825 cases and 9675 deaths worldwide only in 2014 and with an average diseases fatality rate between 25 % and 90 %. although, medical technology has tried to handle the problems, there is no food and drug administration (fda)-approved therapeutics or vaccines available for the prevention, post exposure, or treatment of ebola virus disease (evd). | 2015 | 26820892 |
| human and murine ifit1 proteins do not restrict infection of negative-sense rna viruses of the orthomyxoviridae, bunyaviridae, and filoviridae families. | interferon-induced protein with tetratricopeptide repeats 1 (ifit1) is a host protein with reported cell-intrinsic antiviral activity against several rna viruses. the proposed basis for the activity against negative-sense rna viruses is the binding to exposed 5'-triphosphates (5'-ppp) on the genome of viral rna. however, recent studies reported relatively low binding affinities of ifit1 for 5'-ppp rna, suggesting that ifit1 may not interact efficiently with this moiety under physiological condit ... | 2015 | 26157117 |
| systematic genome-wide screening and prediction of micrornas in ebov during the 2014 ebolavirus outbreak. | recently, several thousand people have been killed by the ebolavirus disease (evd) in west africa, yet no current antiviral medications and treatments are available. systematic investigation of ebolavirus whole genomes during the 2014 outbreak may shed light on the underlying mechanisms of evd development. here, using the genome-wide screening in ebolavirus genome sequences, we predicted four putative viral microrna precursors (pre-mirnas) and seven putative mature micrornas (mirnas). combing bi ... | 2015 | 26011078 |
| backs against the wall: novel and existing strategies used during the 2014-2015 ebola virus outbreak. | the 2014-2015 outbreak of ebola virus (ebov), originating from guinea, is now responsible for the infection of >20,000 people in 9 countries. whereas past filovirus outbreaks in sub-saharan africa have been rapidly brought under control with comparably few cases, this outbreak has been particularly resistant to containment efforts. both the general population and primary health care workers have been affected by this outbreak, with hundreds of doctors and nurses being infected in the line of dut ... | 0 | 25972518 |
| critical care medicine and infectious diseases: an emerging combined subspecialty in the united states. | the recent rise in unfilled training positions among infectious diseases (id) fellowship programs nationwide indicates that id is declining as a career choice among internal medicine residency graduates. supplementing id training with training in critical care medicine (ccm) might be a way to regenerate interest in the specialty. hands-on patient care and higher salaries are obvious attractions. high infection prevalence and antibiotic resistance in intensive care units, expanding immunosuppress ... | 2015 | 25944345 |
| good and bad news about ebola. | | 2015 | 25764305 |
| ebola virus: the need to take some preventive measures. | | 0 | 26101517 |
| treatment of ebola virus infection with antibodies from reconvalescent donors. | clinical evidence suggests that antibodies from reconvalescent donors (persons who have recovered from infection) may be effective in the treatment of ebola virus infection. administration of this treatment to ebola virus-infected patients while preventing the transmission of other pathogenic viruses may be best accomplished by use of virus-inactivated reconvalescent plasma. | 0 | 25695274 |
| virion-associated phosphatidylethanolamine promotes tim1-mediated infection by ebola, dengue, and west nile viruses. | phosphatidylserine (ps) receptors contribute to two crucial biological processes: apoptotic clearance and entry of many enveloped viruses. in both cases, they recognize ps exposed on the plasma membrane. here we demonstrate that phosphatidylethanolamine (pe) is also a ligand for ps receptors and that this phospholipid mediates phagocytosis and viral entry. we show that a subset of ps receptors, including t-cell immunoglobulin (ig) mucin domain protein 1 (tim1), efficiently bind pe. we further sh ... | 2015 | 26575624 |
| calcium regulation of hemorrhagic fever virus budding: mechanistic implications for host-oriented therapeutic intervention. | hemorrhagic fever viruses, including the filoviruses (ebola and marburg) and arenaviruses (lassa and junín viruses), are serious human pathogens for which there are currently no fda approved therapeutics or vaccines. importantly, transmission of these viruses, and specifically late steps of budding, critically depend upon host cell machinery. consequently, strategies which target these mechanisms represent potential targets for broad spectrum host oriented therapeutics. an important cellular sig ... | 2015 | 26513362 |
| hepatitis, hiv and ebola: light at the end of the tunnel. | | 0 | 26958003 |
| advancing one health policy and implementation through the concept of one medicine one science. | numerous interspecies disease transmission events, ebola virus being a recent and cogent example, highlight the complex interactions between human, animal, and environmental health and the importance of addressing medicine and health in a comprehensive scientific manner. the diversity of information gained from the natural, social, behavioral, and systems sciences is critical to developing and sustainably promoting integrated health approaches that can be implemented at the local, national, and ... | 2015 | 26421234 |
| fc receptors and their influence on efficacy of therapeutic antibodies for treatment of viral diseases. | the lack of vaccines against several important viral diseases necessitates the development of therapeutics to save lives and control epidemics. in recent years, therapeutic antibodies have received considerable attention due to their good safety profiles and clinical success when used against viruses such as respiratory syncytial virus, ebola virus and hendra virus. the binding affinity of these antibodies can directly impact their therapeutic efficacy. however, we and others have also demonstra ... | 2015 | 26466016 |
| 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 |
| ebola virus disease. | | 2014 | 25497512 |
| tim-family proteins promote infection of multiple enveloped viruses through virion-associated phosphatidylserine. | human t-cell immunoglobulin and mucin-domain containing proteins (tim1, 3, and 4) specifically bind phosphatidylserine (ps). tim1 has been proposed to serve as a cellular receptor for hepatitis a virus and ebola virus and as an entry factor for dengue virus. here we show that tim1 promotes infection of retroviruses and virus-like particles (vlps) pseudotyped with a range of viral entry proteins, in particular those from the filovirus, flavivirus, new world arenavirus and alphavirus families. tim ... | 2013 | 23555248 |
| acquired immunity and asymptomatic reservoir impact on frontline and airport ebola outbreak syndromic surveillance and response. | the number of surveillance networks for infectious disease diagnosis and response has been growing. in 2000, the world health organization (who) established the global outbreak alert and response network, which has been endorsed by each of the 46 who african members since then. yet, taming the dynamics and plague of the vicious ebola virus disease (evd) in african countries has been patchy and erratic due to inadequate surveillance and contact tracing, community defiance and resistance, a lack o ... | 2014 | 25699182 |
| the interconnected and cross-border nature of risks posed by infectious diseases. | infectious diseases can constitute public health emergencies of international concern when a pathogen arises, acquires new characteristics, or is deliberately released, leading to the potential for loss of human lives as well as societal disruption. a wide range of risk drivers are now known to lead to and/or exacerbate the emergence and spread of infectious disease, including global trade and travel, the overuse of antibiotics, intensive agriculture, climate change, high population densities, a ... | 2014 | 25308818 |
| safety and immunogenicity of dna vaccines encoding ebolavirus and marburgvirus wild-type glycoproteins in a phase i clinical trial. | ebolavirus and marburgvirus cause severe hemorrhagic fever with high mortality and are potential bioterrorism agents. there are no available vaccines or therapeutic agents. previous clinical trials evaluated transmembrane-deleted and point-mutation ebolavirus glycoproteins (gps) in candidate vaccines. constructs evaluated in this trial encode wild-type (wt) gp from ebolavirus zaire and sudan species and the marburgvirus angola strain expressed in a dna vaccine. | 2014 | 25225676 |
| development and evaluation of a panel of filovirus sequence capture probes for pathogen detection by next-generation sequencing. | a detailed understanding of the circulating pathogens in a particular geographic location aids in effectively utilizing targeted, rapid diagnostic assays, thus allowing for appropriate therapeutic and containment procedures. this is especially important in regions prevalent for highly pathogenic viruses co-circulating with other endemic pathogens such as the malaria parasite. the importance of biosurveillance is highlighted by the ongoing ebola virus disease outbreak in west africa. for example, ... | 2014 | 25207553 |
| positive-unlabeled learning for the prediction of conformational b-cell epitopes. | the incomplete ground truth of training data of b-cell epitopes is a demanding issue in computational epitope prediction. the challenge is that only a small fraction of the surface residues of an antigen are confirmed as antigenic residues (positive training data); the remaining residues are unlabeled. as some of these uncertain residues can possibly be grouped to form novel but currently unknown epitopes, it is misguided to unanimously classify all the unlabeled residues as negative training da ... | 2015 | 26681157 |
| aptamers in diagnostics and treatment of viral infections. | aptamers are in vitro selected dna or rna molecules that are capable of binding a wide range of nucleic and non-nucleic acid molecules with high affinity and specificity. they have been conducted through the process known as selex (systematic evolution of ligands by exponential enrichment). it serves to reach specificity and considerable affinity to target molecules, including those of viral origin, both proteins and nucleic acids. properties of aptamers allow detecting virus infected cells or v ... | 2015 | 25690797 |
| purification of monoclonal antibody against ebola gp1 protein expressed in nicotiana benthamiana. | monoclonal antibodies (mabs) are one of the fastest growing drug molecules targeting the treatment of diseases ranging from arthritis, immune disorders, and infectious diseases to cancer. due to its unique application principle, antibodies are commonly produced in large quantities. plants, such as nicotiana benthamiana, offer a unique production platform for bio-therapeutics due to their ability to produce large amounts of biomolecules in a relatively quick manner. however, purification of a tar ... | 2015 | 25746758 |
| adapting high-throughput screening methods and assays for biocontainment laboratories. | high-throughput screening (hts) has been integrated into the drug discovery process, and multiple assay formats have been widely used in many different disease areas but with limited focus on infectious agents. in recent years, there has been an increase in the number of hts campaigns using infectious wild-type pathogens rather than surrogates or biochemical pathogen-derived targets. concurrently, enhanced emerging pathogen surveillance and increased human mobility have resulted in an increase i ... | 0 | 25710545 |
| focus on ebola virus research. | | 0 | 25565061 |
| ebola outbreak in western africa 2014: what is going on with ebola virus? | the 2014 outbreak of ebola virus disease (evd) in west africa, caused by ebola virus (zaire ebola virus species), is the largest outbreak of evd in history. it cause hemorrhagic fever in human and nonhuman primates with high mortality rate up to 90% and can be transmitted by direct contact with blood, body fluids, skin of evd patients or persons who have died of evd. as of december 17, 2014, 450 healthcare personnel are known to have been infected with ebola, of whom 244 died. for development of ... | 2015 | 25648530 |
| assessing community reactions to ebola virus disease and other disasters: using social psychological research to enhance public health and disaster communications. | drawing on the lessons learned from previous disaster and disease outbreak studies over the past two decades, in the following article we review research related to social psychological assessment of community attitudes, knowledge, and beliefs associated with the recent ebola outbreak and other public health threats, and discuss the use of this information to assist in future disaster planning and crisis communications. psychologists, physicians, and others in the healthcare field need to be awa ... | 0 | 25844070 |
| reservoir host immune responses to emerging zoonotic viruses. | zoonotic viruses, such as hiv, ebola virus, coronaviruses, influenza a viruses, hantaviruses, or henipaviruses, can result in profound pathology in humans. in contrast, populations of the reservoir hosts of zoonotic pathogens often appear to tolerate these infections with little evidence of disease. why are viruses more dangerous in one species than another? immunological studies investigating quantitative and qualitative differences in the host-virus equilibrium in animal reservoirs will be key ... | 2014 | 25533784 |
| filovirus emergence and vaccine development: a perspective for health care practitioners in travel medicine. | recent case reports of viral hemorrhagic fever in europe and the united states have raised concerns about the possibility for increased importation of filoviruses to non-endemic areas. this emerging threat is concerning because of the increase in global air travel and the rise of tourism in central and eastern africa and the greater dispersion of military troops to areas of infectious disease outbreaks. marburg viruses (marv) and ebola viruses (ebov) have been associated with outbreaks of severe ... | 2010 | 21208830 |
| treatment with hyperimmune equine immunoglobulin or immunoglobulin fragments completely protects rodents from ebola virus infection. | recent successes with monoclonal antibody cocktails zmapp(tm) and mil77 against ebola virus (ebov) infections have reignited interest in antibody-based therapeutics. since the production process for monoclonal antibodies can be prolonged and costly, alternative treatments should be investigated. we produced purified equine antisera from horses hyperimmunized with ebov virus-like particles, and tested the post-exposure efficacy of the antisera in a mouse model of infection. balb/c mice were given ... | 2016 | 27067649 |
| neglected tropical diseases in the anthropocene: the cases of zika, ebola, and other infections. | | 2016 | 27058728 |
| cell-targeting antibodies in immunity to ebola. | as the 2014-15 ebola virus epidemic in west africa evolved from emergency to lesson, developers of both vaccines and therapeutic antibodies were left with the puzzlement of what kinds of anti-ebola antibodies are predictably desirable in treating the afflicted, and what antibodies might account for the specific and lasting protection elicited by the more effective vaccines. the facile answer in virology is that neutralizing antibody (nab) is desired and required. however, with ebola and other fi ... | 2016 | 27005312 |
| consortia's critical role in developing medical countermeasures for re-emerging viral infections: a usa perspective. | viral infections, such as ebola, severe acute respiratory syndrome/middle east respiratory syndrome and west nile virus have emerged as a serious health threat with no effective therapies. these infections have little commercial potential and are not a high priority for the pharmaceutical industry. however, the academic community has been active in this area for many years. the challenge is how to take this academic virology knowledge into a drug discovery and development domain. one approach is ... | 2016 | 27325914 |
| targeting innate immunity for antiviral therapy through small molecule agonists of the rlr pathway. | the cellular response to virus infection is initiated when pathogen recognition receptors (prr) engage viral pathogen-associated molecular patterns (pamps). this process results in induction of downstream signaling pathways that activate the transcription factor interferon regulatory factor 3 (irf3). irf3 plays a critical role in antiviral immunity to drive the expression of innate immune response genes, including those encoding antiviral factors, type 1 interferon, and immune modulatory cytokin ... | 2015 | 26676770 |
| transcriptional analysis of antiviral small molecule therapeutics as agonists of the rlr pathway. | the recognition of pathogen associated molecular patterns (pamps) by pattern recognition receptors (prr) during viral infection initiates the induction of antiviral signaling pathways, including activation of the interferon regulator factor 3 (irf3). we identified small molecule compounds that activate irf3 through mavs, thereby inhibiting infection by viruses of the families flaviviridae (west nile virus, dengue virus and hepatitis c virus), filoviridae (ebola virus), orthomyxoviridae (influenz ... | 2016 | 26981429 |
| vectorborne infections, mali. | | 0 | 26812625 |
| navigating the zika panic. | the epidemics of ebola virus in west africa and zika virus in america highlight how viruses can explosively emerge into new territories. these epidemics also exposed how unprepared we are to handle infectious disease emergencies. this is also true when we consider hypothesized new clinical features of infection, such as the associations between zika virus infection and severe neurological disease, including microcephaly and guillain-barré syndrome. on the surface, these pathologies appear to be ... | 2016 | 27746903 |
| exposure-specific and age-specific attack rates for ebola virus disease in ebola-affected households, sierra leone. | using histories of household members of ebola virus disease (evd) survivors in sierra leone, we calculated risk of evd by age and exposure level, adjusting for confounding and clustering, and estimated relative risks. of 937 household members in 94 households, 448 (48%) had had evd. highly correlated with exposure, evd risk ranged from 83% for touching a corpse to 8% for minimal contact and varied by age group: 43% for children <2 years of age; 30% for those 5-14 years of age; and >60% for adult ... | 2016 | 27144428 |
| inhibitory antibodies targeting emerging viruses: advancements and mechanisms. | from ebola virus outbreaks in western africa to the introduction of chikungunya and zika viruses in the americas, new and neglected viruses continue to emerge and spread around the world. due to a lack of existing vaccines or specific therapeutics, little other than supportive care and attempts to interrupt transmission can be provided during initial outbreaks. this has prompted a shift in vaccine design and development to identify novel epitopes and mechanisms of protection that may offer a bro ... | 2016 | 27226280 |
| packaging of actin into ebola virus vlps. | the actin cytoskeleton has been implicated in playing an important role assembly and budding of several rna virus families including retroviruses and paramyxoviruses. in this report, we sought to determine whether actin is incorporated into ebola vlps, and thus may play a role in assembly and/or budding of ebola virus. our results indicated that actin and ebola virus vp40 strongly co-localized in transfected cells as determined by confocal microscopy. in addition, actin was packaged into budding ... | 2005 | 16367999 |
| single-particle tracking demonstrates that actin coordinates the movement of the ebola virus matrix protein. | the ebola virus causes severe hemorrhagic fever and has a mortality rate that can be as high as 90%, yet no vaccines or approved therapeutics, to our knowledge, are available. to replicate and egress the infected host cell the ebola virus uses vp40, its major matrix protein to assemble at the inner leaflet of the plasma membrane. the assembly and budding of vp40 from the plasma membrane of host cells seem still poorly understood. we investigated the assembly and egress of vp40 at the plasma memb ... | 0 | 23199932 |
| the baboon (papio spp.) as a model of human ebola virus infection. | baboons are susceptible to natural ebola virus (ebov) infection and share 96% genetic homology with humans. despite these characteristics, baboons have rarely been utilized as experimental models of human ebov infection to evaluate the efficacy of prophylactics and therapeutics in the united states. this review will summarize what is known about the pathogenesis of ebov infection in baboons compared to ebov infection in humans and other old world nonhuman primates. in addition, we will discuss h ... | 2012 | 23202470 |
| the etiology of ebola virus disease-like illnesses in ebola virusnegative patients from sierra leone. | during the 2014 ebola virus disease (evd) outbreak, less than half of evd-suspected cases were laboratory tested as ebola virus (ebov)-negative, but disease identity remained unknown. in this study we investigated the etiology of evd-like illnesses in ebov-negative cases. from november 13, 2014 to march 16, 2015, evd-suspected patients were admitted to jui government hospital and assessed for ebov infection by real-time pcr. of 278 ebov negative patients, 223 (80.21%), 142 (51.08%), 123 (44.24%) ... | 0 | 27058894 |
| development and evaluation of reverse transcription-loop-mediated isothermal amplification (rt-lamp) assay coupled with a portable device for rapid diagnosis of ebola virus disease in guinea. | given the current absence of specific drugs or vaccines for ebola virus disease (evd), rapid, sensitive, and reliable diagnostic methods are required to stem the transmission chain of the disease. we have developed a rapid detection assay for zaire ebolavirus based on reverse transcription-loop-mediated isothermal amplification (rt-lamp) and coupled with a novel portable isothermal amplification and detection platform. the rt-lamp assay is based on primer sets that target the untranscribed trail ... | 2016 | 26900929 |
| viral hemorrhagic fever diagnostics. | there are 4 families of viruses that cause viral hemorrhagic fever (vhf), including filoviridae. ebola virus is one virus within the family filoviridae and the cause of the current outbreak of vhf in west africa. vhf-endemic areas are found throughout the world, yet traditional diagnosis of vhf has been performed in large reference laboratories centered in europe and the united states. the large amount of capital needed, as well as highly trained and skilled personnel, has limited the availabili ... | 2015 | 26354968 |
| emerging viral threats in gabon: health capacities and response to the risk of emerging zoonotic diseases in central africa. | emerging infectious diseases (eid) are currently the major threat to public health worldwide and most eid events have involved zoonotic infectious agents. central africa in general and gabon in particular are privileged areas for the emergence of zoonotic eids. indeed, human incursions in gabonese forests for exploitation purposes lead to intensified contacts between humans and wildlife thus generating an increased risk of emergence of zoonotic diseases. in gabon, 51 endemic or potential endemic ... | 2010 | 22460397 |
| inhibition of innate immune responses is key to pathogenesis by arenaviruses. | mammalian arenaviruses are zoonotic viruses that cause asymptomatic, persistent infections in their rodent hosts but can lead to severe and lethal hemorrhagic fever with bleeding and multiorgan failure in human patients. lassa virus (lasv), for example, is endemic in several west african countries, where it is responsible for an estimated 500,000 infections and 5,000 deaths annually. there are currently no fda-licensed therapeutics or vaccines available to combat arenavirus infection. a hallmark ... | 2016 | 26865707 |
| the deadly ebola threat in the midst of an overwhelming dengue epidemic. | the recent death tolls and morbidities associated with two deadly viral haemorrhagic fevers (vhfs), i.e., ebola and dengue, are simply shocking. by the end of august 2014, 65 672 people were afflicted with dengue fever (df) in malaysia, with 9505 from kelantan, and there were 128 reported deaths. more astounding are the death tolls associated with ebola: 3091 deaths from 6574 reported cases so far. it is not difficult to imagine the potential disaster if ebola spreads beyond africa. vhfs are cha ... | 0 | 25897277 |
| ebola hemorrhagic fever and the current state of vaccine development. | current ebola virus outbreak in west africa already reached the total number of 1,323 including 729 deaths by july 31st. the fatality is around 55% in the southeastern area of guinea, sierra leone, liberia, and nigeria. the number of patients with ebola hemorrhagic fever (ehf) was continuously increasing even though the any effective therapeutics or vaccines has not been developed yet. the ebola virus in guinea showed 98% homology with zaire ebola virus. study of the pathogenesis of ebola virus ... | 2014 | 25562048 |
| camouflage and misdirection: the full-on assault of ebola virus disease. | ebolaviruses cause a severe hemorrhagic fever syndrome that is rapidly fatal to humans and nonhuman primates. ebola protein interactions with host cellular proteins disrupt type i and type ii interferon responses, rnai antiviral responses, antigen presentation, t-cell-dependent b cell responses, humoral antibodies, and cell-mediated immunity. this multifaceted approach to evasion and suppression of innate and adaptive immune responses in their target hosts leads to the severe immune dysregulatio ... | 2014 | 25417101 |
| tim-family proteins inhibit hiv-1 release. | accumulating evidence indicates that t-cell immunoglobulin (ig) and mucin domain (tim) proteins play critical roles in viral infections. herein, we report that the tim-family proteins strongly inhibit hiv-1 release, resulting in diminished viral production and replication. expression of tim-1 causes hiv-1 gag and mature viral particles to accumulate on the plasma membrane. mutation of the phosphatidylserine (ps) binding sites of tim-1 abolishes its ability to block hiv-1 release. tim-1, but to a ... | 2014 | 25136083 |
| the application of biomedical engineering techniques to the diagnosis and management of tropical diseases: a review. | this paper reviews a number of biomedical engineering approaches to help aid in the detection and treatment of tropical diseases such as dengue, malaria, cholera, schistosomiasis, lymphatic filariasis, ebola, leprosy, leishmaniasis, and american trypanosomiasis (chagas). many different forms of non-invasive approaches such as ultrasound, echocardiography and electrocardiography, bioelectrical impedance, optical detection, simplified and rapid serological tests such as lab-on-chip and micro-/nano ... | 2015 | 25806872 |
| antiviral therapies against ebola and other emerging viral diseases using existing medicines that block virus entry. | emerging viral diseases pose a threat to the global population as intervention strategies are mainly limited to basic containment due to the lack of efficacious and approved vaccines and antiviral drugs. the former was the only available intervention when the current unprecedented ebolavirus (ebov) outbreak in west africa began. prior to this, the development of ebov vaccines and anti-viral therapies required time and resources that were not available. therefore, focus has turned to re-purposing ... | 2015 | 26069727 |
| viral immune surveillance: toward a th17/th9 gate to the central nervous system. | viral cellular immune surveillance is a dynamic and fluid system that is driven by finely regulated cellular processes including cytokines and other factors locally in the microenvironment and systemically throughout the body. it is questionable as to what extent the central nervous system (cns) is an immune-privileged organ protected by the blood-brain barrier (bbb). recent evidence suggests converging pathways through which viral infection, and its associated immune surveillance processes, may ... | 2015 | 25780281 |
| progress of vaccine and drug development for ebola preparedness. | since the first case of ebola virus disease (evd) in guinea was reported in march 2014 by world health organization (who), the outbreak has continued through the year and the total number of 19,065 patients was reported as the confirmed or suspected in the evd-affected countries. among the cases, 7,388 patients were reported death by 19 december. currently, available therapeutics to treat the infected patients or vaccines to prevent people from infection is not developed yet while viral diagnost ... | 2015 | 25648233 |
| multiplex nucleic acid suspension bead arrays for detection and subtyping of filoviruses. | here we describe multiplex suspension bead array systems that allow fast and reliable detection of reverse transcriptase (rt) pcr amplified filovirus genomes and also enable subtyping of ebola virus species and marburg virus strains. these systems have an analytical sensitivity equivalent to that of rt-pcr. | 2015 | 25631793 |
| comparative analysis of host cell entry of ebola virus from sierra leone, 2014, and zaire, 1976. | the ongoing ebola virus (ebov) disease (evd) epidemic in western africa is the largest evd outbreak recorded to date and requires the rapid development and deployment of antiviral measures. the viral glycoprotein (gp) facilitates host cell entry and, jointly with cellular interaction partners, constitutes a potential target for antiviral intervention. however, it is unknown whether the gps of the currently and previously circulating ebovs use the same mechanisms for cellular entry and are thus s ... | 2015 | 25840443 |
| 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 |
| differential transcriptional responses to ebola and marburg virus infection in bat and human cells. | the unprecedented outbreak of ebola in west africa resulted in over 28,000 cases and 11,000 deaths, underlining the need for a better understanding of the biology of this highly pathogenic virus to develop specific counter strategies. two filoviruses, the ebola and marburg viruses, result in a severe and often fatal infection in humans. however, bats are natural hosts and survive filovirus infections without obvious symptoms. the molecular basis of this striking difference in the response to fil ... | 2016 | 27713552 |
| short report: serological evidence of under-reported dengue circulation in sierra leone. | dengue virus (denv) is thought to have emerged from a sylvatic cycle in africa but has since become adapted to an urban-centric transmission cycle. these urban areas include villages in west africa where denv is not often routinely considered for patients presenting with febrile illnesses, as other endemic diseases (malaria, lassa fever, e.g.) present with similar non-specific symptoms. thus, dengue is likely under diagnosed in the region. these plaque reduction neutralization test-50 (prnt50) s ... | 2016 | 27116605 |
| a rapid and low-cost pcr thermal cycler for infectious disease diagnostics. | the ability to make rapid diagnosis of infectious diseases broadly available in a portable, low-cost format would mark a great step forward in global health. many molecular diagnostic assays are developed based on using thermal cyclers to carry out polymerase chain reaction (pcr) and reverse-transcription pcr for dna and rna amplification and detection, respectively. unfortunately, most commercial thermal cyclers are expensive and need continuous electrical power supply, so they are not suitable ... | 2016 | 26872358 |
| bispecific antibody affords complete post-exposure protection of mice from both ebola (zaire) and sudan viruses. | filoviruses (ebola and marburg) cause severe hemorrhagic fever. there are five species of ebolavirus; among these, the ebola (zaire) and sudan viruses (ebov and sudv, respectively) are highly pathogenic and have both caused recurring, large outbreaks. however, the ebov and sudv glycoprotein (gp) sequences are 45% divergent and thus antigenically distinct. few antibodies with cross-neutralizing properties have been described to date. we used antibody engineering to develop novel bispecific antibo ... | 2016 | 26758505 |
| immunosuppression by hemorrhagic fever-causing viruses. | | 0 | 26657729 |
| protective mabs and cross-reactive mabs raised by immunization with engineered marburg virus gps. | the filoviruses, which include the marburg- and ebolaviruses, have caused multiple outbreaks among humans this decade. antibodies against the filovirus surface glycoprotein (gp) have been shown to provide life-saving therapy in nonhuman primates, but such antibodies are generally virus-specific. many monoclonal antibodies (mabs) have been described against ebola virus. in contrast, relatively few have been described against marburg virus. here we present ten mabs elicited by immunization of mice ... | 2015 | 26115029 |
| space and place for who health development dialogues in the african region. | majority of the countries in the world health organization (who) african region are not on track to achieve the health-related millennium development goals, yet even more ambitious sustainable development goals (sdgs), including sdg 3 on heath, have been adopted. this paper highlights the challenges - amplified by the recent ebola virus disease (evd) outbreak in west africa - that require who and other partners' dialogue in support of the countries, and debate on how who can leverage the existin ... | 2016 | 27455065 |
| requirements within the ebola viral glycoprotein for tetherin antagonism. | tetherin is an interferon-induced, intrinsic cellular response factor that blocks release of numerous viruses, including ebola virus, from infected cells. as with many viruses targeted by host factors, ebola virus employs a tetherin antagonist, the viral glycoprotein (ebogp), to counteract restriction and promote virus release. unlike other tetherin antagonists such as hiv-1 vpu or kshv k5, the features within ebogp needed to overcome tetherin are not well characterized. here, we describe sequen ... | 2015 | 26516900 |
| experiences and psychosocial impact of west africa ebola deployment on us health care volunteers. | this qualitative study was designed to assess health care volunteers' experiences and psychosocial impacts associated with deployment to the west africa ebola epidemic. | 2016 | 27803840 |
| suramin is a potent inhibitor of chikungunya and ebola virus cell entry. | chikungunya virus (chikv) is a mosquito-transmitted alphavirus that causes high fever, rash, and recurrent arthritis in humans. it has efficiently adapted to aedes albopictus, which also inhabits temperate regions and currently causes large outbreaks in the caribbean and latin america. ebola virus (ebov) is a member of the filovirus family. it causes the ebola virus disease (edv), formerly known as ebola hemorrhagic fever in humans and has a mortality rate of up to 70 %. the last outbreak in wes ... | 2016 | 27581733 |
| antibody treatment of ebola and sudan virus infection via a uniquely exposed epitope within the glycoprotein receptor-binding site. | previous efforts to identify cross-neutralizing antibodies to the receptor-binding site (rbs) of ebolavirus glycoproteins have been unsuccessful, largely because the rbs is occluded on the viral surface. we report a monoclonal antibody (fvm04) that targets a uniquely exposed epitope within the rbs; cross-neutralizes ebola (ebov), sudan (sudv), and, to a lesser extent, bundibugyo viruses; and shows protection against ebov and sudv in mice and guinea pigs. the antibody cocktail zmapp™ is remarkabl ... | 2016 | 27160900 |
| transmission or within-host dynamics driving pulses of zoonotic viruses in reservoir-host populations. | progress in combatting zoonoses that emerge from wildlife is often constrained by limited knowledge of the biology of pathogens within reservoir hosts. we focus on the host-pathogen dynamics of four emerging viruses associated with bats: hendra, nipah, ebola, and marburg viruses. spillover of bat infections to humans and domestic animals often coincides with pulses of viral excretion within bat populations, but the mechanisms driving such pulses are unclear. three hypotheses dominate current res ... | 2016 | 27489944 |
| toward a common secure future: four global commissions in the wake of ebola. | lawrence gostin and colleagues offer a set of priorities for global health preparedness and response for future infectious disease threats. | 2016 | 27195954 |
| exploiting genetic interference for antiviral therapy. | rapidly evolving viruses are a major threat to human health. such viruses are often highly pathogenic (e.g., influenza virus, hiv, ebola virus) and routinely circumvent therapeutic intervention through mutational escape. error-prone genome replication generates heterogeneous viral populations that rapidly adapt to new selection pressures, leading to resistance that emerges with treatment. however, population heterogeneity bears a cost: when multiple viral variants replicate within a cell, they c ... | 2016 | 27149616 |
| potential impact of sexual transmission on ebola virus epidemiology: sierra leone as a case study. | sexual transmission of ebola virus disease (evd) 6 months after onset of symptoms has been recently documented, and ebola virus rna has been detected in semen of survivors up to 9 months after onset of symptoms. as countries affected by the 2013-2015 epidemic in west africa, by far the largest to date, are declared free of ebola virus disease (evd), it remains unclear what threat is posed by rare sexual transmission events that could arise from survivors. | 2016 | 27135922 |
| pandemics, ebola, and the family doctor. | | 0 | 26975910 |
| infectious diseases. beyond ebola. | | 0 | 26912880 |
| international health regulations, ebola, and emerging infectious diseases in latin america and the caribbean. | the world health organization's determination of the ebola virus disease outbreak as a public health event of international concern prompted nonaffected countries to implement measures to prevent, detect, and manage the introduction of the virus in their territories. the outbreak provided an opportunity to assess the operational implementation of the international health regulations' core capacities and health systems' preparedness to handle a potential or confirmed case of ebola virus disease. ... | 2015 | 26691130 |