Publications
| Title | Abstract | Year Filter | PMID(sorted ascending) Filter |
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| her2-mediated enhancement of ebola virus entry. | multiple cell surface molecules including tam receptors (tyro3, axl, and mertk), a family of tyrosine kinase receptors, can serve as attachment receptors for ebola virus (ebov) entry into cells. the interaction of these receptors with ebov particles is believed to trigger the initial internalization events that lead to macropinocytosis. however, the details of how these interactions lead to ebov internalization have yet to be elucidated. here, we screened receptor tyrosine kinase (rtk) inhibitor ... | 2020 | 33052961 |
| longitudinal antibody and t cell responses in ebola virus disease survivors and contacts: an observational cohort study. | the 2013-16 ebola virus disease epidemic in west africa caused international alarm due to its rapid and extensive spread resulting in a significant death toll and social unrest within the affected region. the large number of cases provided an opportunity to study the long-term kinetics of zaire ebolavirus-specific immune response of survivors in addition to known contacts of those infected with the virus. | 2020 | 33065039 |
| immunity to ebola virus: the full picture is being revealed. | 2020 | 33065040 | |
| reflecting on knowledge translation strategies from global health research projects in tunisia and the republic of côte d'ivoire. | we describe the knowledge translation strategies in two projects and share lessons learned about knowledge sharing and uptake. | 2020 | 33068122 |
| knowledge, (mis-)conceptions, risk perception, and behavior change during pandemics: a scoping review of 149 studies. | the severe acute respiratory syndrome-coronavirus-2 pandemic has spread rapidly and has a growing impact on individuals, communities, and healthcare systems worldwide. at the core of any pandemic response is the ability of authorities and other stakeholders to react appropriately by promoting hygiene and social distancing behaviors. successfully reaching this goal requires both individual and collective efforts to drastically modify daily routines and activities. there is a need to clarify how k ... | 2020 | 33073717 |
| implementation of accelerated research: strategies for implementation as applied in a phase 1 ad26.zebov, mva-bn-filo two-dose ebola vaccine clinical trial in uganda. | the 2013-2016 ebola epidemic in west africa is the worst ever caused by ebolaviruses with over 28,000 human cases and 11,325 deaths. the world health organisation (who) declared the epidemic a public health crisis that required accelerated development of novel interventions including vaccines. the medical research council/uganda virus research institute and london school of hygiene and tropical medicine uganda research unit (mrc/uvri & lshtm uganda research unit) was among the african research s ... | 2020 | 33073737 |
| the brighton collaboration standardized template for collection of key information for risk/benefit assessment of a modified vaccinia ankara (mva) vaccine platform. | the brighton collaboration viral vector vaccines safety working group (v3swg) was formed to evaluate the safety and characteristics of live, recombinant viral vector vaccines. the modified vaccinia ankara (mva) vector system is being explored as a platform for development of multiple vaccines. this paper reviews the molecular and biological features specifically of the mva-bn vector system, followed by a template with details on the safety and characteristics of an mva-bn based vaccine against z ... | 2020 | 33077299 |
| the ebola outbreak is finally slowing down. | 2019 | 33077971 | |
| modelling the daily risk of ebola in the presence and absence of a potential vaccine. | ebola virus - one of the deadliest viral diseases, with a mortality rate around 90% - damages the immune system and organs, with symptoms including episodic fever, chills, malaise and myalgia. the recombinant vesicular stomatitis virus-based candidate vaccine (rvsv-zebov) has demonstrated clinical efficacy against ebola in ring-vaccination clinical trials. in order to evaluate the potential effect of this candidate vaccine, we developed risk equations for the daily risk of ebola infection both c ... | 2020 | 33078134 |
| immunological perspective for ebola virus infection and various treatment measures taken to fight the disease. | ebolaviruses, discovered in 1976, belongs to the filoviridae family, which also includes marburg and lloviu viruses. they are negative-stranded rna viruses with six known species identified to date. ebola virus (ebov) is a member of zaire ebolavirus species and can cause the ebola virus disease (evd), an emerging zoonotic disease that results in homeostatic imbalance and multi-organ failure. there are three ebov outbreaks documented in the last six years resulting in significant morbidity (> 32, ... | 2020 | 33080902 |
| mental models of infectious diseases and public understanding of covid-19 prevention. | the emergence of viral diseases such as ebola virus disease, zika virus disease, and the coronavirus disease (covid-19) has posed considerable challenges to health care systems around the world. public health strategy to address emerging infectious diseases has depended in part on human behavior change and yet the perceptions and knowledge motivating that behavior have been at times inconsistent with the latest consensus of peer-reviewed science. part of that disjuncture likely involves the exis ... | 2020 | 33081500 |
| bayesian reconstruction of transmission trees from genetic sequences and uncertain infection times. | genetic sequence data of pathogens are increasingly used to investigate transmission dynamics in both endemic diseases and disease outbreaks. such research can aid in the development of appropriate interventions and in the design of studies to evaluate them. several computational methods have been proposed to infer transmission chains from sequence data; however, existing methods do not generally reliably reconstruct transmission trees because genetic sequence data or inferred phylogenetic trees ... | 2020 | 33085643 |
| local perspectives on ebola during its tenth outbreak in dr congo: a nationwide qualitative study. | the democratic republic of congo (dr congo) struggled to end the tenth outbreak of ebola virus disease (ebola), which appeared in north kivu in 2018. it was reported that rumors were hampering the response effort. we sought to identify any rumors that could have influenced outbreak containment and affected prevention in unaffected areas of dr congo. | 2020 | 33091054 |
| molecular determinants of ebola nucleocapsid stability from molecular dynamics simulations. | ebola virus (ebov) is a human pathogen with the ability to cause hemorrhagic fever and bleeding diathesis in hosts. the life cycle of ebov depends on its nucleocapsid. the ebola nucleocapsid consists of a helical assembly of nucleoproteins (nps) encapsidating single-stranded viral rna (ssrna). knowledge of the molecular determinants of ebola nucleocapsid stability is essential for the development of therapeutics against ebov. however, large degrees of freedom associated with the ebola nucleocaps ... | 2020 | 33092380 |
| development of a multiplex microsphere immunoassay for the detection of antibodies against highly pathogenic viruses in human and animal serum samples. | surveillance of highly pathogenic viruses circulating in both human and animal populations is crucial to unveil endemic infections and potential zoonotic reservoirs. monitoring the burden of disease by serological assay could be used as an early warning system for imminent outbreaks as an increased seroprevalance often precedes larger outbreaks. however, the multitude of highly pathogenic viruses necessitates the need to identify specific antibodies against several targets from both humans as we ... | 2020 | 33095766 |
| meta-analysis of predictive symptoms for ebola virus disease. | one of the leading challenges in the 2013-2016 west african ebola virus disease (evd) outbreak was how best to quickly identify patients with evd, separating them from those without the disease, in order to maximise limited isolation bed capacity and keep health systems functioning. | 2020 | 33095771 |
| innate immune responses to acute viral infection during pregnancy. | immunological adaptations in pregnancy allow maternal tolerance of the semi-allogeneic fetus but also increase maternal susceptibility to infection. at implantation, the endometrial stroma, glands, arteries and immune cells undergo anatomical and functional transformation to create the decidua, the specialized secretory endometrium of pregnancy. the maternal decidua and the invading fetal trophoblast constitute a dynamic junction that facilitates a complex immunological dialogue between the two. ... | 2020 | 33101294 |
| role of platelet cytokines in dengue virus infection. | platelets are anucleated blood cells derived from bone marrow megakaryocytes and play a crucial role in hemostasis and thrombosis. platelets contain specialized storage organelles, called alpha-granules, contents of which are rich in cytokines such as c-x-c motif chemokine ligand (cxcl) 1/4/7, (c-c motif) ligand (ccl) 5/3, cxcl8 (also called as interleukin 8, il-8), and transforming growth factor β (tgf-β). activation of platelets lead to degranulation and release of contents into the plasma. pl ... | 2020 | 33102253 |
| nurses' experiences of their decision-making process when participating in clinical trials during the 2014-2016 west african ebola crisis. | due to the absence of a licenced vaccine or drug for treatment of ebola patients during the 2014-2016 west africa outbreak, frontline nurses were at increased risk of exposure. hence, they were prioritized to participate in clinical trials to receive experimental therapeutics. to our knowledge no study has explored the nurses' experiences of their decision-making process when volunteering in clinical trials using unproven agents, which is the purpose of this qualitative study. | 2020 | 33111332 |
| presence of ebola virus in breast milk and risk of mother-to-child transmission: synthesis of evidence. | to help inform global guidelines on infant feeding, this systematic review synthesizes evidence related to the presence of the ebola virus (ebov) in breast milk and its potential risk of viral transmission to the infant when breastfeeding. we relied on a comprehensive search strategy to identify studies including women with suspected, probable, or confirmed ebov infection, intending to breastfeed or give breast milk to an infant. our search identified 10,454 records, and after deduplication and ... | 2020 | 33113592 |
| the use of near-infrared light-emitting fluorescent nanodiamond particles to detect ebola virus glycoprotein: technology development and proof of principle. | there is a dire need for rapid diagnostic tests of high sensitivity, efficiency, and point-of-test reporting capability to mitigate lethal viral epidemic outbreaks. | 2020 | 33116489 |
| ebola, quarantine, and the need for a new ethical framework. | quarantine is a broad public health strategy used to control infectious diseases outbreaks. an arguably most aggressive public health intervention, quarantine limits the asymptomatic individuals' liberty and can result in significant harm. quarantine was used in an attempt to control several ebola outbreaks during the ebola epidemic in west africa in 2014. the most concerning quarantine intervention occurred at west point, a slum of 75,000 people in the capital liberian capital, monrovia. this w ... | 2020 | 33117502 |
| method feasibility for cross-species testing, qualification, and validation of the filovirus animal nonclinical group anti-ebola virus glycoprotein immunoglobulin g enzyme-linked immunosorbent assay for non-human primate serum samples. | an anti-zaire ebola virus (ebov) glycoprotein (gp) immunoglobulin g (igg) enzyme linked immunosorbent assay (elisa) was developed to quantify the serum levels of anti-ebov igg in human and non-human primate (nhp) serum following vaccination and/or exposure to ebov. this method was validated for testing human serum samples as previously reported. however, for direct immunobridging comparability between humans and nhps, additional testing was warranted. first, method feasibility experiments were p ... | 2020 | 33119638 |
| update on biosafety and emerging infections for the clinical microbiology laboratory. | biosafety risks are prevalent in all areas of the clinical laboratories. clinical laboratorians have become accustomed to accepting these risks. when an emerging pathogen appears, the concerns become elevated. since the appearance of ebola virus in the united states in 2014, biosafety practices have made progress. a recent association of public health laboratories survey shows that clinical laboratories are unprepared for current and emerging biosafety challenges. this article focuses on the bio ... | 2020 | 33121616 |
| screening for anti-influenza actives of prefractionated traditional chinese medicines. | traditional chinese medicines (tcms) have proven to possess advantages in counteracting virus infections according to clinical practices. it's therefore of great value to discover novel antivirals from tcms. in this paper, one hundred medicinal plants which have been included in tcm prescriptions for antiviral treatment were selected and prefractionated into 5 fractions each by sequentially using cyclohexane, dichloromethane, ethyl acetate, n-butanol, and water. 500 tcm-simplified extracts were ... | 2020 | 33123207 |
| addressing obstacles to the inclusion of palliative care in humanitarian health projects: a qualitative study of humanitarian health professionals' and policy makers' perceptions. | humanitarian non-governmental organizations provide assistance to communities affected by war, disaster and epidemic. a primary focus of healthcare provision by these organizations is saving lives; however, curative care will not be sufficient, appropriate, or available for some patients. in these instances, palliative care approaches to ease suffering and promote dignity are needed. though several recent initiatives have increased the probability of palliative care being included in humanitaria ... | 2020 | 33133234 |
| insights of novel coronavirus (sars-cov-2) disease outbreak, management and treatment. | emerging and re-emerging viral diseases poses a threat to living organisms, and led to serious concern to humankind and public health. the last two decades, viral epidemics such as the severe acute respiratory syndrome (sars-cov) reported in the years 2002-2003, and h1n1 influenza (swine flu) in 2009, middle east respiratory syndrome (mers-cov) from saudi arabia in 2012, ebola virus in 2014-2016, and zika virus in 2015. the recent outbreak of 2019-cov-2 or severe acute respiratory syndrome-2 (sa ... | 2020 | 33134740 |
| quantification of ebola virus replication kinetics in vitro. | mathematical modelling has successfully been used to provide quantitative descriptions of many viral infections, but for the ebola virus, which requires biosafety level 4 facilities for experimentation, modelling can play a crucial role. ebola modelling efforts have primarily focused on in vivo virus kinetics, e.g., in animal models, to aid the development of antivirals and vaccines. but, thus far, these studies have not yielded a detailed specification of the infection cycle, which could provid ... | 2020 | 33137116 |
| evaluation of novel hiv vaccine candidates using recombinant vesicular stomatitis virus vector produced in serum-free vero cell cultures. | acquired immune deficiency syndrome (aids) in humans is a result of the destruction of the immune system caused by human immunodeficiency virus (hiv) infection. this serious epidemic is still progressing world-wide. despite advances in treatment, a safe and effective preventive hiv vaccine is desired to combat this disease, and to save millions of lives. however, such a vaccine is not available yet although extensive amounts of resources in research and development have been invested over three ... | 2020 | 33139138 |
| the two-stage interaction of ebola virus vp40 with nucleoprotein results in a switch from viral rna synthesis to virion assembly/budding. | ebola virus (ebov) is an enveloped negative-sense rna virus and a member of the filovirus family. nucleoprotein (np) expression alone leads to the formation of inclusion bodies (ibs), which are critical for viral rna synthesis. the matrix protein, vp40, not only plays a critical role in virus assembly/budding, but also can regulate transcription and replication of the viral genome. however, the molecular mechanism by which vp40 regulates viral rna synthesis and virion assembly/budding is unknown ... | 2020 | 33141416 |
| development of an antigen detection assay for early point-of-care diagnosis of zaire ebolavirus. | the 2013-2016 ebola virus (ebov) outbreak in west africa and the ongoing cases in the democratic republic of the congo have spurred development of a number of medical countermeasures, including rapid ebola diagnostic tests. the likelihood of transmission increases as the disease progresses due to increasing viral load and potential for contact with others. early diagnosis of ebov is essential for halting spread of the disease. polymerase chain reaction assays are the gold standard for diagnosing ... | 2020 | 33141837 |
| fda approves antibody cocktail for ebola virus. | 2020 | 33144717 | |
| [ebola, the first vaccines available]. | in the recent years, ebola virus has been responsible for several major epidemics. research efforts have allowed the development and evaluation in the field of several vaccine candidates. at present, two of them are already approved and used in the fight against the virus in the democratic republic of congo. this review aims to describe the different candidates, the clinical trials that have been conducted as well as the first results in the field. | 2020 | 33151849 |
| a paramyxovirus-like model for ebola virus bipartite promoters. | paramyxo- and filovirus nucleocapsids (ncs) have bipartite promoters at their 3' ends to initiate rna synthesis. the 2 elements, promoter element 1 (pe1) and promoter element 2 (pe2), are separated by a spacer region that must be exactly a multiple of 6 nucleotides (nt) long. paramyxovirus ncs have 13 nucleoprotein (np) subunits/turn, such that pe1 and pe2 are juxtaposed on the same face of the nc helix, for concerted recognition by the viral polymerase. ebola virus (ebov) ncs, in contrast, have ... | 2020 | 33152032 |
| contemporary understanding of ebola and zika virus in pregnancy. | understanding the pathophysiology, management, and prevention of emerging infectious diseases among pregnant women is imperative to achieve a successful response from the medical community. ebola and zika viruses represent infections with profound public health implications. in particular, ebola virus is associated with high case fatality and pregnancy and neonatal loss rates, while zika virus has been associated with multiple congenital anomalies; these features present critical clinical dilemm ... | 2020 | 33153665 |
| single-cell profiling of ebola virus disease in vivo reveals viral and host dynamics. | ebola virus (ebov) causes epidemics with high mortality yet remains understudied due to the challenge of experimentation in high-containment and outbreak settings. here, we used single-cell transcriptomics and cytof-based single-cell protein quantification to characterize peripheral immune cells during ebov infection in rhesus monkeys. we obtained 100,000 transcriptomes and 15,000,000 protein profiles, finding that immature, proliferative monocyte-lineage cells with reduced antigen-presentation ... | 2020 | 33159858 |
| short communication: expanding the range of services to the survivors of ebola virus disease in the democratic republic of the congo. | the objectives of the article are to assess the role of a strategic response in the prevention and control of the disease and the need for extending supports to the survivors of disease. | 2020 | 33163027 |
| [ocular manifestations of viral diseases]. | viral infections may involve all ocular tissues and may have short and long-term sight-threatening consequences. among them, ocular infections caused by herpesviruses are the most frequent. hsv-1 keratitis and kerato-uveitis affect approximately are the leading cause of infectious blindness in the western world, mainly because of corneal opacification caused by recurrences. for this reason, they may warrant long-term antiviral prophylaxis. herpes zoster ophthalmicus, accounts for 10 to 20% of al ... | 2020 | 33168354 |
| spillover of ebolaviruses into people in eastern democratic republic of congo prior to the 2018 ebola virus disease outbreak. | the second largest ebola virus disease (evd) outbreak began in the democratic republic of congo in july 2018 in north kivu province. data suggest the outbreak is not epidemiologically linked to the 2018 outbreak in equateur province, and that independent introduction of ebola virus (ebov) into humans occurred. we tested for antibodies to ebolaviruses in febrile patients seeking care in north kivu province prior to the evd outbreak. | 2020 | 33169111 |
| nonhuman primate to human immunobridging to infer the protective effect of an ebola virus vaccine candidate. | it has been proven challenging to conduct traditional efficacy trials for ebola virus (ebov) vaccines. in the absence of efficacy data, immunobridging is an approach to infer the likelihood of a vaccine protective effect, by translating vaccine immunogenicity in humans to a protective effect, using the relationship between vaccine immunogenicity and the desired outcome in a suitable animal model. we here propose to infer the protective effect of the ad26.zebov, mva-bn-filo vaccine regimen with a ... | 2020 | 33335092 |
| icu-like care of nonhuman primates with ebola virus disease. | ebola virus disease (evd) supportive care strategies are largely guided by retrospective observational research. this study investigated the effect of evd supportive care algorithms on duration of survival in a controlled nonhuman primate (nhp) model. | 2020 | 33367826 |
| a descriptive study of zoonotic disease risk at the human-wildlife interface in a biodiversity hot spot in south western uganda. | zoonotic diseases pose a significant health challenge at the human-wildlife interface, especially in sub-saharan africa where ecosystem services contribute significantly to local livelihoods and individual well-being. in uganda, the fragmented forests of hoima district, form part of a biodiversity and emerging infectious disease hotspot composed of communities with high dependency on these wildlife protected areas, unaware of the associated health risks. we conducted a cross-sectional mixed meth ... | 2021 | 33406074 |
| tetravalent rabies-vectored filovirus and lassa fever vaccine induces long-term immunity in nonhuman primates. | the objective of this study is to evaluate the immunogenicity of adjuvanted monovalent rabies virus-based vaccine candidates against ebola virus (filorab1), sudan virus (filorab2), marburg virus (filorab3), lassa virus (lassarab1), and combined trivalent vaccine candidate (filorab1-3) and tetravalent vaccine candidate (filorab1-3 and lassarab) in nonhuman primates. | 2021 | 33421072 |
| the ecology of nipah virus in bangladesh: a nexus of land-use change and opportunistic feeding behavior in bats. | nipah virus is a bat-borne paramyxovirus that produces yearly outbreaks of fatal encephalitis in bangladesh. understanding the ecological conditions that lead to spillover from bats to humans can assist in designing effective interventions. to investigate the current and historical processes that drive nipah spillover in bangladesh, we analyzed the relationship among spillover events and climatic conditions, the spatial distribution and size of pteropus medius roosts, and patterns of land-use ch ... | 2021 | 33498685 |
| rapid protection from covid-19 in nonhuman primates vaccinated intramuscularly but not intranasally with a single dose of a recombinant vaccine. | the ongoing pandemic of coronavirus disease 2019 (covid-19) continues to exert a significant burden on health care systems worldwide. with limited treatments available, vaccination remains an effective strategy to counter transmission of severe acute respiratory syndrome coronavirus 2 (sars-cov-2). recent discussions concerning vaccination strategies have focused on identifying vaccine platforms, number of doses, route of administration, and time to reach peak immunity against sars-cov-2. here, ... | 2021 | 33501447 |
| development of a well-characterized rhesus macaque model of ebola virus disease for support of product development. | ebola virus (ebov) is a negative-sense rna virus that can infect humans and nonhuman primates with severe health consequences. development of countermeasures requires a thorough understanding of the interaction between host and pathogen, and the course of disease. the goal of this study was to further characterize ebov disease in a uniformly lethal rhesus macaque model, in order to support development of a well-characterized model following rigorous quality standards. rhesus macaques were intram ... | 2021 | 33652589 |
| multivalent dna vaccines as a strategy to combat multiple concurrent epidemics: mosquito-borne and hemorrhagic fever viruses. | the emergence of multiple concurrent infectious diseases localized in the world creates a complex burden on global public health systems. outbreaks of ebola, lassa, and marburg viruses in overlapping regions of central and west africa and the co-circulation of zika, dengue, and chikungunya viruses in areas with a. aegypti mosquitos highlight the need for a rapidly deployable, safe, and versatile vaccine platform readily available to respond. the dna vaccine platform stands out as such an applica ... | 2021 | 33673603 |
| igy antibodies against ebola virus possess post-exposure protection in a murine pseudovirus challenge model and excellent thermostability. | ebola virus (ebov) is one of the most virulent pathogens that causes hemorrhagic fever and displays high mortality rates and low prognosis rates in both humans and nonhuman primates. the post-exposure antibody therapies to prevent ebov infection are considered effective as of yet. however, owing to the poor thermal stability of mammalian antibodies, their application in the tropics has remained limited. therefore, a thermostable therapeutic antibody against ebov was developed modelled on the pou ... | 2021 | 33711011 |
| hunting and consumption of rodents by children in the lassa fever endemic area of faranah, guinea. | as a consequence of the ebola outbreak, human-animal contact has gained importance for zoonotic transmission surveillance. in faranah (upper guinea), daily life is intertwined with rodents, such as the natal multimammate mouse, mastomys natalensis; a reservoir for lassa virus (lasv). however, this contact is rarely perceived as a health risk by residents, although lassa fever (lf) is known to be endemic to this region. conversely, these observations remain a great concern for global health agend ... | 2021 | 33730025 |
| lack of molecular mimicry between nonhuman primates and infectious pathogens: the possible genetic bases. | recently, it was found that proteomes from poliovirus, measles virus, dengue virus, and severe acute respiratory syndrome-related coronavirus 2 (sars-cov-2) have high molecular mimicry at the heptapeptide level with the human proteome, while heptapeptide commonality is minimal or absent with proteomes from nonhuman primates, that is, gorilla, chimpanzee, and rhesus macaque. to acquire more data on the issue, analyses here have been expanded to ebola virus, francisella tularensis , human immunode ... | 2021 | 33748822 |
| development and validation of a triplex assay to study an antibody cocktail against ebola virus in cynomolgus serum. | background: to support the rapid development of an antibody cocktail against ebola virus and avoid unnecessary exposure to infectious environments, an automatic and fast turnover triplex assay was developed using simoa® (quanterix corporation, ma, usa). materials & methods: a robust triplex assay was developed and validated for simultaneous quantification of the antibody cocktail against ebola virus in cynomolgus serum. results: the assay had a quantitation range of 78.1-5000 ng/ml. the intra- a ... | 2021 | 33792406 |
| metagenomic snapshots of viral components in guinean bats. | to prevent the emergence of zoonotic infectious diseases and reduce their epidemic potential, we need to understand their origins in nature. bats in the order chiroptera are widely distributed worldwide and are natural reservoirs of prominent zoonotic viruses, including nipah virus, marburg virus, and possibly sars-cov-2. in this study, we applied unbiased metagenomic and metatranscriptomic approaches to decipher the virosphere of frugivorous and insectivorous bat species captured in guéckédou, ... | 2021 | 33803988 |
| mucosal challenge ferret models of ebola virus disease. | recent studies have shown the domestic ferret (mustela putorius furo) to be a promising small animal model for the study of ebola virus (ebov) disease and medical countermeasure evaluation. to date, most studies have focused on traditional challenge routes, predominantly intramuscular and intranasal administration. here, we present results from a non-clinical pathogenicity study examining oronasal, oral, and ocular mucosal challenge routes in ferrets. animals were challenged with 1, 10, or 100 p ... | 2021 | 33806375 |
| transcriptomic analysis reveals host mirnas correlated with immune gene dysregulation during fatal disease progression in the ebola virus cynomolgus macaque disease model. | ebola virus is a continuing threat to human populations, causing a virulent hemorrhagic fever disease characterized by dysregulation of both the innate and adaptive host immune responses. severe cases are distinguished by an early, elevated pro-inflammatory response followed by a pronounced lymphopenia with b and t cells unable to mount an effective anti-viral response. the precise mechanisms underlying the dysregulation of the host immune system are poorly understood. in recent years, focus on ... | 2021 | 33806942 |
| prodrugs of a 1'-cn-4-aza-7,9-dideazaadenosine c-nucleoside leading to the discovery of remdesivir (gs-5734) as a potent inhibitor of respiratory syncytial virus with efficacy in the african green monkey model of rsv. | a discovery program targeting respiratory syncytial virus (rsv) identified c-nucleoside 4 (rsv a2 ec50 = 530 nm) as a phenotypic screening lead targeting the rsv rna-dependent rna polymerase (rdrp). prodrug exploration resulted in the discovery of remdesivir (1, gs-5734) that is >30-fold more potent than 4 against rsv in hep-2 and nhbe cells. metabolism studies in vitro confirmed the rapid formation of the active triphosphate metabolite, 1-ntp, and in vivo studies in cynomolgus and african green ... | 2021 | 33835812 |
| the ferret as a model for filovirus pathogenesis and countermeasure evaluation. | the domestic ferret (mustela putorius furo) has long been a popular animal model for evaluating viral pathogenesis and transmission as well as the efficacy of candidate countermeasures. without question, the ferret has been most widely implemented for modeling respiratory viruses, particularly influenza viruses; however, in recent years, it has gained attention as a novel animal model for characterizing filovirus infections. although ferrets appear resistant to infection and disease caused by ma ... | 2021 | 33951727 |
| distinct transcriptional responses to fatal ebola virus infection in cynomolgus and rhesus macaques suggest species-specific immune responses. | ebola virus (ebov) is a negative single-stranded rna virus within the filoviridae family and the causative agent of ebola virus disease (evd). nonhuman primates (nhps), including cynomolgus and rhesus macaques, are considered the gold standard animal model to interrogate mechanisms of ebov pathogenesis. however, despite significant genetic similarity (>90%), nhp species display different clinical presentation following ebov infection, notably a ∼1-2 days delay in disease progression. consequentl ... | 2021 | 34112056 |
| identification and characterization of defective viral genomes in ebola virus-infected rhesus macaques. | ebola virus (ebov), of the family filoviridae, is an rna virus that can cause a hemorrhagic fever with a high mortality rate. defective viral genomes (dvgs) are truncated genomes that have been observed during multiple rna virus infections, including in vitro ebov infection, and have previously been associated with viral persistence and immunostimulatory activity. as dvgs have been detected in cells persistently infected with ebov, we hypothesized that dvgs may also accumulate during viral repli ... | 2021 | 34160256 |
| serological evidence of filovirus infection in nonhuman primates in zambia. | ebolaviruses and marburgviruses are filoviruses that are known to cause severe hemorrhagic fever in humans and nonhuman primates (nhps). while some bat species are suspected to be natural reservoirs of these filoviruses, wild nhps often act as intermediate hosts for viral transmission to humans. using an enzyme-linked immunosorbent assay, we screened two nhp species, wild baboons and vervet monkeys captured in zambia, for their serum igg antibodies specific to the envelope glycoproteins of filov ... | 2021 | 34209295 |
| natural history of disease in cynomolgus monkeys exposed to ebola virus kikwit strain demonstrates the reliability of this non-human primate model for ebola virus disease. | filoviruses (family filoviridae genera ebolavirus and marburgvirus) are negative-stranded rna viruses that cause severe health effects in humans and non-human primates, including death. except in outbreak settings, vaccines and other medical countermeasures against ebola virus (ebov) will require testing under the fda animal rule. multiple vaccine candidates have been evaluated using cynomolgus monkeys (cm) exposed to ebov kikwit strain. to the best of our knowledge, however, animal model develo ... | 2021 | 34214118 |
| why remdesivir failed: preclinical assumptions overestimate the clinical efficacy of remdesivir for covid-19 and ebola. | remdesivir is a nucleoside monophosphoramidate prodrug that has been fda-approved for covid-19. however, the clinical efficacy of remdesivir for covid-19 remains contentious, as several trials have not found statistically significant differences in either time to clinical improvement or mortality between remdesivir-treated and control groups. similarly, the inability for remdesivir to provide a clinically significant benefit above other investigational agents in patients with ebola contrasts wit ... | 2021 | 34252308 |
| bundibugyo ebolavirus survival is associated with early activation of adaptive immunity and reduced myeloid-derived suppressor cell signaling. | ebolaviruses bundibugyo virus (bdbv) and ebola virus (ebov) cause fatal hemorrhagic disease in humans and nonhuman primates. while the host response to ebov is well characterized, less is known about bdbv infection. moreover, immune signatures that mediate natural protection against all ebolaviruses remain poorly defined. to explore these knowledge gaps, we transcriptionally profiled bdbv-infected rhesus macaques, a disease model that results in incomplete lethality. this approach enabled us to ... | 2021 | 34372693 |
| single dose rvsvδg-junvgp vaccine protects guinea pigs against lethal junin virus challenge. | junin virus (junv) is a pathogen of biodefense importance due to its potential for aerosol transmission and mortality rates reaching 30%. currently, there are no junv vaccines licensed by the united states food and drug administration (fda) for at-risk individuals. a vaccine based on recombinant vesicular stomatitis virus (rvsv) has been effectively used to prevent ebola virus disease in humans. here, we evaluated the protective efficacy of a rvsv expressing the junv glycoprotein (rvsvδg-junvgp) ... | 2021 | 34373461 |