-
Nature Reviews. Disease Primers Feb 2020Ebola virus disease (EVD) is a severe and frequently lethal disease caused by Ebola virus (EBOV). EVD outbreaks typically start from a single case of probable zoonotic... (Review)
Review
Ebola virus disease (EVD) is a severe and frequently lethal disease caused by Ebola virus (EBOV). EVD outbreaks typically start from a single case of probable zoonotic transmission, followed by human-to-human transmission via direct contact or contact with infected bodily fluids or contaminated fomites. EVD has a high case-fatality rate; it is characterized by fever, gastrointestinal signs and multiple organ dysfunction syndrome. Diagnosis requires a combination of case definition and laboratory tests, typically real-time reverse transcription PCR to detect viral RNA or rapid diagnostic tests based on immunoassays to detect EBOV antigens. Recent advances in medical countermeasure research resulted in the recent approval of an EBOV-targeted vaccine by European and US regulatory agencies. The results of a randomized clinical trial of investigational therapeutics for EVD demonstrated survival benefits from two monoclonal antibody products targeting the EBOV membrane glycoprotein. New observations emerging from the unprecedented 2013-2016 Western African EVD outbreak (the largest in history) and the ongoing EVD outbreak in the Democratic Republic of the Congo have substantially improved the understanding of EVD and viral persistence in survivors of EVD, resulting in new strategies toward prevention of infection and optimization of clinical management, acute illness outcomes and attendance to the clinical care needs of patients.
Topics: Africa, Western; Ebolavirus; Hemorrhagic Fever, Ebola; Humans; Pandemics
PubMed: 32080199
DOI: 10.1038/s41572-020-0147-3 -
Uirusu 2015Ebola virus is an enveloped virus with filamentous structure and causes a severe hemorrhagic fever in human and nonhuman primates. Host cell entry is the first essential... (Review)
Review
Ebola virus is an enveloped virus with filamentous structure and causes a severe hemorrhagic fever in human and nonhuman primates. Host cell entry is the first essential step in the viral life cycle, which has been extensively studied as one of the therapeutic targets. A virus factor of cell entry is a surface glycoprotein (GP), which is an only essential viral protein in the step, as well as the unique particle structure. The virus also interacts with a lot of host factors to successfully enter host cells. Ebola virus at first binds to cell surface proteins and internalizes into cells, followed by trafficking through endosomal vesicles to intracellular acidic compartments. There, host proteases process GPs, which can interact with an intracellular receptor. Then, under an appropriate circumstance, viral and endosomal membranes are fused, which is enhanced by major structural changes of GPs, to complete host cell entry. Recently the basic research of Ebola virus infection mechanism has markedly progressed, largely contributed by identification of host factors and detailed structural analyses of GPs. This article highlights the mechanism of Ebola virus host cell entry, including recent findings.
Topics: Animals; Cell Physiological Phenomena; Cells; Ebolavirus; Host-Pathogen Interactions; Humans; Hydrogen-Ion Concentration; Membrane Glycoproteins; Multivesicular Bodies; Peptide Hydrolases; Receptors, Virus; Viral Proteins; Virus Attachment; Virus Internalization; Virus Replication
PubMed: 26923960
DOI: 10.2222/jsv.65.71 -
Folia Medica Cracoviensia 2014Epidemic of Ebola hemorrhagic fever which appeared in the countries of West Africa in 2014, is the largest outbreak which occurred so far. The virus causing this... (Review)
Review
Epidemic of Ebola hemorrhagic fever which appeared in the countries of West Africa in 2014, is the largest outbreak which occurred so far. The virus causing this epidemic, Zaire Ebolavirus (ZEBOV), along with four other species of Ebolaviruses is classified to the genus Ebolavirus in the family Filoviridae. ZEBOV is one of the most virulent pathogens among the viral haemorrhagic fevers, and case fatality rates up to 90% have been reported. Mortality is the result of multi-organ failure and severe bleeding complications. The aim of this review is to present the general characteristics of the virus and its biological properties, pathogenicity and epidemiology, with a focus on laboratory methods used in the diagnosis of these infections.
Topics: Africa, Western; Communicable Disease Control; Disease Outbreaks; Disease Reservoirs; Ebolavirus; Hemorrhagic Fever, Ebola; Humans
PubMed: 25694096
DOI: No ID Found -
Folia Medica Cracoviensia 2014Ebola zoonotic RNA filovirus represents human most virulent and lethal pathogens, which induces acute hemorrhagic fever and death within few days in a range of 60-90% of... (Review)
Review
Ebola zoonotic RNA filovirus represents human most virulent and lethal pathogens, which induces acute hemorrhagic fever and death within few days in a range of 60-90% of symptomatic individuals. Last outbreak in 2014 in West Africa caused panic that Ebola epidemic can be spread to other continents. Number of deaths in late December reached almost 8,000 individuals out of more than 20,000 symptomatic patients. It seems that only a coordinated international response could counteract the further spread of Ebola. Major innate immunity mechanisms against Ebola are associated with the production of interferons, that are inhibited by viral proteins. Activation of host NK cells was recognized as a leading immune function responsible for recovery of infected people. Uncontrolled cell infection by Ebola leads to an impairment of immunity with cytokine storm, coagulopathy, systemic bleeding, multi-organ failure and death. Tested prevention strategies to induce antiviral immunity include: i. recombinant virus formulations (vaccines); ii. cocktail of monoclonal antibodies (serotherapy); iii. alternative RNA-interference-based antiviral methods. Maintaining the highest standards of aseptic and antiseptic precautions is equally important. Present brief review summarizes a current knowledge concerning pathogenesis of Ebola hemorrhagic disease and the virus interaction with the immune system and discusses recent advances in prevention of Ebola infection by vaccination and serotherapy.
Topics: Africa, Western; Communicable Disease Control; Disease Outbreaks; Disease Reservoirs; Ebola Vaccines; Ebolavirus; Hemorrhagic Fever, Ebola; Humans
PubMed: 25694094
DOI: No ID Found -
Drugs Apr 2021Ansuvimab (ansuvimab-zykl; EBANGA™) is a human monoclonal antibody developed by Ridgeback Biotherapeutics, which binds to the glycoprotein on Zaire ebolavirus (Ebola... (Review)
Review
Ansuvimab (ansuvimab-zykl; EBANGA™) is a human monoclonal antibody developed by Ridgeback Biotherapeutics, which binds to the glycoprotein on Zaire ebolavirus (Ebola virus) to block its entry into host cells. Ansuvimab has been recently approved in the USA for the treatment of infection caused by Z. ebolavirus in adult and paediatric patients, including in neonates born to a mother who is RT-PCR positive for Z. ebolavirus infection, following the results of the PALM phase II/III trial. This article summarizes the milestones in the development of ansuvimab leading to this first approval for the treatment of infections caused by Ebola virus in adults and paediatric patients.
Topics: Antibodies, Monoclonal, Humanized; Antiviral Agents; Ebolavirus; Humans; Virus Internalization
PubMed: 33751449
DOI: 10.1007/s40265-021-01483-4 -
Cell May 2017Ebola virus disease poses a global health threat. Here, two studies by Wec et al. and Zhao et al. identified vulnerability in an internal fusion loop of an ebolavirus...
Ebola virus disease poses a global health threat. Here, two studies by Wec et al. and Zhao et al. identified vulnerability in an internal fusion loop of an ebolavirus glycoprotein. Monoclonal antibodies elicited from immunization and isolated from a human survivor that recognized epitopes in this area neutralized all five ebolaviruses, guiding the development of a pan-ebolavirus immunotherapy.
Topics: Animals; Antibodies, Monoclonal; Antibodies, Viral; Ebolavirus; Epitopes; Hemorrhagic Fever, Ebola; Humans; Mice; Mice, Inbred BALB C
PubMed: 28525748
DOI: 10.1016/j.cell.2017.05.008 -
PLoS Pathogens 2015The past year has marked the most devastating Ebola outbreak the world has ever witnessed, with over 28,000 cases and over 11,000 deaths. Ebola virus (EBOV) has now been... (Review)
Review
The past year has marked the most devastating Ebola outbreak the world has ever witnessed, with over 28,000 cases and over 11,000 deaths. Ebola virus (EBOV) has now been around for almost 50 years. In this review, we discuss past and present outbreaks of EBOV and how those variants evolved over time. We explore and discuss selective pressures that drive the evolution of different Ebola variants, and how they may modify the efficacy of therapeutic treatments and vaccines currently being developed. Finally, given the unprecedented size and spread of the outbreak, as well as the extended period of replication in human hosts, specific attention is given to the 2014-2015 West African outbreak variant (Makona).
Topics: Africa, Western; Animals; Biological Evolution; Disease Outbreaks; Ebolavirus; Genetic Variation; Hemorrhagic Fever, Ebola; Humans; Time Factors
PubMed: 26562671
DOI: 10.1371/journal.ppat.1005221 -
PLoS Neglected Tropical Diseases May 2018In 2014, the world witnessed the largest Ebolavirus outbreak in recorded history. The subsequent humanitarian effort spurred extensive research, significantly enhancing... (Review)
Review
In 2014, the world witnessed the largest Ebolavirus outbreak in recorded history. The subsequent humanitarian effort spurred extensive research, significantly enhancing our understanding of ebolavirus replication and pathogenicity. The main functions of each ebolavirus protein have been studied extensively since the discovery of the virus in 1976; however, the recent expansion of ebolavirus research has led to the discovery of new protein functions. These newly discovered roles are revealing new mechanisms of virus replication and pathogenicity, whilst enhancing our understanding of the broad functions of each ebolavirus viral protein (VP). Many of these new functions appear to be unrelated to the protein's primary function during virus replication. Such new functions range from bystander T-lymphocyte death caused by VP40-secreted exosomes to new roles for VP24 in viral particle formation. This review highlights the newly discovered roles of ebolavirus proteins in order to provide a more encompassing view of ebolavirus replication and pathogenicity.
Topics: Animals; Ebolavirus; Hemorrhagic Fever, Ebola; Humans; Viral Proteins; Virus Replication
PubMed: 29723187
DOI: 10.1371/journal.pntd.0006349 -
The Journal of Infectious Diseases Nov 2023Filoviruses, including ebolaviruses and marburgviruses, can cause severe and often fatal disease in humans. Over the past several years, antibody therapy has emerged as...
Filoviruses, including ebolaviruses and marburgviruses, can cause severe and often fatal disease in humans. Over the past several years, antibody therapy has emerged as a promising strategy for the treatment of filovirus disease. Here, we describe 2 distinct cross-reactive monoclonal antibodies (mAbs) isolated from mice immunized with recombinant vesicular stomatitis virus-based filovirus vaccines. Both mAbs recognized the glycoproteins of multiple different ebolaviruses and exhibited broad but differential in vitro neutralization activities against these viruses. By themselves, each mAb provided partial to full protection against Ebola virus in mice, and in combination, the mAbs provided 100% protection against Sudan virus challenge in guinea pigs. This study identified novel mAbs that were elicited through immunization and able to provide protection from ebolavirus infection, thus enriching the pool of candidate therapeutics for treating Ebola disease.
Topics: Humans; Animals; Guinea Pigs; Mice; Hemorrhagic Fever, Ebola; Ebolavirus; Antibodies, Monoclonal; Combined Antibody Therapeutics; Antibodies, Neutralizing; Antibodies, Viral
PubMed: 37288609
DOI: 10.1093/infdis/jiad205 -
International Journal of Clinical... Jan 2015On 23 March 2014, the World Health Organization first announced a new Ebola virus outbreak that started in December 2013 in the eastern part of the Republic of Guinea....
On 23 March 2014, the World Health Organization first announced a new Ebola virus outbreak that started in December 2013 in the eastern part of the Republic of Guinea. Human infections shortly emerged in Liberia, Sierra Leone, and Nigeria. On 30 September 2014, the Centers for Disease Control and Prevention confirmed through laboratory testing the first Ebola virus infection diagnosed in the USA, in a patient who travelled from West Africa to Texas. On 6 October 2014, the first human infection occurring outside of Africa was reported, in a Spanish nurse who treated two priests, both of whom died, and on 23 October 2014, the first human infection was reported in New York City. To date, the 2014 Ebola virus outbreak is the longest, largest, and most persistent one since 1976, when the virus was first identified in humans, and the number of human cases exceeded, as of mid-September 2014, the cumulative number of infections from all the previous outbreaks. The early clinical presentation overlaps with other infectious diseases, opening differential diagnosis difficulties. Understanding the transmission routes and identifying the natural reservoir of the virus are additional challenges in studying Ebola hemorrhagic fever outbreaks. Ebola virus is as much a public health challenge for developing countries as it is for the developed world, and previous outbreaks underscored that the relative contribution of the risk factors may differ among outbreaks. The implementation of effective preparedness plans is contingent on integrating teachings from previous Ebola virus outbreaks with those from the current outbreak and with lessons provided by other infectious diseases, along with developing a multifaceted inter-disciplinary and cross-disciplinary framework that should be established and shaped by biomedical as well as sociopolitical sciences.
Topics: Africa, Western; Disease Outbreaks; Ebolavirus; Hemorrhagic Fever, Ebola; Humans; Risk Factors; Travel
PubMed: 25496121
DOI: 10.1111/ijcp.12593