Spread Of Ebola Virus Research Articles

Blocking of ebolavirus spread through intercellular connections by an MPER-specific antibody depends on BST2/tetherin

Ebola virus (EBOV) and Bundibugyo virus (BDBV) belong to the family Filoviridae and cause a severe disease in humans. We previously isolated a large panel of monoclonal antibodies from B cells of human survivors from the 2007Uganda BDBV outbreak, 16 survivors from the 2014 EBOV outbreak in the Democratic Republic of the Congo, and one survivor from the West African 2013-2016 EBOV epidemic. Here, we demonstrate that EBOV and BDBV are capable of spreading to neighboring cells through intercellular connections in a process that depends upon actin and Tcell immunoglobulin and mucin 1 protein. We quantify spread through intercellular connections by immunofluorescence microscopy and flow cytometry. One of the antibodies, BDBV223, specific to the membrane-proximal external region, induces virus accumulation at the plasma membrane. The inhibiting activity of BDBV223 depends on BST2/tetherin.

Ebola outbreak in DRC and Uganda; an East African public health concern.

On August 21, 2022, healthcare authorities in the Democratic Republic of the Congo (DRC) announced an outbreak of Ebola virus disease in North Kivu Province, bringing the total to 15 outbreaks nationwide. On September 20, 2022, Uganda's authorities declared an outbreak of the Sudan strain of the Ebola virus following a confirmed a case in Mubende district. As of October 6, 2022, the reported numbers of cases were 63, with 29 deaths in Uganda and 1 case with 1 death in DRC, respectively. Ebola virus causes an acute and severely fatal illness, resulting in death within a very short time if left untreated. In addition, these outbreaks in DRC and Uganda pose a major threat to the health and socioeconomic well-being of the people of East Africa due to multiple cross-border activities. Adequate preparations need to be made by the healthcare authorities of the nations concerned; the government, healthcare workers, and the East-African community as a whole have important roles to play in the effective prevention and control of the spread of Ebola virus within and across their borders.

Disease Mechanism and Treatment Method of Ebola Virus

Ebola virus is a virus with simple structure, but it can assemble itself in the host and cause a chain reaction of washing in the process of disease causing, leading to more serious pathological damage in the body. Its main clinical characteristic is fever, bleeding, and diarrhea and has a high fatality rate, as well as endangering people's physical and mental health. Since Ebola virus was discovered in 1976, the virus has been in periodic outbreaks in Africa, and has also spread to countries and regions outside the African continent. The World Health Organization has twice listed Ebola as a public health emergency of international concern. In view of the huge challenges faced, the search for effective treatment methods and the research and development of preventive vaccines have become one of the problems that the medical community urgently needs to overcome. Antibody drugs also play an important role to prevent the spread of Ebola virus, improving patient protection rate and other aspects, making people see the hope of curing Ebola virus. So far, the American Food and Drug Administration (FDA) have approved REGN-EB3 and mAb114 as medicinal products for Ebola Virus therapy. This article reviews the risk factors, pathogenesis, clinical characteristics and treatment progress of Ebola virus, to provide a theoretical basis for the prevention and treatment of the virus.

MATHEMATICAL MODELLING APPROACH OF THE STUDY OF EBOLA VIRUS DISEASE TRANSMISSION DYNAMICS IN A DEVELOPING COUNTRY.

Ebola Virus causes disease both in human and non-human primates especially in developing countries. In 2014 during its outbreak, it led to majority of deaths especially in some impoverished area of West Africa and its effect is still witnessed up till date. We studied the spread of Ebola virus and obtained a system of equations comprising of eighteen equations which completely described the transmission of Ebola Virus in a population where control measures were incorporated and a major source of contacting the disease which is the traditional washing of dead bodies was also incorporated. We investigated the local stability of the disease-free equilibrium using the Jacobian Matrix approach and the disease- endemic stability using the center manifold theorem. We also investigated the global stability of the equilibrium points using the LaSalle's Invariant principle. The result showed that the disease-free and endemic equilibrium where both local and globally stable and that the system exhibits a forward bifurcation. Numerical simulations were carried out and our graphs show that vaccine and condom use is best for susceptible population, quarantine is best for exposed population, isolation is best for infectious population and proper burial of the diseased dead is the best to avoid further disease spread in the population and have quicker and better recovery.

The impact of sampling bias on viral phylogeographic reconstruction.

Genomic epidemiology plays an ever-increasing role in our understanding of and response to the spread of infectious pathogens. Phylogeography, the reconstruction of the historical location and movement of pathogens from the evolutionary relationships among sampled pathogen sequences, can inform policy decisions related to viral movement among jurisdictions. However, phylogeographic reconstruction is impacted by the fact that the sampling and virus sequencing policies differ among jurisdictions, and these differences can cause bias in phylogeographic reconstructions. Here we assess the potential impacts of geographic-based sampling bias on estimated viral locations in the past, and on whether key viral movements can be detected. We quantify the effect of bias using simulated phylogenies with known geographic histories, and determine the impact of the biased sampling and of the underlying migration rate on the accuracy of estimated past viral locations. We find that overall, the accuracy of phylogeographic reconstruction is high, particularly when the migration rate is low. However, results depend on sampling, and sampling bias can have a large impact on the numbers and nature of estimated migration events. We apply these insights to the geographic spread of Ebolavirus in the 2014-2016 West Africa epidemic. This work highlights how sampling policy can both impact geographic inference and be optimized to best ensure the accuracy of specific features of geographic spread.

Host Regulation of Ebola Virus Egress and Spread: Role of Cytoskeletal Filamin Proteins

Ebola virus (EBOV) causes severe hemorrhagic fever associated with high mortality rates in humans. EBOV and other filoviruses are emerging BSL‐4 pathogens for which the development of novel and effective therapeutics is urgently needed. Egress and spread of EBOV is mediated by the VP40 matrix protein (eVP40), whereby expression of eVP40 alone directs the production and egress of virus‐like particles (VLPs) that accurately mimics the budding process of live infectious virus. We have shown that eVP40 hijacks or recruits select host proteins to facilitate the budding process. On the other hand, we have also identified several host proteins that interact with eVP40 to negatively regulated eVP40‐mediated budding. Thus, a better understanding of the eVP40‐host interactome will provide important insights into the mechanisms of virus egress and spread, as well as inform about potential targets for the development of novel antiviral therapeutics. Here, we investigated the possible role for host filamin A and B proteins (actin crosslinking proteins that function in cell morphology and migration at the plasma membrane) in regulating both entry and egress of EBOV. Toward this end, we employed filamin A (FLNaKD) and filamin B knockdown cells (FLNbKD) to assess EBOV entry by using live EBOV, as well as recombinant viruses and/or pseudotypes expressing the EBOV surface glycoprotein (GP). We also used the KD cells to assess virus egress by using our well‐established eVP40 VLP budding assay. In sum, our results indicate that expression of host filamin proteins appears to be important for EBOV to efficiently complete different stages of its lifecycle.

Treatment with Ad5-Porcine Interferon-α Attenuates Ebolavirus Disease in Pigs.

Under experimental conditions, pigs infected with Ebola Virus (EBOV) develop disease and can readily transmit the virus to non-human primates or pigs. In the event of accidental or intentional EBOV infection of domestic pigs, complex and time-consuming safe depopulation and carcass disposal are expected. Delaying or preventing transmission through a reduction in viral shedding is an absolute necessity to limit the spread of the virus. In this study, we tested whether porcine interferon-α or λ3 (porIFNα or porIFNλ3) delivered by a replication-defective human type 5 adenovirus vector (Ad5-porIFNα or Ad5-porIFNλ3) could limit EBOV replication and shedding in domestic pigs. Our results show that pigs pre-treated with Ad5-porIFNα did not develop measurable clinical signs, did not shed virus RNA, and displayed strongly reduced viral RNA load in tissues. A microarray analysis of peripheral blood mononuclear cells indicated that Ad5-porIFNα treatment led to clear upregulation in immune and inflammatory responses probably involved in protection against disease. Our results indicate that administration of Ad5-porIFNα can potentially be used to limit the spread of EBOV in pigs.

On the possibility of oscillating in the Ebola virus dynamics and investigating the effect of the lifetime of T lymphocytes.

Ebola virus (EBOV) targets immune cells and tries to inactivate dendritic cells and interferon molecules to continue its replication process. Since EBOV detailed mechanism has not been identified so far, it would be useful to understand the growth and spread of EBOV dynamics based on mathematical methods and simulation approaches. Computational approaches such as Cellular Automata (CA) have the advantage of simplicity over solving complicated differential equations. The spread of Ebola virus in lymph nodes is studied using a simplified Cellular Automata model with only four parameters. In addition to considering healthy and infected cells, this paper also considers T lymphocytes as well as cell movement ability during the simulation in order to investigate different scenarios in the dynamics of an EBOV system. It is shown that the value of the probability of death of T cells affects the number of infected cells significantly in the steady-state. For a special case of parameters set, the system shows oscillating dynamics. The results were in good agreement with an ordinary differential equation-based model which indicated CA method in combination with experimental discoveries could help biologists find out more about the EBOV mechanism and hopefully to control the disease.

Characterization of Ebola Virus Risk to Bedside Providers in an Intensive Care Environment.

Background: The 2014–2016 Ebola outbreak in West Africa recapitulated that nosocomial spread of Ebola virus could occur and that health care workers were at particular risk including notable cases in Europe and North America. These instances highlighted the need for centers to better prepare for potential Ebola virus cases; including understanding how the virus spreads and which interventions pose the greatest risk. Methods: We created a fully equipped intensive care unit (ICU), within a Biosafety Level 4 (BSL4) laboratory, and infected multiple sedated non-human primates (NHPs) with Ebola virus. While providing bedside care, we sampled blood, urine, and gastric residuals; as well as buccal, ocular, nasal, rectal, and skin swabs, to assess the risks associated with routine care. We also assessed the physical environment at end-point. Results: Although viral RNA was detectable in blood as early as three days post-infection, it was not detectable in the urine, gastric fluid, or swabs until late-stage disease. While droplet spread and fomite contamination were present on a few of the surfaces that were routinely touched while providing care in the ICU for the infected animal, these may have been abrogated through good routine hygiene practices. Conclusions: Overall this study has helped further our understanding of which procedures may pose the highest risk to healthcare providers and provides temporal evidence of this over the clinical course of disease.

Awareness on Ebola Virus among Undergraduate Dental Students in a Private Dental Institution, Chennai - A Questionnaire Survey

Ebola virus disease (EVD) is a deadly disease with occasional outbreaks that occur primarily on the Africancontinent. EVD most commonly affects people and nonhuman primates (such as monkeys, gorillas, andchimpanzees).The aim of the study to determine the awareness of Ebola virus among the undergraduatedental college students.This study involved the awareness of Ebola virus in the age group of 18 to 25 years. Awell structured questionnaire comprising 14 questions covering socio demographic information, knowledge,attitude, perception was framed and administered to the participants through an online google forms. Surveywas conducted among 100 college students. In that 30.39% male students and 69.61% of female studentshave taken this survey. The association between groups was assessed by Chi Square test where p < 0.05was considered statistically significant. We have observed that association between gender and responsesto awareness on the mode of spread of Ebola virus was statistically significant (p =0.020 ). The awarenesson ebola virus was analysed among the few college students by this survey and more awareness should becreated among the population about the ebola virus.

A non-parametric Hawkes model of the spread of Ebola in west Africa

ABSTRACT Recently developed methods for the non-parametric estimation of Hawkes point process models facilitate their application for describing and forecasting the spread of epidemic diseases. We use data from the 2014 Ebola outbreak in West Africa to evaluate how well a simple Hawkes point process model can forecast the spread of Ebola virus in Guinea, Sierra Leone, and Liberia. For comparison, SEIR models that fit previously to the same data are evaluated using identical metrics. To test the predictive power of each of the models, we simulate the ability to make near real-time predictions during an actual outbreak by using the first 75% of the data for estimation and the subsequent 25% of the data for evaluation. Forecasts generated from Hawkes models more accurately describe the spread of Ebola in each of the three countries investigated and result in a 38% reduction in RMSE for weekly case estimation across all countries when compared to SEIR models (total RMSE of 59.8 cases/week using SEIR compared to 37.1 for Hawkes). We demonstrate that the improved fit from Hawkes modeling cannot be attributed to overfitting and evaluate the advantages and disadvantages of Hawkes models in general for forecasting the spread of epidemic diseases.

Angiomotin regulates budding and spread of Ebola virus

The Ebola virus (EBOV) VP40 matrix protein (eVP40) orchestrates assembly and budding of virions in part by hijacking select WW-domain-bearing host proteins via its PPxY late (L)-domain motif. Angiomotin (Amot) is a multifunctional PPxY-containing adaptor protein that regulates angiogenesis, actin dynamics, and cell migration/motility. Amot also regulates the Hippo signaling pathway via interactions with the WW-domain-containing Hippo effector protein Yes-associated protein (YAP). In this report, we demonstrate that endogenous Amot is crucial for positively regulating egress of eVP40 virus-like particles (VLPs) and for egress and spread of authentic EBOV. Mechanistically, we show that ectopic YAP expression inhibits eVP40 VLP egress and that Amot co-expression rescues budding of eVP40 VLPs in a dose-dependent and PPxY-dependent manner. Moreover, results obtained with confocal and total internal reflection fluorescence microscopy suggested that Amot's role in actin organization and dynamics also contributes to promoting eVP40-mediated egress. In summary, these findings reveal a functional and competitive interplay between virus and host proteins involving the multifunctional PPxY-containing adaptor Amot, which regulates both the Hippo pathway and actin dynamics. We propose that our results have wide-ranging implications for understanding the biology and pathology of EBOV infections.

Serine-Arginine Protein Kinase 1 Regulates Ebola Virus Transcription.

Ebola virus (EBOV) causes a severe and often fatal disease for which no approved vaccines or antivirals are currently available. EBOV VP30 has been described as a viral phosphoprotein, and nonphosphorylated VP30 is essential and sufficient to support secondary transcription in an EBOV-specific minigenome system; however, phosphorylatable serine residues near the N terminus of VP30 are required to support primary viral transcription as well as the reinitiation of VP30-mediated transcription at internal EBOV genes. While the dephosphorylation of VP30 by the cellular phosphatase PP2A was found to be mediated by nucleoprotein, the VP30-specific kinases and the role of phosphorylation remain unknown. Here, we report that serine-arginine protein kinase 1 (SRPK1) and SRPK2 phosphorylate serine 29 of VP30, which is located in an N-terminal R26xxS29 motif. Interaction with VP30 via the R26xxS29 motif recruits SRPK1 into EBOV-induced inclusion bodies, the sites of viral RNA synthesis, and an inhibitor of SRPK1/SRPK2 downregulates primary viral transcription. When the SRPK1 recognition motif of VP30 was mutated in a recombinant EBOV, virus replication was severely impaired. It is presumed that the interplay between SRPK1 and PP2A in the EBOV inclusions provides a comprehensive regulatory circuit to ensure the activity of VP30 in EBOV transcription. Thus, the identification of SRPK1 is an important mosaic stone that completes our picture of the players involved in Ebola virus transcription regulation.IMPORTANCE The largest Ebola virus (EBOV) epidemic in West Africa ever caused more than 28,000 cases and 11,000 deaths, and the current EBOV epidemic in the Democratic Republic of the Congo continues, with more than 3,000 cases to date. Therefore, it is essential to develop antivirals against EBOV. Recently, an inhibitor of the cellular phosphatase PP2A-mediated dephosphorylation of the EBOV transcription factor VP30 has been shown to suppress the spread of Ebola virus. Here, we identified the protein kinase SRPK1 as a VP30-specific kinase that phosphorylates serine 29, the same residue that is dephosphorylated by PP2A. SRPK1-mediated phosphorylation of serine 29 enabled primary viral transcription. Mutation of the SRPK1 recognition motif in VP30 resulted in significant growth inhibition of EBOV. Similarly, elevation of the phosphorylation status of serine 29 by overexpression of SRPK1 inhibited EBOV growth, highlighting the importance of reversible phosphorylation of VP30 as a potential therapeutic target.

Knowledge, attitudes, and behavioural risk factors regarding zoonotic infections among bushmeat hunters and traders in Nsukka, southeast Nigeria.

OBJECTIVESIn light of the dramatic spread of Ebola virus in some parts of Africa and the 2014 outbreak in Nigeria, a study was conducted to evaluate bushmeat dealers’ knowledge and attitudes about zoonotic infections and the risk of transmission to humans.METHODSA cross-sectional survey was conducted in a community in Nsukka, southeast Nigeria. Hunters (n=34) and bushmeat traders (n=42) were interviewed. A semi-structured questionnaire was used to generate the data. The Fisher exact test was used to evaluate the significance of differences between these groups.RESULTSOnly 11.8% of the hunters, as compared to 35.7% of the traders, had no knowledge of possible causes of zoonotic infections (p<0.05). However, 64.7% of the hunters, compared to 38.1% of the traders, were ignorant regarding the responsibility of public health personnel and veterinarians (p<0.05), and 76.5% of the hunters compared to 42.9% of the traders were ignorant regarding the existence of zoonoses in Nigeria (p<0.05). A statistically significant difference was also found between these groups regarding the risk of contracting an infection from ectoparasites (p<0.05). The attitudes of respondents towards zoonotic diseases did not differ significantly between the groups.CONCLUSIONSThe level of awareness about zoonotic diseases was low in this area, underscoring the need for interventions.

A GXXXA Motif in the Transmembrane Domain of the Ebola Virus Glycoprotein Is Required for Tetherin Antagonism.

The interferon-induced antiviral host cell protein tetherin can inhibit the release of several enveloped viruses from infected cells. The Ebola virus (EBOV) glycoprotein (GP) antagonizes tetherin, but the domains and amino acids in GP that are required for tetherin antagonism have not been fully defined. A GXXXA motif within the transmembrane domain (TMD) of EBOV-GP was previously shown to be important for GP-mediated cellular detachment. Here, we investigated whether this motif also contributes to tetherin antagonism. Mutation of the GXXXA motif did not impact GP expression or particle incorporation and only modestly reduced EBOV-GP-driven entry. In contrast, the GXXXA motif was required for tetherin antagonism in transfected cells. Moreover, alteration of the GXXXA motif increased tetherin sensitivity of a replication-competent vesicular stomatitis virus (VSV) chimera encoding EBOV-GP. Although these results await confirmation with authentic EBOV, they indicate that a GXXXA motif in the TMD of EBOV-GP is important for tetherin antagonism. Moreover, they provide the first evidence that GP can antagonize tetherin in the context of an infectious EBOV surrogate.IMPORTANCE The glycoprotein (GP) of Ebola virus (EBOV) inhibits the antiviral host cell protein tetherin and may promote viral spread in tetherin-positive cells. However, tetherin antagonism by GP has so far been demonstrated only with virus-like particles, and it is unknown whether GP can block tetherin in infected cells. Moreover, a mutation in GP that selectively abrogates tetherin antagonism is unknown. Here, we show that a GXXXA motif in the transmembrane domain of EBOV-GP, which was previously reported to be required for GP-mediated cell rounding, is also important for tetherin counteraction. Moreover, analysis of this mutation in the context of vesicular stomatitis virus chimeras encoding EBOV-GP revealed that GP-mediated tetherin counteraction is operative in infected cells. To our knowledge, these findings demonstrate for the first time that GP can antagonize tetherin in infected cells and provide a tool to study the impact of GP-dependent tetherin counteraction on EBOV spread.

Phylodynamic assessment of intervention strategies for the West African Ebola virus outbreak

Genetic analyses have provided important insights into Ebola virus spread during the recent West African outbreak, but their implications for specific intervention scenarios remain unclear. Here, we address this issue using a collection of phylodynamic approaches. We show that long-distance dispersal events were not crucial for epidemic expansion and that preventing viral lineage movement to any given administrative area would, in most cases, have had little impact. However, major urban areas were critical in attracting and disseminating the virus: preventing viral lineage movement to all three capitals simultaneously would have contained epidemic size to one-third. We also show that announcements of border closures were followed by a significant but transient effect on international virus dispersal. By quantifying the hypothetical impact of different intervention strategies, as well as the impact of barriers on dispersal frequency, our study illustrates how phylodynamic analyses can help to address specific epidemiological and outbreak control questions.

Comprehensive Review on Ebola (EBOV) Virus: Future Prospects.

Ebola virus (EBOV) was discovered for the first time in 1976. It belongs to the family Filoviridae, which causes hemorrhagic fever that could lead to death in a few days. West Africa faced a major outbreak where symptoms appeared in the form of chills, myalgia, fever, diarrhea, and vomiting, and the disease finally reached a severe state as a result of hemorrhagic complications and failure of multiple organs. EBOV spreads by contact with body fluids of an infected person such as blood, saliva, urine, and seminal fluid, and also spreads by a contact with contaminated surfaces. Viral infection depends on the virus and host defenses. When the virus invades the body, the immune system becomes activated in an attempt to neutralize it. However, if this fails, EBOV viral infection spreads and leads to impaired innate and adaptive immune responses and uncontrollable viral replication. Consequently, the symptomatic patient is isolated and various medicinal regimens such as BCX-4430n TKM- EBOV are used, to cure EBOV, though, a specific treatment is not available. Accordingly, the aim of the present review is to survey and summarize the recent literature pertaining to the outbreak of EBOV, systematic infection of the human body, along with transmission and treatment. In addition, the review also aims to identify areas that need more research and development in combatting this dangerous virus. In the meantime, it should be noted that there is no fully FDA approved drug to treat infections by this virus. Therefore, there is a pressing need to focus on drug discovery along with public awareness to effectively manage any outbreaks in the future.

The Economic Case for a Pandemic Fund.

The rapid urban spread of Ebola virus in West Africa in 2014 and consequent breakdown of control measures led to a significant economic impact as well as the burden on public health and wellbeing. The US government appropriated $5.4 Billion for FY2015 and WHO proposed a $100 Million emergency fund largely to curtail the threat of future outbreaks. Using epidemiological analyses and economic modeling, we propose that the best use of these and similar funds would be to serve as global insurance against the continued threat of emerging infectious diseases. An effective strategy would involve the initial investment in strengthening mobile and adaptable capacity to deal with the threat and reality of disease emergence, coupled with repeated investment to maintain what is effectively a ‘national guard’ for pandemic prevention and response. This investment would create a capital stock that could also provide access to safe treatment during and between crises in developing countries, lowering risk to developed countries.

Modelling the spread of Ebola virus with Atangana-Baleanu fractional operators

The model of Ebola spread within a targeted population is extended to the concept of fractional differentiation and integration with non-local and non-singular fading memory introduced by Atangana and Baleanu. It is expected that the proposed model will show better approximation than the models established before. The existence and uniqueness of solutions for the spread of Ebola disease model is given via the Picard-Lindelof method. Finally, numerical solutions for the model are given by using different parameter values.

Identifying spatio-temporal dynamics of Ebola in Sierra Leone using virus genomes.

Containing the recent West African outbreak of Ebola virus (EBOV) required the deployment of substantial global resources. Despite recent progress in analysing and modelling EBOV epidemiological data, a complete characterization of the spatio-temporal spread of Ebola cases remains a challenge. In this work, we offer a novel perspective on the EBOV epidemic in Sierra Leone that uses individual virus genome sequences to inform population-level, spatial models. Calibrated to phylogenetic linkages of virus genomes, these spatial models provide unique insight into the disease mobility of EBOV in Sierra Leone without the need for human mobility data. Consistent with other investigations, our results show that the spread of EBOV during the beginning and middle portions of the epidemic strongly depended on the size of and distance between populations. Our phylodynamic analysis also revealed a change in model preference towards a spatial model with power-law characteristics in the latter portion of the epidemic, correlated with the timing of major intervention campaigns. More generally, we believe this framework, pairing molecular diagnostics with a dynamic model selection procedure, has the potential to be a powerful forecasting tool along with offering operationally relevant guidance for surveillance and sampling strategies during an epidemic.