scholarly journals Extracellular Vesicles and Ebola Virus: A New Mechanism of Immune Evasion

Viruses ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 410 ◽  
Author(s):  
Michelle L. Pleet ◽  
Catherine DeMarino ◽  
Spencer W. Stonier ◽  
John M. Dye ◽  
Steven Jacobson ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Immune Evasion ◽  
Immune Cells ◽  
Ebola Virus ◽  
Acute Infection ◽  
Hemorrhagic Fever ◽  
Lymphocyte Apoptosis ◽  
Current Field ◽  
Future Directions ◽  
Pro Inflammatory Cytokines

Ebola virus (EBOV) disease can result in a range of symptoms anywhere from virtually asymptomatic to severe hemorrhagic fever during acute infection. Additionally, spans of asymptomatic persistence in recovering survivors is possible, during which transmission of the virus may occur. In acute infection, substantial cytokine storm and bystander lymphocyte apoptosis take place, resulting in uncontrolled, systemic inflammation in affected individuals. Recently, studies have demonstrated the presence of EBOV proteins VP40, glycoprotein (GP), and nucleoprotein (NP) packaged into extracellular vesicles (EVs) during infection. EVs containing EBOV proteins have been shown to induce apoptosis in recipient immune cells, as well as contain pro-inflammatory cytokines. In this manuscript, we review the current field of knowledge on EBOV EVs including the mechanisms of their biogenesis, their cargo and their effects in recipient cells. Furthermore, we discuss some of the effects that may be induced by EBOV EVs that have not yet been characterized and highlight the remaining questions and future directions.

scholarly journals Excretion of urine extracellular vesicles bearing markers of activated immune cells and calcium/phosphorus physiology differ between calcium kidney stone formers and non-stone formers

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Jiqing Zhang ◽  
Sanjay Kumar ◽  
Muthuvel Jayachandran ◽  
Loren P. Herrera Hernandez ◽  
Stanley Wang ◽  
...  
Keyword(s):  
Urinary Excretion ◽  
Calcium Oxalate ◽  
Extracellular Vesicles ◽  
Immune Cells ◽  
Kidney Stone ◽  
Fibroblast Growth Factor 23 ◽  
Pathogenic Mechanisms ◽  
Phosphorus Excretion ◽  
Stone Formers ◽  
Calcium Phosphorus

Abstract Backgrounds: Previous studies have demonstrated that excretion of urinary extracellular vesicles (EVs) from different nephron segments differs between kidney stone formers and non-stone formers (NSFs), and could reflect pathogenic mechanisms of urinary stone disease. In this study we quantified selected populations of specific urinary EVs carrying protein markers of immune cells and calcium/phosphorus physiology in calcium oxalate stone formers (CSFs) compared to non-stone formers (NSFs). Methods Biobanked urine samples from CSFs (n = 24) undergoing stone removal surgery and age- and sex- matched NSFs (n = 21) were studied. Urinary EVs carrying proteins related to renal calcium/phosphorus physiology (phosphorus transporters (PiT1 and PiT2), Klotho, and fibroblast growth factor 23 (FGF23); markers associated with EV generation (anoctamin-4 (ANO4) and Huntington interacting protein 1 (HIP1)), and markers shed from activated immune cells were quantified by standardized and published method of digital flow cytometry. Results Urine excretion of calcium, oxalate, phosphorus, and calcium oxalate supersaturation (SS) were significantly higher in CSFs compared to NSFs (P < 0.05). Urinary excretion of EVs with markers of total leukocytes (CD45), neutrophils (CD15), macrophages (CD68), Klotho, FGF23, PiT1, PiT2, and ANO4 were each markedly lower in CSFs than NSFs (P < 0.05) whereas excretion of those with markers of monocytes (CD14), T-Lymphocytes (CD3), B-Lymphocytes (CD19), plasma cells (CD138 plus CD319 positive) were not different between the groups. Urinary excretion of EVs expressing PiT1 and PiT2 negatively (P < 0.05) correlated with urinary phosphorus excretion, whereas excretion of EVs expressing FGF23 negatively (P < 0.05) correlated with both urinary calcium and phosphorus excretion. Urinary EVs with markers of HIP1 and ANO4 correlated negatively (P < 0.05) with clinical stone events and basement membrane calcifications on papillary tip biopsies. Conclusions Urinary excretion of EVs derived from specific types of activated immune cells and EVs with proteins related to calcium/phosphorus regulation differed between CSFs and NSFs. Further validation of these and other populations of urinary EVs in larger cohort could identify biomarkers that elucidate novel pathogenic mechanisms of calcium stone formation in specific subsets of patients.

scholarly journals A novel application of bubble-eye strain of Carassius auratus for ex vivo fish immunological studies

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hiroto Nakajima ◽  
Atsushi Miyashita ◽  
Hiroshi Hamamoto ◽  
Kazuhisa Sekimizu
Keyword(s):  
Inflammatory Cytokines ◽  
Immune Cells ◽  
Ex Vivo ◽  
Large Bubble ◽  
Suitable Model ◽  
Bacterial Cells ◽  
Functional Impairments ◽  
Gene Expressions ◽  
Pro Inflammatory Cytokines

AbstractIn this study, we investigated a new application of bubble-eye goldfish (commercially available strain with large bubble-shaped eye sacs) for immunological studies in fishes utilizing the technical advantage of examining immune cells in the eye sac fluid ex vivo without sacrificing animals. As known in many aquatic species, the common goldfish strain showed an increased infection sensitivity at elevated temperature, which we demonstrate may be due to an immune impairment using the bubble-eye goldfish model. Injection of heat-killed bacterial cells into the eye sac resulted in an inflammatory symptom (surface reddening) and increased gene expression of pro-inflammatory cytokines observed in vivo, and elevated rearing temperature suppressed the induction of pro-inflammatory gene expressions. We further conducted ex vivo experiments using the immune cells harvested from the eye sac and found that the induced expression of pro-inflammatory cytokines was suppressed when we increased the temperature of ex vivo culture, suggesting that the temperature response of the eye-sac immune cells is a cell autonomous function. These results indicate that the bubble-eye goldfish is a suitable model for ex vivo investigation of fish immune cells and that the temperature-induced infection susceptibility in the goldfish may be due to functional impairments of immune cells.

scholarly journals Human umbilical cord mesenchymal stem cell-derived extracellular vesicles attenuate experimental autoimmune encephalomyelitis via regulating pro and anti-inflammatory cytokines

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Samira Ahmadvand Koohsari ◽  
Abdorrahim Absalan ◽  
Davood Azadi
Keyword(s):  
Spinal Cord ◽  
Body Weight ◽  
Extracellular Vesicles ◽  
Inflammatory Cytokines ◽  
Clinical Score ◽  
Human Umbilical Cord ◽  
Therapeutic Effects ◽  
Leukocyte Infiltration ◽  
Anti Inflammatory ◽  
Pro Inflammatory Cytokines

AbstractThe therapeutic effects of mesenchymal stem cells-extracellular vesicles have been proved in many inflammatory animal models. In the current study, we aimed to investigate the effect of extracellular vesicles (EVs) derived from human umbilical cord-MSC (hUCSC-EV) on the clinical score and inflammatory/anti-inflammatory cytokines on the EAE mouse model. After induction of EAE in C57Bl/6 mice, they were treated intravenously with hUCSC-EV or vehicle. The clinical score and body weight of all mice was registered every day. On day 30, mice were sacrificed and splenocytes were isolated for cytokine assay by ELISA. Cytokine expression of pro-/anti-inflammatory cytokine by real-time PCR, leukocyte infiltration by hematoxylin and eosin (H&E) staining, and the percent of glial fibrillary acidic protein (GFAP) and myelin basic protein (MBP) positive cells by immunohistochemistry were assessed in the spinal cord. Our results showed that hUCSC-EV-treated mice have lower maximum mean clinical score (MMCS), pro-inflammatory cytokines, and inflammatory score in comparison to the control mice. We also showed that hUCSC-EV administration significantly improved body weight and increased the anti-inflammatory cytokines and the frequency of Treg cells in the spleen. There was no significant difference in the percent of GFAP and MBP positive cells in the spinal cord of experimental groups. Finally, we suggest that intravenous administration of hUCSC-EV alleviate induce-EAE by reducing the pro-inflammatory cytokines, such as IL-17a, TNF-α, and IFN-γ, and increasing the anti-inflammatory cytokines, IL-4 and IL-10, and also decrease the leukocyte infiltration in a model of MS. It seems that EVs from hUC-MSCs have the same therapeutic effects similar to EVs from other sources of MSCs, such as adipose or bone marrow MSCs.

scholarly journals Human Fatal Zaire Ebola Virus Infection Is Associated with an Aberrant Innate Immunity and with Massive Lymphocyte Apoptosis

2010 ◽  
Vol 4 (10) ◽  
pp. e837 ◽  
Author(s):  
Nadia Wauquier ◽  
Pierre Becquart ◽  
Cindy Padilla ◽  
Sylvain Baize ◽  
Eric M. Leroy
Keyword(s):  
Innate Immunity ◽  
Virus Infection ◽  
Ebola Virus ◽  
Lymphocyte Apoptosis ◽  
Ebola Virus Infection

scholarly journals Structure of the Ebola virus envelope protein MPER/TM domain and its interaction with the fusion loop explains their fusion activity

2017 ◽  
Vol 114 (38) ◽  
pp. E7987-E7996 ◽  
Author(s):  
Jinwoo Lee ◽  
David A. Nyenhuis ◽  
Elizabeth A. Nelson ◽  
David S. Cafiso ◽  
Judith M. White ◽  
...  
Keyword(s):  
Membrane Fusion ◽  
Viral Entry ◽  
Ebola Virus ◽  
Rna Virus ◽  
Hemorrhagic Fever ◽  
Virus Envelope ◽  
Tm Domain ◽  
Virus Envelope Protein ◽  
Niemann Pick ◽  
Fusion Loop

Ebolavirus (EBOV), an enveloped filamentous RNA virus causing severe hemorrhagic fever, enters cells by macropinocytosis and membrane fusion in a late endosomal compartment. Fusion is mediated by the EBOV envelope glycoprotein GP, which consists of subunits GP1 and GP2. GP1 binds to cellular receptors, including Niemann-Pick C1 (NPC1) protein, and GP2 is responsible for low pH-induced membrane fusion. Proteolytic cleavage and NPC1 binding at endosomal pH lead to conformational rearrangements of GP2 that include exposing the hydrophobic fusion loop (FL) for insertion into the cellular target membrane and forming a six-helix bundle structure. Although major portions of the GP2 structure have been solved in pre- and postfusion states and although current models place the transmembrane (TM) and FL domains of GP2 in close proximity at critical steps of membrane fusion, their structures in membrane environments, and especially interactions between them, have not yet been characterized. Here, we present the structure of the membrane proximal external region (MPER) connected to the TM domain: i.e., the missing parts of the EBOV GP2 structure. The structure, solved by solution NMR and EPR spectroscopy in membrane-mimetic environments, consists of a helix-turn-helix architecture that is independent of pH. Moreover, the MPER region is shown to interact in the membrane interface with the previously determined structure of the EBOV FL through several critical aromatic residues. Mutation of aromatic and neighboring residues in both binding partners decreases fusion and viral entry, highlighting the functional importance of the MPER/TM–FL interaction in EBOV entry and fusion.

scholarly journals Equine-Origin Immunoglobulin Fragments Protect Nonhuman Primates from Ebola Virus Disease

2018 ◽  
Vol 93 (5) ◽  
Author(s):  
Hualei Wang ◽  
Gary Wong ◽  
Wenjun Zhu ◽  
Shihua He ◽  
Yongkun Zhao ◽  
...  
Keyword(s):  
Large Scale ◽  
Nonhuman Primates ◽  
Ebola Virus ◽  
Virus Disease ◽  
Hemorrhagic Fever ◽  
West African ◽  
Clinical Testing ◽  
The Past ◽  
Over 40 Years

ABSTRACT Ebola virus (EBOV) infections result in aggressive hemorrhagic fever in humans, with fatality rates reaching 90% and with no licensed specific therapeutics to treat ill patients. Advances over the past 5 years have firmly established monoclonal antibody (MAb)-based products as the most promising therapeutics for treating EBOV infections, but production is costly and quantities are limited; therefore, MAbs are not the best candidates for mass use in the case of an epidemic. To address this need, we generated EBOV-specific polyclonal F(ab′)2 fragments from horses hyperimmunized with an EBOV vaccine. The F(ab′)2 was found to potently neutralize West African and Central African EBOV in vitro. Treatment of nonhuman primates (NHPs) with seven doses of 100 mg/kg F(ab′)2 beginning 3 or 5 days postinfection (dpi) resulted in a 100% survival rate. Notably, NHPs for which treatment was initiated at 5 dpi were already highly viremic, with observable signs of EBOV disease, which demonstrated that F(ab′)2 was still effective as a therapeutic agent even in symptomatic subjects. These results show that F(ab′)2 should be advanced for clinical testing in preparation for future EBOV outbreaks and epidemics. IMPORTANCE EBOV is one of the deadliest viruses to humans. It has been over 40 years since EBOV was first reported, but no cure is available. Research breakthroughs over the past 5 years have shown that MAbs constitute an effective therapy for EBOV infections. However, MAbs are expensive and difficult to produce in large amounts and therefore may only play a limited role during an epidemic. A cheaper alternative is required, especially since EBOV is endemic in several third world countries with limited medical resources. Here, we used a standard protocol to produce large amounts of antiserum F(ab′)2 fragments from horses vaccinated with an EBOV vaccine, and we tested the protectiveness in monkeys. We showed that F(ab′)2 was effective in 100% of monkeys even after the animals were visibly ill with EBOV disease. Thus, F(ab′)2 could be a very good option for large-scale treatments of patients and should be advanced to clinical testing.

A point-of-care diagnostic for differentiating Ebola from endemic febrile diseases

2018 ◽  
Vol 10 (471) ◽  
pp. eaat0944 ◽  
Author(s):  
David Sebba ◽  
Alexander G. Lastovich ◽  
Melody Kuroda ◽  
Eric Fallows ◽  
Joshua Johnson ◽  
...  
Keyword(s):  
Ebola Virus ◽  
Clinical Symptoms ◽  
Point Of Care ◽  
Hemorrhagic Fever ◽  
Diagnostic Methods ◽  
Outbreak Detection ◽  
Molecular Diagnostic ◽  
Clinical Samples ◽  
Live Virus ◽  
And Control

Hemorrhagic fever outbreaks such as Ebola are difficult to detect and control because of the lack of low-cost, easily deployable diagnostics and because initial clinical symptoms mimic other endemic diseases such as malaria. Current molecular diagnostic methods such as polymerase chain reaction require trained personnel and laboratory infrastructure, hindering diagnostics at the point of need. Although rapid tests such as lateral flow can be broadly deployed, they are typically not well-suited for differentiating among multiple diseases presenting with similar symptoms. Early detection and control of Ebola outbreaks require simple, easy-to-use assays that can detect and differentiate infection with Ebola virus from other more common febrile diseases. Here, we developed and tested an immunoassay technology that uses surface-enhanced Raman scattering (SERS) tags to simultaneously detect antigens from Ebola, Lassa, and malaria within a single blood sample. Results are provided in <30 min for individual or batched samples. Using 190 clinical samples collected from the 2014 West African Ebola outbreak, along with 163 malaria positives and 233 negative controls, we demonstrated Ebola detection with 90.0% sensitivity and 97.9% specificity and malaria detection with 100.0% sensitivity and 99.6% specificity. These results, along with corresponding live virus and nonhuman primate testing of an Ebola, Lassa, and malaria 3-plex assay, indicate the potential of the SERS technology as an important tool for outbreak detection and clinical triage in low-resource settings.

scholarly journals Ebola Hemorrhagic Fever: Recent Update On Disease Status, Current Therapies And Advances In Treatment

2017 ◽  
Vol 5 (2) ◽  
pp. 217-234
Author(s):  
Jaskaran Singh ◽  
Thapa Komal ◽  
Sandeep Arora ◽  
Amarjot Kaur ◽  
Thakur Gurjeet Singh
Keyword(s):  
Ebola Virus ◽  
Hemorrhagic Fever ◽  
Disease Status ◽  
Clinical Test ◽  
Assessment Development ◽  
Hiv Virus ◽  
The World ◽  
New Guidelines ◽  
Virus Zika ◽  
Grade Methodology

Swiftly growing viruses are a major intimidation to human health. Such viruses are extremely pathogenic like Ebola virus, influenza virus, HIV virus, Zika virus etc . Ebola virus, a type of Filovirus, is an extremely infectious, single-stranded ribonucleic acid virus that infects both humans and apes, prompting acute fever with hemorrhagic syndrome. The high infectivity, severity and mortality of Ebola has plagued the world for the past fifty years with its first outbreak in 1976 in Marburg, Germany, and Frankfurt along with Belgrade and Serbia. The world has perceived about 28,000 cases and over 11,000 losses. The high lethality of Ebola makes it a candidate for use in bioterrorism thereby arising more concern. New guidelines have been framed for providing best possible care to the patients suffering from Ebola virus i.e Grading of Recommendation Assessment, Development And Evaluation (GRADE) methodology to develop evidence-based strategy for the treatment in future outbreak of Ebola virus. No drugs have been approved, while many potent drugs like rVSV-EBOV, Favipiravir, ZMapp are on clinical test for human safety. In this review we will discover and discuss perspective aspects that lead to the evolution of different Ebola variants as well as advances in various drugs and vaccines for treatment of the disease.

scholarly journals SPATIOTEMPORAL ANALYSIS OF THE EBOLA HEMORRHAGIC FEVER IN WEST AFRICA IN 2014

2017 ◽  
Vol XLII-2/W7 ◽  
pp. 1413-1417
Author(s):  
M. Xu ◽  
C. X. Cao ◽  
H. F. Guo
Keyword(s):  
Cluster Analysis ◽  
West Africa ◽  
Ebola Virus ◽  
Regional Distribution ◽  
Temporal Distribution ◽  
Hemorrhagic Fever ◽  
Space Time ◽  
Hotspot Analysis ◽  
Ebola Hemorrhagic Fever ◽  
Time Space

Ebola hemorrhagic fever (EHF) is an acute hemorrhagic diseases caused by the Ebola virus, which is highly contagious. This paper aimed to explore the possible gathering area of EHF cases in West Africa in 2014, and identify endemic areas and their tendency by means of time-space analysis. We mapped distribution of EHF incidences and explored statistically significant space, time and space-time disease clusters. We utilized hotspot analysis to find the spatial clustering pattern on the basis of the actual outbreak cases. spatial-temporal cluster analysis is used to analyze the spatial or temporal distribution of agglomeration disease, examine whether its distribution is statistically significant. Local clusters were investigated using Kulldorff’s scan statistic approach. The result reveals that the epidemic mainly gathered in the western part of Africa near north Atlantic with obvious regional distribution. For the current epidemic, we have found areas in high incidence of EVD by means of spatial cluster analysis.

scholarly journals EMERGENCY USE AUTHORIZATION: AT ZERO HOUR

2018 ◽  
Vol 3 (4) ◽  
pp. 18-23
Author(s):  
V. Balamuralidhara ◽  
Vaishnav A.M. ◽  
Bachu V. ◽  
Pramod Kumar T.M.
Keyword(s):  
Homeland Security ◽  
Ebola Virus ◽  
Hemorrhagic Fever ◽  
The United States ◽  
Vital Role ◽  
Test Device ◽  
Department Of Homeland Security ◽  
The Public ◽  
Life Threatening ◽  
Us Fda

The Emergency Use Authorisation (EUA) authority plays a vital role in US FDA. They provide the authority/permission to use the unregistered products/registered product with unregistered route to treat the life threatening damages to the patients in world in some emergency conditions. The aim of this work is to give an overview on EUA in life threatening conditions and there challenges in getting the permissions under regulations with example of E-bola virus. The e-bola is a virus. It is a hemorrhagic fever deadly disease caused by one of the E-bola viral strain, which is wide spread in West Africa. The -Secretary of the Department of homeland security (DHS), determined, pursuant to section 319F-2 of the Public Health Service Act, that the Ebola virus presents a material threat against the United States population sufficient to affect national security. Issuance of EUA by the FDA Commissioner requires several steps under section 564 of the FD&C Act. The FDA Commissioner, can only issue the EUA, if criteria for issuance under the statute are met. This study’s highlights the importance of the EUA in emergency when there is no medicine for disease/virus in the world. For example the FDA has issued a EUA to use the ReEBOV which is the Rapid Antigen Test device designed by Lusys lab co. Pvt. Ltd. for detecting the Zaire Ebola virus.

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