scholarly journals Ebola Virus ? A Global Threat

2015 ◽  
Vol 5 (1) ◽  
pp. 44-51
Author(s):  
Mejbah Uddin Ahmed ◽  
Sushmita Roy
Keyword(s):  
Nonhuman Primates ◽  
Ebola Virus ◽  
Rna Virus ◽  
Close Contact ◽  
Multiorgan Failure ◽  
Hemorrhagic Fever ◽  
Human Infection ◽  
Current Data ◽  
Sub Saharan Africa ◽  
Virus Infections

Ebola virus is a filamentous, enveloped, non-segmented, single-stranded, negative-sense RNA virus. It belongs to the Filoviridae and was first recognized near the Ebola River valley in Zaire in 1976. Since then most of the outbreaks have occurred to both human and nonhuman primates in sub-Saharan Africa. Ebola virus causes highly fatal hemorrhagic fever in human and nonhuman primates. In addition to hemorrhagic fever, it could be used as a bioterrorism agent. Although its natural reservoir is yet to be proven, current data suggest that fruit bats are the possibility. Infection has also been documented through the handling of infected chimpanzees, gorillas, monkeys, forest antelope and porcupines. Human infection is caused through close contact with the blood, secretion, organ or other body fluids of infected animal. Human-to-human transmission is also possible. Ebola virus infections are characterized by immune suppression and a systemic inflammatory response that causes impairment of the vascular, coagulation, and immune systems, leading to multiorgan failure and shock. The virus constitutes an important public health threat in Africa and also worldwide as no effective treatment or vaccine is available till now DOI: http://dx.doi.org/10.3329/jemc.v5i1.21497 J Enam Med Col 2015; 5(1): 44-51

scholarly journals Identification and characterization of defective viral genomes in Ebola virus infected rhesus macaques

2021 ◽  
Author(s):  
Rebecca I. Johnson ◽  
Beata Boczkowska ◽  
Kendra Alfson ◽  
Taylor Weary ◽  
Heather Menzie ◽  
...  
Keyword(s):  
Nonhuman Primates ◽  
Ebola Virus ◽  
Sequence Data ◽  
Rna Virus ◽  
Hemorrhagic Fever ◽  
Marburg Virus ◽  
Immunostimulatory Activity ◽  
Viral Genomes

Ebola virus (EBOV), of the family Filoviridae, is an RNA virus that can cause 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 replication in filovirus-infected hosts. Therefore, we interrogated sequence data from serum and tissues using a bioinformatics tool in order to identify the presence of DVGs in nonhuman primates (NHPs) infected with EBOV, Sudan virus (SUDV) or Marburg virus (MARV). Multiple 5’ copy-back DVGs (cbDVGs) were detected in NHP serum during the acute phase of filovirus infection. While the relative abundance of total DVGs in most animals was low, serum collected during acute EBOV and SUDV infections, but not MARV infection, contained a higher proportion of short trailer sequence cbDVGs than the challenge stock. This indicated an accumulation of these DVGs throughout infection, potentially due to the preferential replication of short DVGs over the longer viral genome. Using RT-PCR and deep sequencing, we also confirmed the presence of 5’ cbDVGs in EBOV-infected NHP testes, which is of interest due to EBOV persistence in semen of male survivors of infection. This work suggests that DVGs play a role in EBOV infection in vivo and further study will lead to a better understanding of EBOV pathogenesis. Importance The study of filovirus pathogenesis is critical for understanding the consequences of infection and the development of strategies to ameliorate future outbreaks. Defective viral genomes (DVGs) have been detected during EBOV infections in vitro , however their presence in in vivo infections remains unknown. In this study, DVGs were detected in samples collected from EBOV- and SUDV-infected nonhuman primates (NHPs). The accumulation of these DVGs in the trailer region of the genome during infection indicates a potential role in EBOV and SUDV pathogenesis. In particular, the presence of DVGs in the testes of infected NHPs requires further investigation as it may be linked to the establishment of persistence.

scholarly journals Vaccine To Confer to Nonhuman Primates Complete Protection against Multistrain Ebola and Marburg Virus Infections

2008 ◽  
Vol 15 (3) ◽  
pp. 460-467 ◽  
Author(s):  
Dana L. Swenson ◽  
Danher Wang ◽  
Min Luo ◽  
Kelly L. Warfield ◽  
Jan Woraratanadharm ◽  
...  
Keyword(s):  
Nonhuman Primates ◽  
Ebola Virus ◽  
De Novo ◽  
Lethal Dose ◽  
Hemorrhagic Fever ◽  
Mortality Rates ◽  
Marburg Virus ◽  
Virus Infections ◽  
Biological Attack ◽  
Protection Against Infection

ABSTRACT Filoviruses (Ebola and Marburg viruses) are among the deadliest viruses known to mankind, with mortality rates nearing 90%. These pathogens are highly infectious through contact with infected body fluids and can be easily aerosolized. Additionally, there are currently no licensed vaccines available to prevent filovirus outbreaks. Their high mortality rates and infectious capabilities when aerosolized and the lack of licensed vaccines available to prevent such infectious make Ebola and Marburg viruses serious bioterrorism threats, placing them both on the category A list of bioterrorism agents. Here we describe a panfilovirus vaccine based on a complex adenovirus (CAdVax) technology that expresses multiple antigens from five different filoviruses de novo. Vaccination of nonhuman primates demonstrated 100% protection against infection by two species of Ebola virus and three Marburg virus subtypes, each administered at 1,000 times the lethal dose. This study indicates the feasibility of vaccination against all current filovirus threats in the event of natural hemorrhagic fever outbreak or biological attack.

scholarly journals Liposomal Systems as Nanocarriers for the Antiviral Agent Ivermectin

2016 ◽  
Vol 2016 ◽  
pp. 1-15 ◽  
Author(s):  
Romina Croci ◽  
Elisabetta Bottaro ◽  
Kitti Wing Ki Chan ◽  
Satoru Watanabe ◽  
Margherita Pezzullo ◽  
...  
Keyword(s):  
Yellow Fever ◽  
Rna Virus ◽  
Multiorgan Failure ◽  
Antiviral Agent ◽  
Drug Carriers ◽  
Virus Infections ◽  
Starting Point ◽  
Significant Public Health ◽  
High Cytotoxicity

RNA virus infections can lead to the onset of severe diseases such as fever with haemorrhage, multiorgan failure, and mortality. The emergence and reemergence of RNA viruses continue to pose a significant public health threat worldwide with particular attention to the increasing incidence of flaviviruses, among others Dengue, West Nile Virus, and Yellow Fever viruses. Development of new and potent antivirals is thus urgently needed. Ivermectin, an already known antihelminthic drug, has shown potent effectsin vitroonFlavivirushelicase, with EC50values in the subnanomolar range for Yellow Fever and submicromolar EC50for Dengue Fever, Japanese encephalitis, and tick-borne encephalitis viruses. However ivermectin is hampered in its application by pharmacokinetic problems (little solubility and high cytotoxicity). To overcome such problems we engineered different compositions of liposomes as ivermectin carriers characterizing and testing them on several cell lines for cytotoxicity. The engineered liposomes were less cytotoxic than ivermectin alone and they showed a significant increase of the antiviral activity in all the Dengue stains tested (1, 2, and S221). In the current study ivermectin is confirmed to be an effective potential antiviral and liposomes, as drug carriers, are shown to modulate the drug activity. All together the results represent a promising starting point for future improvement of ivermectin as antiviral and its delivery.

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.

Viral hemorrhagic fever – a vascular disease?

2003 ◽  
Vol 89 (06) ◽  
pp. 967-972 ◽  
Author(s):  
Heinz Feldmann ◽  
Hans Schnittler
Keyword(s):  
Ebola Virus ◽  
Vascular System ◽  
Current Knowledge ◽  
Hemorrhagic Fever ◽  
Host Cells ◽  
Fluid Distribution ◽  
Target Cells ◽  
Viral Hemorrhagic Fever ◽  
Virus Infections ◽  
Cytokines And Chemokines

SummaryThe syndrome of “viral hemorrhagic fever” in man caused by certain viruses, such as Ebola, Lassa, Dengue, and Crimean-Congo hemorrhagic fever viruses, is often associated with a shock syndrome of undetermined pathogenesis. However, the vascular system, particularly the vascular endothelium, seems to be directly and indirectly targeted by all these viruses. Here we briefly summarize the current knowledge on Marburg and Ebola virus infections, the prototype viral hemorrhagic fever agents, and formulate a working hypothesis for the pathogenesis of viral hemorrhagic fever. Infections with filoviruses show lethality up to 89% and in severe cases lead to a shock syndrome associated with hypotension, coagulation disorders and an imbalance of fluid distribution between the intravascular and extravascular tissue space. The primary target cells for filovi-ruses are mononuclear phagocytotic cells which are activated upon infection and release certain cytokines and chemokines. These mediators indirectly target the endothelium and are thought to play a key role in the pathogenesis of filoviral hemorrhagic fever. In addition, direct infection and subsequent destruction of endothelial cells might contribute to the pathogenesis. Filoviruses, particularly Ebola virus, encode nonstructural glycoproteins which are released from infected host cells. Their function as potential determinants in pathogenicity remains to be investigated.

scholarly journals Macaque Monoclonal Antibodies Targeting Novel Conserved Epitopes within Filovirus Glycoprotein

2015 ◽  
Vol 90 (1) ◽  
pp. 279-291 ◽  
Author(s):  
Zhen-Yong Keck ◽  
Sven G. Enterlein ◽  
Katie A. Howell ◽  
Hong Vu ◽  
Sergey Shulenin ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Nonhuman Primates ◽  
Ebola Virus ◽  
Virus Disease ◽  
Protective Efficacy ◽  
Hemorrhagic Fever ◽  
Marburg Virus ◽  
Human Pathogens ◽  
Content Type ◽  
The Core

ABSTRACTFiloviruses cause highly lethal viral hemorrhagic fever in humans and nonhuman primates. Current immunotherapeutic options for filoviruses are mostly specific to Ebola virus (EBOV), although other members ofFiloviridaesuch as Sudan virus (SUDV), Bundibugyo virus (BDBV), and Marburg virus (MARV) have also caused sizeable human outbreaks. Here we report a set of pan-ebolavirus and pan-filovirus monoclonal antibodies (MAbs) derived from cynomolgus macaques immunized repeatedly with a mixture of engineered glycoproteins (GPs) and virus-like particles (VLPs) for three different filovirus species. The antibodies recognize novel neutralizing and nonneutralizing epitopes on the filovirus glycoprotein, including conserved conformational epitopes within the core regions of the GP1 subunit and a novel linear epitope within the glycan cap. We further report the first filovirus antibody binding to a highly conserved epitope within the fusion loop of ebolavirus and marburgvirus species. One of the antibodies binding to the core GP1 region of all ebolavirus species and with lower affinity to MARV GP cross neutralized both SUDV and EBOV, the most divergent ebolavirus species. In a mouse model of EBOV infection, this antibody provided 100% protection when administered in two doses and partial, but significant, protection when given once at the peak of viremia 3 days postinfection. Furthermore, we describe novel cocktails of antibodies with enhanced protective efficacy compared to individual MAbs. In summary, the present work describes multiple novel, cross-reactive filovirus epitopes and innovative combination concepts that challenge the current therapeutic models.IMPORTANCEFiloviruses are among the most deadly human pathogens. The 2014-2015 outbreak of Ebola virus disease (EVD) led to more than 27,000 cases and 11,000 fatalities. While there are five species ofEbolavirusand several strains of marburgvirus, the current immunotherapeutics primarily target Ebola virus. Since the nature of future outbreaks cannot be predicted, there is an urgent need for therapeutics with broad protective efficacy against multiple filoviruses. Here we describe a set of monoclonal antibodies cross-reactive with multiple filovirus species. These antibodies target novel conserved epitopes within the envelope glycoprotein and exhibit protective efficacy in mice. We further present novel concepts for combination of cross-reactive antibodies against multiple epitopes that show enhanced efficacy compared to monotherapy and provide complete protection in mice. These findings set the stage for further evaluation of these antibodies in nonhuman primates and development of effective pan-filovirus immunotherapeutics for use in future outbreaks.

scholarly journals Dengue virus: A review

2022 ◽  
Vol 8 (4) ◽  
pp. 243-247
Author(s):  
Narinder Singh ◽  
Ajeet Pal Singh ◽  
Amar Pal Singh
Keyword(s):  
Public Health ◽  
Dengue Virus ◽  
Dengue Fever ◽  
Rna Virus ◽  
Hemorrhagic Fever ◽  
Health Concern ◽  
Virus Infections ◽  
Public Health Concern ◽  
Viral Illness ◽  
Life Threatening

Dengue fever is a mosquito-borne viral illness that is quickly spreading over the globe, with significant death and morbidity rates. Dengue fever is an acute viral infection transmitted by Aedes mosquitos and caused by an RNA virus from the Flaviviridae family. The symptoms might vary from asymptomatic fever to life-threatening complications including hemorrhagic fever and shock. Although dengue virus infections are normally self-limiting, the disease has become a public health concern in tropical and subtropical countries. Dengue fever is a major public health concern owing to its rapid worldwide spread, and its burdens are now unmet due to a lack of accurate therapy and a simple diagnostic approach for the early stages of illness.

scholarly journals Bioinformatics approach reveals the gene targets of Ebola virus microRNAs involved in the human skin microbiome

2017 ◽  
Author(s):  
Pei-Chun Hsu ◽  
Bin-Hao Chiou ◽  
Chun-Ming Huang
Keyword(s):  
Endothelial Cell ◽  
Ebola Virus ◽  
Propionibacterium Acnes ◽  
Immune Escape ◽  
Rna Virus ◽  
Normal Skin ◽  
Hemorrhagic Fever ◽  
Cell Swelling ◽  
Skin Microbiome ◽  
Rna Sequences

The Ebola virus, a negative-sense single-stranded RNA virus, causes severe viral hemorrhagic fever and is highly lethal. Histopathology and immunopathologic study of Ebola virus have revealed that histopathologic changes in skin tissue were mainly various degrees of endothelial cell swelling and necrosis. The interactions of microbes within or on a host are a crucial aspect of the skin immune shield. The discovery of microRNAs in Ebola virus implies that immune escape, endothelial cell rupture and tissue dissolution during Ebola virus infection are all results of the action of Ebola virus miRNAs. Keratinocytes obtained from normal skin and subsequently attached and spread on the thrombospondin protein family may play a role in initiating cell-mediated immune responses in the skin. Several miRNAs have been observed to bind the 3' untranslated region of the thrombospondin mRNA, thereby controlling its stability and translational activity. In this study, we first discover short RNA sequences that might act as miRNAs from Propionibacterium acnes by design a practical workflow of bioinformatics methods. Subsequently, we deciphered the common target gene. These RNA sequences tend to binding to the same thrombospondin protein. These RNA sequences tend to bind to the same protein , THSD4, emphasizing the potential importance of the synergistic binding of miRNAs from Ebola virus, Propionibacterium acnes , and humans to the target. By RNA expression validation, we prove the potential synergistic binding of the miRNA from Ebola virus, Propionibacterium acnes and human to the target.

scholarly journals Ebola and Marburg Viruses

2011 ◽  
Vol 6 (4) ◽  
pp. 381-389 ◽  
Author(s):  
Eri Nakayama ◽  
◽  
Ayato Takada
Keyword(s):  
Nonhuman Primates ◽  
Ebola Virus ◽  
Hemorrhagic Fever ◽  
Disease Outbreak ◽  
Marburg Virus ◽  
Virus Group ◽  
Imported Cases ◽  
Control Disease ◽  
Animal Reservoirs ◽  
Biosafety Level

Ebola and Marburg viruses, members of the filovirus family, cause severe hemorrhagic fever in human and nonhuman primates and are classified as biosafety level 4 agents. No effective filovirus-specific prophylaxis or treatment is yet commercially available. Filovirus species vary genetically, with one in the Marburg virus group and five in the Ebola virus group. Epidemiological efforts to prevent outbreaks lie mainly in identifying natural animal reservoirs. Increasingly frequent outbreaks in Africa and concerns about bioterrorism and imported cases in nonendemic areas point to the importance of public health in two ways – finding strategies to control disease outbreak and developing effective vaccines and drugs.

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