151 results match your criteria wild-type ebov

The Ferret as a Model for Filovirus Pathogenesis and Countermeasure Evaluation.

ILAR J 2021 May 5. Epub 2021 May 5.

Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, Canada.

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 Marburg and Ravn viruses, they are highly susceptible to lethal disease caused by Ebola, Sudan, Bundibugyo, and Reston viruses. Read More

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High dose of vesicular stomatitis virus-vectored Ebola virus vaccine causes vesicular disease in swine without horizontal transmission.

Emerg Microbes Infect 2021 Dec;10(1):651-663

Department of Diagnostic Medicine/Pathobiology, Center of Excellence for Emerging and Zoonotic Animal Diseases (CEEZAD), College of Veterinary Medicine, Kansas State University, Manhattan, KS, USA.

The recent impact of Ebola virus disease (EVD) on public health in Africa clearly demonstrates the need for a safe and efficacious vaccine to control outbreaks and mitigate its threat to global health. ERVEBO® is an effective recombinant Vesicular Stomatitis Virus (VSV)-vectored Ebola virus vaccine (VSV-EBOV) that was approved by the FDA and EMA in late 2019 for use in prevention of EVD. Since the parental virus VSV, which was used to construct VSV-EBOV, is pathogenic for livestock and the vaccine virus may be shed at low levels by vaccinated humans, widespread deployment of the vaccine requires investigation into its infectivity and transmissibility in VSV-susceptible livestock species. Read More

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December 2021

Ebola virus glycoprotein interacts with cholesterol to enhance membrane fusion and cell entry.

Nat Struct Mol Biol 2021 02 18;28(2):181-189. Epub 2021 Jan 18.

Center for Membrane and Cell Physiology, University of Virginia, Charlottesville, VA, USA.

Cholesterol serves critical roles in enveloped virus fusion by modulating membrane properties. The glycoprotein (GP) of Ebola virus (EBOV) promotes fusion in the endosome, a process that requires the endosomal cholesterol transporter NPC1. However, the role of cholesterol in EBOV fusion is unclear. Read More

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February 2021

Transcriptional Analysis of Lymphoid Tissues from Infected Nonhuman Primates Reveals the Basis for Attenuation and Immunogenicity of an Ebola Virus Encoding a Mutant VP35 Protein.

J Virol 2021 02 24;95(6). Epub 2021 Feb 24.

Department of Molecular Biology and Biochemistry, College of Biological Sciences, University of California, Irvine, Irvine, California, USA

Infection with (EBOV), a member of the family, causes a disease characterized by high levels of viremia, aberrant inflammation, coagulopathy, and lymphopenia. EBOV initially replicates in lymphoid tissues and disseminates via dendritic cells (DCs) and monocytes to liver, spleen, adrenal gland, and other secondary organs. EBOV protein VP35 is a critical immune evasion factor that inhibits type I interferon signaling and DC maturation. Read More

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February 2021

Annexin A2 depletion exacerbates the intracerebral microhemorrhage induced by acute rickettsia and Ebola virus infections.

PLoS Negl Trop Dis 2020 07 20;14(7):e0007960. Epub 2020 Jul 20.

Department of Pathology, University of Texas Medical Branch, Galveston, Texas, United States of America.

Intracerebral microhemorrhages (CMHs) are small foci of hemorrhages in the cerebrum. Acute infections induced by some intracellular pathogens, including rickettsia, can result in CMHs. Annexin a2 (ANXA2) has been documented to play a functional role during intracellular bacterial adhesion. Read More

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Discovery of Adamantane Carboxamides as Ebola Virus Cell Entry and Glycoprotein Inhibitors.

ACS Med Chem Lett 2020 Jun 1;11(6):1160-1167. Epub 2020 May 1.

Arisan Therapeutics, 11189 Sorrento Valley Road, Suite 104, San Diego, California 92121, United States.

We identified and explored the structure-activity-relationship (SAR) of an adamantane carboxamide chemical series of Ebola virus (EBOV) inhibitors. Selected analogs exhibited half-maximal inhibitory concentrations (EC values) of ∼10-15 nM in (VSV) pseudotyped EBOV (pEBOV) infectivity assays, low hundred nanomolar EC activity against wild type EBOV, aqueous solubility >20 mg/mL, and attractive metabolic stability in human and nonhuman liver microsomes. X-ray cocrystallographic characterizations of a lead compound with the EBOV glycoprotein (GP) established the EBOV GP as a target for direct compound inhibitory activity and further provided relevant structural models that may assist in identifying optimized therapeutic candidates. Read More

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A Conserved Tryptophan in the Ebola Virus Matrix Protein C-Terminal Domain Is Required for Efficient Virus-Like Particle Formation.

Pathogens 2020 May 22;9(5). Epub 2020 May 22.

Department of Medicinal Chemistry and Molecular Pharmacology and the Purdue Institute for Inflammation, Immunology and Infectious Disease, Purdue University, West Lafayette, IN 47907, USA.

The Ebola virus (EBOV) harbors seven genes, one of which is the matrix protein eVP40, a peripheral protein that is sufficient to induce the formation of virus-like particles from the host cell plasma membrane. eVP40 can form different structures to fulfil different functions during the viral life cycle, although the structural dynamics of eVP40 that warrant dimer, hexamer, and octamer formation are still poorly understood. eVP40 has two conserved Trp residues at positions 95 and 191. Read More

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Frontline Science: CD40 signaling restricts RNA virus replication in Mϕs, leading to rapid innate immune control of acute virus infection.

J Leukoc Biol 2021 02 22;109(2):309-325. Epub 2020 May 22.

Department of Microbiology and Immunology, University of Iowa, Iowa City, Iowa, USA.

Many acute viral infections target tissue Mϕs, yet the mechanisms of Mϕ-mediated control of viruses are poorly understood. Here, we report that CD40 expressed by peritoneal Mϕs restricts early infection of a broad range of RNA viruses. Loss of CD40 expression enhanced virus replication as early as 12-24 h of infection and, conversely, stimulation of CD40 signaling with an agonistic Ab blocked infection. Read More

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February 2021

An Investigation of the Effect of Transfected Defective, Ebola Virus Genomes on Ebola Replication.

Front Cell Infect Microbiol 2020 21;10:159. Epub 2020 Apr 21.

CBR Division, Dstl Porton Down, Salisbury, United Kingdom.

As the ongoing outbreak in the Democratic Republic of Congo illustrates, Ebola virus disease continues to pose a significant risk to humankind and this necessitates the continued development of therapeutic options. One option that warrants evaluation is that of defective genomes; these can potentially parasitize resources from the wild-type virus and may even be packaged for repeated co-infection cycles. Deletion and copy-back defective genomes have been identified and reported in the literature. Read More

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Engineered Human Cathelicidin Antimicrobial Peptides Inhibit Ebola Virus Infection.

iScience 2020 Apr 22;23(4):100999. Epub 2020 Mar 22.

Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68198, USA. Electronic address:

The 2014-2016 West Africa Ebola virus (EBOV) outbreak coupled with the most recent outbreaks in Central Africa underscore the need to develop effective treatment strategies against EBOV. Although several therapeutic options have shown great potential, developing a wider breadth of countermeasures would increase our efforts to combat the highly lethal EBOV. Here we show that human cathelicidin antimicrobial peptide (AMP) LL-37 and engineered LL-37 AMPs inhibit the infection of recombinant virus pseudotyped with EBOV glycoprotein (GP) and the wild-type EBOV. Read More

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Mucin-Like Domain of Ebola Virus Glycoprotein Enhances Selective Oncolytic Actions against Brain Tumors.

J Virol 2020 03 31;94(8). Epub 2020 Mar 31.

Department of Neurosurgery, Yale University School of Medicine, New Haven, Connecticut, USA

Given that the Ebola virus (EBOV) infects a wide array of organs and cells yet displays a relative lack of neurotropism, we asked whether a chimeric vesicular stomatitis virus (VSV) expressing the EBOV glycoprotein (GP) might selectively target brain tumors. The mucin-like domain (MLD) of the EBOV GP may enhance virus immune system evasion. Here, we compared chimeric VSVs in which EBOV GP replaces the VSV glycoprotein, thereby reducing the neurotoxicity associated with wild-type VSV. Read More

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IL-4/IL-13 polarization of macrophages enhances Ebola virus glycoprotein-dependent infection.

PLoS Negl Trop Dis 2019 12 11;13(12):e0007819. Epub 2019 Dec 11.

Department of Microbiology and Immunology, University of Iowa, Iowa City, IA United States of America.

Background: Ebolavirus (EBOV) outbreaks, while sporadic, cause tremendous morbidity and mortality. No therapeutics or vaccines are currently licensed; however, a vaccine has shown promise in clinical trials. A critical step towards development of effective therapeutics is a better understanding of factors that govern host susceptibility to this pathogen. Read More

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December 2019

Randomized, Blinded, Dose-Ranging Trial of an Ebola Virus Glycoprotein Nanoparticle Vaccine With Matrix-M Adjuvant in Healthy Adults.

J Infect Dis 2020 07;222(4):572-582

Novavax, Inc., Gaithersburg, Maryland, USA.

Background: Ebola virus (EBOV) epidemics pose a major public health risk. There currently is no licensed human vaccine against EBOV. The safety and immunogenicity of a recombinant EBOV glycoprotein (GP) nanoparticle vaccine formulated with or without Matrix-M adjuvant were evaluated to support vaccine development. Read More

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A VP35 Mutant Ebola Virus Lacks Virulence but Can Elicit Protective Immunity to Wild-Type Virus Challenge.

Cell Rep 2019 09;28(12):3032-3046.e6

Center for Microbial Pathogenesis, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USA. Electronic address:

Zaire ebolavirus (EBOV) VP35 protein is a suppressor of type I interferon (IFN) production, an inhibitor of dendritic cell maturation, and a putative virulence determinant. Here, a recombinant EBOV encoding a mutant VP35 virus (VP35m) is demonstrated to activate RIG-I-like receptor signaling and innate antiviral pathways. When inoculated into cynomolgus macaques, VP35m exhibits dramatic attenuation as compared to wild-type EBOV (wtEBOV), with 20 or 300 times the standard 100% lethal challenge dose not causing EBOV disease (EVD). Read More

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September 2019

Effect of Gamma Irradiation on the Antibody Response Measured in Human Serum from Subjects Vaccinated with Recombinant Vesicular Stomatitis Virus-Zaire Ebola Virus Envelope Glycoprotein Vaccine.

Am J Trop Med Hyg 2019 07;101(1):207-213

Merck & Co., Inc., Kenilworth, New Jersey.

rVSVΔG-ZEBOV-GP vaccine is a live recombinant (r) vesicular stomatitis virus (VSV), where the VSV G protein is replaced with the Zaire Ebola virus (ZEBOV) glycoprotein (GP). For vaccine immunogenicity testing, clinical trial sera collected during an active ZEBOV outbreak underwent gamma irradiation (GI) before testing in biosafety level 2 laboratories to inactivate possible wild-type ZEBOV. Before irradiating pivotal trial samples, two independent studies evaluated the impact of GI (50 kGy) on binding ZEBOV-GP (ELISA) antibodies against rVSVΔG-ZEBOV-GP, using sera from a North American phase 1 study. Read More

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Generation and Characterization of Anti-Filovirus Nucleoprotein Monoclonal Antibodies.

Viruses 2019 03 14;11(3). Epub 2019 Mar 14.

Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, 1015 Arlington Street, Winnipeg, MB, R3E 3R2, Canada.

Filoviruses cause lethal hemorrhagic fever in humans. The filovirus nucleoprotein (NP) is expressed in high abundance in infected cells and is essential for virus replication. To generate anti-filovirus monoclonal antibodies (mAbs) against the NP, mice were immunized with peptides known as B-cell epitopes corresponding to different filovirus NPs, and hybridomas were screened using FLAG-tagged filovirus NP constructs. Read More

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Characterization of Reston virus infection in ferrets.

Antiviral Res 2019 05 2;165:1-10. Epub 2019 Mar 2.

Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, Canada; Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba, Canada. Electronic address:

Among the five currently recognized type viruses within the genus Ebolavirus, Reston virus (RESTV) is not known to cause disease in humans, although asymptomatic infections have been confirmed in the past. Intriguingly, despite the absence of pathogenicity in humans, RESTV is highly lethal to nonhuman primates and has been isolated from domestic pigs co-infected with other viruses in the Philippines and China. Whether infection in these animals can support the eventual emergence of a human-pathogenic RESTV remains unclear and requires further investigation. Read More

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Filovirus Virulence in Interferon α/β and γ Double Knockout Mice, and Treatment with Favipiravir.

Viruses 2019 02 3;11(2). Epub 2019 Feb 3.

Sealy Institute for Vaccine Science, University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA.

The 2014 Ebolavirus outbreak in West Africa highlighted the need for vaccines and therapeutics to prevent and treat filovirus infections. A well-characterized small animal model that is susceptible to wild-type filoviruses would facilitate the screening of anti-filovirus agents. To that end, we characterized knockout mice lacking α/β and γ interferon receptors (IFNAGR KO) as a model for wild-type filovirus infection. Read More

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February 2019

The efficacy of poly-ICLC against Ebola-Zaire virus (EBOV) infection in mice and cynomolgus monkeys.

Antiviral Res 2019 03 3;163:179-184. Epub 2019 Jan 3.

Oncovir, Inc., 3203 Cleveland Avenue, Washington, D.C, 20008, USA.

The potential protection of poly-ICLC (Hiltonol) a double stranded RNA (dsRNA) against EBOV infection was assessed with prophylactic and therapeutic administration to wild type and TLR3-negative mice, and in non-human primates (NHPs) by measuring EBOL serum titers, survival extension, and serum liver and kidney function markers. Various doses of aqueous and liposomal poly-ICLC monotherapy provided robust protection in otherwise lethal murine EBOV challenge models, when treatment is started on the day 0 or one day after virus challenge. There was no advantage of liposomal vs. Read More

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Intramuscular Exposure of to Low Doses of Low Passage- or Cell Culture-Adapted Sudan Virus or Ebola Virus.

Viruses 2018 11 16;10(11). Epub 2018 Nov 16.

Department of Virology and Immunology, Texas Biomedical Research Institute, San Antonio, TX 78227, USA.

The filoviruses Ebola virus (EBOV) and Sudan virus (SUDV) can cause severe diseases, and there are currently no licensed countermeasures available for use against them. Transmission occurs frequently via contact with bodily fluids from infected individuals. However, it can be difficult to determine when or how someone became infected, or the quantity of infectious virus to which they were exposed. Read More

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November 2018

Naturally Occurring Single Mutations in Ebola Virus Observably Impact Infectivity.

J Virol 2019 01 10;93(1). Epub 2018 Dec 10.

Special Pathogens Program, Public Health Agency of Canada, Winnipeg, Manitoba, Canada

Sequencing of Ebola virus (EBOV) genomes during the 2014-2016 epidemic identified several naturally occurring, dominant mutations potentially impacting virulence or tropism. In this study, we characterized EBOV variants carrying one of the following substitutions: A82V in the glycoprotein (GP), R111C in the nucleoprotein (NP), or D759G in the RNA-dependent RNA polymerase (L). Compared with the wild-type (WT) EBOV C07 isolate, NP and L mutants conferred a replication advantage in monkey Vero E6, human A549, and insectivorous bat Tb1. Read More

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January 2019

Ebola Virus VP40 Modulates Cell Cycle and Biogenesis of Extracellular Vesicles.

J Infect Dis 2018 11;218(suppl_5):S365-S387

Laboratory of Molecular Virology, School of Systems Biology, George Mason University, Manassas, Virginia.

Background: Ebola virus (EBOV) mainly targets myeloid cells; however, extensive death of T cells is often observed in lethal infections. We have previously shown that EBOV VP40 in exosomes causes recipient immune cell death.

Methods: Using VP40-producing clones, we analyzed donor cell cycle, extracellular vesicle (EV) biogenesis, and recipient immune cell death. Read More

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November 2018

Ebolavirus Chimerization for the Development of a Mouse Model for Screening of Bundibugyo-Specific Antibodies.

J Infect Dis 2018 11;218(suppl_5):S418-S422

Department of Pathology, University of Texas Medical Branch, Galveston.

Screening of monoclonal antibodies against ebolaviruses requires small-animal models. Wild-type mice require adaptation of ebolaviruses, whereas immunodeficient mice are still resistant to nonadapted Bundibugyo ebolavirus. Swapping of Ebola virus glycoprotein with that from Bundibugyo virus resulted in a replication-competent chimeric virus, which caused 100% lethal infection in STAT1 knockout mice. Read More

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November 2018

Fully Human Immunoglobulin G From Transchromosomic Bovines Treats Nonhuman Primates Infected With Ebola Virus Makona Isolate.

J Infect Dis 2018 11;218(suppl_5):S636-S648

SAB Biotherapeutics Inc., Sioux Falls, South Dakota.

Transchromosomic bovines (Tc-bovines) adaptively produce fully human polyclonal immunoglobulin (Ig)G antibodies after exposure to immunogenic antigen(s). The National Interagency Confederation for Biological Research and collaborators rapidly produced and then evaluated anti-Ebola virus IgG immunoglobulins (collectively termed SAB-139) purified from Tc-bovine plasma after sequential hyperimmunization with an Ebola virus Makona isolate glycoprotein nanoparticle vaccine. SAB-139 was characterized by several in vitro production, research, and clinical level assays using wild-type Makona-C05 or recombinant virus/antigens from different Ebola virus variants. Read More

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November 2018

Marburg and Ravn Viruses Fail to Cause Disease in the Domestic Ferret (Mustela putorius furo).

J Infect Dis 2018 11;218(suppl_5):S448-S452

Department of Microbiology and Immunology.

The domestic ferret was recently described as a uniformly lethal model for 3 species of Ebolavirus. More importantly, this new model utilizes nonadapted wild-type Ebolaviruses. Here, in a proof-of-concept study, we infected ferrets with different variants of the closely related Marburg and Ravn viruses using different doses and routes of exposure. Read More

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November 2018

Characterization of Influenza Virus Pseudotyped with Ebolavirus Glycoprotein.

J Virol 2018 02 30;92(4). Epub 2018 Jan 30.

Human Immunology Unit, Weatherall Institute of Molecular Medicine, Oxford, United Kingdom

We have produced a new Ebola virus pseudotype, E-S-FLU, that can be handled in biosafety level 1/2 containment for laboratory analysis. The E-S-FLU virus is a single-cycle influenza virus coated with Ebolavirus glycoprotein, and it encodes enhanced green fluorescence protein as a reporter that replaces the influenza virus hemagglutinin. MDCK-SIAT1 cells were transduced to express Ebolavirus glycoprotein as a stable transmembrane protein for E-S-FLU virus production. Read More

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February 2018

Intracellular Crosslinking of Filoviral Nucleoproteins with Xintrabodies Restricts Viral Packaging.

Front Immunol 2017 27;8:1197. Epub 2017 Sep 27.

Department of Virology and Immunology, Texas Biomedical Research Institute, San Antonio, TX, United States.

Viruses assemble large macromolecular repeat structures that become part of the infectious particles or virions. Ribonucleocapsids (RNCs) of negative strand RNA viruses are a prime example where repetition of nucleoprotein (NP) along the genome creates a core polymeric helical scaffold that accommodates other nucleocapsid proteins including viral polymerase. The RNCs are transported through the cytosol for packaging into virions through association with viral matrix proteins at cell membranes. Read More

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September 2017

Characterization of the catalytic center of the Ebola virus L polymerase.

PLoS Negl Trop Dis 2017 Oct 9;11(10):e0005996. Epub 2017 Oct 9.

Institute for Molecular Virology and Cell Biology, Friedrich-Loeffler-Institut, Greifswald-Insel Riems, Germany.

Background: Ebola virus (EBOV) causes a severe hemorrhagic fever in humans and non-human primates. While no licensed therapeutics are available, recently there has been tremendous progress in developing antivirals. Targeting the ribonucleoprotein complex (RNP) proteins, which facilitate genome replication and transcription, and particularly the polymerase L, is a promising antiviral approach since these processes are essential for the virus life cycle. Read More

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October 2017

Cooperation of the Ebola Virus Proteins VP40 and GP with BST2 To Activate NF-κB Independently of Virus-Like Particle Trapping.

J Virol 2017 11 27;91(22). Epub 2017 Oct 27.

University of California San Diego, La Jolla, California, USA

BST2 is a host protein with dual functions in response to viral infections: it traps newly assembled enveloped virions at the plasma membrane in infected cells, and it induces NF-κB activity, especially in the context of retroviral assembly. In this study, we examined whether Ebola virus proteins affect BST2-mediated induction of NF-κB. We found that the Ebola virus matrix protein, VP40, and envelope glycoprotein, GP, each cooperate with BST2 to induce NF-κB activity, with maximal activity when all three proteins are expressed. Read More

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November 2017

Investigating Ebola virus pathogenicity using molecular dynamics.

BMC Genomics 2017 08 11;18(Suppl 5):566. Epub 2017 Aug 11.

School of Biosciences, University of Kent, Kent, UK.

Background: Ebolaviruses have been known to cause deadly disease in humans for 40 years and have recently been demonstrated in West Africa to be able to cause large outbreaks. Four Ebolavirus species cause severe disease associated with high mortality in humans. Reston viruses are the only Ebolaviruses that do not cause disease in humans. Read More

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