Sample records for virus ebola virus

  1. Ebola Virus Disease

    MedlinePLUS

    Ebola virus disease Fact sheet N°103 Updated April 2015 Key facts Ebola virus disease (EVD), formerly ... live Ebola virus in vaginal secretions. Symptoms of Ebola virus disease The incubation period, that is, the ...

  2. Ebola Virus University Preparedness for Ebola

    E-print Network

    Shepard, Kenneth

    Ebola Virus University Preparedness for Ebola Columbia University Travel Policy to Ebola Bellevue 11/11/2014 Communication from CUMC Dean Goldman and NYPH CEO Dr. Corwin - Update on NYC Ebola Case 10/24/2014 Communication from President Bollinger Ebola Update 10/23/2014 Frequently Asked Questions

  3. Postmortem Stability of Ebola Virus

    PubMed Central

    Prescott, Joseph; Bushmaker, Trenton; Fischer, Robert; Miazgowicz, Kerri; Judson, Seth

    2015-01-01

    The ongoing Ebola virus outbreak in West Africa has highlighted questions regarding stability of the virus and detection of RNA from corpses. We used Ebola virus–infected macaques to model humans who died of Ebola virus disease. Viable virus was isolated <7 days posteuthanasia; viral RNA was detectable for 10 weeks. PMID:25897646

  4. Ebola virus disease.

    PubMed

    Richardson, Kathleen J

    2015-01-01

    Ebola is an unfamiliar disease with a high mortality rate. Until recently, it occurred only in rural tropical regions and most health care providers had only read about it in epidemiology classes. With globalization, international travel, and foreign medical missions, it is possible that a patient with Ebola exposure and/or symptoms may present in any emergency department. All health care providers must be familiar with identifying the signs and symptoms of Ebola and capable of initiating an appropriate response. This article presents an overview of Ebola virus disease for health care providers, covering pathophysiology, identification, treatment, and general considerations for hospitals and providers to consider when developing policies and procedures. PMID:25929221

  5. Frequently Asked Questions on Ebola Virus Disease

    MedlinePLUS

    ... Response Network Biorisk Reduction Frequently asked questions on Ebola virus disease May 2015 FAQs from August 2014 ... based on recent evidence. For more information on Ebola virus disease Fact sheet on Ebola virus disease ...

  6. Treatment of ebola virus disease.

    PubMed

    Kilgore, Paul E; Grabenstein, John D; Salim, Abdulbaset M; Rybak, Michael

    2015-01-01

    In March 2014, the largest Ebola outbreak in history exploded across West Africa. As of November 14, 2014, the World Health Organization has reported a total of 21,296 Ebola virus disease (EVD) cases, including 13,427 laboratory-confirmed EVD cases reported from the three most affected countries (Guinea, Liberia, and Sierra Leone). As the outbreak of EVD has spread, clinical disease severity and national EVD case-fatality rates have remained high (21.2-60.8%). Prior to 2013, several EVD outbreaks were controlled by using routine public health interventions; however, the widespread nature of the current EVD outbreak as well as cultural practices in the affected countries have challenged even the most active case identification efforts. In addition, although treatment centers provide supportive care, no effective therapeutic agents are available for EVD-endemic countries. The ongoing EVD outbreak has stimulated investigation of several different therapeutic strategies that target specific viral structures and mechanisms of Ebola viruses. Six to eight putative pharmacotherapies or immunologically based treatments have demonstrated promising results in animal studies. In addition, agents composed of small interfering RNAs targeting specific proteins of Ebola viruses, traditional hyperimmune globulin isolated from Ebola animal models, monoclonal antibodies, and morpholino oligomers (small molecules used to block viral gene expression). A number of EVD therapeutic agents are now entering accelerated human trials in EVD-endemic countries. The goal of therapeutic agent development includes postexposure prevention and EVD cure. As knowledge of Ebola virus virology and pathogenesis grows, it is likely that new therapeutic tools will be developed. Deployment of novel Ebola therapies will require unprecedented cooperation as well as investment to ensure that therapeutic tools become available to populations at greatest risk for EVD and its complications. In this article, we review several agents and strategies that are now under active development. PMID:25630412

  7. THE EBOLA VIRUS BY R. AARON ROBISON

    E-print Network

    Faraon, Andrei

    OUTBREAK: THE EBOLA VIRUS BY R. AARON ROBISON IN JULY OF 1976, A SUDANESE STOREKEEPER BECAME forests of central Africa. The virus that killed him eventually became known as Ebola, named after a river traveling from Africa started exhibiting Ebola-like symptoms, sparking a brief media bonanza before she

  8. Fruit bats as reservoirs of Ebola virus

    Microsoft Academic Search

    Eric M. Leroy; Brice Kumulungui; Xavier Pourrut; Pierre Rouquet; Alexandre Hassanin; Philippe Yaba; André Délicat; Janusz T. Paweska; Jean-Paul Gonzalez; Robert Swanepoel

    2005-01-01

    The first recorded human outbreak of Ebola virus was in 1976, but the wild reservoir of this virus is still unknown. Here we test for Ebola in more than a thousand small vertebrates that were collected during Ebola outbreaks in humans and great apes between 2001 and 2003 in Gabon and the Republic of the Congo. We find evidence of

  9. Characteristics of Filoviridae: Marburg and Ebola Viruses

    NASA Astrophysics Data System (ADS)

    Beer, Brigitte; Kurth, Reinhard; Bukreyev, Alexander

    Filoviruses are enveloped, nonsegmented negative-stranded RNA viruses. The two species, Marburg and Ebola virus, are serologically, biochemically, and genetically distinct. Marburg virus was first isolated during an outbreak in Europe in 1967, and Ebola virus emerged in 1976 as the causative agent of two simultaneous outbreaks in southern Sudan and northern Zaire. Although the main route of infection is known to be person-to-person transmission by intimate contact, the natural reservoir for filoviruses still remains a mystery.

  10. Ebola virus disease: radiology preparedness.

    PubMed

    Bluemke, David A; Meltzer, Carolyn C

    2015-02-01

    At present, there is a major emphasis on Ebola virus disease (EVD) preparedness training at medical facilities throughout the United States. Failure to have proper EVD procedures in place was cited as a major reason for infection of medical personnel in the United States. Medical imaging does not provide diagnosis of EVD, but patient assessment in the emergency department and treatment isolation care unit is likely to require imaging services. The purpose of this article is to present an overview of relevant aspects of EVD disease and preparedness relevant to the radiologic community. PMID:25405643

  11. [Modern threat of Ebola virus].

    PubMed

    P?usa, Tadeusz

    2014-11-01

    Since the detection of Ebola virus in 1976. recorded 13 major epidemics in Africa. The current threat in Guinea, Liberia and Sierra Leone absorbs another victims and threatened pandemic. Picture of the disease is initially very non-characteristic (influenza-like symptoms) and quickly leads to dehydration, shock and disseminated intravascular coagulation syndrome, which is responsible for high mortality. Lack of effective antibiotic therapy and vaccine hampers the existing situation. For this reason, there is an absolute necessity to introduce regimes sanitation, quarantine at the suspects and maintain the highest safety measures for emergency responders. Developed procedures require absolute compliance. PMID:25546984

  12. Ebola Virus Disease The current outbreak of Ebola Virus Disease (EVD) in West Africa has involved the

    E-print Network

    MacAdam, Keith

    Ebola Virus Disease The current outbreak of Ebola Virus Disease (EVD) in West Africa has involved the countries of Sierra Leone, Liberia, Guinea, and Nigeria. This has become the largest outbreak of Ebola want to make sure you have the most accurate information about this illness. What is Ebola Virus

  13. Successful delivery of RRT in Ebola virus disease.

    PubMed

    Connor, Michael J; Kraft, Colleen; Mehta, Aneesh K; Varkey, Jay B; Lyon, G Marshall; Crozier, Ian; Ströher, Ute; Ribner, Bruce S; Franch, Harold A

    2015-01-01

    AKI has been observed in cases of Ebola virus disease. We describe the protocol for the first known successful delivery of RRT with subsequent renal recovery in a patient with Ebola virus disease treated at Emory University Hospital, in Atlanta, Georgia. Providing RRT in Ebola virus disease is complex and requires meticulous attention to safety for the patient, healthcare workers, and the community. We specifically describe measures to decrease the risk of transmission of Ebola virus disease and report pilot data demonstrating no detectable Ebola virus genetic material in the spent RRT effluent waste. This article also proposes clinical practice guidelines for acute RRT in Ebola virus disease. PMID:25398785

  14. Successful Delivery of RRT in Ebola Virus Disease

    PubMed Central

    Kraft, Colleen; Mehta, Aneesh K.; Varkey, Jay B.; Lyon, G. Marshall; Crozier, Ian; Ströher, Ute; Ribner, Bruce S.

    2015-01-01

    AKI has been observed in cases of Ebola virus disease. We describe the protocol for the first known successful delivery of RRT with subsequent renal recovery in a patient with Ebola virus disease treated at Emory University Hospital, in Atlanta, Georgia. Providing RRT in Ebola virus disease is complex and requires meticulous attention to safety for the patient, healthcare workers, and the community. We specifically describe measures to decrease the risk of transmission of Ebola virus disease and report pilot data demonstrating no detectable Ebola virus genetic material in the spent RRT effluent waste. This article also proposes clinical practice guidelines for acute RRT in Ebola virus disease. PMID:25398785

  15. Ebola virus disease and the veterinary perspective.

    PubMed

    Gumusova, Semra; Sunbul, Mustafa; Leblebicioglu, Hakan

    2015-01-01

    Ebola virus disease (EVD) is a potentially fatal haemorrhagic disease of humans. The last and most serious outbreak of Ebola virus (EBOV) started in December 2013 in West Africa and also affected other continents. Animals such as fruit bats and non-human primates are potential sources of EBOV. This review highlights the clinical features of EVD in humans and animals and addresses the public health implications of EVD outbreaks from the veterinary perspective. PMID:26018030

  16. An Ebola virus-centered knowledge base

    PubMed Central

    Kamdar, Maulik R.; Dumontier, Michel

    2015-01-01

    Ebola virus (EBOV), of the family Filoviridae viruses, is a NIAID category A, lethal human pathogen. It is responsible for causing Ebola virus disease (EVD) that is a severe hemorrhagic fever and has a cumulative death rate of 41% in the ongoing epidemic in West Africa. There is an ever-increasing need to consolidate and make available all the knowledge that we possess on EBOV, even if it is conflicting or incomplete. This would enable biomedical researchers to understand the molecular mechanisms underlying this disease and help develop tools for efficient diagnosis and effective treatment. In this article, we present our approach for the development of an Ebola virus-centered Knowledge Base (Ebola-KB) using Linked Data and Semantic Web Technologies. We retrieve and aggregate knowledge from several open data sources, web services and biomedical ontologies. This knowledge is transformed to RDF, linked to the Bio2RDF datasets and made available through a SPARQL 1.1 Endpoint. Ebola-KB can also be explored using an interactive Dashboard visualizing the different perspectives of this integrated knowledge. We showcase how different competency questions, asked by domain users researching the druggability of EBOV, can be formulated as SPARQL Queries or answered using the Ebola-KB Dashboard. Database URL: http://ebola.semanticscience.org. PMID:26055098

  17. An Ebola virus-centered knowledge base.

    PubMed

    Kamdar, Maulik R; Dumontier, Michel

    2015-01-01

    Ebola virus (EBOV), of the family Filoviridae viruses, is a NIAID category A, lethal human pathogen. It is responsible for causing Ebola virus disease (EVD) that is a severe hemorrhagic fever and has a cumulative death rate of 41% in the ongoing epidemic in West Africa. There is an ever-increasing need to consolidate and make available all the knowledge that we possess on EBOV, even if it is conflicting or incomplete. This would enable biomedical researchers to understand the molecular mechanisms underlying this disease and help develop tools for efficient diagnosis and effective treatment. In this article, we present our approach for the development of an Ebola virus-centered Knowledge Base (Ebola-KB) using Linked Data and Semantic Web Technologies. We retrieve and aggregate knowledge from several open data sources, web services and biomedical ontologies. This knowledge is transformed to RDF, linked to the Bio2RDF datasets and made available through a SPARQL 1.1 Endpoint. Ebola-KB can also be explored using an interactive Dashboard visualizing the different perspectives of this integrated knowledge. We showcase how different competency questions, asked by domain users researching the druggability of EBOV, can be formulated as SPARQL Queries or answered using the Ebola-KB Dashboard.Database URL: http://ebola.semanticscience.org. PMID:26055098

  18. Ebola Virus Evolving, but Isn't Getting Deadlier

    MedlinePLUS

    ... nlm.nih.gov/medlineplus/news/fullstory_152012.html Ebola Virus Evolving, But Isn't Getting Deadlier, Study ... 2015 TUESDAY, April 14, 2015 (HealthDay News) -- The Ebola virus has evolved but hasn't become more ...

  19. Ebola virus (EboV) infection causes fatal

    E-print Network

    Chandran, Kartik

    Ebola virus (EboV) infection causes fatal haemorrhagic fever with mortality rates exceeding 75 Carette, J. E. et al. Ebola virus entry requires the cholesterol transporter Niemann­Pick C1. Nature 24 is essential for Ebola virus infection. Nature 24 Aug 2011 (doi:10.1038/nature10380) ANTIVIRALS Achilles heel

  20. Ebola Virus Infection: What Should Be Known?

    PubMed Central

    Wiwanitkit, Viroj

    2014-01-01

    Ebola virus infection is the present global consideration. This deadly virus can result in a deadly acute febrile hemorrhagic illness. The patient can have several clinical manifestations. As a new emerging infection, the knowledge on this infection is extremely limited. The interesting issues to be discussed include a) the atypical clinical presentation, b) new diagnostic tool, c) new treatment, and d) disease prevention. Those topics will be discussed in this special review. PMID:25535601

  1. Ocular problem in Ebola virus infection: A short review.

    PubMed

    Wiwanitkit, Somsri; Wiwanitkit, Viroj

    2015-01-01

    In 2014, the outbreak of Ebola virus infection occured in Africa and became the global concern. The infection is an acute febrile illness and the patient can have several clinical manifestations including the hemorrhage. The ocular manifestation of Ebola infection is interesting. In this brief review, the authors summarize on the ocular manifestation in Ebola virus infection. PMID:26155084

  2. Ocular problem in Ebola virus infection: A short review

    PubMed Central

    Wiwanitkit, Somsri; Wiwanitkit, Viroj

    2015-01-01

    In 2014, the outbreak of Ebola virus infection occured in Africa and became the global concern. The infection is an acute febrile illness and the patient can have several clinical manifestations including the hemorrhage. The ocular manifestation of Ebola infection is interesting. In this brief review, the authors summarize on the ocular manifestation in Ebola virus infection.

  3. Endosomal Proteolysis of the Ebola Virus Glycoprotein Is

    E-print Network

    Chandran, Kartik

    Endosomal Proteolysis of the Ebola Virus Glycoprotein Is Necessary for Infection Kartik Chandran,1 Nancy J. Sullivan,2 Ute Felbor,3 Sean P. Whelan,4 James M. Cunningham1,4 * Ebola virus (EboV) causes the multiplication of infectious EboV-Zaire in cultured cells and may merit investigation as anti- EboV drugs. Ebola

  4. EbolaVirus Disease (Ebola) Algorithm for Evaluation of the ReturnedTraveler

    E-print Network

    Thaxton, Christopher S.

    EbolaVirus Disease (Ebola) Algorithm for Evaluation of the ReturnedTraveler Reportasymptomatic the hospital Infection Control Program and other appropriate sta 4. Evaluate for any risk exposures for Ebola 5 membrane contact with blood or body uids from an Ebola patient OR Direct skin contact with, or exposure

  5. Drug Might Fight Ebola-Like Marburg Virus

    MedlinePLUS

    Drug Might Fight Ebola-like Marburg Virus Study found infected monkeys were less likely to die with treatment To use the sharing features ... the deadly Marburg virus, which is similar to Ebola. Monkeys didn't die from Marburg virus after ...

  6. Possible sexual transmission of Ebola virus - Liberia, 2015.

    PubMed

    Christie, Athalia; Davies-Wayne, Gloria J; Cordier-Lasalle, Thierry; Blackley, David J; Laney, A Scott; Williams, Desmond E; Shinde, Shivam A; Badio, Moses; Lo, Terrence; Mate, Suzanne E; Ladner, Jason T; Wiley, Michael R; Kugelman, Jeffrey R; Palacios, Gustavo; Holbrook, Michael R; Janosko, Krisztina B; de Wit, Emmie; van Doremalen, Neeltje; Munster, Vincent J; Pettitt, James; Schoepp, Randal J; Verhenne, Leen; Evlampidou, Iro; Kollie, Karsor K; Sieh, Sonpon B; Gasasira, Alex; Bolay, Fatorma; Kateh, Francis N; Nyenswah, Tolbert G; De Cock, Kevin M

    2015-05-01

    On March 20, 2015, 30 days after the most recent confirmed Ebola Virus Disease (Ebola) patient in Liberia was isolated, Ebola was laboratory confirmed in a woman in Monrovia. The investigation identified only one epidemiologic link to Ebola: unprotected vaginal intercourse with a survivor. Published reports from previous outbreaks have demonstrated Ebola survivors can continue to harbor virus in immunologically privileged sites for a period of time after convalescence. Ebola virus has been isolated from semen as long as 82 days after symptom onset and viral RNA has been detected in semen up to 101 days after symptom onset. One instance of possible sexual transmission of Ebola has been reported, although the accompanying evidence was inconclusive. In addition, possible sexual transmission of Marburg virus, a filovirus related to Ebola, was documented in 1968. This report describes the investigation by the Government of Liberia and international response partners of the source of Liberia's latest Ebola case and discusses the public health implications of possible sexual transmission of Ebola virus. Based on information gathered in this investigation, CDC now recommends that contact with semen from male Ebola survivors be avoided until more information regarding the duration and infectiousness of viral shedding in body fluids is known. If male survivors have sex (oral, vaginal, or anal), a condom should be used correctly and consistently every time. PMID:25950255

  7. Release of Viral Glycoproteins during Ebola Virus Infection

    Microsoft Academic Search

    Viktor E. Volchkov; Valentina A. Volchkova; Werner Slenczka; Hans-Dieter Klenk; Heinz Feldmann

    1998-01-01

    Maturation and release of the Ebola virus glycoprotein GP were studied in cells infected with either Ebola or recombinant vaccinia viruses. Significant amounts of GP were found in the culture medium in nonvirion forms. The major form represented the large subunit GP1that was shed after release of its disulfide linkage to the smaller transmembrane subunit GP2. The minor form were

  8. Ebola virus disease: preparedness in Japan.

    PubMed

    Ashino, Yugo; Chagan-Yasutan, Haorile; Egawa, Shinichi; Hattori, Toshio

    2015-02-01

    The current outbreak of Ebola virus disease (EVD) is due to a lack of resources, untrained medical personnel, and the specific contact-mediated type of infection of this virus. In Japan's history, education and mass vaccination of the native Ainu people successfully eradicated epidemics of smallpox. Even though a zoonotic virus is hard to control, appropriate precautions and personal protection, as well as anti-symptomatic treatment, will control the outbreak of EVD. Ebola virus utilizes the antibody-dependent enhancement of infection to seed the cells of various organs. The pathogenesis of EVD is due to the cytokine storm of pro-inflammatory cytokines and the lack of antiviral interferon-?2. Matricellular proteins of galectin-9 and osteopontin might also be involved in the edema and abnormality of the coagulation system in EVD. Anti-fibrinolytic treatment will be effective. In the era of globalization, interviews of travelers with fever within 3 weeks of departure from the affected areas will be necessary. Not only the hospitals designated for specific biohazards but every hospital should be aware of the biology of biohazards and establish measures to protect both patients and the community. PMID:25399765

  9. Proteolytic Processing of the Ebola Virus Glycoprotein Is Not Critical for Ebola Virus Replication in Nonhuman Primates

    Microsoft Academic Search

    Gabriele Neumann; Thomas W. Geisbert; Hideki Ebihara; Joan B. Geisbert; Kathleen M. Daddario-DiCaprio; Heinz Feldmann; Yoshihiro Kawaoka

    2007-01-01

    Enveloped viruses often require cleavage of a surface glycoprotein by a cellular endoprotease such as furin for infectivity and virulence. Previously, we showed that Ebola virus glycoprotein does not require the furin cleavage motif for virus replication in cell culture. Here, we show that there are no appreciable differences in disease progression, hematology, serum biochemistry, virus titers, or lethality in

  10. Protection from Ebola Virus Mediated by Cytotoxic T Lymphocytes Specific for the Viral Nucleoprotein

    Microsoft Academic Search

    JULIE A. WILSON; MARY KATE HART

    2001-01-01

    Cytotoxic T lymphocytes (CTLs) are proposed to be critical for protection from intracellular pathogens such as Ebola virus. However, there have been no demonstrations that protection against Ebola virus is mediated by Ebola virus-specific CTLs. Here, we report that C57BL\\/6 mice vaccinated with Venezuelan equine enceph- alitis virus replicons encoding the Ebola virus nucleoprotein (NP) survived lethal challenge with Ebola

  11. Overview of Ebola virus disease in 2014.

    PubMed

    Tseng, Chih-Peng; Chan, Yu-Jiun

    2015-01-01

    In late December 2013, a deadly infectious epidemic, Ebola virus disease (EVD), emerged from West Africa and resulted in a formidable outbreak in areas including Guinea, Liberia, Sierra Leone and Nigeria. EVD is a zoonotic disease with a high mortality rate. Person-to-person transmission occurs through blood or body fluid exposure, which can jeopardize first-line healthcare workers if there is a lack of stringent infection control or no proper personal protective equipment available. Currently, there is no standard treatment for EVD. To promptly identify patients and prevent further spreading, physicians should be aware of travel or contact history for patients with constitutional symptoms. PMID:25547820

  12. Favipiravir: a new medication for the Ebola virus disease pandemic.

    PubMed

    Nagata, Takashi; Lefor, Alan K; Hasegawa, Manabu; Ishii, Masami

    2015-02-01

    The purpose of this report is to advocate speedy approval and less stringent regulations for the use of experimental drugs such as favipiravir in emergencies. Favipiravir is a new antiviral medication that can be used in emerging viral pandemics such as Ebola virus, 2009 pandemic influenza H1N1 virus, Lassa fever, and Argentine hemorrhagic fever. Although favipiravir is one of the choices for the treatment of patients with Ebola virus, several concerns exist. First, a clinical trial of favipiravir in patients infected with the Ebola virus has not yet been conducted, and further studies are required. Second, favipiravir has a risk for teratogenicity and embryotoxicity. Therefore, the Ministry of Health, Welfare and Labor of Japan has approved this medication with strict regulations for its production and clinical use. However, owing to the emerging Ebola virus epidemic in West Africa, on August 15, 2014, the Minister of Health, Welfare and Labor of Japan approved the use of favipiravir, if needed. PMID:25544306

  13. Ebola virus disease outbreak: what's going on.

    PubMed

    Giraldi, G; Marsella, L T

    2015-01-01

    The current West African Ebola Virus Disease (EVD) outbreak was confirmed in March, 2014, and after months of slow, fragmented responses, the EVD has been recognized as a public health emergency of international concern. The early diagnosis of the disease is difficult without laboratory testing, because its symptoms can be seen in many other infections. In the wake of international agencies advices, the Italian Ministry of Health, on October 1, 2014, released to the Healthcare Professional Workers (HPWs) the Protocol about the management of cases and contacts within the national territory. Due to the increasing number of humanitarian groups and HPWs involved in the field, the probability to have new cases of contamination is higher than ever. Proven specific treatments against EVD are not yet available, however, a variety of compounds have been under testing. The most effective are select monoclonal antibodies that have a high neutralizing potential against epitopes of Ebola Virus. For facing the matter, it is important a comprehensive approach according to the recommendations proposed by the international agencies because no single institution or country has all the capacities to respond to a new and emerging infectious disease. PMID:25748509

  14. Downregulation of ?1 Integrins by Ebola Virus Glycoprotein: Implication for Virus Entry

    Microsoft Academic Search

    Ayato Takada; Shinji Watanabe; Hiroshi Ito; Katsunori Okazaki; Hiroshi Kida; Yoshihiro Kawaoka

    2000-01-01

    Filoviruses, including Ebola virus, are cytotoxic. To investigate the role of the Ebola virus glycoprotein (GP) in this cytopathic effect, we transiently expressed the GP in human kidney 293T cells. Expression of wild-type GP, but not the secretory form of the molecule lacking a membrane anchor, induced rounding and detachment of the cells, as did a chimeric GP containing its

  15. Molecular Dynamics Simulations of Folding and Insertion of the Ebola Virus Fusion Peptide into a

    E-print Network

    Molecular Dynamics Simulations of Folding and Insertion of the Ebola Virus Fusion Peptide- residue Ebola virus fusion peptide into a membrane bilayer. We applied a multi-resolution computational-energy landscape, virus-host interactions 1 Introduction Ebola and Marburg viruses are nonsegmented, negative

  16. An Introduction to Ebola: The Virus and the Disease

    Microsoft Academic Search

    1999-01-01

    A number of colleagues, both in the laboratory and in the field, agreed to prepare reports reflecting recent research, thus permitting this supplement to the Journal of Infectious Dis- Ebola, the Second Known Filovirus eases, which provides a single source for substantial new, peer- reviewed information. We have somewhat arbitrarily divided Humans Meet Ebola Virus in Africa, 1976 the supplement

  17. Isolation and partial characterisation of a new strain of Ebola We have isolated a new strain of Ebola virus from a non-

    E-print Network

    1271 Isolation and partial characterisation of a new strain of Ebola virus Summary We have isolated a new strain of Ebola virus from a non- fatal human case infected during the autopsy of a wild about the natural reservoir of the Ebola virus. Lancet 1995; 345: 1271-74 Introduction Ebola virus

  18. On the Quarantine Period for Ebola Virus

    PubMed Central

    Haas, Charles N.

    2014-01-01

    Background: 21 days has been regarded as the appropriate quarantine period for holding individuals potentially exposed to Ebola Virus (EV) to reduce risk of contagion. There does not appear to be a systematic discussion of the basis for this period. Methods: The prior estimates for incubation time to EV were examined, along with data on the first 9 months of the current outbreak. These provided estimates of the distribution of incubation times. Results: A 21 day period for quarantine may result in the release of individuals with a 0.2 - 12% risk of release prior to full opportunity for the incubation to proceed. It is suggested that a detailed cost-benefit assessment, including considering full transmission risks, needs to occur in order to determine the appropriate quarantine period for potentially exposed individuals. PMID:25642371

  19. ISCB Ebola Award for Important Future Research on the Computational Biology of Ebola Virus

    PubMed Central

    Karp, Peter D.; Berger, Bonnie; Kovats, Diane; Lengauer, Thomas; Linial, Michal; Sabeti, Pardis; Hide, Winston; Rost, Burkhard

    2015-01-01

    Speed is of the essence in combating Ebola; thus, computational approaches should form a significant component of Ebola research. As for the development of any modern drug, computational biology is uniquely positioned to contribute through comparative analysis of the genome sequences of Ebola strains as well as 3-D protein modeling. Other computational approaches to Ebola may include large-scale docking studies of Ebola proteins with human proteins and with small-molecule libraries, computational modeling of the spread of the virus, computational mining of the Ebola literature, and creation of a curated Ebola database. Taken together, such computational efforts could significantly accelerate traditional scientific approaches. In recognition of the need for important and immediate solutions from the field of computational biology against Ebola, the International Society for Computational Biology (ISCB) announces a prize for an important computational advance in fighting the Ebola virus. ISCB will confer the ISCB Fight against Ebola Award, along with a prize of US$2,000, at its July 2016 annual meeting (ISCB Intelligent Systems for Molecular Biology [ISMB] 2016, Orlando, Florida).

  20. ISCB Ebola Award for Important Future Research on the Computational Biology of Ebola Virus

    PubMed Central

    Karp, Peter D.; Berger, Bonnie; Kovats, Diane; Lengauer, Thomas; Linial, Michal; Sabeti, Pardis; Hide, Winston; Rost, Burkhard

    2015-01-01

    Speed is of the essence in combating Ebola; thus, computational approaches should form a significant component of Ebola research. As for the development of any modern drug, computational biology is uniquely positioned to contribute through comparative analysis of the genome sequences of Ebola strains as well as 3-D protein modeling. Other computational approaches to Ebola may include large-scale docking studies of Ebola proteins with human proteins and with small-molecule libraries, computational modeling of the spread of the virus, computational mining of the Ebola literature, and creation of a curated Ebola database. Taken together, such computational efforts could significantly accelerate traditional scientific approaches. In recognition of the need for important and immediate solutions from the field of computational biology against Ebola, the International Society for Computational Biology (ISCB) announces a prize for an important computational advance in fighting the Ebola virus. ISCB will confer the ISCB Fight against Ebola Award, along with a prize of US$2,000, at its July 2016 annual meeting (ISCB Intelligent Systems for Molecular Biology (ISMB) 2016, Orlando, Florida).

  1. Designed protein mimics of the Ebola virus glycoprotein GP2 -helical bundle: stability

    E-print Network

    Chandran, Kartik

    Designed protein mimics of the Ebola virus glycoprotein GP2 -helical bundle: stability and p.lai@einstein.yu.edu Running Title: Mimicry of the Ebola virus GP2 -helical bundle. (This manuscript contains 25 total pages, 1

  2. Human Ebola virus infection results in substantial immune activation

    PubMed Central

    McElroy, Anita K.; Akondy, Rama S.; Davis, Carl W.; Ellebedy, Ali H.; Mehta, Aneesh K.; Kraft, Colleen S.; Lyon, G. Marshall; Ribner, Bruce S.; Varkey, Jay; Sidney, John; Sette, Alessandro; Campbell, Shelley; Ströher, Ute; Damon, Inger; Nichol, Stuart T.; Spiropoulou, Christina F.; Ahmed, Rafi

    2015-01-01

    Four Ebola patients received care at Emory University Hospital, presenting a unique opportunity to examine the cellular immune responses during acute Ebola virus infection. We found striking activation of both B and T cells in all four patients. Plasmablast frequencies were 10–50% of B cells, compared with less than 1% in healthy individuals. Many of these proliferating plasmablasts were IgG-positive, and this finding coincided with the presence of Ebola virus-specific IgG in the serum. Activated CD4 T cells ranged from 5 to 30%, compared with 1–2% in healthy controls. The most pronounced responses were seen in CD8 T cells, with over 50% of the CD8 T cells expressing markers of activation and proliferation. Taken together, these results suggest that all four patients developed robust immune responses during the acute phase of Ebola virus infection, a finding that would not have been predicted based on our current assumptions about the highly immunosuppressive nature of Ebola virus. Also, quite surprisingly, we found sustained immune activation after the virus was cleared from the plasma, observed most strikingly in the persistence of activated CD8 T cells, even 1 mo after the patients’ discharge from the hospital. These results suggest continued antigen stimulation after resolution of the disease. From these convalescent time points, we identified CD4 and CD8 T-cell responses to several Ebola virus proteins, most notably the viral nucleoprotein. Knowledge of the viral proteins targeted by T cells during natural infection should be useful in designing vaccines against Ebola virus. PMID:25775592

  3. NIH Study Finds No Evidence of Accelerated Ebola Virus Evolution in West Africa

    MedlinePLUS

    ... EST NIH study finds no evidence of accelerated Ebola virus evolution in West Africa The Ebola virus circulating in humans in West Africa is ... Sierra Leone (June 2014) and Mali (November 2014). Ebola virus, isolated in November 2014 from patient blood ...

  4. Estimating the Reproduction Number of Ebola Virus (EBOV) During the 2014 Outbreak in

    E-print Network

    Rockwell, Robert F.

    Estimating the Reproduction Number of Ebola Virus (EBOV) During the 2014 Outbreak in West Africa), University of Bern, Bern, Switzerland Althaus CL. Estimating the Reproduction Number of Ebola Virus (EBOV.1371/currents.outbreaks.91afb5e0f279e7f29e7056095255b288. Abstract The 2014 Ebola virus (EBOV) outbreak in West

  5. The Ebola virus glycoprotein mediates entry via a non-classical dynamin-dependent macropinocytic pathway

    E-print Network

    Chandran, Kartik

    The Ebola virus glycoprotein mediates entry via a non-classical dynamin-dependent macropinocytic for revision 21 June 2011 Accepted 8 August 2011 Available online 9 September 2011 Keywords: Ebola virus Endocytosis Macropinocytosis Pak-1 Dynamin Antigen presenting cells Monocytes Dendritic cells Ebola virus

  6. Vesicular Stomatitis Virus–Based Vaccines against Lassa and Ebola Viruses

    PubMed Central

    Marzi, Andrea; Feldmann, Friederike; Geisbert, Thomas W.; Feldmann, Heinz

    2015-01-01

    We demonstrated that previous vaccination with a vesicular stomatitis virus (VSV)–based Lassa virus vaccine does not alter protective efficacy of subsequent vaccination with a VSV-based Ebola virus vaccine. These findings demonstrate the utility of VSV-based vaccines against divergent viral pathogens, even when preexisting immunity to the vaccine vector is present. PMID:25625358

  7. Production of novel ebola virus-like particles from cDNAs: an alternative to ebola virus generation by reverse genetics.

    PubMed

    Watanabe, Shinji; Watanabe, Tokiko; Noda, Takeshi; Takada, Ayato; Feldmann, Heinz; Jasenosky, Luke D; Kawaoka, Yoshihiro

    2004-01-01

    We established a plasmid-based system for generating infectious Ebola virus-like particles (VLPs), which contain an Ebola virus-like minigenome consisting of a negative-sense copy of the green fluorescent protein gene. This system produced nearly 10(3) infectious particles per ml of supernatant, equivalent to the titer of Ebola virus generated by a reverse genetics system. Interestingly, infectious Ebola VLPs were generated, even without expression of VP24. Transmission and scanning electron microscopic analyses showed that the morphology of the Ebola VLPs was indistinguishable from that of authentic Ebola virus. Thus, this system allows us to study Ebola virus entry, replication, and assembly without biosafety level 4 containment. Furthermore, it may be useful in vaccine production against this highly pathogenic agent. PMID:14694131

  8. Ebola virus disease: awareness among junior doctors in England.

    PubMed

    Fazekas, B; Fazekas, J; Moledina, M; Fazekas, B; Karolyhazy, K

    2015-07-01

    The current Ebola virus epidemic continues to pose a threat to the UK. Junior clinicians are often at the frontline of medical care in hospitals and their awareness of the clinical features and management of the Ebola virus disease (EVD) may significantly influence the timely implementation of infection control measures. In view of this, we carried out a cross-sectional survey of 119 junior doctors across four different hospitals in England in order to assess their level of knowledge of EVD. We demonstrate that there is currently a deficiency of knowledge about critical aspects of EVD in this population. PMID:25933917

  9. Rapid Detection and Quantification of RNA of Ebola and Marburg Viruses, Lassa Virus, Crimean-Congo Hemorrhagic Fever Virus, Rift Valley Fever Virus, Dengue Virus, and Yellow Fever Virus by Real-Time Reverse Transcription-PCR

    Microsoft Academic Search

    Christian Drosten; Stephan Göttig; Stefan Schilling; Marcel Asper; Marcus Panning; Herbert Schmitz; Stephan Günther

    2002-01-01

    Viral hemorrhagic fevers (VHFs) are acute infections with high case fatality rates. Important VHF agents are Ebola and Marburg viruses (MBGV\\/EBOV), Lassa virus (LASV), Crimean-Congo hemorrhagic fever virus (CCHFV), Rift Valley fever virus (RVFV), dengue virus (DENV), and yellow fever virus (YFV). VHFs are clinically difficult to diagnose and to distinguish; a rapid and reliable laboratory diagnosis is required in

  10. Control of Ebola virus disease - firestone district, liberia, 2014.

    PubMed

    Reaves, Erik J; Mabande, Lyndon G; Thoroughman, Douglas A; Arwady, M Allison; Montgomery, Joel M

    2014-10-24

    On March 30, 2014, the Ministry of Health and Social Welfare (MOHSW) of Liberia alerted health officials at Firestone Liberia, Inc. (Firestone) of the first known case of Ebola virus disease (Ebola) inside the Firestone rubber tree plantation of Liberia. The patient, who was the wife of a Firestone employee, had cared for a family member with confirmed Ebola in Lofa County, the epicenter of the Ebola outbreak in Liberia during March-April 2014. To prevent a large outbreak among Firestone's 8,500 employees, their dependents, and the surrounding population, the company responded by 1) establishing an incident management system, 2) instituting procedures for the early recognition and isolation of Ebola patients, 3) enforcing adherence to standard Ebola infection control guidelines, and 4) providing differing levels of management for contacts depending on their exposure, including options for voluntary quarantine in the home or in dedicated facilities. In addition, Firestone created multidisciplinary teams to oversee the outbreak response, address case detection, manage cases in a dedicated unit, and reintegrate convalescent patients into the community. The company also created a robust risk communication, prevention, and social mobilization campaign to boost community awareness of Ebola and how to prevent transmission. During August 1-September 23, a period of intense Ebola transmission in the surrounding areas, 71 cases of Ebola were diagnosed among the approximately 80,000 Liberians for whom Firestone provides health care (cumulative incidence = 0.09%). Fifty-seven (80%) of the cases were laboratory confirmed; 39 (68%) of these cases were fatal. Aspects of Firestone's response appear to have minimized the spread of Ebola in the local population and might be successfully implemented elsewhere to limit the spread of Ebola and prevent transmission to health care workers (HCWs). PMID:25340914

  11. GP mRNA of Ebola Virus Is Edited by the Ebola Virus Polymerase and by T7 and Vaccinia Virus Polymerases 1

    Microsoft Academic Search

    VIKTOR E. VOLCHKOV; STEPHAN BECKER; VALENTINA A. VOLCHKOVA; VLADIMIR A. TERNOVOJ; ALEKSANDR N. KOTOV; SERGEJ V. NETESOV; HANS-DIETER KLENK

    1995-01-01

    The glycoprotein gene of Ebola virus contains a translational stop codon in the middle, thus preventing synthesis of full-length glycoprotein. Twenty percent of the mRNA isolated from Ebola virus-infected cells was shown to be edited, containing one additional nontemplate A in a stretch of seven consecutive A residues. Only the edited mRNA species encoded full-length glycoprotein, whereas the exact copies

  12. 10/16/2014 Prepared by the Purdue Public Health Emergency Planning Committee. For the latest information, please see www.cdc.gov/ebola Ebola Virus Disease FAQ for the Purdue Community

    E-print Network

    Ginzel, Matthew

    information, please see www.cdc.gov/ebola Ebola Virus Disease FAQ for the Purdue Community What is Ebola? Ebola virus disease (EVD), previously known as Ebola hemorrhagic fever is a rare and deadly disease caused by infection with one of the Ebola virus strains. See CDC website for more detailed information

  13. Ebola

    MedlinePLUS

    What Is Ebola? Ebola is a dangerous virus that can cause people to get very sick and even die. The virus ... others is low. What Happens When Someone Has Ebola? Ebola often starts with fever and headache, kind ...

  14. Histopathological and Immunohistochemical Studies of Lesions Associated with Ebola Virus in a Naturally Infected Chimpanzee

    E-print Network

    S54 Histopathological and Immunohistochemical Studies of Lesions Associated with Ebola Virus'Ivoire Lesions caused by the Co^te d'Ivoire subtype of Ebola virus in a naturally infected young chimpan- zee, so perti-A new subtype of Ebola (EBO) filovirus designated EBO nent laboratory analyses were done

  15. LETTER doi:10.1038/nature10348 Ebola virus entry requires the cholesterol transporter

    E-print Network

    Gleeson, Joseph G.

    LETTER doi:10.1038/nature10348 Ebola virus entry requires the cholesterol transporter Niemann { Infections by the Ebola and Marburg filoviruses cause a rapidly fatal haemorrhagic fever in humans for which cells to identify host factors required for Ebola virus entry. Our screen uncovered 67 mutations

  16. Information regarding Ebola Virus Disease (EVD) for Campus Personnel and Visitors September 5, 2014

    E-print Network

    Gerdes, J. Christian

    Information regarding Ebola Virus Disease (EVD) for Campus Personnel and Visitors September 5, 2014 You are likely very much aware of the ongoing attention focused on the Ebola Virus Disease (EVD Control and Prevention (CDC) considers Ebola to pose little risk to persons in the U.S. at this time. We

  17. EbolaVirus Disease (EVD) Algorithm for Evaluation of the ReturnedTraveler

    E-print Network

    EbolaVirus Disease (EVD) Algorithm for Evaluation of the ReturnedTraveler Reportasymptomatic (including during funeral rites) in an Ebola affected area** without appropriate PPE LOW-RISK EXPOSURE after their last exposure to an Ebola patient YES NO ** CDCWebsite to check current affected areas: www.cdc.gov/vhf/ebola

  18. How Ebola and Marburg viruses battle the immune system

    Microsoft Academic Search

    Lieping Chen; Mansour Mohamadzadeh; Alan L. Schmaljohn

    2007-01-01

    The filoviruses Ebola and Marburg have emerged in the past decade from relative obscurity to serve now as archetypes for some of the more intriguing and daunting challenges posed by such agents. Public imagination is captured by deadly outbreaks of these viruses and reinforced by the specter of bioterrorism. As research on these agents has accelerated, it has been found

  19. Small molecules with antiviral activity against the Ebola virus.

    PubMed

    Litterman, Nadia; Lipinski, Christopher; Ekins, Sean

    2015-01-01

    The recent outbreak of the Ebola virus in West Africa has highlighted the clear shortage of broad-spectrum antiviral drugs for emerging viruses. There are numerous FDA approved drugs and other small molecules described in the literature that could be further evaluated for their potential as antiviral compounds. These molecules are in addition to the few new antivirals that have been tested in Ebola patients but were not originally developed against the Ebola virus, and may play an important role as we await an effective vaccine. The balance between using FDA approved drugs versus novel antivirals with minimal safety and no efficacy data in humans should be considered. We have evaluated 55 molecules from the perspective of an experienced medicinal chemist as well as using simple molecular properties and have highlighted 16 compounds that have desirable qualities as well as those that may be less desirable. In addition we propose that a collaborative database for sharing such published and novel information on small molecules is needed for the research community studying the Ebola virus. PMID:25713700

  20. Evaluation in Nonhuman Primates of Vaccines against Ebola Virus

    Microsoft Academic Search

    Thomas W. Geisbert; Peter Pushko; Kevin Anderson; Jonathan Smith; Kelly J. Davis; Peter B. Jahrling

    2002-01-01

    Ebola virus (EBOV) causes acute hemorrhagic fever that is fatal in up to 90% of cases in both humans and nonhuman primates. No vaccines or treatments are available for human use. We evaluated the effects in nonhuman primates of vaccine strategies that had protected mice or guinea pigs from lethal EBOV infec- tion. The following immunogens were used: RNA replicon

  1. Ebola

    MedlinePLUS

    ... Digestive System How the Body Works Main Page Ebola KidsHealth > Kids > Health Problems > Infections > Ebola Print A ... Kids Need to Do About Ebola? What Is Ebola? Ebola is a dangerous virus that can cause ...

  2. A case of Ebola virus infection

    Microsoft Academic Search

    R T Emond; B Evans; Etw Bowen; G Lloyd

    1977-01-01

    In November 1976 an investigator at the Microbiological Research Establishment accidentally inoculated himself while processing material from patients in Africa who had been suffering from a haemorrhagic fever of unknown cause. He developed an illness closely resembling Marburg disease, and a virus was isolated from his blood that resembled Marburg virus but was distinct serologically. The course of the illness

  3. Modeling the lifecycle of Ebola virus under biosafety level 2 conditions with virus-like particles containing tetracistronic minigenomes.

    PubMed

    Hoenen, Thomas; Watt, Ari; Mora, Anita; Feldmann, Heinz

    2014-01-01

    Ebola viruses cause severe hemorrhagic fevers in humans and non-human primates, with case fatality rates as high as 90%. There are no approved vaccines or specific treatments for the disease caused by these viruses, and work with infectious Ebola viruses is restricted to biosafety level 4 laboratories, significantly limiting the research on these viruses. Lifecycle modeling systems model the virus lifecycle under biosafety level 2 conditions; however, until recently such systems have been limited to either individual aspects of the virus lifecycle, or a single infectious cycle. Tetracistronic minigenomes, which consist of Ebola virus non-coding regions, a reporter gene, and three Ebola virus genes involved in morphogenesis, budding, and entry (VP40, GP1,2, and VP24), can be used to produce replication and transcription-competent virus-like particles (trVLPs) containing these minigenomes. These trVLPs can continuously infect cells expressing the Ebola virus proteins responsible for genome replication and transcription, allowing us to safely model multiple infectious cycles under biosafety level 2 conditions. Importantly, the viral components of this systems are solely derived from Ebola virus and not from other viruses (as is, for example, the case in systems using pseudotyped viruses), and VP40, GP1,2 and VP24 are not overexpressed in this system, making it ideally suited for studying morphogenesis, budding and entry, although other aspects of the virus lifecycle such as genome replication and transcription can also be modeled with this system. Therefore, the tetracistronic trVLP assay represents the most comprehensive lifecycle modeling system available for Ebola viruses, and has tremendous potential for use in investigating the biology of Ebola viruses in future. Here, we provide detailed information on the use of this system, as well as on expected results. PMID:25285674

  4. Contribution of Ebola Virus Glycoprotein, Nucleoprotein, and VP24 to Budding of VP40 Virus-Like Particles

    Microsoft Academic Search

    Jillian M. Licata; Reed F. Johnson; Ziying Han; Ronald N. Harty

    2004-01-01

    The VP40 matrix protein of Ebola virus buds from cells in the form of virus-like particles (VLPs) and plays a central role in virus assembly and budding. In this study, we utilized a functional budding assay and cotransfection experiments to examine the contributions of the glycoprotein (GP), nucleoprotein (NP), and VP24 of Ebola virus in facilitating release of VP40 VLPs.

  5. Inactivation of Lassa, Marburg, and Ebola viruses by gamma irradiation

    SciTech Connect

    Elliott, L.H.; McCormick, J.B.; Johnson, K.M.

    1982-10-01

    Because of the cumbersome conditions experienced in a maximum containment laboratory, methods for inactivating highly pathogenic viruses were investigated. The infectivity of Lassa, Marburg, and Ebola viruses was inactivated without altering the immunological activity after radiation with /sup 60/CO gamma rays. At 4 degrees C, Lassa virus was the most difficult to inactivate with a rate of 5.3 X 10(-6) log 50% tissue culture infective dose per rad of /sup 60/CO radiation, as compared with 6.8 X 10(-6) log 50% tissue culture infective dose per rad for Ebola virus and 8.4 X 10(-6) log 50% tissue culture infective dose per rad for Marburg virus. Experimental inactivation curves, as well as curves giving the total radiation needed to inactivate a given concentration of any of the three viruses, are presented. The authors found this method of inactivation to be superior to UV light or beta-propiolactone inactivation and now routinely use it for preparation of material for protein-chemistry studies or for preparation of immunological reagents.

  6. Inactivation of Lassa, Marburg, and Ebola viruses by gamma irradiation

    SciTech Connect

    Elliott, L.H.; McCormick, J.B.; Johnson, K.M.

    1982-10-01

    Because of the cumbersome conditions experienced in a maximum containment laboratory, methods for inactivating highly pathogenic viruses were investigated. The infectivity of Lassa, Marburg, and Ebola viruses was inactivated without altering the immunological activity after radiation with /sup 60/Co gamma rays. At 4 degrees C, Lassa virus was the most difficult to inactivate with a rate of 5.3 X 10(-6) log 50% tissue culture infective dose per rad of /sup 60/Co radiation, as compared with 6.8 X 10(-6) log 50% tissue culture infective dose per rad for Ebola virus and 8.4 X 10(-6) log 50% tissue culture infective dose per rad for Marburg virus. Experimental inactivation curves, as well as curves giving the total radiation needed to inactivate a given concentration of any of the three viruses, are presented. We found this method of inactivation to be superior to UV light or beta-propiolactone inactivation and now routinely use it for preparation of material for protein-chemistry studies or for preparation of immunological reagents.

  7. Distinct Mechanisms of Entry by Envelope Glycoproteins of Marburg and Ebola (Zaire) Viruses

    Microsoft Academic Search

    STEPHEN Y. CHAN; ROBERTO F. SPECK; MELISSA C. MA; MARK A. GOLDSMITH

    2000-01-01

    Since the Marburg (MBG) and Ebola (EBO) viruses have sequence homology and cause similar diseases, we hypothesized that they associate with target cells by similar mechanisms. Pseudotype viruses prepared with a luciferase-containing human immunodeficiency virus type 1 backbone and packaged by the MBG virus or the Zaire subtype EBO virus glycoproteins (GP) mediated infection of a comparable wide range of

  8. Elucidating the role of ebola virus GP in virus entry and characterization of antibodies against VEE E3

    Microsoft Academic Search

    Laura J Hughes

    2010-01-01

    Ebola virus causes severe hemorrhagic fever, is a level 4 pathogen that has no treatment, vaccine, or cure, and is classified as a potential biological weapon. Ebola virus enters the host cell via receptor-mediated endocytosis. Cathepsin B and L cleave the glycoprotein (GP) and an undefined low pH event initiates fusion between the viral membrane and the vesicle membrane releasing

  9. Comparison of the Transcription and Replication Strategies of Marburg Virus and Ebola Virus by Using Artificial Replication Systems

    Microsoft Academic Search

    ELKE MUHLBERGER; MICHAEL WEIK; VIKTOR E. VOLCHKOV; HANS-DIETER KLENK; STEPHAN BECKER

    1999-01-01

    The members of the family Filoviridae, Marburg virus (MBGV) and Ebola virus (EBOV), are very similar in terms of morphology, genome organization, and protein composition. To compare the replication and tran- scription strategies of both viruses, an artificial replication system based on the vaccinia virus T7 expression system was established for EBOV. Specific transcription and replication of an artificial monocistronic

  10. Mapping the zoonotic niche of Ebola virus disease in Africa.

    PubMed

    Pigott, David M; Golding, Nick; Mylne, Adrian; Huang, Zhi; Henry, Andrew J; Weiss, Daniel J; Brady, Oliver J; Kraemer, Moritz U G; Smith, David L; Moyes, Catherine L; Bhatt, Samir; Gething, Peter W; Horby, Peter W; Bogoch, Isaac I; Brownstein, John S; Mekaru, Sumiko R; Tatem, Andrew J; Khan, Kamran; Hay, Simon I

    2014-01-01

    Ebola virus disease (EVD) is a complex zoonosis that is highly virulent in humans. The largest recorded outbreak of EVD is ongoing in West Africa, outside of its previously reported and predicted niche. We assembled location data on all recorded zoonotic transmission to humans and Ebola virus infection in bats and primates (1976-2014). Using species distribution models, these occurrence data were paired with environmental covariates to predict a zoonotic transmission niche covering 22 countries across Central and West Africa. Vegetation, elevation, temperature, evapotranspiration, and suspected reservoir bat distributions define this relationship. At-risk areas are inhabited by 22 million people; however, the rarity of human outbreaks emphasises the very low probability of transmission to humans. Increasing population sizes and international connectivity by air since the first detection of EVD in 1976 suggest that the dynamics of human-to-human secondary transmission in contemporary outbreaks will be very different to those of the past. PMID:25201877

  11. Persistence of Ebola Virus in Ocular Fluid during Convalescence.

    PubMed

    Varkey, Jay B; Shantha, Jessica G; Crozier, Ian; Kraft, Colleen S; Lyon, G Marshall; Mehta, Aneesh K; Kumar, Gokul; Smith, Justine R; Kainulainen, Markus H; Whitmer, Shannon; Ströher, Ute; Uyeki, Timothy M; Ribner, Bruce S; Yeh, Steven

    2015-06-18

    Among the survivors of Ebola virus disease (EVD), complications that include uveitis can develop during convalescence, although the incidence and pathogenesis of EVD-associated uveitis are unknown. We describe a patient who recovered from EVD and was subsequently found to have severe unilateral uveitis during convalescence. Viable Zaire ebolavirus (EBOV) was detected in aqueous humor 14 weeks after the onset of EVD and 9 weeks after the clearance of viremia. PMID:25950269

  12. Learning from Ebola Virus: How to Prevent Future Epidemics.

    PubMed

    Kekulé, Alexander S

    2015-01-01

    The recent Ebola virus disease (EVD) epidemic in Guinea, Liberia and Sierra Leone demonstrated that the World Health Organization (WHO) is incapable to control outbreaks of infectious diseases in less developed regions of the world. This essay analyses the causes for the failure of the international response and proposes four measures to improve resilience, early detection and response to future outbreaks of infectious diseases. PMID:26184283

  13. The pathology of experimental Ebola virus infection in monkeys.

    PubMed

    Baskerville, A; Bowen, E T; Platt, G S; McArdell, L B; Simpson, D I

    1978-07-01

    Six rhesus and two vervet monkeys were infected intraperitoneally with Ebola virus. They developed an acute haemorrhagic fever with skin rash 4 days later and died 6--12 days after infection. Histopathological lesions of acute necrosis were present in the liver, spleen, lymph nodes, lungs and testes. The presence of fibrin thrombi in several organs was suggestive of the occurrence of disseminated intravascular coagulation during the infection. PMID:102747

  14. Vesicular Release of Ebola Virus Matrix Protein VP40

    Microsoft Academic Search

    Joanna Timmins; Sandra Scianimanico; Guy Schoehn; Winfried Weissenhorn

    2001-01-01

    We have analysed the expression and cellular localisation of the matrix protein VP40 from Ebola virus. Full-length VP40 and an N-terminal truncated construct missing the first 31 residues [VP40(31–326)] both locate to the plasma membrane of 293T cells when expressed transiently, while a C-terminal truncation of residues 213 to 326 [VP40(31–212)] shows only expression in the cytoplasm, when analysed by

  15. A DNA vaccine for the prevention of Ebola virus infection.

    PubMed

    Dery, Markalain; Bausch, Daniel G

    2008-06-01

    The NIH and Vical Inc are developing an intramuscular needle-free DNA vaccine containing plasmids encoding the envelope glycoprotein of Ebola virus (EBOV) from the Sudan and Zaire strains, and the nucleoprotein of EBOV Zaire strain. A phase I clinical trial demonstrated a good safety profile, with most adverse events limited to the site of injection and largely attributable to the delivery. PMID:18535936

  16. Reverse Genetics Demonstrates that Proteolytic Processing of the Ebola Virus Glycoprotein Is Not Essential for Replication in Cell Culture

    Microsoft Academic Search

    Gabriele Neumann; Heinz Feldmann; Shinji Watanabe; Igor Lukashevich; Yoshihiro Kawaoka

    2002-01-01

    Ebola virus, a prime example of an emerging pathogen, causes fatal hemorrhagic fever in humans and in nonhuman primates. Identification of major determinants of Ebola virus pathogenicity has been hampered by the lack of effective strategies for experimental mutagenesis. Here we exploit a reverse genetics system that allows the generation of Ebola virus from cloned cDNA to engineer a mutant

  17. Ebola virus outbreak, updates on current therapeutic strategies.

    PubMed

    Elshabrawy, Hatem A; Erickson, Timothy B; Prabhakar, Bellur S

    2015-07-01

    Filoviruses are enveloped negative-sense single-stranded RNA viruses, which include Ebola and Marburg viruses, known to cause hemorrhagic fever in humans with a case fatality of up to 90%. There have been several Ebola virus outbreaks since the first outbreak in the Democratic Republic of Congo in 1976 of which, the recent 2013-2015 epidemic in Guinea, Liberia, and Sierra Leone is the largest in recorded history. Within a few months of the start of the outbreak in December 2013, thousands of infected cases were reported with a significant number of deaths. As of March 2015, according to the Centers for Disease Control and Prevention, there have been nearly 25?000 suspected cases, with 15?000 confirmed by laboratory testing, and over 10?000 deaths. The large number of cases and the high mortality rate, combined with the lack of effective Food and Drug Administration-approved treatments, necessitate the development of potent and safe therapeutic measures to combat the current and future outbreaks. Since the beginning of the outbreak, there have been considerable efforts to develop and characterize protective measures including vaccines and antiviral small molecules, and some have proven effective in vitro and in animal models. Most recently, a cocktail of monoclonal antibodies has been shown to be highly effective in protecting non-human primates from Ebola virus infection. In this review, we will discuss what is known about the nature of the virus, phylogenetic classification, genomic organization and replication, disease transmission, and viral entry and highlight the current approaches and efforts, in the development of therapeutics, to control the outbreak. Copyright © 2015 John Wiley & Sons, Ltd. PMID:25962887

  18. Ebola FAQs for Managers and Employees Ebola is not transmitted through the air, food, or water. The virus can ONLY be transmitted through

    E-print Network

    Ebola FAQs for Managers and Employees Ebola is not transmitted through the air, food, or water are at risk of contracting Ebola. It is transmitted only by direct contact with the blood or bodily uids to work without fear of being exposed to Ebola virus. Do I need to wear protective gear on campus? No

  19. Ebola FAQs for Masters, Deans, Parents, Students Ebola is not transmitted through the air, food, or water. The virus can ONLY be transmitted through

    E-print Network

    Ebola FAQs for Masters, Deans, Parents, Students Ebola is not transmitted through the air, food of contracting Ebola, which is transmitted only by direct contact with the blood or bodily uids of an infected should go to class without fear of being exposed to Ebola virus. Can I eat in the dining hall? Go

  20. Ebola Virus Can Be Effectively Neutralized by Antibody Produced in Natural Human Infection

    Microsoft Academic Search

    TOSHIAKI MARUYAMA; LUIS L. RODRIGUEZ; PETER B. JAHRLING; ANTHONY SANCHEZ; ALI S. KHAN; STUART T. NICHOL; C. J. PETERS; PAUL W. H. I. PARREN; DENNIS R. BURTON; Fort Detrick

    1999-01-01

    The activity of antibodies against filoviruses is poorly understood but has important consequences for vaccine design and passive prophylaxis. To investigate this activity, a panel of recombinant human monoclonal antibodies to Ebola virus antigens was isolated from phage display libraries constructed from RNA from donors who recovered from infection in the 1995 Ebola virus outbreak in Kikwit, Democratic Republic of

  1. Accelerated vaccination for Ebola virus haemorrhagic fever in non-human primates

    Microsoft Academic Search

    Nancy J. Sullivan; Thomas W. Geisbert; Joan B. Geisbert; Ling Xu; Zhi-yong Yang; Mario Roederer; Richard A. Koup; Peter B. Jahrling; Gary J. Nabel

    2003-01-01

    Containment of highly lethal Ebola virus outbreaks poses a serious public health challenge. Although an experimental vaccine has successfully protected non-human primates against disease, more than six months was required to complete the immunizations, making it impractical to limit an acute epidemic. Here, we report the development of accelerated vaccination against Ebola virus in non-human primates. The antibody response to

  2. Lack of protection against ebola virus from chloroquine in mice and hamsters.

    PubMed

    Falzarano, Darryl; Safronetz, David; Prescott, Joseph; Marzi, Andrea; Feldmann, Friederike; Feldmann, Heinz

    2015-06-01

    The antimalarial drug chloroquine has been suggested as a treatment for Ebola virus infection. Chloroquine inhibited virus replication in vitro, but only at cytotoxic concentrations. In mouse and hamster models, treatment did not improve survival. Chloroquine is not a promising treatment for Ebola. Efforts should be directed toward other drug classes. PMID:25988934

  3. Lack of Protection Against Ebola Virus from Chloroquine in Mice and Hamsters

    PubMed Central

    Falzarano, Darryl; Safronetz, David; Prescott, Joseph; Marzi, Andrea; Feldmann, Friederike

    2015-01-01

    The antimalarial drug chloroquine has been suggested as a treatment for Ebola virus infection. Chloroquine inhibited virus replication in vitro, but only at cytotoxic concentrations. In mouse and hamster models, treatment did not improve survival. Chloroquine is not a promising treatment for Ebola. Efforts should be directed toward other drug classes. PMID:25988934

  4. Evaluation in nonhuman primates of vaccines against Ebola virus.

    PubMed

    Geisbert, Thomas W; Pushko, Peter; Anderson, Kevin; Smith, Jonathan; Davis, Kelly J; Jahrling, Peter B

    2002-05-01

    Ebola virus (EBOV) causes acute hemorrhagic fever that is fatal in up to 90% of cases in both humans and nonhuman primates. No vaccines or treatments are available for human use. We evaluated the effects in nonhuman primates of vaccine strategies that had protected mice or guinea pigs from lethal EBOV infection. The following immunogens were used: RNA replicon particles derived from an attenuated strain of Venezuelan equine encephalitis virus (VEEV) expressing EBOV glycoprotein and nucleoprotein; recombinant Vaccinia virus expressing EBOV glycoprotein; liposomes containing lipid A and inactivated EBOV; and a concentrated, inactivated whole-virion preparation. None of these strategies successfully protected nonhuman primates from robust challenge with EBOV. The disease observed in primates differed from that in rodents, suggesting that rodent models of EBOV may not predict the efficacy of candidate vaccines in primates and that protection of primates may require different mechanisms. PMID:11996686

  5. External Quality Assessment of Molecular Detection of Ebola Virus in China

    PubMed Central

    Wang, Guojing; Sun, Yu; Zhang, Kuo; Jia, Tingting; Hao, Mingju; Zhang, Dong; Chang, Le; Zhang, Lei; Zhang, Rui; Lin, Guigao; Peng, Rongxue; Li, Jinming

    2015-01-01

    In 2014, Ebola hemorrhagic fever broke out in West Africa. As contact between China and West Africa is frequent, the possibility that Ebola virus would enter China was high. Thus, an external assessment of the quality of Ebola virus detection was organized by the National Center for Clinical Laboratories in China. Virus-like particles encapsulating known sequences of epidemic strains of Ebola virus from 2014 were prepared as positive quality controls. The sample panel, which was composed of seven positive and three negative samples, was dispatched to 19 laboratories participating in this assessment of Ebola virus detection. Accurate detection was reported at 14 of the 19 participating laboratories, with a sensitivity of 91.43% and a specificity of 100%. Four participants (21.05%) reported false-negative results and were classified as “acceptable.” One participant (5.26%) did not detect any positive samples and was thus classified as “improvable.” Based on the results returned, the ability to detect weakly positive Ebola specimens should be improved. Furthermore, commercial assays and the standard primers offered by the Chinese Centers for Disease Control and Prevention were found to be most accurate and dependable for Ebola detection. A two-target detection approach is recommended for Ebola screening; this approach could reduce the probability of false-negative results. Additionally, standardization of operations and punctual adjustment of instruments are necessary for the control and prevention of Ebola virus. PMID:26177537

  6. Community Knowledge, Attitudes, and Practices Regarding Ebola Virus Disease - Five Counties, Liberia, September-October, 2014.

    PubMed

    Kobayashi, Miwako; Beer, Karlyn D; Bjork, Adam; Chatham-Stephens, Kevin; Cherry, Cara C; Arzoaquoi, Sampson; Frank, Wilmot; Kumeh, Odell; Sieka, Joseph; Yeiah, Adolphus; Painter, Julia E; Yoder, Jonathan S; Flannery, Brendan; Mahoney, Frank; Nyenswah, Tolbert G

    2015-07-10

    As of July 1, 2015, Guinea, Liberia, and Sierra Leone have reported a total of 27,443 confirmed, probable, and suspected Ebola virus disease (Ebola) cases and 11,220 deaths. Guinea and Sierra Leone have yet to interrupt transmission of Ebola virus. In May, 2015, Liberia successfully achieved Ebola transmission-free status, with no new Ebola cases occurring during a 42-day period; however, new Ebola cases were reported beginning June 29, 2015. Local cultural practices and beliefs have posed challenges to disease control, and therefore, targeted, timely health messages are needed to address practices and misperceptions that might hinder efforts to stop the spread of Ebola. As early as September 2014, Ebola spread to most counties in Liberia. To assess Ebola-related knowledge, attitudes, and practices (KAP) in the community, CDC epidemiologists who were deployed to the counties (field team), carried out a survey conducted by local trained interviewers. The survey was conducted in September and October 2014 in five counties in Liberia with varying cumulative incidence of Ebola cases. Survey results indicated several findings. First, basic awareness of Ebola was high across all surveyed populations (median correct responses = 16 of 17 questions on knowledge of Ebola transmission; range = 2-17). Second, knowledge and understanding of Ebola symptoms were incomplete (e.g., 61% of respondents said they would know if they had Ebola symptoms). Finally, certain fears about the disease were present: >90% of respondents indicated a fear of Ebola patients, >40% a fear of cured patients, and >50% a fear of treatment units (expressions of this last fear were greater in counties with lower Ebola incidence). This survey, which was conducted at a time when case counts were rapidly increasing in Liberia, indicated limited knowledge of Ebola symptoms and widespread fear of Ebola treatment units despite awareness of communication messages. Continued efforts are needed to address cultural practices and beliefs to interrupt Ebola transmission. PMID:26158352

  7. Comparison of individual and combination DNA vaccines for B. anthracis, Ebola virus, Marburg virus and Venezuelan equine encephalitis virus

    Microsoft Academic Search

    Jenny Riemenschneider; Aura Garrison; Joan Geisbert; Peter Jahrling; Michael Hevey; Diane Negley; Alan Schmaljohn; John Lee; Mary Kate Hart; Lorna Vanderzanden; David Custer; Mike Bray; Albert Ruff; Bruce Ivins; Anthony Bassett; Cynthia Rossi; Connie Schmaljohn

    2003-01-01

    Multiagent DNA vaccines for highly pathogenic organisms offer an attractive approach for preventing naturally occurring or deliberately introduced diseases. Few animal studies have compared the feasibility of combining unrelated gene vaccines. Here, we demonstrate that DNA vaccines to four dissimilar pathogens that are known biowarfare agents, Bacillus anthracis, Ebola (EBOV), Marburg (MARV), and Venezuelan equine encephalitis virus (VEEV), can elicit

  8. The Ebola contagion and forecasting virus: evidence from four African countries.

    PubMed

    Nadhem, Selmi; Nejib, Hachicha D

    2015-12-01

    This paper is focused on examining the number of deaths' increases participation in the propagating the Ebola virus during the period ranging from March to October 2014. An application of the MGARCH-DCC model regressions on four countries has led to discover that the finding that human contact play a significant role in transmitting the Ebola virus. Our findings also reveal that Guinea has already suffered from a spread-like virus originating from Sierra Lione and Liberia. Noteworthy also, other countries are now liable to such a risk; for instance, Nigeria is a country vulnerable to the propagation of this virus. Consequently, we undertake to conduct our forecasts for EGARCH model estimates implements; which has estimated a decrease in the Ebola virus incurred number of deadly Ebola virus over the two months following the November and December. PMID:26070395

  9. Molecular mechanisms of Ebola virus pathogenesis: focus on cell death.

    PubMed

    Falasca, L; Agrati, C; Petrosillo, N; Di Caro, A; Capobianchi, M R; Ippolito, G; Piacentini, M

    2015-08-01

    Ebola virus (EBOV) belongs to the Filoviridae family and is responsible for a severe disease characterized by the sudden onset of fever and malaise accompanied by other non-specific signs and symptoms; in 30-50% of cases hemorrhagic symptoms are present. Multiorgan dysfunction occurs in severe forms with a mortality up to 90%. The EBOV first attacks macrophages and dendritic immune cells. The innate immune reaction is characterized by a cytokine storm, with secretion of numerous pro-inflammatory cytokines, which induces a huge number of contradictory signals and hurts the immune cells, as well as other tissues. Other highly pathogenic viruses also trigger cytokine storms, but Filoviruses are thought to be particularly lethal because they affect a wide array of tissues. In addition to the immune system, EBOV attacks the spleen and kidneys, where it kills cells that help the body to regulate its fluid and chemical balance and that make proteins that help the blood to clot. In addition, EBOV causes liver, lungs and kidneys to shut down their functions and the blood vessels to leak fluid into surrounding tissues. In this review, we analyze the molecular mechanisms at the basis of Ebola pathogenesis with a particular focus on the cell death pathways induced by the virus. We also discuss how the treatment of the infection can benefit from the recent experience of blocking/modulating cell death in human degenerative diseases. PMID:26024394

  10. In vivo oligomerization and raft localization of Ebola virus protein VP40 during vesicular budding

    Microsoft Academic Search

    Rekha G. Panchal; Gordon Ruthel; Tara A. Kenny; George H. Kallstrom; Shirin S. Badie; Limin Li; Sina Bavari; M. Javad Aman

    2003-01-01

    The matrix protein VP40 plays a critical role in Ebola virus assembly and budding, a process that utilizes specialized membrane domains known as lipid rafts. Previous studies with purified protein suggest a role for oligomerization of VP40 in this process. Here, we demonstrate VP40 oligomers in lipid rafts of mammalian cells, virus-like particles, and in the authentic Ebola virus. By

  11. A serological survey of Ebola virus infection in central African nonhuman primates.

    PubMed

    Leroy, E M; Telfer, P; Kumulungui, B; Yaba, P; Rouquet, P; Roques, P; Gonzalez, J-P; Ksiazek, T G; Rollin, P E; Nerrienet, E

    2004-12-01

    We used an ELISA to determine the prevalence of IgG antibodies specific for the Zaire subtype of Ebola virus in 790 nonhuman primates, belonging to 20 species, studied between 1985 and 2000 in Cameroon, Gabon, and the Republic of Congo. The seroprevalence rate of Ebola antibody in wild-born chimpanzees was 12.9%, indicating that (1) Ebola virus circulates in the forests of a large region of central Africa, including countries such as Cameroon, where no human cases of Ebola infections have been reported; (2) Ebola virus was present in the area before recent outbreaks in humans; (3) chimpanzees are continuously in contact with the virus; and (4) nonlethal Ebola infection can occur in chimpanzees. These results, together with the unexpected detection of Ebola-specific IgG in other species (5 drills, 1 baboon, 1 mandrill, and 1 Cercopithecus), may help to narrow the search for the reservoir of Ebola virus. They also suggest that future Ebola outbreaks may occur anywhere in the central African forest region. PMID:15529251

  12. Ebola Virus Disease: A Perspective for the United States.

    PubMed

    Madariaga, Miguel G

    2015-07-01

    Ebola virus caused an epidemic of unprecedented extension in West Africa. There was concern that the outbreak would not be controlled for a prolonged period of time. Two cases of infected returning travelers have been reported in the US. One of the cases has been associated with secondary transmission and other infected subjects have been repatriated for treatment. This article reviews the etiology, pathogenesis, transmission, clinical manifestations, diagnosis, treatment, and prevention of the disease with emphasis on the identification and management in the US. PMID:25731139

  13. Recombinant RNA replicons derived from attenuated Venezuelan equine encephalitis virus protect guinea pigs and mice from Ebola hemorrhagic fever virus

    Microsoft Academic Search

    Peter Pushko; Mike Bray; George V Ludwig; Michael Parker; Alan Schmaljohn; Anthony Sanchez; Peter B Jahrling; Jonathan F Smith

    2000-01-01

    RNA replicons derived from an attenuated strain of Venezuelan equine encephalitis virus (VEE), an alphavirus, were configured as candidate vaccines for Ebola hemorrhagic fever. The Ebola nucleoprotein (NP) or glycoprotein (GP) genes were introduced into the VEE RNA downstream from the VEE 26S promoter in place of the VEE structural protein genes. The resulting recombinant replicons, expressing the NP or

  14. Serological evidence of Ebola virus infection in Indonesian orangutans.

    PubMed

    Nidom, Chairul A; Nakayama, Eri; Nidom, Reviany V; Alamudi, Mohamad Y; Daulay, Syafril; Dharmayanti, Indi N L P; Dachlan, Yoes P; Amin, Mohamad; Igarashi, Manabu; Miyamoto, Hiroko; Yoshida, Reiko; Takada, Ayato

    2012-01-01

    Ebola virus (EBOV) and Marburg virus (MARV) belong to the family Filoviridae and cause severe hemorrhagic fever in humans and nonhuman primates. Despite the discovery of EBOV (Reston virus) in nonhuman primates and domestic pigs in the Philippines and the serological evidence for its infection of humans and fruit bats, information on the reservoirs and potential amplifying hosts for filoviruses in Asia is lacking. In this study, serum samples collected from 353 healthy Bornean orangutans (Pongo pygmaeus) in Kalimantan Island, Indonesia, during the period from December 2005 to December 2006 were screened for filovirus-specific IgG antibodies using a highly sensitive enzyme-linked immunosorbent assay (ELISA) with recombinant viral surface glycoprotein (GP) antigens derived from multiple species of filoviruses (5 EBOV and 1 MARV species). Here we show that 18.4% (65/353) and 1.7% (6/353) of the samples were seropositive for EBOV and MARV, respectively, with little cross-reactivity among EBOV and MARV antigens. In these positive samples, IgG antibodies to viral internal proteins were also detected by immunoblotting. Interestingly, while the specificity for Reston virus, which has been recognized as an Asian filovirus, was the highest in only 1.4% (5/353) of the serum samples, the majority of EBOV-positive sera showed specificity to Zaire, Sudan, Cote d'Ivoire, or Bundibugyo viruses, all of which have been found so far only in Africa. These results suggest the existence of multiple species of filoviruses or unknown filovirus-related viruses in Indonesia, some of which are serologically similar to African EBOVs, and transmission of the viruses from yet unidentified reservoir hosts into the orangutan populations. Our findings point to the need for risk assessment and continued surveillance of filovirus infection of human and nonhuman primates, as well as wild and domestic animals, in Asia. PMID:22815803

  15. Molecular Cell, Vol. 2, 605616, November, 1998, Copyright 1998 by Cell Press Crystal Structure of the Ebola Virus

    E-print Network

    Harrison, Stephen C.

    of the Ebola Virus Membrane Fusion Subunit, GP2, from the Envelope Glycoprotein Ectodomain (Schnittler et al entry by membrane fusion such as those of the myxovi- ruses, paramyxoviruses, and retroviruses, Ebola activity and to form a stable con- Ebola virus membrane fusion glycoprotein by X-ray crys- formation

  16. To our campus community: The recent cases of Ebola Virus in the United States have led to some questions about

    E-print Network

    Wong, Pak Kin

    To our campus community: The recent cases of Ebola Virus in the United States have led to some questions about the University of Arizona's plan in the unlikely event of an Ebola case on campus. We want community. We also want to make sure that you have accurate information about the virus. Since the Ebola

  17. Surveillance and preparedness for Ebola virus disease -- New York City, 2014.

    PubMed

    Benowitz, Isaac; Ackelsberg, Joel; Balter, Sharon E; Baumgartner, Jennifer C; Dentinger, Catherine; Fine, Anne D; Harper, Scott A; Jones, Lucretia E; Laraque, Fabienne; Lee, Ellen H; Merizalde, Giselle; Yacisin, Kari A; Varma, Jay K; Layton, Marcelle C

    2014-10-17

    In July 2014, as the Ebola virus disease (Ebola) epidemic expanded in Guinea, Liberia, and Sierra Leone, an air traveler brought Ebola to Nigeria and two American health care workers in West Africa were diagnosed with Ebola and later medically evacuated to a U.S. hospital. New York City (NYC) is a frequent port of entry for travelers from West Africa, a home to communities of West African immigrants who travel back to their home countries, and a home to health care workers who travel to West Africa to treat Ebola patients. Ongoing transmission of Ebolavirus in West Africa could result in an infected person arriving in NYC. The announcement on September 30 of an Ebola case diagnosed in Texas in a person who had recently arrived from an Ebola-affected country further reinforced the need in NYC for local preparedness for Ebola. PMID:25321072

  18. Ebola virus disease in Africa: epidemiology and nosocomial transmission.

    PubMed

    Shears, P; O'Dempsey, T J D

    2015-05-01

    The 2014 Ebola outbreak in West Africa, primarily affecting Guinea, Sierra Leone, and Liberia, has exceeded all previous Ebola outbreaks in the number of cases and in international response. There have been 20 significant outbreaks of Ebola virus disease in Sub-Saharan Africa prior to the 2014 outbreak, the largest being that in Uganda in 2000, with 425 cases and a mortality of 53%. Since the first outbreaks in Sudan and Zaire in 1976, transmission within health facilities has been of major concern, affecting healthcare workers and acting as amplifiers of spread into the community. The lack of resources for infection control and personal protective equipment are the main reasons for nosocomial transmission. Local strategies to improve infection control, and a greater understanding of local community views on the disease, have helped to bring outbreaks under control. Recommendations from previous outbreaks include improved disease surveillance to enable more rapid health responses, the wider availability of personal protective equipment, and greater international preparedness. PMID:25655197

  19. Ebola Virus Glycoprotein: Proteolytic Processing, Acylation, Cell Tropism, and Detection of Neutralizing Antibodies

    Microsoft Academic Search

    HIROSHI ITO; SHINJI WATANABE; AYATO TAKADA; YOSHIHIRO KAWAOKA

    2001-01-01

    Using the vesicular stomatitis virus (VSV) pseudotype system, we studied the functional properties of the Ebola virus glycoprotein (GP). Amino acid substitutions at the GP cleavage site, which reduce glycoprotein cleavability and viral infectivity in some viruses, did not appreciably change the infectivity of VSV pseudotyped with GP. Likewise, removal of two acylated cysteine residues in the transmembrane region of

  20. Folate Receptor-? Is a Cofactor for Cellular Entry by Marburg and Ebola Viruses

    Microsoft Academic Search

    Stephen Y. Chan; Cyril J. Empig; Frank J. Welte; Roberto F. Speck; Alan Schmaljohn; Jason F. Kreisberg; Mark A. Goldsmith

    2001-01-01

    Human infections by Marburg (MBG) and Ebola (EBO) viruses result in lethal hemorrhagic fever. To identify cellular entry factors employed by MBG virus, noninfectible cells transduced with an expression library were challenged with a selectable pseudotype virus packaged by MBG glycoproteins (GP). A cDNA encoding the folate receptor-? (FR-?) was recovered from cells exhibiting reconstitution of viral entry. A FR-?

  1. EbolaTracks: an automated SMS system for monitoring persons potentially exposed to Ebola virus disease.

    PubMed

    Tracey, L E; Regan, A K; Armstrong, P K; Dowse, G K; Effler, P V

    2015-01-01

    We report development and implementation of a short message service (SMS)-based system to facilitate active monitoring of persons potentially exposed to Ebola virus disease (EVD), whether returning from EVD-affected countries, or contacts of local cases, should they occur. The system solicits information on symptoms and temperature twice daily. We demonstrated proof-of-concept; however this system would likely be even more useful where there are many local contacts to confirmed EVD cases or travellers from EVD-affected countries. PMID:25613652

  2. The 2014 Ebola virus disease outbreak in West Africa.

    PubMed

    Gatherer, Derek

    2014-08-01

    On 23 March 2014, the World Health Organization issued its first communiqué on a new outbreak of Ebola virus disease (EVD), which began in December 2013 in Guinée Forestière (Forested Guinea), the eastern sector of the Republic of Guinea. Located on the Atlantic coast of West Africa, Guinea is the first country in this geographical region in which an outbreak of EVD has occurred, leaving aside the single case reported in Ivory Coast in 1994. Cases have now also been confirmed across Guinea as well as in the neighbouring Republic of Liberia. The appearance of cases in the Guinean capital, Conakry, and the transit of another case through the Liberian capital, Monrovia, presents the first large urban setting for EVD transmission. By 20 April 2014, 242 suspected cases had resulted in a total of 147 deaths in Guinea and Liberia. The causative agent has now been identified as an outlier strain of Zaire Ebola virus. The full geographical extent and degree of severity of the outbreak, its zoonotic origins and its possible spread to other continents are sure to be subjects of intensive discussion over the next months. PMID:24795448

  3. Rapid Detection of Ebola Virus with a Reagent-Free, Point-of-Care Biosensor

    PubMed Central

    Baca, Justin T.; Severns, Virginia; Lovato, Debbie; Branch, Darren W.; Larson, Richard S.

    2015-01-01

    Surface acoustic wave (SAW) sensors can rapidly detect Ebola antigens at the point-of-care without the need for added reagents, sample processing, or specialized personnel. This preliminary study demonstrates SAW biosensor detection of the Ebola virus in a concentration-dependent manner. The detection limit with this methodology is below the average level of viremia detected on the first day of symptoms by PCR. We observe a log-linear sensor response for highly fragmented Ebola viral particles, with a detection limit corresponding to 1.9 × 104 PFU/mL prior to virus inactivation. We predict greatly improved sensitivity for intact, infectious Ebola virus. This point-of-care methodology has the potential to detect Ebola viremia prior to symptom onset, greatly enabling infection control and rapid treatment. This biosensor platform is powered by disposable AA batteries and can be rapidly adapted to detect other emerging diseases in austere conditions. PMID:25875186

  4. INHIBITION OF EBOLA VIRUS ENTRY BY A C-PEPTIDE TARGETED TO ENDOSOMES Emily Happy Miller1,2

    E-print Network

    Chandran, Kartik

    1 INHIBITION OF EBOLA VIRUS ENTRY BY A C-PEPTIDE TARGETED TO ENDOSOMES Emily Happy Miller1.lai@einstein.yu.edu. Ebola virus (EboV) and Marburg virus (MarV) (filoviruses) are the causative agents of severe hemorrhagic

  5. The Assembly of Ebola Virus Nucleocapsid Requires Virion-Associated Proteins 35 and 24 and Posttranslational Modification of Nucleoprotein

    Microsoft Academic Search

    Yue Huang; Ling Xu; Yongnian Sun; Gary J Nabel

    2002-01-01

    Ebola virus encodes seven viral structural and regulatory proteins that support its high rates of replication, but little is known about nucleocapsid assembly of this virus in infected cells. We report here that three viral proteins are necessary and sufficient for formation of Ebola virus particles and that intracellular posttranslational modification regulates this process. Expression of the nucleoprotein (NP) and

  6. Persistence and Genetic Stability of Ebola Virus during the Outbreak in Kikwit, Democratic Republic of the Congo, 1995

    Microsoft Academic Search

    A. De Roo; Y. Guimard; A. Sanchez; D. Bressler; J. Bertolli

    1999-01-01

    Ebola virus persistence was examined in body fluids from 12 convalescent patients by virus isolation and reverse transcription - polymerase chain reaction (RT-PCR) during the 1995 Ebola hemorrhagic fever outbreak in Kikwit, Democratic Republic of the Congo. Virus RNA could be detected for up to 33 days in vaginal, rectal, and conjunctival swabs of 1 patient and up to 101

  7. In silico analysis suggests repurposing of ibuprofen for prevention and treatment of EBOLA virus disease

    PubMed Central

    Veljkovic, Veljko; Goeijenbier, Marco; Glisic, Sanja; Veljkovic, Nevena; Perovic, Vladimir R.; Sencanski, Milan; Branch, Donald R.; Paessler, Slobodan

    2015-01-01

    The large 2014/2015 Ebola virus outbreak in West Africa points out the urgent need to develop new preventive and therapeutic approaches that are effective against Ebola viruses and  can be rapidly utilized. Recently, a simple theoretical criterion for the virtual screening of molecular libraries for candidate inhibitors of Ebola virus infection was proposed. Using this method the ‘drug space’ was screened and 267 approved and 382 experimental drugs as candidates for treatment of the Ebola virus disease (EVD) have been selected. Detailed analysis of these drugs revealed the non-steroidal anti-inflammatory drug ibuprofen as an inexpensive, widely accessible and minimally toxic candidate for prevention and treatment of EVD. Furthermore, the molecular mechanism underlying this possible protective effect of ibuprofen against EVD is suggested in this article.

  8. Requirements for cell rounding and surface protein down-regulation by Ebola virus glycoprotein

    Microsoft Academic Search

    Joseph R. Francica; Meghan K. Matukonis; Paul Bates

    2009-01-01

    Ebola virus causes an acute hemorrhagic fever that is associated with high morbidity and mortality. The viral glycoprotein is thought to contribute to pathogenesis, though precise mechanisms are unknown. Cellular pathogenesis can be modeled in vitro by expression of the Ebola viral glycoprotein (GP) in cells, which causes dramatic morphological changes, including cell rounding and surface protein down-regulation. These effects

  9. Apoptosis in fatal Ebola infection. Does the virus toll the bell for immune system?

    Microsoft Academic Search

    S. Baize; E. M. Leroy; E. Mavoungou; S. P. Fisher-Hoch

    2000-01-01

    In fatal Ebola virus hemorrhagic fever massive intravascular apoptosis develops rapidly following infection and progressing relentlessly until death. While data suggest that T lymphocytes are mainly deleted by apoptosis in PBMC of human fatal cases, experimental Ebola infection in animal models have shown some evidence of destruction of lymphocytes in spleen and lymph nodes probably involving both T and B

  10. VP35 Knockdown Inhibits Ebola Virus Amplification and Protects against Lethal Infection in Mice

    Microsoft Academic Search

    Sven Enterlein; Kelly L. Warfield; Dana L. Swenson; David A. Stein; Jeffery L. Smith; C. Scott Gamble; Andrew D. Kroeker; Patrick L. Iversen; Sina Bavari; Elke Muhlberger

    2006-01-01

    Phosphorodiamidate morpholino oligomers (PMO) are a class of uncharged single-stranded DNA analogs modified such that each subunit includes a phosphorodiamidate linkage and morpholine ring. PMO antisense agents have been reported to effectively interfere with the replication of several positive-strand RNA viruses in cell culture. The filoviruses, Marburg virus and Ebola virus (EBOV), are negative-strand RNA viruses that cause up to

  11. Chimeric human parainfluenza virus bearing the Ebola virus glycoprotein as the sole surface protein is immunogenic and highly protective against Ebola virus challenge

    SciTech Connect

    Bukreyev, Alexander [National Institute of Allergy and Infectious Diseases, Building 50, Room 6505, NIAID, National Institutes of Health, 50 South Dr. MSC 8007, Bethesda, MD 20892-8007 (United States)], E-mail: abukreyev@nih.gov; Marzi, Andrea; Feldmann, Friederike [Special Pathogens Program, National Microbiology Laboratory, Canadian Science Centre for Human and Animal Health, Winnipeg (Canada); Zhang Liqun [Cystic Fibrosis/Pulmonary Research and Treatment Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina (United States); Yang Lijuan; Ward, Jerrold M. [National Institute of Allergy and Infectious Diseases, Building 50, Room 6505, NIAID, National Institutes of Health, 50 South Dr. MSC 8007, Bethesda, MD 20892-8007 (United States); Dorward, David W. [Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana (United States); Pickles, Raymond J. [Cystic Fibrosis/Pulmonary Research and Treatment Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina (United States); Murphy, Brian R. [National Institute of Allergy and Infectious Diseases, Building 50, Room 6505, NIAID, National Institutes of Health, 50 South Dr. MSC 8007, Bethesda, MD 20892-8007 (United States); Feldmann, Heinz [Special Pathogens Program, National Microbiology Laboratory, Canadian Science Centre for Human and Animal Health, Winnipeg (Canada); Department of Medical Microbiology, University of Manitoba (Canada); Collins, Peter L. [National Institute of Allergy and Infectious Diseases, Building 50, Room 6505, NIAID, National Institutes of Health, 50 South Dr. MSC 8007, Bethesda, MD 20892-8007 (United States)

    2009-01-20

    We generated a new live-attenuated vaccine against Ebola virus (EBOV) based on a chimeric virus HPIV3/{delta}F-HN/EboGP that contains the EBOV glycoprotein (GP) as the sole transmembrane envelope protein combined with the internal proteins of human parainfluenza virus type 3 (HPIV3). Electron microscopy analysis of the virus particles showed that they have an envelope and surface spikes resembling those of EBOV and a particle size and shape resembling those of HPIV3. When HPIV3/{delta}F-HN/EboGP was inoculated via apical surface of an in vitro model of human ciliated airway epithelium, the virus was released from the apical surface; when applied to basolateral surface, the virus infected basolateral cells but did not spread through the tissue. Following intranasal (IN) inoculation of guinea pigs, scattered infected cells were detected in the lungs by immunohistochemistry, but infectious HPIV3/{delta}F-HN/EboGP could not be recovered from the lungs, blood, or other tissues. Despite the attenuation, the virus was highly immunogenic, and a single IN dose completely protected the animals against a highly lethal intraperitoneal challenge of guinea pig-adapted EBOV.

  12. Amino acid mutations in Ebola virus glycoprotein of the 2014 epidemic.

    PubMed

    Giovanetti, Marta; Grifoni, Alba; Lo Presti, Alessandra; Cella, Eleonora; Montesano, Carla; Zehender, Gianguglielmo; Colizzi, Vittorio; Amicosante, Massimo; Ciccozzi, Massimo

    2015-06-01

    Zaire Ebola virus (EBOV) is an enveloped non-segmented negative strand RNA virus of 19?kb in length belonging to the family Filoviridae. The virus was isolated and identified in 1976 during the epidemic of hemorrhagic fever in Zaire. The most recent outbreak of EBOV among humans, was that occurred in the forested areas of south eastern Guinea, that began in February 2014 and is still ongoing. The recent Ebola outbreak, is affecting other countries in West Africa, in addiction to Guinea: Liberia, Nigeria, and Sierra Leone. In this article, a selective pressure analysis and homology modeling based on the G Glycoprotein (GP) sequences retrieved from public databases were used to investigate the genetic diversity and modification of antibody response in the recent outbreak of Ebola Virus. Structural and the evolutionary analysis underline the 2014 epidemic virus being under negative selective pressure does not change with respect to the old epidemic in terms of genome adaptation. PMID:25783989

  13. Being ready to treat Ebola virus disease patients.

    PubMed

    Brett-Major, David M; Jacob, Shevin T; Jacquerioz, Frederique A; Risi, George F; Fischer, William A; Kato, Yasuyuki; Houlihan, Catherine F; Crozier, Ian; Bosa, Henry Kyobe; Lawler, James V; Adachi, Takuya; Hurley, Sara K; Berry, Louise E; Carlson, John C; Button, Thomas C; McLellan, Susan L; Shea, Barbara J; Kuniyoshi, Gary G; Ferri, Mauricio; Murthy, Srinivas G; Petrosillo, Nicola; Lamontagne, Francois; Porembka, David T; Schieffelin, John S; Rubinson, Lewis; O'Dempsey, Tim; Donovan, Suzanne M; Bausch, Daniel G; Fowler, Robert A; Fletcher, Thomas E

    2015-02-01

    As the outbreak of Ebola virus disease (EVD) in West Africa continues, clinical preparedness is needed in countries at risk for EVD (e.g., United States) and more fully equipped and supported clinical teams in those countries with epidemic spread of EVD in Africa. Clinical staff must approach the patient with a very deliberate focus on providing effective care while assuring personal safety. To do this, both individual health care providers and health systems must improve EVD care. Although formal guidance toward these goals exists from the World Health Organization, Medecin Sans Frontières, the Centers for Disease Control and Prevention, and other groups, some of the most critical lessons come from personal experience. In this narrative, clinicians deployed by the World Health Organization into a wide range of clinical settings in West Africa distill key, practical considerations for working safely and effectively with patients with EVD. PMID:25510724

  14. Infection of XC Cells by MLVs and Ebola Virus Is Endosome-Dependent but Acidification-Independent

    Microsoft Academic Search

    Haruka Kamiyama; Katsura Kakoki; Hiroaki Yoshii; Masatomo Iwao; Tsukasa Igawa; Hideki Sakai; Hideki Hayashi; Toshifumi Matsuyama; Naoki Yamamoto; Yoshinao Kubo; Robert J. Geraghty

    2011-01-01

    Inhibitors of endosome acidification or cathepsin proteases attenuated infections mediated by envelope proteins of xenotropic murine leukemia virus-related virus (XMRV) and Ebola virus, as well as ecotropic, amphotropic, polytropic, and xenotropic murine leukemia viruses (MLVs), indicating that infections by these viruses occur through acidic endosomes and require cathepsin proteases in the susceptible cells such as TE671 cells. However, as previously

  15. Apoptosis in fatal Ebola infection. Does the virus toll the bell for immune system?

    PubMed

    Baize, S; Leroy, E M; Mavoungou, E; Fisher-Hoch, S P

    2000-02-01

    In fatal Ebola virus hemorrhagic fever massive intravascular apoptosis develops rapidly following infection and progressing relentlessly until death. While data suggest that T lymphocytes are mainly deleted by apoptosis in PBMC of human fatal cases, experimental Ebola infection in animal models have shown some evidence of destruction of lymphocytes in spleen and lymph nodes probably involving both T and B cells. Nevertheless, we are able to conclude from the accumulated evidence that early interactions between Ebola virus and the immune system, probably via macrophages, main targets for viral replication, lead to massive destruction of immune cells in fatal cases. PMID:11227491

  16. The Organisation of Ebola Virus Reveals a Capacity for Extensive, Modular Polyploidy

    PubMed Central

    Beniac, Daniel R.; Melito, Pasquale L.; deVarennes, Shauna L.; Hiebert, Shannon L.; Rabb, Melissa J.; Lamboo, Lindsey L.; Jones, Steven M.; Booth, Timothy F.

    2012-01-01

    Background Filoviruses, including Ebola virus, are unusual in being filamentous animal viruses. Structural data on the arrangement, stoichiometry and organisation of the component molecules of filoviruses has until now been lacking, partially due to the need to work under level 4 biological containment. The present study provides unique insights into the structure of this deadly pathogen. Methodology and Principal Findings We have investigated the structure of Ebola virus using a combination of cryo-electron microscopy, cryo-electron tomography, sub-tomogram averaging, and single particle image processing. Here we report the three-dimensional structure and architecture of Ebola virus and establish that multiple copies of the RNA genome can be packaged to produce polyploid virus particles, through an extreme degree of length polymorphism. We show that the helical Ebola virus inner nucleocapsid containing RNA and nucleoprotein is stabilized by an outer layer of VP24-VP35 bridges. Elucidation of the structure of the membrane-associated glycoprotein in its native state indicates that the putative receptor-binding site is occluded within the molecule, while a major neutralizing epitope is exposed on its surface proximal to the viral envelope. The matrix protein VP40 forms a regular lattice within the envelope, although its contacts with the nucleocapsid are irregular. Conclusions The results of this study demonstrate a modular organization in Ebola virus that accommodates a well-ordered, symmetrical nucleocapsid within a flexible, tubular membrane envelope. PMID:22247782

  17. Treating the Host Response to Ebola Virus Disease with Generic Statins and Angiotensin Receptor Blockers

    PubMed Central

    Jacobson, Jeffrey R.; Rordam, Ole Martin; Opal, Steven M.

    2015-01-01

    ABSTRACT Treatments targeting the Ebola virus may eventually be shown to work, but they will not have an impact on overall Ebola mortality in West Africa. Endothelial dysfunction is responsible for the fluid and electrolyte imbalances seen in Ebola patients. Because inexpensive generic statins and angiotensin receptor blockers restore endothelial barrier integrity, they can be used to treat the host response in these patients. In Sierra Leone, approximately 100 Ebola patients were treated with this combination, and reports indicate that survival was greatly improved. PMID:26106080

  18. Treating the Host Response to Ebola Virus Disease with Generic Statins and Angiotensin Receptor Blockers.

    PubMed

    Fedson, David S; Jacobson, Jeffrey R; Rordam, Ole Martin; Opal, Steven M

    2015-01-01

    Treatments targeting the Ebola virus may eventually be shown to work, but they will not have an impact on overall Ebola mortality in West Africa. Endothelial dysfunction is responsible for the fluid and electrolyte imbalances seen in Ebola patients. Because inexpensive generic statins and angiotensin receptor blockers restore endothelial barrier integrity, they can be used to treat the host response in these patients. In Sierra Leone, approximately 100 Ebola patients were treated with this combination, and reports indicate that survival was greatly improved. PMID:26106080

  19. Individual and Bivalent Vaccines Based on Alphavirus Replicons Protect Guinea Pigs against Infection with Lassa and Ebola Viruses

    PubMed Central

    Pushko, Peter; Geisbert, Joan; Parker, Michael; Jahrling, Peter; Smith, Jonathan

    2001-01-01

    Lassa and Ebola viruses cause acute, often fatal, hemorrhagic fever diseases, for which no effective vaccines are currently available. Although lethal human disease outbreaks have been confined so far to sub-Saharan Africa, they also pose significant epidemiological concern worldwide as demonstrated by several instances of accidental importation of the viruses into North America and Europe. In the present study, we developed experimental individual vaccines for Lassa virus and bivalent vaccines for Lassa and Ebola viruses that are based on an RNA replicon vector derived from an attenuated strain of Venezuelan equine encephalitis virus. The Lassa and Ebola virus genes were expressed from recombinant replicon RNAs that also encoded the replicase function and were capable of efficient intracellular self-amplification. For vaccinations, the recombinant replicons were incorporated into virus-like replicon particles. Guinea pigs vaccinated with particles expressing Lassa virus nucleoprotein or glycoprotein genes were protected from lethal challenge with Lassa virus. Vaccination with particles expressing Ebola virus glycoprotein gene also protected the animals from lethal challenge with Ebola virus. In order to evaluate a single vaccine protecting against both Lassa and Ebola viruses, we developed dual-expression particles that expressed glycoprotein genes of both Ebola and Lassa viruses. Vaccination of guinea pigs with either dual-expression particles or with a mixture of particles expressing Ebola and Lassa virus glycoprotein genes protected the animals against challenges with Ebola and Lassa viruses. The results showed that immune responses can be induced against multiple vaccine antigens coexpressed from an alphavirus replicon and suggested the possibility of engineering multivalent vaccines based upon alphavirus vectors for arenaviruses, filoviruses, and possibly other emerging pathogens. PMID:11689649

  20. Ebola Virus Stability on Surfaces and in Fluids in Simulated Outbreak Environments

    PubMed Central

    Fischer, Robert; Judson, Seth; Miazgowicz, Kerri; Bushmaker, Trenton; Prescott, Joseph

    2015-01-01

    We evaluated the stability of Ebola virus on surfaces and in fluids under simulated environmental conditions for the climate of West Africa and for climate-controlled hospitals. This virus remains viable for a longer duration on surfaces in hospital conditions than in African conditions and in liquid than in dried blood. PMID:26079114

  1. Ebola Virus Stability on Surfaces and in Fluids in Simulated Outbreak Environments.

    PubMed

    Fischer, Robert; Judson, Seth; Miazgowicz, Kerri; Bushmaker, Trenton; Prescott, Joseph; Munster, Vincent J

    2015-07-01

    We evaluated the stability of Ebola virus on surfaces and in fluids under simulated environmental conditions for the climate of West Africa and for climate-controlled hospitals. This virus remains viable for a longer duration on surfaces in hospital conditions than in African conditions and in liquid than in dried blood. PMID:26079114

  2. Differential induction of cellular detachment by envelope glycoproteins of Marburg and Ebola (Zaire) viruses

    Microsoft Academic Search

    Stephen Y. Chan; Melissa C. Ma; Mark A. Goldsmith

    Human infection by Marburg (MBG) or Ebola (EBO) virus is associated with fatal haemorrhagic fevers. While these filoviruses may both incite disease as a result of explosive virus replication, we hypothe- sized that expression of individual viral gene pro- ducts, such as the envelope glycoprotein (GP), may directly alter target cells and contribute to patho- genesis. We found that expression

  3. Mechanisms of Immunity in Post-Exposure Vaccination against Ebola Virus Infection

    PubMed Central

    Bradfute, Steven B.; Anthony, Scott M.; Stuthman, Kelly S.; Ayithan, Natarajan; Tailor, Prafullakumar; Shaia, Carl I.; Bray, Mike; Ozato, Keiko; Bavari, Sina

    2015-01-01

    Ebolaviruses can cause severe hemorrhagic fever that is characterized by rapid viral replication, coagulopathy, inflammation, and high lethality rates. Although there is no clinically proven vaccine or treatment for Ebola virus infection, a virus-like particle (VLP) vaccine is effective in mice, guinea pigs, and non-human primates when given pre-infection. In this work, we report that VLPs protect Ebola virus-infected mice when given 24 hours post-infection. Analysis of cytokine expression in serum revealed a decrease in pro-inflammatory cytokine and chemokine levels in mice given VLPs post-exposure compared to infected, untreated mice. Using knockout mice, we show that VLP-mediated post-exposure protection requires perforin, B cells, macrophages, conventional dendritic cells (cDCs), and either CD4+ or CD8+ T cells. Protection was Ebola virus-specific, as marburgvirus VLPs did not protect Ebola virus-infected mice. Increased antibody production in VLP-treated mice correlated with protection, and macrophages were required for this increased production. However, NK cells, IFN-gamma, and TNF-alpha were not required for post-exposure-mediated protection. These data suggest that a non-replicating Ebola virus vaccine can provide post-exposure protection and that the mechanisms of immune protection in this setting require both increased antibody production and generation of cytotoxic T cells. PMID:25785602

  4. Animal models for Ebola and Marburg virus infections

    PubMed Central

    Nakayama, Eri; Saijo, Masayuki

    2013-01-01

    Ebola and Marburg hemorrhagic fevers (EHF and MHF) are caused by the Filoviridae family, Ebolavirus and Marburgvirus (ebolavirus and marburgvirus), respectively. These severe diseases have high mortality rates in humans. Although EHF and MHF are endemic to sub-Saharan Africa. A novel filovirus, Lloviu virus, which is genetically distinct from ebolavirus and marburgvirus, was recently discovered in Spain where filoviral hemorrhagic fever had never been reported. The virulence of this virus has not been determined. Ebolavirus and marburgvirus are classified as biosafety level-4 (BSL-4) pathogens and Category A agents, for which the US government requires preparedness in case of bioterrorism. Therefore, preventive measures against these viral hemorrhagic fevers should be prepared, not only in disease-endemic regions, but also in disease-free countries. Diagnostics, vaccines, and therapeutics need to be developed, and therefore the establishment of animal models for EHF and MHF is invaluable. Several animal models have been developed for EHF and MHF using non-human primates (NHPs) and rodents, which are crucial to understand pathophysiology and to develop diagnostics, vaccines, and therapeutics. Rhesus and cynomolgus macaques are representative models of filovirus infection as they exhibit remarkably similar symptoms to those observed in humans. However, the NHP models have practical and ethical problems that limit their experimental use. Furthermore, there are no inbred and genetically manipulated strains of NHP. Rodent models such as mouse, guinea pig, and hamster, have also been developed. However, these rodent models require adaptation of the virus to produce lethal disease and do not mirror all symptoms of human filovirus infection. This review article provides an outline of the clinical features of EHF and MHF in animals, including humans, and discusses how the animal models have been developed to study pathophysiology, vaccines, and therapeutics. PMID:24046765

  5. Cathepsin B & L Are Not Required for Ebola Virus Replication

    PubMed Central

    Marzi, Andrea; Reinheckel, Thomas; Feldmann, Heinz

    2012-01-01

    Ebola virus (EBOV), family Filoviridae, emerged in 1976 on the African continent. Since then it caused several outbreaks of viral hemorrhagic fever in humans with case fatality rates up to 90% and remains a serious Public Health concern and biothreat pathogen. The most pathogenic and best-studied species is Zaire ebolavirus (ZEBOV). EBOV encodes one viral surface glycoprotein (GP), which is essential for replication, a determinant of pathogenicity and an important immunogen. GP mediates viral entry through interaction with cellular surface molecules, which results in the uptake of virus particles via macropinocytosis. Later in this pathway endosomal acidification activates the cysteine proteases Cathepsin B and L (CatB, CatL), which have been shown to cleave ZEBOV-GP leading to subsequent exposure of the putative receptor-binding and fusion domain and productive infection. We studied the effect of CatB and CatL on in vitro and in vivo replication of EBOV. Similar to previous findings, our results show an effect of CatB, but not CatL, on ZEBOV entry into cultured cells. Interestingly, cell entry by other EBOV species (Bundibugyo, Côte d'Ivoire, Reston and Sudan ebolavirus) was independent of CatB or CatL as was EBOV replication in general. To investigate whether CatB and CatL have a role in vivo during infection, we utilized the mouse model for ZEBOV. Wild-type (control), catB?/? and catL?/? mice were equally susceptible to lethal challenge with mouse-adapted ZEBOV with no difference in virus replication and time to death. In conclusion, our results show that CatB and CatL activity is not required for EBOV replication. Furthermore, EBOV glycoprotein cleavage seems to be mediated by an array of proteases making targeted therapeutic approaches difficult. PMID:23236527

  6. High-Dose Mannose-Binding Lectin Therapy for Ebola Virus Infection

    PubMed Central

    Michelow, Ian C.; Lear, Calli; Scully, Corinne; Prugar, Laura I.; Longley, Clifford B.; Yantosca, L. Michael; Ji, Xin; Karpel, Marshall; Brudner, Matthew; Takahashi, Kazue; Spear, Gregory T.; Ezekowitz, R. Alan B.; Olinger, Gene G.

    2011-01-01

    Mannose-binding lectin (MBL) targets diverse microorganisms for phagocytosis and complement-mediated lysis by binding specific surface glycans. Although recombinant human MBL (rhMBL) trials have focused on reconstitution therapy, safety studies have identified no barriers to its use at higher levels. Ebola viruses cause fatal hemorrhagic fevers for which no treatment exists and that are feared as potential biothreat agents. We found that mice whose rhMBL serum concentrations were increased ?7-fold above average human levels survived otherwise fatal Ebola virus infections and became immune to virus rechallenge. Because Ebola glycoproteins potentially model other glycosylated viruses, rhMBL may offer a novel broad-spectrum antiviral approach. PMID:21288816

  7. A Mutation in the Ebola Virus Envelope Glycoprotein Restricts Viral Entry in a Host Species-and Cell-Type-Specific Manner

    E-print Network

    Chandran, Kartik

    A Mutation in the Ebola Virus Envelope Glycoprotein Restricts Viral Entry in a Host Species, Bronx, New York, USAb Zaire Ebola virus (EBOV) is a zoonotic pathogen that causes severe hemorrhagic APCs. Zaire Ebola virus (EBOV) is an emerging zoonotic pathogen that causes hemorrhagic fever in humans

  8. Passive Transfer of Antibodies Protects Immunocompetent and Immunodeficient Mice against Lethal Ebola Virus Infection without Complete Inhibition of Viral Replication

    Microsoft Academic Search

    MANISHA GUPTA; SIDDHARTHA MAHANTY; MIKE BRAY; RAFI AHMED; PIERRE E. ROLLIN

    2001-01-01

    Ebola hemorrhagic fever is a severe, usually fatal illness caused by Ebola virus, a member of the filovirus family. The use of nonhomologous immune serum in animal studies and blood from survivors in two anecdotal reports of Ebola hemorrhagic fever in humans has shown promise, but the efficacy of these treatments has not been demonstrated definitively. We have evaluated the

  9. A replication-deficient rabies virus vaccine expressing Ebola virus glycoprotein is highly attenuated for neurovirulence

    SciTech Connect

    Papaneri, Amy B. [Emerging Viral Pathogens Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, MD 21702 (United States)] [Emerging Viral Pathogens Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, MD 21702 (United States); Wirblich, Christoph [Department of Microbiology and Immunology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107 (United States)] [Department of Microbiology and Immunology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107 (United States); Cann, Jennifer A.; Cooper, Kurt [Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick MD, 21702 (United States)] [Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick MD, 21702 (United States); Jahrling, Peter B. [Emerging Viral Pathogens Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, MD 21702 (United States) [Emerging Viral Pathogens Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, MD 21702 (United States); Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick MD, 21702 (United States); Schnell, Matthias J., E-mail: matthias.schnell@jefferson.edu [Department of Microbiology and Immunology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107 (United States); Jefferson Vaccine Center, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107 (United States); Blaney, Joseph E., E-mail: jblaney@niaid.nih.gov [Emerging Viral Pathogens Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, MD 21702 (United States)

    2012-12-05

    We are developing inactivated and live-attenuated rabies virus (RABV) vaccines expressing Ebola virus (EBOV) glycoprotein for use in humans and endangered wildlife, respectively. Here, we further characterize the pathogenesis of the live-attenuated RABV/EBOV vaccine candidates in mice in an effort to define their growth properties and potential for safety. RABV vaccines expressing GP (RV-GP) or a replication-deficient derivative with a deletion of the RABV G gene (RV{Delta}G-GP) are both avirulent after intracerebral inoculation of adult mice. Furthermore, RV{Delta}G-GP is completely avirulent upon intracerebral inoculation of suckling mice unlike parental RABV vaccine or RV-GP. Analysis of RV{Delta}G-GP in the brain by quantitative PCR, determination of virus titer, and immunohistochemistry indicated greatly restricted virus replication. In summary, our findings indicate that RV-GP retains the attenuation phenotype of the live-attenuated RABV vaccine, and RV{Delta}G-GP would appear to be an even safer alternative for use in wildlife or consideration for human use.

  10. Search for the Ebola Virus Reservoir in Kikwit, Democratic Republic of the Congo: Reflections on a Vertebrate Collection

    Microsoft Academic Search

    Herwig Leirs; Dudu Akaibe; Neal Woollen; George Ludwig

    1999-01-01

    A 3-month ecologic investigation was done to identify the reservoir of Ebola virus following the 1995 outbreak in Kikwit, Democratic Republic of the Congo. Efforts focused on the fields where the putative primary case had worked but included other habitats near Kikwit. Samples were collected from 3066 vertebrates and tested for the presence of antibodies to Ebola (subtype Zaire) virus:

  11. Acceptability and Willingness-to-Pay for a Hypothetical Ebola Virus Vaccine in Nigeria

    PubMed Central

    Ughasoro, Maduka Donatus; Esangbedo, Dorothy Omono; Tagbo, Beckie Nnenna; Mejeha, Ijeoma Chigozie

    2015-01-01

    Background Ebola virus disease is a highly virulent and transmissible disease. The largest recorded fatality from Ebola virus disease epidemic is ongoing in a few countries in West Africa, and this poses a health risk to the entire population of the world because arresting the transmission has been challenging. Vaccination is considered a key intervention that is capable of arresting further spread of the disease and preventing future outbreak. However, no vaccine has yet been approved for public use, although various recombinant vaccines are undergoing trials and approval for public use is imminent. Therefore, this study aimed to determine the acceptability of and willingness-to-pay for Ebola virus vaccine by the public. Methods The study was a community-based cross-sectional qualitative and quantitative interventional study conducted in two communities, each in two states in Nigeria. An interviewer-administered questionnaire was used to collect information on respondents’ knowledge of the Ebola virus, the ways to prevent the disease, and their preventive practices, as well as their acceptability of and willingness-to-pay for a hypothetical vaccine against Ebola virus disease. The association between acceptability of the vaccine and other independent variables were evaluated using multivariate regression analysis. Results Ebola virus disease was considered to be a very serious disease by 38.5% of the 582 respondents (224/582), prior to receiving health education on Ebola virus and its vaccine. Eighty percent (80%) accepted to be vaccinated with Ebola vaccine. However, among those that accepted to be vaccinated, most would only accept after observing the outcome on others who have received the vaccine. More than 87.5% was willing to pay for the vaccine, although 55.2% was of the opinion that the vaccine should be provided free of charge. Conclusion The level of acceptability of Ebola virus vaccine among respondents was impressive (though conditional), as well as their willingness to pay for it if the vaccine is not publicly funded. In order to achieve a high uptake of the vaccine, information and education on the vaccine should be extensively shared with the public prior to the introduction of the vaccine, and the vaccine should be provided free of charge by government. PMID:26076007

  12. The multifunctional Ebola virus VP40 matrix protein is a promising therapeutic target

    PubMed Central

    Madara, Jonathan J; Han, Ziying; Ruthel, Gordon; Freedman, Bruce D; Harty, Ronald N

    2015-01-01

    The highly virulent nature of Ebola virus, evident from the 2014 West African pandemic, highlights the need to develop vaccines or therapeutic agents that limit the pathogenesis and spread of this virus. While vaccines represent an obvious approach, targeting virus interactions with host proteins that critically regulate the virus lifecycle also represent important therapeutic strategies. Among Ebola virus proteins at this critical interface is its matrix protein, VP40, which is abundantly expressed during infection and plays a number of critical roles in the viral lifecycle. In addition to regulating viral transcription, VP40 coordinates virion assembly and budding from infected cells. Details of the molecular mechanisms underpinning these essential functions are currently being elucidated, with a particular emphasis on its interactions with host proteins that control virion assembly and egress. This review focuses on the strategies geared toward developing novel therapeutic agents that target VP40-specific control of host functions critical to virion transcription, assembly and egress.

  13. [Stabilization of peroxidase conjugates used in enzyme immunoassay systems to detect Ebola and Marburg virus antigens].

    PubMed

    Pirozhkov, A P; Borisevich, I V; Snetkova, O Iu; Androshchuk, I A; Syromiatnikova, S I; Khmelev, A L; Shatokhina, I V; Kudrin, V Iu; Timofeev, M A; Pantiukhov, V B; Borisevich, S V; Markov, V I; Bondarev, V P

    2010-01-01

    The time course of changes in the activity of solutions of horseradish peroxidase conjugates with immunoglobulins against Ebola and Marburg fevers was studied in the presence of different components. The series of the conjugates of ELISA kits for the detection of Ebola and Marburg virus antigens, which were prepared on the basis of the designed stabilizing solution, preserved at less than 90% of its baseline activity during 10 months at a storage temperature of 2 to 8 degrees C. PMID:20364672

  14. Systems for rapidly detecting and treating persons with ebola virus disease--United States.

    PubMed

    Koonin, Lisa M; Jamieson, Denise J; Jernigan, John A; Van Beneden, Chris A; Kosmos, Christine; Harvey, Melissa Cole; Pietz, Harald; Bertolli, Jeanne; Perz, Joseph F; Whitney, Cynthia G; Halpin, Alison Sheehan-Laufer; Daley, W Randolph; Pesik, Nicki; Margolis, Gregg S; Tumpey, Abbigail; Tappero, Jordan; Damon, Inger

    2015-03-01

    The U.S. Department of Health and Human Services (HHS), CDC, other U.S. government agencies, the World Health Organization (WHO), and international partners are taking multiple steps to respond to the current Ebola virus disease (Ebola) outbreak in West Africa to reduce its toll there and to reduce the chances of international spread. At the same time, CDC and HHS are working to ensure that persons who have a risk factor for exposure to Ebola and who develop symptoms while in the United States are rapidly identified and isolated, and safely receive treatment. HHS and CDC have actively worked with state and local public health authorities and other partners to accelerate health care preparedness to care for persons under investigation (PUI) for Ebola or with confirmed Ebola. This report describes some of these efforts and their impact. PMID:25742383

  15. Crystal structure of the matrix protein VP40 from Ebola virus.

    PubMed

    Dessen, A; Volchkov, V; Dolnik, O; Klenk, H D; Weissenhorn, W

    2000-08-15

    Ebola virus maturation occurs at the plasma membrane of infected cells and involves the clustering of the viral matrix protein VP40 at the assembly site as well as its interaction with the lipid bilayer. Here we report the X-ray crystal structure of VP40 from Ebola virus at 2.0 A resolution. The crystal structure reveals that Ebola virus VP40 is topologically distinct from all other known viral matrix proteins, consisting of two domains with unique folds, connected by a flexible linker. The C-terminal domain, which is absolutely required for membrane binding, contains large hydrophobic patches that may be involved in the interaction with lipid bilayers. Likewise, a highly basic region is shared between the two domains. The crystal structure reveals how the molecule may be able to switch from a monomeric conformation to a hexameric form, as observed in vitro. Its implications for the assembly process are discussed. PMID:10944105

  16. A screen of approved drugs and molecular probes identifies therapeutics with anti-Ebola virus activity.

    PubMed

    Johansen, Lisa M; DeWald, Lisa Evans; Shoemaker, Charles J; Hoffstrom, Benjamin G; Lear-Rooney, Calli M; Stossel, Andrea; Nelson, Elizabeth; Delos, Sue E; Simmons, James A; Grenier, Jill M; Pierce, Laura T; Pajouhesh, Hassan; Lehár, Joseph; Hensley, Lisa E; Glass, Pamela J; White, Judith M; Olinger, Gene G

    2015-06-01

    Currently, no approved therapeutics exist to treat or prevent infections induced by Ebola viruses, and recent events have demonstrated an urgent need for rapid discovery of new treatments. Repurposing approved drugs for emerging infections remains a critical resource for potential antiviral therapies. We tested ~2600 approved drugs and molecular probes in an in vitro infection assay using the type species, Zaire ebolavirus. Selective antiviral activity was found for 80 U.S. Food and Drug Administration-approved drugs spanning multiple mechanistic classes, including selective estrogen receptor modulators, antihistamines, calcium channel blockers, and antidepressants. Results using an in vivo murine Ebola virus infection model confirmed the protective ability of several drugs, such as bepridil and sertraline. Viral entry assays indicated that most of these antiviral drugs block a late stage of viral entry. By nature of their approved status, these drugs have the potential to be rapidly advanced to clinical settings and used as therapeutic countermeasures for Ebola virus infections. PMID:26041706

  17. Amiodarone and metabolite MDEA inhibit Ebola virus infection by interfering with the viral entry process.

    PubMed

    Salata, Cristiano; Baritussio, Aldo; Munegato, Denis; Calistri, Arianna; Ha, Huy Riem; Bigler, Laurent; Fabris, Fabrizio; Parolin, Cristina; Palù, Giorgio; Mirazimi, Ali

    2015-07-01

    Ebola virus disease (EVD) is one of the most lethal transmissible infections characterized by a high fatality rate, and a treatment has not been developed yet. Recently, it has been shown that cationic amphiphiles, among them the antiarrhythmic drug amiodarone, inhibit filovirus infection. In the present work, we investigated how amiodarone interferes with Ebola virus infection. Wild-type Sudan ebolavirus and recombinant vesicular stomatitis virus, pseudotyped with the Zaire ebolavirus glycoprotein, were used to gain further insight into the ability of amiodarone to affect Ebola virus infection. We show that amiodarone decreases Ebola virus infection at concentrations close to those found in the sera of patients treated for arrhythmias. The drug acts by interfering with the fusion of the viral envelope with the endosomal membrane. We also show that MDEA, the main amiodarone metabolite, contributes to the antiviral activity. Finally, studies with amiodarone analogues indicate that the antiviral activity is correlated with drug ability to accumulate into and interfere with the endocytic pathway. Considering that it is well tolerated, especially in the acute setting, amiodarone appears to deserve consideration for clinical use in EVD. PMID:25933611

  18. Ebola virus disease in a humanitarian aid worker - New York City, October 2014.

    PubMed

    Yacisin, Kari; Balter, Sharon; Fine, Annie; Weiss, Don; Ackelsberg, Joel; Prezant, David; Wilson, Ross; Starr, David; Rakeman, Jennifer; Raphael, Marisa; Quinn, Celia; Toprani, Amita; Clark, Nancy; Link, Nathan; Daskalakis, Demetre; Maybank, Aletha; Layton, Marcelle; Varma, Jay K

    2015-04-01

    In late October 2014, Ebola virus disease (Ebola) was diagnosed in a humanitarian aid worker who recently returned from West Africa to New York City (NYC). The NYC Department of Health and Mental Hygiene (DOHMH) actively monitored three close contacts of the patient and 114 health care personnel. No secondary cases of Ebola were detected. In collaboration with local and state partners, DOHMH had developed protocols to respond to such an event beginning in July 2014. These protocols included safely transporting a person at the first report of symptoms to a local hospital prepared to treat a patient with Ebola, laboratory testing for Ebola, and monitoring of contacts. In response to this single case of Ebola, initial health care worker active monitoring protocols needed modification to improve clarity about what types of exposure should be monitored. The response costs were high in both human resources and money: DOHMH alone spent $4.3 million. However, preparedness activities that include planning and practice in effectively monitoring the health of workers involved in Ebola patient care can help prevent transmission of Ebola. PMID:25837242

  19. Ebola virus disease in health care workers--Sierra Leone, 2014.

    PubMed

    Kilmarx, Peter H; Clarke, Kevin R; Dietz, Patricia M; Hamel, Mary J; Husain, Farah; McFadden, Jevon D; Park, Benjamin J; Sugerman, David E; Bresee, Joseph S; Mermin, Jonathan; McAuley, James; Jambai, Amara

    2014-12-12

    Health care workers (HCWs) are at increased risk for infection in outbreaks of Ebola virus disease (Ebola). To characterize Ebola in HCWs in Sierra Leone and guide prevention efforts, surveillance data from the national Viral Hemorrhagic Fever database were analyzed. In addition, site visits and interviews with HCWs and health facility administrators were conducted. As of October 31, 2014, a total of 199 (5.2%) of the total of 3,854 laboratory-confirmed Ebola cases reported from Sierra Leone were in HCWs, representing a much higher estimated cumulative incidence of confirmed Ebola in HCWs than in non-HCWs, based on national data on the number of HCW. The peak number of confirmed Ebola cases in HCWs was reported in August (65 cases), and the highest number and percentage of confirmed Ebola cases in HCWs was in Kenema District (65 cases, 12.9% of cases in Kenema), mostly from Kenema General Hospital. Confirmed Ebola cases in HCWs continued to be reported through October and were from 12 of 14 districts in Sierra Leone. A broad range of challenges were reported in implementing infection prevention and control measures. In response, the Ministry of Health and Sanitation and partners are developing standard operating procedures for multiple aspects of infection prevention, including patient isolation and safe burials; recruiting and training staff in infection prevention and control; procuring needed commodities and equipment, including personal protective equipment and vehicles for safe transport of Ebola patients and corpses; renovating and constructing Ebola care facilities designed to reduce risk for nosocomial transmission; monitoring and evaluating infection prevention and control practices; and investigating new cases of Ebola in HCWs as sentinel public health events to identify and address ongoing prevention failures. PMID:25503921

  20. Development of RNA aptamers targeting Ebola virus VP35

    PubMed Central

    Binning, Jennifer M.; Wang, Tianjiao; Luthra, Priya; Shabman, Reed S.; Borek, Dominika M.; Liu, Gai; Xu, Wei; Leung, Daisy W.; Basler, Christopher F.; Amarasinghe, Gaya K.

    2014-01-01

    Viral protein 35 (VP35), encoded by filoviruses, are multifunctional dsRNA binding proteins that play important roles in viral replication, innate immune evasion and pathogenesis. The multifunctional nature of these proteins also presents opportunities to develop countermeasures that target distinct functional regions. However, functional validation and the establishment of therapeutic approaches toward such multifunctional proteins, particularly for non-enzymatic targets, are often challenging. Our previous work on filoviral VP35 proteins defined conserved basic residues located within its C-terminal dsRNA binding interferon (IFN) inhibitory domain (IID) as important for VP35 mediated IFN antagonism and viral polymerase co-factor functions. In the current study, we used a combination of structural and functional data to determine regions of Ebola virus (EBOV) VP35 (eVP35) to target for aptamer selection using SELEX. Select aptamers, representing two distinct classes, were further characterized based on their interaction properties to eVP35 IID. These results revealed that the aptamers bind to distinct regions of eVP35 IID with high affinity (10–50 nM) and specificity. These aptamers can compete with dsRNA for binding to eVP35 and disrupt the eVP35-nucleoprotein (NP) interaction. Consistent with the ability to antagonize eVP35-NP interaction, select aptamers can inhibit the function of the EBOV polymerase complex reconstituted by expression of select viral proteins. Taken together, our results support the identification of two aptamers that bind filoviral VP35 proteins with high affinity and specificity and have the capacity to potentially target filoviral VP35 proteins as a therapeutic target. PMID:24067086

  1. Ebola Virus VP40Induced Particle Formation and Association with the Lipid Bilayer

    Microsoft Academic Search

    LUKE D. JASENOSKY; GABRIELE NEUMANN; IGOR LUKASHEVICH; YOSHIHIRO KAWAOKA

    2001-01-01

    Viral protein 40 (VP40) of Ebola virus appears equivalent to matrix proteins of other viruses, yet little is known about its role in the viral life cycle. To elucidate the functions of VP40, we investigated its ability to induce the formation of membrane-bound particles when it was expressed apart from other viral proteins. We found that VP40 is indeed able

  2. Endosomal Proteolysis of the Ebola Virus Glycoprotein Is Necessary for Infection

    Microsoft Academic Search

    Kartik Chandran; Nancy J. Sullivan; Ute Felbor; Sean P. Whelan; James M. Cunningham

    2005-01-01

    Ebola virus (EboV) causes rapidly fatal hemorrhagic fever in humans and there is currently no effective treatment. We found that the infection of African green monkey kidney (Vero) cells by vesicular stomatitis viruses bearing the EboV glycoprotein (GP) requires the activity of endosomal cysteine proteases. Using selective protease inhibitors and protease-deficient cell lines, we identified an essential role for cathepsin

  3. Apoptosis Induced In Vitro and In Vivo During Infection by Ebola and Marburg Viruses

    Microsoft Academic Search

    Thomas W Geisbert; Lisa E Hensley; Tammy R Gibb; Keith E Steele; Nancy K Jaax; Peter B Jahrling

    2000-01-01

    Induction of apoptosis has been documented during infection with a number of different viruses. In this study, we used transmission electron microscopy (TEM) and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling to investigate the effects of Ebola and Marburg viruses on apoptosis of different cell populations during in vitro and in vivo infections. Tissues from 18 filovirus-infected nonhuman primates killed

  4. SCIENCE sciencemag.org 5 SEPTEMBER 2014 VOL 345 ISSUE 6201 1101 he current crisis with the Ebola virus vividly illus-

    E-print Network

    Napp, Nils

    with the Ebola virus vividly illus- trates the priority that must be given to infectious diseases because research on Ebola and the expedited development of a cure; however, recent incidents in biocontain- ment, when it investigated the first outbreaks of Ebola virus in Zaire and Sudan. Nevertheless, its labs

  5. Ebola virus-like particles produced in insect cells exhibit dendritic cell stimulating activity and induce neutralizing antibodies

    SciTech Connect

    Ye Ling [Department of Microbiology and Immunology and Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322 (United States); Lin Jianguo [Department of Microbiology and Immunology and Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322 (United States); Sun Yuliang [Department of Microbiology and Immunology and Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322 (United States); Bennouna, Soumaya [Department of Microbiology and Immunology and Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322 (United States); Department of Pathology, Emory University School of Medicine, Atlanta, GA 30322 (United States); Lo, Michael [Department of Microbiology and Immunology and Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322 (United States); Department of Pathology, Emory University School of Medicine, Atlanta, GA 30322 (United States); Wu Qingyang [Department of Microbiology and Immunology and Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322 (United States); Bu Zhigao [Department of Microbiology and Immunology and Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322 (United States); Pulendran, Bali [Department of Microbiology and Immunology and Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322 (United States); Department of Pathology, Emory University School of Medicine, Atlanta, GA 30322 (United States); Compans, Richard W. [Department of Microbiology and Immunology and Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322 (United States)]. E-mail: compans@microbio.emory.edu; Yang Chinglai [Department of Microbiology and Immunology and Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322 (United States)]. E-mail: chyang@emory.edu

    2006-08-01

    Recombinant baculoviruses (rBV) expressing Ebola virus VP40 (rBV-VP40) or GP (rBV-GP) proteins were generated. Infection of Sf9 insect cells by rBV-VP40 led to assembly and budding of filamentous particles from the cell surface as shown by electron microscopy. Ebola virus-like particles (VLPs) were produced by coinfection of Sf9 cells with rBV-VP40 and rBV-GP, and incorporation of Ebola GP into VLPs was demonstrated by SDS-PAGE and Western blot analysis. Recombinant baculovirus infection of insect cells yielded high levels of VLPs, which were shown to stimulate cytokine secretion from human dendritic cells similar to VLPs produced in mammalian cells. The immunogenicity of Ebola VLPs produced in insect cells was evaluated by immunization of mice. Analysis of antibody responses showed that most of the GP-specific antibodies were of the IgG2a subtype, while no significant level of IgG1 subtype antibodies specific for GP was induced, indicating the induction of a Th1-biased immune response. Furthermore, sera from Ebola VLP immunized mice were able to block infection by Ebola GP pseudotyped HIV virus in a single round infection assay, indicating that a neutralizing antibody against the Ebola GP protein was induced. These results show that production of Ebola VLPs in insect cells using recombinant baculoviruses represents a promising approach for vaccine development against Ebola virus infection.

  6. The Virion Glycoproteins of Ebola Viruses are Encoded in Two Reading Frames and are Expressed through Transcriptional Editing

    Microsoft Academic Search

    Anthony Sanchez; Sam G. Trappier; Brian W. J. Mahy; Clarence J. Peters; Stuart T. Nichol

    1996-01-01

    In late 1994 and early 1995, Ebola (EBO) virus dramatically reemerged in Africa, causing human disease in the Ivory Coast and Zaire. Analysis of the entire glycoprotein genes of these viruses and those of other EBO virus subtypes has shown that the virion glycoprotein (130 kDa) is encoded in two reading frames, which are linked by transcriptional editing. This editing

  7. Activation of Triggering Receptor Expressed on Myeloid Cells1 on Human Neutrophils by Marburg and Ebola Viruses

    Microsoft Academic Search

    Mansour Mohamadzadeh; Sadie S. Coberley; Gene G. Olinger; Warren V. Kalina; Gordon Ruthel; Claudette L. Fuller; Dana L. Swenson; William D. Pratt; Douglas B. Kuhns; Alan L. Schmaljohn

    2006-01-01

    Marburg virus (MARV) and Ebola virus (EBOV), members of the viral family Filoviridae, cause fatal hemorrhagic fevers in humans and nonhuman primates. High viral burden is coincident with inadequate adaptive immune responses and robust inflammatory responses, and virus-mediated dysregulation of early host defenses has been proposed. Recently, a novel class of innate receptors called the triggering receptors expressed in myeloid

  8. Inhibition of Ebola virus glycoprotein-mediated cytotoxicity by targeting its transmembrane domain and cholesterol.

    PubMed

    Hacke, Moritz; Björkholm, Patrik; Hellwig, Andrea; Himmels, Patricia; de Almodóvar, Carmen Ruiz; Brügger, Britta; Wieland, Felix; Ernst, Andreas M

    2015-01-01

    The high pathogenicity of the Ebola virus reflects multiple concurrent processes on infection. Among other important determinants, Ebola fusogenic glycoprotein (GP) has been associated with the detachment of infected cells and eventually leads to vascular leakage and haemorrhagic fever. Here we report that the membrane-anchored GP is sufficient to induce the detachment of adherent cells. The results show that the detachment induced through either full-length GP1,2 or the subunit GP2 depends on cholesterol and the structure of the transmembrane domain. These data reveal a novel molecular mechanism in which GP regulates Ebola virus assembly and suggest that cholesterol-reducing agents could be useful as therapeutics to counteract GP-mediated cell detachment. PMID:26158910

  9. Lipid nanoparticle siRNA treatment of Ebola-virus-Makona-infected nonhuman primates.

    PubMed

    Thi, Emily P; Mire, Chad E; Lee, Amy C H; Geisbert, Joan B; Zhou, Joy Z; Agans, Krystle N; Snead, Nicholas M; Deer, Daniel J; Barnard, Trisha R; Fenton, Karla A; MacLachlan, Ian; Geisbert, Thomas W

    2015-05-21

    The current outbreak of Ebola virus in West Africa is unprecedented, causing more cases and fatalities than all previous outbreaks combined, and has yet to be controlled. Several post-exposure interventions have been employed under compassionate use to treat patients repatriated to Europe and the United States. However, the in vivo efficacy of these interventions against the new outbreak strain of Ebola virus is unknown. Here we show that lipid-nanoparticle-encapsulated short interfering RNAs (siRNAs) rapidly adapted to target the Makona outbreak strain of Ebola virus are able to protect 100% of rhesus monkeys against lethal challenge when treatment was initiated at 3 days after exposure while animals were viraemic and clinically ill. Although all infected animals showed evidence of advanced disease including abnormal haematology, blood chemistry and coagulopathy, siRNA-treated animals had milder clinical features and fully recovered, while the untreated control animals succumbed to the disease. These results represent the first, to our knowledge, successful demonstration of therapeutic anti-Ebola virus efficacy against the new outbreak strain in nonhuman primates and highlight the rapid development of lipid-nanoparticle-delivered siRNA as a countermeasure against this highly lethal human disease. PMID:25901685

  10. Ebola Virus Glycoproteins Induce Global Surface Protein Down-Modulation and Loss of Cell Adherence

    Microsoft Academic Search

    Graham Simmons; Rouven J. Wool-Lewis; Frédéric Baribaud; Robert C. Netter; Paul Bates

    2002-01-01

    The Ebola virus envelope glycoprotein (GP) derived from the pathogenic Zaire subtype mediates cell rounding and detachment from the extracellular matrix in 293T cells. In this study we provide evidence that GPs from the other pathogenic subtypes, Sudan and Côte d'Ivoire, as well as from Reston, a strain thought to be nonpathogenic in humans, also induced cell rounding, albeit at

  11. Comparison of individual and combination DNA vaccines for B. anthracis, Ebola virus, Marburg virus and Venezuelan equine encephalitis virus.

    PubMed

    Riemenschneider, Jenny; Garrison, Aura; Geisbert, Joan; Jahrling, Peter; Hevey, Michael; Negley, Diane; Schmaljohn, Alan; Lee, John; Hart, Mary Kate; Vanderzanden, Lorna; Custer, David; Bray, Mike; Ruff, Albert; Ivins, Bruce; Bassett, Anthony; Rossi, Cynthia; Schmaljohn, Connie

    2003-09-01

    Multiagent DNA vaccines for highly pathogenic organisms offer an attractive approach for preventing naturally occurring or deliberately introduced diseases. Few animal studies have compared the feasibility of combining unrelated gene vaccines. Here, we demonstrate that DNA vaccines to four dissimilar pathogens that are known biowarfare agents, Bacillus anthracis, Ebola (EBOV), Marburg (MARV), and Venezuelan equine encephalitis virus (VEEV), can elicit protective immunity in relevant animal models. In addition, a combination of all four vaccines is shown to be equally as effective as the individual vaccines for eliciting immune responses in a single animal species. These results demonstrate for the first time the potential of combined DNA vaccines for these agents and point to a possible method of rapid development of multiagent vaccines for disparate pathogens such as those that might be encountered in a biological attack. PMID:12922144

  12. Evaluation of the Potential Impact of Ebola Virus Genomic Drift on the Efficacy of Sequence-Based Candidate Therapeutics

    E-print Network

    Kugelman, Jeffrey R.

    Until recently, Ebola virus (EBOV) was a rarely encountered human pathogen that caused disease among small populations with extraordinarily high lethality. At the end of 2013, EBOV initiated an unprecedented disease outbreak ...

  13. Requirements for cell rounding and surface protein down-regulation by Ebola virus glycoprotein.

    PubMed

    Francica, Joseph R; Matukonis, Meghan K; Bates, Paul

    2009-01-20

    Ebola virus causes an acute hemorrhagic fever that is associated with high morbidity and mortality. The viral glycoprotein is thought to contribute to pathogenesis, though precise mechanisms are unknown. Cellular pathogenesis can be modeled in vitro by expression of the Ebola viral glycoprotein (GP) in cells, which causes dramatic morphological changes, including cell rounding and surface protein down-regulation. These effects are known to be dependent on the presence of a highly glycosylated region of the glycoprotein, the mucin domain. Here we show that the mucin domain from the highly pathogenic Zaire subtype of Ebola virus is sufficient to cause characteristic cytopathology when expressed in the context of a foreign glycoprotein. Similarly to full length Ebola GP, expression of the mucin domain causes rounding, detachment from the extracellular matrix, and the down-regulation of cell surface levels of beta1 integrin and major histocompatibility complex class 1. These effects were not seen when the mucin domain was expressed in the context of a glycophosphatidylinositol-anchored isoform of the foreign glycoprotein. In contrast to earlier analysis of full length Ebola glycoproteins, chimeras carrying the mucin domains from the Zaire and Reston strains appear to cause similar levels of down-modulation and cell detachment. Cytopathology associated with Ebola glycoprotein expression does not occur when GP expression is restricted to the endoplasmic reticulum. In contrast to a previously published report, our results demonstrate that GP-induced surface protein down-regulation is not mediated through a dynamin-dependent pathway. Overall, these results support a model in which the mucin domain of Ebola GP acts at the cell surface to induce protein down modulation and cytopathic effects. PMID:19013626

  14. Infectious Disease Physician Assessment of Hospital Preparedness for Ebola Virus Disease.

    PubMed

    Polgreen, Philip M; Santibanez, Scott; Koonin, Lisa M; Rupp, Mark E; Beekmann, Susan E; Del Rio, Carlos

    2015-09-01

    Background. ?The first case of Ebola diagnosed in the United States and subsequent cases among 2 healthcare workers caring for that patient highlighted the importance of hospital preparedness in caring for Ebola patients. Methods. ?From October 21, 2014 to November 11, 2014, infectious disease physicians who are part of the Emerging Infections Network (EIN) were surveyed about current Ebola preparedness at their institutions. Results. ?Of 1566 EIN physician members, 869 (55.5%) responded to this survey. Almost all institutions represented in this survey showed a substantial degree of preparation for the management of patients with suspected and confirmed Ebola virus disease. Despite concerns regarding shortages of personal protective equipment, approximately two thirds of all respondents reported that their facilities had sufficient and ready availability of hoods, full body coveralls, and fluid-resistant or impermeable aprons. The majority of respondents indicated preference for transfer of Ebola patients to specialized treatment centers rather than caring for them locally. In general, we found that larger hospitals and teaching hospitals reported higher levels of preparedness. Conclusions. ?Prior to the Centers for Disease Control and Prevention's plan for a tiered approach that identified specific roles for frontline, assessment, and designated treatment facilities, our query of infectious disease physicians suggested that healthcare facilities across the United States were making preparations for screening, diagnosis, and treatment of Ebola patients. Nevertheless, respondents from some hospitals indicated that they were relatively unprepared. PMID:26180836

  15. Infectious Disease Physician Assessment of Hospital Preparedness for Ebola Virus Disease

    PubMed Central

    Polgreen, Philip M.; Santibanez, Scott; Koonin, Lisa M.; Rupp, Mark E.; Beekmann, Susan E.; del Rio, Carlos

    2015-01-01

    Background.?The first case of Ebola diagnosed in the United States and subsequent cases among 2 healthcare workers caring for that patient highlighted the importance of hospital preparedness in caring for Ebola patients. Methods.?From October 21, 2014 to November 11, 2014, infectious disease physicians who are part of the Emerging Infections Network (EIN) were surveyed about current Ebola preparedness at their institutions. Results.?Of 1566 EIN physician members, 869 (55.5%) responded to this survey. Almost all institutions represented in this survey showed a substantial degree of preparation for the management of patients with suspected and confirmed Ebola virus disease. Despite concerns regarding shortages of personal protective equipment, approximately two thirds of all respondents reported that their facilities had sufficient and ready availability of hoods, full body coveralls, and fluid-resistant or impermeable aprons. The majority of respondents indicated preference for transfer of Ebola patients to specialized treatment centers rather than caring for them locally. In general, we found that larger hospitals and teaching hospitals reported higher levels of preparedness. Conclusions.?Prior to the Centers for Disease Control and Prevention's plan for a tiered approach that identified specific roles for frontline, assessment, and designated treatment facilities, our query of infectious disease physicians suggested that healthcare facilities across the United States were making preparations for screening, diagnosis, and treatment of Ebola patients. Nevertheless, respondents from some hospitals indicated that they were relatively unprepared. PMID:26180836

  16. C-Type Lectins DC-SIGN and L-SIGN Mediate Cellular Entry by Ebola Virus in cis and in trans

    Microsoft Academic Search

    Carmen P. Alvarez; Fátima Lasala; Jaime Carrillo; O. Muniz; A. L. Corbi; Rafael Delgado

    2002-01-01

    Ebola virus is a highly lethal pathogen responsible for several outbreaks of hemorrhagic fever. Here we show that the primate lentiviral binding C-type lectins DC-SIGN and L-SIGN act as cofactors for cellular entry by Ebola virus. Furthermore, DC-SIGN on the surface of dendritic cells is able to function as a trans receptor, binding Ebola virus-pseudotyped lentiviral particles and transmitting infection

  17. Cluster of Ebola Virus Disease, Bong and Montserrado Counties, Liberia

    PubMed Central

    Nyenswah, Tolbert G.; Fallah, Mosaka; Calvert, Geoffrey M.; Duwor, Stanley; Hamilton, E. Dutch; Mokashi, Vishwesh; Arzoaquoi, Sampson; Dweh, Emmanuel; Burbach, Ryan; Dlouhy, Diane; Oeltmann, John E.

    2015-01-01

    Lack of trust in government-supported services after the death of a health care worker with symptoms of Ebola resulted in ongoing Ebola transmission in 2 Liberia counties. Ebola transmission was facilitated by attempts to avoid cremation of the deceased patient and delays in identifying and monitoring contacts. PMID:26079309

  18. Cluster of Ebola Virus Disease, Bong and Montserrado Counties, Liberia.

    PubMed

    Nyenswah, Tolbert G; Fallah, Mosaka; Calvert, Geoffrey M; Duwor, Stanley; Hamilton, E Dutch; Mokashi, Vishwesh; Arzoaquoi, Sampson; Dweh, Emmanuel; Burbach, Ryan; Dlouhy, Diane; Oeltmann, John E; Moonan, Patrick K

    2015-07-01

    Lack of trust in government-supported services after the death of a health care worker with symptoms of Ebola resulted in ongoing Ebola transmission in 2 Liberia counties. Ebola transmission was facilitated by attempts to avoid cremation of the deceased patient and delays in identifying and monitoring contacts. PMID:26079309

  19. Mapping of conserved and species-specific antibody epitopes on the Ebola virus nucleoprotein

    PubMed Central

    Changula, Katendi; Yoshida, Reiko; Noyori, Osamu; Marzi, Andrea; Miyamoto, Hiroko; Ishijima, Mari; Yokoyama, Ayaka; Kajihara, Masahiro; Feldmann, Heinz; Mweene, Aaron S.; Takada, Ayato

    2013-01-01

    Filoviruses (viruses in the genus Ebolavirus and Marburgvirus in the family Filoviridae) cause severe haemorrhagic fever in humans and nonhuman primates. Rapid, highly sensitive, and reliable filovirus-specific assays are required for diagnostics and outbreak control. Characterisation of antigenic sites in viral proteins can aid in the development of viral antigen detection assays such immunochromatography-based rapid diagnosis. We generated a panel of mouse monoclonal antibodies (mAbs) to the nucleoprotein (NP) of Ebola virus belonging to the species Zaire ebolavirus. The mAbs were divided into seven groups based on the profiles of their specificity and cross-reactivity to other species in the Ebolavirus genus. Using synthetic peptides corresponding to the Ebola virus NP sequence, the mAb binding sites were mapped to seven antigenic regions in the C-terminal half of the NP, including two highly conserved regions among all five Ebolavirus species currently known. Furthermore, we successfully produced species-specific rabbit antisera to synthetic peptides predicted to represent unique filovirus B-cell epitopes. Our data provide useful information for the development of Ebola virus antigen detection assays. PMID:23702199

  20. Mapping of conserved and species-specific antibody epitopes on the Ebola virus nucleoprotein.

    PubMed

    Changula, Katendi; Yoshida, Reiko; Noyori, Osamu; Marzi, Andrea; Miyamoto, Hiroko; Ishijima, Mari; Yokoyama, Ayaka; Kajihara, Masahiro; Feldmann, Heinz; Mweene, Aaron S; Takada, Ayato

    2013-09-01

    Filoviruses (viruses in the genus Ebolavirus and Marburgvirus in the family Filoviridae) cause severe haemorrhagic fever in humans and nonhuman primates. Rapid, highly sensitive, and reliable filovirus-specific assays are required for diagnostics and outbreak control. Characterisation of antigenic sites in viral proteins can aid in the development of viral antigen detection assays such immunochromatography-based rapid diagnosis. We generated a panel of mouse monoclonal antibodies (mAbs) to the nucleoprotein (NP) of Ebola virus belonging to the species Zaire ebolavirus. The mAbs were divided into seven groups based on the profiles of their specificity and cross-reactivity to other species in the Ebolavirus genus. Using synthetic peptides corresponding to the Ebola virus NP sequence, the mAb binding sites were mapped to seven antigenic regions in the C-terminal half of the NP, including two highly conserved regions among all five Ebolavirus species currently known. Furthermore, we successfully produced species-specific rabbit antisera to synthetic peptides predicted to represent unique filovirus B-cell epitopes. Our data provide useful information for the development of Ebola virus antigen detection assays. PMID:23702199

  1. FDA-Approved Selective Estrogen Receptor Modulators Inhibit Ebola Virus Infection

    PubMed Central

    Johansen, Lisa M.; Brannan, Jennifer M.; Delos, Sue E.; Shoemaker, Charles J.; Stossel, Andrea; Lear, Calli; Hoffstrom, Benjamin G.; DeWald, Lisa Evans; Schornberg, Kathryn L.; Scully, Corinne; Lehár, Joseph; Hensley, Lisa E.; White, Judith M.; Olinger, Gene G.

    2014-01-01

    Ebola viruses remain a substantial threat to both civilian and military populations as bioweapons, during sporadic outbreaks, and from the possibility of accidental importation from endemic regions by infected individuals. Currently, no approved therapeutics exist to treat or prevent infection by Ebola viruses. Therefore, we performed an in vitro screen of Food and Drug Administration (FDA)– and ex–US-approved drugs and selected molecular probes to identify drugs with antiviral activity against the type species Zaire ebolavirus (EBOV). From this screen, we identified a set of selective estrogen receptor modulators (SERMs), including clomiphene and toremifene, which act as potent inhibitors of EBOV infection. Anti-EBOV activity was confirmed for both of these SERMs in an in vivo mouse infection model. This anti-EBOV activity occurred even in the absence of detectable estrogen receptor expression, and both SERMs inhibited virus entry after internalization, suggesting that clomiphene and toremifene are not working through classical pathways associated with the estrogen receptor. Instead, the response appeared to be an off-target effect where the compounds interfere with a step late in viral entry and likely affect the triggering of fusion. These data support the screening of readily available approved drugs to identify therapeutics for the Ebola viruses and other infectious diseases. The SERM compounds described in this report are an immediately actionable class of approved drugs that can be repurposed for treatment of filovirus infections. PMID:23785035

  2. Ebola Hemorrhagic Fever: Transmission

    MedlinePLUS

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  3. Ebola Hemorrhagic Fever: Diagnosis

    MedlinePLUS

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  4. Ebola Hemorrhagic Fever: Treatment

    MedlinePLUS

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  5. Ebola Hemorrhagic Fever: Prevention

    MedlinePLUS

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  6. ISCB Ebola Award for Important Future Research on the Computational Biology of Ebola Virus

    E-print Network

    Karp, Peter D.

    Speed is of the essence in combating Ebola; thus, computational approaches should form a significant component of Ebola research. As for the development of any modern drug, computational biology is uniquely positioned to ...

  7. Physicochemical inactivation of Lassa, Ebola, and Marburg viruses and effect on clinical laboratory analyses

    SciTech Connect

    Mitchell, S.W.; McCormick, J.B.

    1984-09-01

    Clinical specimens from patients infected with Lassa, Ebola, or Marburg virus may present a serious biohazard to laboratory workers. The authors have examined the effects of heat, alteration of pH, and gamma radiation on these viruses in human blood and on the electrolytes, enzymes, and coagulation factors measured in laboratory tests that are important in the care of an infected patient. Heating serum at 60 degrees C for 1 h reduced high titers of these viruses to noninfectious levels without altering the serum levels of glucose, blood urea nitrogen, and electrolytes. Dilution of blood in 3% acetic acid, diluent for a leukocyte count, inactivated all of these viruses. All of the methods tested for viral inactivation markedly altered certain serum proteins, making these methods unsuitable for samples that are to be tested for certain enzyme levels and coagulation factors.

  8. Laboratory support during and after the Ebola virus endgame: towards a sustained laboratory infrastructure.

    PubMed

    Goodfellow, I; Reusken, C; Koopmans, M

    2015-01-01

    The Ebola virus epidemic in West Africa is on the brink of entering a second phase in which the (inter)national efforts to slow down virus transmission will be engaged to end the epidemic. The response community must consider the longevity of their current laboratory support, as it is essential that diagnostic capacity in the affected countries be supported beyond the end of the epidemic. The emergency laboratory response should be used to support building structural diagnostic and outbreak surveillance capacity. PMID:25846492

  9. Inhibition of IRF-3 Activation by VP35 Is Critical for the High Level of Virulence of Ebola Virus

    Microsoft Academic Search

    Amy L. Hartman; Brian H. Bird; Jonathan S. Towner; Zoi-Anna Antoniadou; Sherif R. Zaki; Stuart T. Nichol

    2008-01-01

    Zaire ebolavirus causes a rapidly progressing hemorrhagic disease with high mortality. Identification of the viral virulence factors that contribute to the severity of disease induced by Ebola virus is critical for the design of therapeutics and vaccines against the disease. Given the rapidity of disease progression, virus interaction with the innate immune system early in the course of infection likely

  10. Effects of Ebola Virus Glycoproteins on Endothelial Cell Activation and Barrier Function

    Microsoft Academic Search

    Victoria M. Wahl-Jensen; Tatiana A. Afanasieva; Jochen Seebach; Ute Stroher; Heinz Feldmann; Hans-Joachim Schnittler

    2005-01-01

    Ebola virus causes severe hemorrhagic fever with high mortality rates in humans and nonhuman primates. Vascular instability and dysregulation are disease-decisive symptoms during severe infection. While the transmembrane glycoprotein GP1,2 has been shown to cause endothelial cell destruction, the role of the soluble glycoproteins in pathogenesis is largely unknown; however, they are hypothesized to be of biological relevance in terms

  11. Biochemical Analysis of the Secreted and Virion Glycoproteins of Ebola Virus

    Microsoft Academic Search

    ANTHONY SANCHEZ; ZHI-YONG YANG; LING XU; GARY J. NABEL; TAMARA CREWS

    1998-01-01

    The glycoproteins expressed by a Zaire species of Ebola virus were analyzed for cleavage, oligomerization, and other structural properties to better define their functions. The 50- to 70-kDa secreted and 150-kDa virion\\/structural glycoproteins (SGP and GP, respectively), which share the 295 N-terminal residues, are cleaved near the N terminus by signalase. A second cleavage event, occurring in GP at a

  12. Crystal Structure of the Ebola Virus Membrane Fusion Subunit, GP2, from the Envelope Glycoprotein Ectodomain

    Microsoft Academic Search

    Winfried Weissenhorn; Andrea Carfí; Kon-Ho Lee; John J. Skehel; Don C. Wiley

    1998-01-01

    We have determined the structure of GP2 from the Ebola virus membrane fusion glycoprotein by X-ray crystallography. The molecule contains a central triple-stranded coiled coil followed by a disulfide-bonded loop homologous to an immunosuppressive sequence in retroviral glycoproteins, which reverses the chain direction and connects to an ? helix packed antiparallel to the core helices. The structure suggests that fusion

  13. Isolation and partial characterisation of a new strain of Ebola virus

    Microsoft Academic Search

    B. Le Guenno; P Formentry; M. Wyers; P. Gounon; F. Walker; C. Boesch

    1995-01-01

    We have isolated a new strain of Ebola virus from a non-fatal human case infected during the autopsy of a wild chimpanzee in the Cote-d'Ivoire. The wild troop to which this animal belonged has been decimated by outbreaks of haemorrhagic syndromes. This is the first time that a human infection has been connected to naturally-infected monkeys in Africa. Data from

  14. Endoproteolytic Processing of the Ebola Virus Envelope Glycoprotein: Cleavage Is Not Required for Function

    Microsoft Academic Search

    ROUVEN J. WOOL-LEWIS; PAUL BATES

    1999-01-01

    Proteolytic processing is required for the activation of numerous viral glycoproteins. Here we show that the envelope glycoprotein from the Zaire strain of Ebola virus (Ebo-GP) is proteolytically processed into two subunits, GP1 and GP2, that are likely covalently associated through a disulfide linkage. Murine leukemia virions pseudotyped with Ebo-GP contain almost exclusively processed glycoprotein, indicating that this is the

  15. Ebola Virus VP24 Binds Karyopherin  1 and Blocks STAT1 Nuclear Accumulation

    Microsoft Academic Search

    St. P. Reid; Lawrence W. Leung; Amy L. Hartman; Osvaldo Martinez; Megan L. Shaw; Caroline Carbonnelle; Viktor E. Volchkov; Stuart T. Nichol; Christopher F. Basler

    2006-01-01

    Ebola virus (EBOV) infection blocks cellular production of alpha\\/beta interferon (IFN-\\/) and the ability of cells to respond to IFN-\\/ or IFN-. The EBOV VP35 protein has previously been identified as an EBOV-encoded inhibitor of IFN-\\/ production. However, the mechanism by which EBOV infection inhibits responses to IFNs has not previously been defined. Here we demonstrate that the EBOV VP24

  16. Emerging targets and novel approaches to Ebola virus prophylaxis and treatment.

    PubMed

    Choi, Jin Huk; Croyle, Maria A

    2013-12-01

    Ebola is a highly virulent pathogen causing severe hemorrhagic fever with a high case fatality rate in humans and non-human primates (NHPs). Although safe and effective vaccines or other medicinal agents to block Ebola infection are currently unavailable, a significant effort has been put forth to identify several promising candidates for the treatment and prevention of Ebola hemorrhagic fever. Among these, recombinant adenovirus-based vectors have been identified as potent vaccine candidates, with some affording both pre- and post-exposure protection from the virus. Recently, Investigational New Drug (IND) applications have been approved by the US Food and Drug Administration (FDA) and phase I clinical trials have been initiated for two small-molecule therapeutics: anti-sense phosphorodiamidate morpholino oligomers (PMOs: AVI-6002, AVI-6003) and lipid nanoparticle/small interfering RNA (LNP/siRNA: TKM-Ebola). These potential alternatives to vector-based vaccines require multiple doses to achieve therapeutic efficacy, which is not ideal with regard to patient compliance and outbreak scenarios. These concerns have fueled a quest for even better vaccination and treatment strategies. Here, we summarize recent advances in vaccines or post-exposure therapeutics for prevention of Ebola hemorrhagic fever. The utility of novel pharmaceutical approaches to refine and overcome barriers associated with the most promising therapeutic platforms are also discussed. PMID:23813435

  17. Molecular docking based screening of predicted potential inhibitors for VP40 from Ebola virus

    PubMed Central

    Abazari, Danya; Moghtadaei, Mehrad; Behvarmanesh, Ali; Ghannadi, Bahareh; Aghaei, Monireh; Behruznia, Mahboobeh; Rigi, Garshasb

    2015-01-01

    Ebola virus is a member of Filoviridae and cause severe human disease with 90 percent mortality. The life cycle of Ebola contains an assembly stage which is mediated by VP40 proteins. VP40 subunits oligomerize and form ring-structures which are either octamers or hexamers. Prevention of VP40 matrix protein assembly prevents virus particle formation as well as virus budding. In the present study we simulated the biological condition for a single VP40 subunit. Then a library containing 120.000 drugs like chemicals was used as the virtual screening database. Top 10 successive hits were then analyzed regarding absorption, distribution, metabolism, and excretion properties. Moreover probable accessorial human protein targets and toxicity properties of successive hits were analyzed by in silico tools. We found 4 chemicals that could bind VP40 subunits in a manner that by making an interfering steric condense prevents matrix protein oligomerization. The pharmacokinetic and toxicity studies also validated the potential of 4 finlay successive hits to be considered as a new anti-Ebola drugs.

  18. Ebola

    MedlinePLUS

    Ebola hemorrhagic fever is caused by a virus. It is a severe and often fatal disease. It can affect humans and ... after exposure to the virus. Symptoms usually include Fever Headache Joint and muscle aches Weakness Diarrhea Vomiting ...

  19. Identification of 53 compounds that block Ebola virus-like particle entry via a repurposing screen of approved drugs

    PubMed Central

    Kouznetsova, Jennifer; Sun, Wei; Martínez-Romero, Carles; Tawa, Gregory; Shinn, Paul; Chen, Catherine Z; Schimmer, Aaron; Sanderson, Philip; McKew, John C; Zheng, Wei; García-Sastre, Adolfo

    2014-01-01

    In light of the current outbreak of Ebola virus disease, there is an urgent need to develop effective therapeutics to treat Ebola infection, and drug repurposing screening is a potentially rapid approach for identifying such therapeutics. We developed a biosafety level 2 (BSL-2) 1536-well plate assay to screen for entry inhibitors of Ebola virus-like particles (VLPs) containing the glycoprotein (GP) and the matrix VP40 protein fused to a beta-lactamase reporter protein and applied this assay for a rapid drug repurposing screen of Food and Drug Administration (FDA)-approved drugs. We report here the identification of 53 drugs with activity of blocking Ebola VLP entry into cells. These 53 active compounds can be divided into categories including microtubule inhibitors, estrogen receptor modulators, antihistamines, antipsychotics, pump/channel antagonists, and anticancer/antibiotics. Several of these compounds, including microtubule inhibitors and estrogen receptor modulators, had previously been reported to be active in BSL-4 infectious Ebola virus replication assays and in animal model studies. Our assay represents a robust, effective and rapid high-throughput screen for the identification of lead compounds in drug development for the treatment of Ebola virus infection. PMID:26038505

  20. Understanding the emergence of ebola virus disease in sierra leone: stalking the virus in the threatening wake of emergence.

    PubMed

    Wauquier, Nadia; Bangura, James; Moses, Lina; Humarr Khan, Sheik; Coomber, Moinya; Lungay, Victor; Gbakie, Michael; Sesay, Mohammed S K; Gassama, Ibrahim A K; Massally, James L B; Gbakima, Aiah; Squire, James; Lamin, Mohamed; Kanneh, Lansana; Yillah, Mohammed; Kargbo, Kandeh; Roberts, Willie; Vandi, Mohammed; Kargbo, David; Vincent, Tom; Jambai, Amara; Guttieri, Mary; Fair, Joseph; Souris, Marc; Gonzalez, Jean Paul

    2015-01-01

    Since Ebola Virus Disease (EVD) was first identified in 1976 in what is now the Democratic Republic of Congo, and despite the numerous outbreaks recorded to date, rarely has an epidemic origin been identified. Indeed, among the twenty-one most documented EVD outbreaks in Africa, an index case has been identified four times, and hypothesized in only two other instances. The initial steps of emergence and spread of a virus are critical in the development of a potential outbreak and need to be thoroughly dissected and understood in order to improve on preventative strategies. In the current West African outbreak of EVD, a unique index case has been identified, pinpointing the geographical origin of the epidemic in Guinea. Herein, we provide an accounting of events that serve as the footprint of EVD emergence in Sierra Leone and a road map for risk mitigation fueled by lessons learned. PMID:25969797

  1. Understanding the Emergence of Ebola Virus Disease in Sierra Leone: Stalking the Virus in the Threatening Wake of Emergence

    PubMed Central

    Wauquier, Nadia; Bangura, James; Moses, Lina; Humarr Khan, Sheik; Coomber, Moinya; Lungay, Victor; Gbakie, Michael; Sesay, Mohammed S.K.; Gassama, Ibrahim A.K.; Massally, James L.B.; Gbakima, Aiah; Squire, James; Lamin, Mohamed; Kanneh, Lansana; Yillah, Mohammed; Kargbo, Kandeh; Roberts, Willie; Vandi, Mohammed; Kargbo, David; Vincent, Tom; Jambai, Amara; Guttieri, Mary; Fair, Joseph; Souris, Marc; Gonzalez, Jean Paul

    2015-01-01

    Since Ebola Virus Disease (EVD) was first identified in 1976 in what is now the Democratic Republic of Congo, and despite the numerous outbreaks recorded to date, rarely has an epidemic origin been identified. Indeed, among the twenty-one most documented EVD outbreaks in Africa, an index case has been identified four times, and hypothesized in only two other instances. The initial steps of emergence and spread of a virus are critical in the development of a potential outbreak and need to be thoroughly dissected and understood in order to improve on preventative strategies. In the current West African outbreak of EVD, a unique index case has been identified, pinpointing the geographical origin of the epidemic in Guinea. Herein, we provide an accounting of events that serve as the footprint of EVD emergence in Sierra Leone and a road map for risk mitigation fueled by lessons learned. PMID:25969797

  2. Structures of protective antibodies reveal sites of vulnerability on Ebola virus

    PubMed Central

    Murin, Charles D.; Fusco, Marnie L.; Bornholdt, Zachary A.; Qiu, Xiangguo; Olinger, Gene G.; Zeitlin, Larry; Kobinger, Gary P.; Ward, Andrew B.; Saphire, Erica Ollmann

    2014-01-01

    Ebola virus (EBOV) and related filoviruses cause severe hemorrhagic fever, with up to 90% lethality, and no treatments are approved for human use. Multiple recent outbreaks of EBOV and the likelihood of future human exposure highlight the need for pre- and postexposure treatments. Monoclonal antibody (mAb) cocktails are particularly attractive candidates due to their proven postexposure efficacy in nonhuman primate models of EBOV infection. Two candidate cocktails, MB-003 and ZMAb, have been extensively evaluated in both in vitro and in vivo studies. Recently, these two therapeutics have been combined into a new cocktail named ZMapp, which showed increased efficacy and has been given compassionately to some human patients. Epitope information and mechanism of action are currently unknown for most of the component mAbs. Here we provide single-particle EM reconstructions of every mAb in the ZMapp cocktail, as well as additional antibodies from MB-003 and ZMAb. Our results illuminate key and recurring sites of vulnerability on the EBOV glycoprotein and provide a structural rationale for the efficacy of ZMapp. Interestingly, two of its components recognize overlapping epitopes and compete with each other for binding. Going forward, this work now provides a basis for strategic selection of next-generation antibody cocktails against Ebola and related viruses and a model for predicting the impact of ZMapp on potential escape mutations in ongoing or future Ebola outbreaks. PMID:25404321

  3. The cyanobacterial lectin scytovirin displays potent in vitro and in vivo activity against Zaire Ebola virus.

    PubMed

    Garrison, Aura R; Giomarelli, Barbara G; Lear-Rooney, Calli M; Saucedo, Carrie J; Yellayi, Srikanth; Krumpe, Lauren R H; Rose, Maura; Paragas, Jason; Bray, Mike; Olinger, Gene G; McMahon, James B; Huggins, John; O'Keefe, Barry R

    2014-12-01

    The cyanobacterial lectin scytovirin (SVN) binds with high affinity to mannose-rich oligosaccharides on the envelope glycoprotein (GP) of a number of viruses, blocking entry into target cells. In this study, we assessed the ability of SVN to bind to the envelope GP of Zaire Ebola virus (ZEBOV) and inhibit its replication. SVN interacted specifically with the protein's mucin-rich domain. In cell culture, it inhibited ZEBOV replication with a 50% virus-inhibitory concentration (EC50) of 50 nM, and was also active against the Angola strain of the related Marburg virus (MARV), with a similar EC50. Injected subcutaneously in mice, SVN reached a peak plasma level of 100 nm in 45 min, but was cleared within 4h. When ZEBOV-infected mice were given 30 mg/kg/day of SVN by subcutaneous injection every 6h, beginning the day before virus challenge, 9 of 10 animals survived the infection, while all infected, untreated mice died. When treatment was begun one hour or one day after challenge, 70-90% of mice survived. Quantitation of infectious virus and viral RNA in samples of serum, liver and spleen collected on days 2 and 5 postinfection showed a trend toward lower titers in treated than control mice, with a significant decrease in liver titers on day 2. Our findings provide further evidence of the potential of natural lectins as therapeutic agents for viral infections. PMID:25265598

  4. Structural and Functional Characterization of Reston Ebola Virus VP35 Interferon Inhibitory Domain

    SciTech Connect

    Leung, Daisy W.; Shabman, Reed S.; Farahbakhsh, Mina; Prins, Kathleen C.; Borek, Dominika M.; Wang, Tianjiao; Mühlberger, Elke; Basler, Christopher F.; Amarasinghe, Gaya K. (Sinai); (BU-M); (Iowa State); (UTSMC)

    2010-09-21

    Ebolaviruses are causative agents of lethal hemorrhagic fever in humans and nonhuman primates. Among the filoviruses characterized thus far, Reston Ebola virus (REBOV) is the only Ebola virus that is nonpathogenic to humans despite the fact that REBOV can cause lethal disease in nonhuman primates. Previous studies also suggest that REBOV is less effective at inhibiting host innate immune responses than Zaire Ebola virus (ZEBOV) or Marburg virus. Virally encoded VP35 protein is critical for immune suppression, but an understanding of the relative contributions of VP35 proteins from REBOV and other filoviruses is currently lacking. In order to address this question, we characterized the REBOV VP35 interferon inhibitory domain (IID) using structural, biochemical, and virological studies. These studies reveal differences in double-stranded RNA binding and interferon inhibition between the two species. These observed differences are likely due to increased stability and loss of flexibility in REBOV VP35 IID, as demonstrated by thermal shift stability assays. Consistent with this finding, the 1.71-{angstrom} crystal structure of REBOV VP35 IID reveals that it is highly similar to that of ZEBOV VP35 IID, with an overall backbone r.m.s.d. of 0.64 {angstrom}, but contains an additional helical element at the linker between the two subdomains of VP35 IID. Mutations near the linker, including swapping sequences between REBOV and ZEBOV, reveal that the linker sequence has limited tolerance for variability. Together with the previously solved ligand-free and double-stranded-RNA-bound forms of ZEBOV VP35 IID structures, our current studies on REBOV VP35 IID reinforce the importance of VP35 in immune suppression. Functional differences observed between REBOV and ZEBOV VP35 proteins may contribute to observed differences in pathogenicity, but these are unlikely to be the major determinant. However, the high level of similarity in structure and the low tolerance for sequence variability, coupled with the multiple critical roles played by Ebola virus VP35 proteins, highlight the viability of VP35 as a potential target for therapeutic development.

  5. Clinical predictors of mortality in patients with ebola virus disease.

    PubMed

    Barry, Moumié; Touré, Abdoulaye; Traoré, Fodé Amara; Sako, Fodé-Bangaly; Sylla, Djibril; Kpamy, Dimai Ouo; Bah, Elhadj Ibrahima; Bangoura, M'Mah; Poncin, Marc; Keita, Sakoba; Tounkara, Thierno Mamadou; Cisse, Mohamed; Vanhems, Philippe

    2015-06-15

    In an observational cohort study including 89 Ebola patients, predictive factors of death were analyzed. The crude mortality rate was 43.8%. Myalgia (adjusted odds ratio [OR], 4.04; P = .02), hemorrrhage (adjusted OR, 3.5; P = .02), and difficulty breathing (adjusted OR, 5.75; P = .01) were independently associated with death. PMID:25770172

  6. Ebola Virus Epidemiology, Transmission, and Evolution during Seven Months in Sierra Leone

    PubMed Central

    Park, Daniel J.; Dudas, Gytis; Wohl, Shirlee; Goba, Augustine; Whitmer, Shannon L.M.; Andersen, Kristian G.; Sealfon, Rachel S.; Ladner, Jason T.; Kugelman, Jeffrey R.; Matranga, Christian B.; Winnicki, Sarah M.; Qu, James; Gire, Stephen K.; Gladden-Young, Adrianne; Jalloh, Simbirie; Nosamiefan, Dolo; Yozwiak, Nathan L.; Moses, Lina M.; Jiang, Pan-Pan; Lin, Aaron E.; Schaffner, Stephen F.; Bird, Brian; Towner, Jonathan; Mamoh, Mambu; Gbakie, Michael; Kanneh, Lansana; Kargbo, David; Massally, James L.B.; Kamara, Fatima K.; Konuwa, Edwin; Sellu, Josephine; Jalloh, Abdul A.; Mustapha, Ibrahim; Foday, Momoh; Yillah, Mohamed; Erickson, Bobbie R.; Sealy, Tara; Blau, Dianna; Paddock, Christopher; Brault, Aaron; Amman, Brian; Basile, Jane; Bearden, Scott; Belser, Jessica; Bergeron, Eric; Campbell, Shelley; Chakrabarti, Ayan; Dodd, Kimberly; Flint, Mike; Gibbons, Aridth; Goodman, Christin; Klena, John; McMullan, Laura; Morgan, Laura; Russell, Brandy; Salzer, Johanna; Sanchez, Angela; Wang, David; Jungreis, Irwin; Tomkins-Tinch, Christopher; Kislyuk, Andrey; Lin, Michael F.; Chapman, Sinead; MacInnis, Bronwyn; Matthews, Ashley; Bochicchio, James; Hensley, Lisa E.; Kuhn, Jens H.; Nusbaum, Chad; Schieffelin, John S.; Birren, Bruce W.; Forget, Marc; Nichol, Stuart T.; Palacios, Gustavo F.; Ndiaye, Daouda; Happi, Christian; Gevao, Sahr M.; Vandi, Mohamed A.; Kargbo, Brima; Holmes, Edward C.; Bedford, Trevor; Gnirke, Andreas; Ströher, Ute; Rambaut, Andrew; Garry, Robert F.; Sabeti, Pardis C.

    2015-01-01

    Summary The 2013–2015 Ebola virus disease (EVD) epidemic is caused by the Makona variant of Ebola virus (EBOV). Early in the epidemic, genome sequencing provided insights into virus evolution and transmission and offered important information for outbreak response. Here, we analyze sequences from 232 patients sampled over 7 months in Sierra Leone, along with 86 previously released genomes from earlier in the epidemic. We confirm sustained human-to-human transmission within Sierra Leone and find no evidence for import or export of EBOV across national borders after its initial introduction. Using high-depth replicate sequencing, we observe both host-to-host transmission and recurrent emergence of intrahost genetic variants. We trace the increasing impact of purifying selection in suppressing the accumulation of nonsynonymous mutations over time. Finally, we note changes in the mucin-like domain of EBOV glycoprotein that merit further investigation. These findings clarify the movement of EBOV within the region and describe viral evolution during prolonged human-to-human transmission. PMID:26091036

  7. Ebola Virus Epidemiology, Transmission, and Evolution during Seven Months in Sierra Leone.

    PubMed

    Park, Daniel J; Dudas, Gytis; Wohl, Shirlee; Goba, Augustine; Whitmer, Shannon L M; Andersen, Kristian G; Sealfon, Rachel S; Ladner, Jason T; Kugelman, Jeffrey R; Matranga, Christian B; Winnicki, Sarah M; Qu, James; Gire, Stephen K; Gladden-Young, Adrianne; Jalloh, Simbirie; Nosamiefan, Dolo; Yozwiak, Nathan L; Moses, Lina M; Jiang, Pan-Pan; Lin, Aaron E; Schaffner, Stephen F; Bird, Brian; Towner, Jonathan; Mamoh, Mambu; Gbakie, Michael; Kanneh, Lansana; Kargbo, David; Massally, James L B; Kamara, Fatima K; Konuwa, Edwin; Sellu, Josephine; Jalloh, Abdul A; Mustapha, Ibrahim; Foday, Momoh; Yillah, Mohamed; Erickson, Bobbie R; Sealy, Tara; Blau, Dianna; Paddock, Christopher; Brault, Aaron; Amman, Brian; Basile, Jane; Bearden, Scott; Belser, Jessica; Bergeron, Eric; Campbell, Shelley; Chakrabarti, Ayan; Dodd, Kimberly; Flint, Mike; Gibbons, Aridth; Goodman, Christin; Klena, John; McMullan, Laura; Morgan, Laura; Russell, Brandy; Salzer, Johanna; Sanchez, Angela; Wang, David; Jungreis, Irwin; Tomkins-Tinch, Christopher; Kislyuk, Andrey; Lin, Michael F; Chapman, Sinead; MacInnis, Bronwyn; Matthews, Ashley; Bochicchio, James; Hensley, Lisa E; Kuhn, Jens H; Nusbaum, Chad; Schieffelin, John S; Birren, Bruce W; Forget, Marc; Nichol, Stuart T; Palacios, Gustavo F; Ndiaye, Daouda; Happi, Christian; Gevao, Sahr M; Vandi, Mohamed A; Kargbo, Brima; Holmes, Edward C; Bedford, Trevor; Gnirke, Andreas; Ströher, Ute; Rambaut, Andrew; Garry, Robert F; Sabeti, Pardis C

    2015-06-18

    The 2013-2015 Ebola virus disease (EVD) epidemic is caused by the Makona variant of Ebola virus (EBOV). Early in the epidemic, genome sequencing provided insights into virus evolution and transmission and offered important information for outbreak response. Here, we analyze sequences from 232 patients sampled over 7 months in Sierra Leone, along with 86 previously released genomes from earlier in the epidemic. We confirm sustained human-to-human transmission within Sierra Leone and find no evidence for import or export of EBOV across national borders after its initial introduction. Using high-depth replicate sequencing, we observe both host-to-host transmission and recurrent emergence of intrahost genetic variants. We trace the increasing impact of purifying selection in suppressing the accumulation of nonsynonymous mutations over time. Finally, we note changes in the mucin-like domain of EBOV glycoprotein that merit further investigation. These findings clarify the movement of EBOV within the region and describe viral evolution during prolonged human-to-human transmission. PMID:26091036

  8. Ebola virus disease epidemic in West Africa: lessons learned and issues arising from West African countries.

    PubMed

    Oleribe, Obinna O; Salako, Babatunde L; Ka, M Mourtalla; Akpalu, Albert; McConnochie, Mairi; Foster, Matthew; Taylor-Robinson, Simon D

    2015-02-01

    The current Ebola virus disease (EVD) outbreak ravaging three nations in West Africa has affected more than 14,000 persons and killed over 5,000. It is the longest and most widely spread Ebola epidemic ever seen. At the time of this overview (written November 2014), having affected eight different nations, Nigeria and Senegal were able to control and eliminate the virus within a record time. Ghana has successfully, to date, kept the virus away from the country, despite economic and social relationships with affected nations. What lessons can we learn from Nigeria, Senegal and Ghana in the current epidemic? How can the world improve the health systems in low- and middle-income countries to effectively manage future outbreaks? Recently, the Royal College of Physicians launched a new partnership with the West African College of Physicians to curtail the effects of HIV/AIDS, malaria and tuberculosis in the region. We believe that strengthened health systems, skilled human resources for health and national ownership of problems are key to effective management of outbreaks such as EVD. PMID:25650199

  9. Membrane association induces a conformational change in the Ebola virus matrix protein

    PubMed Central

    Scianimanico, Sandra; Schoehn, Guy; Timmins, Joanna; Ruigrok, Rob H.W.; Klenk, Hans-Dieter; Weissenhorn, Winfried

    2000-01-01

    The matrix protein VP40 from Ebola virus is targeted to the plasma membrane, where it is thought to induce assembly and budding of virions through its association with the lipid bilayer. Ebola virus VP40 is expressed as a monomeric molecule in solution, consisting of two loosely associated domains. Here we show that a C-terminal truncation of seven residues destabilizes the monomeric closed conformation and induces spontaneous hexamerization in solution, as indicated by chemical cross-linking and electron microscopy. Three-dimensional reconstruction of electron microscopy images shows ring-like structures consisting of the N-terminal domain along with evidence for flexibly attached C-terminal domains. In vitro destabilization of the monomer by urea treatment results in similar hexameric molecules in solution. In addition, we demonstrate that membrane association of wild-type VP40 also induces the conformational switch from monomeric to hexameric molecules that may form the building blocks for initiation of virus assembly and budding. Such a conformational change induced by bilayer targeting may be a common feature of many viral matrix proteins and its potential inhibition may result in new anti-viral therapies. PMID:11118208

  10. Enhanced methods for unbiased deep sequencing of Lassa and Ebola RNA viruses from clinical and biological samples.

    PubMed

    Matranga, Christian B; Andersen, Kristian G; Winnicki, Sarah; Busby, Michele; Gladden, Adrianne D; Tewhey, Ryan; Stremlau, Matthew; Berlin, Aaron; Gire, Stephen K; England, Eleina; Moses, Lina M; Mikkelsen, Tarjei S; Odia, Ikponmwonsa; Ehiane, Philomena E; Folarin, Onikepe; Goba, Augustine; Kahn, S Humarr; Grant, Donald S; Honko, Anna; Hensley, Lisa; Happi, Christian; Garry, Robert F; Malboeuf, Christine M; Birren, Bruce W; Gnirke, Andreas; Levin, Joshua Z; Sabeti, Pardis C

    2014-01-01

    We have developed a robust RNA sequencing method for generating complete de novo assemblies with intra-host variant calls of Lassa and Ebola virus genomes in clinical and biological samples. Our method uses targeted RNase H-based digestion to remove contaminating poly(rA) carrier and ribosomal RNA. This depletion step improves both the quality of data and quantity of informative reads in unbiased total RNA sequencing libraries. We have also developed a hybrid-selection protocol to further enrich the viral content of sequencing libraries. These protocols have enabled rapid deep sequencing of both Lassa and Ebola virus and are broadly applicable to other viral genomics studies. PMID:25403361

  11. Monitoring of Ebola Virus Makona Evolution through Establishment of Advanced Genomic Capability in Liberia.

    PubMed

    Kugelman, Jeffrey R; Wiley, Michael R; Mate, Suzanne; Ladner, Jason T; Beitzel, Brett; Fakoli, Lawrence; Taweh, Fahn; Prieto, Karla; Diclaro, Joseph W; Minogue, Timothy; Schoepp, Randal J; Schaecher, Kurt E; Pettitt, James; Bateman, Stacey; Fair, Joseph; Kuhn, Jens H; Hensley, Lisa; Park, Daniel J; Sabeti, Pardis C; Sanchez-Lockhart, Mariano; Bolay, Fatorma K; Palacios, Gustavo

    2015-07-01

    To support Liberia's response to the ongoing Ebola virus (EBOV) disease epidemic in Western Africa, we established in-country advanced genomic capabilities to monitor EBOV evolution. Twenty-five EBOV genomes were sequenced at the Liberian Institute for Biomedical Research, which provided an in-depth view of EBOV diversity in Liberia during September 2014-February 2015. These sequences were consistent with a single virus introduction to Liberia; however, shared ancestry with isolates from Mali indicated at least 1 additional instance of movement into or out of Liberia. The pace of change is generally consistent with previous estimates of mutation rate. We observed 23 nonsynonymous mutations and 1 nonsense mutation. Six of these changes are within known binding sites for sequence-based EBOV medical countermeasures; however, the diagnostic and therapeutic impact of EBOV evolution within Liberia appears to be low. PMID:26079255

  12. [Hematological and immunological parameters during Ebola virus passages in guinea-pigs].

    PubMed

    Dadaeva, A A; Sizikova, L P; Subbotina, E L; Chepurnov, A A

    2006-01-01

    The trend in hematological and immunological parameters during Ebola virus passages in guinea-pigs indicated that pathophysiological changes occurred just during the second passage and further became stronger. The increase of some parameters and their correlation with the occurrence of fatal outcomes allowed the authors to reveal the most significant changes as increased juvenile platelets, whole blood virus appearance, higher echinocytes, a rise in the pro mil of blast cells and megakaryocytes in the bone marrow, and decreased neutrophilic phagocytic activity. Viral acquisition of the properties of lethality to guinea-pigs depends on the fine mechanisms responsible for viral interaction with host cells, which may lead to viral genetic changes during passages. PMID:16929596

  13. Endosomal proteolysis of the Ebola virus glycoprotein is necessary for infection.

    PubMed

    Chandran, Kartik; Sullivan, Nancy J; Felbor, Ute; Whelan, Sean P; Cunningham, James M

    2005-06-10

    Ebola virus (EboV) causes rapidly fatal hemorrhagic fever in humans and there is currently no effective treatment. We found that the infection of African green monkey kidney (Vero) cells by vesicular stomatitis viruses bearing the EboV glycoprotein (GP) requires the activity of endosomal cysteine proteases. Using selective protease inhibitors and protease-deficient cell lines, we identified an essential role for cathepsin B (CatB) and an accessory role for cathepsin L (CatL) in EboV GP-dependent entry. Biochemical studies demonstrate that CatB and CatL mediate entry by carrying out proteolysis of the EboV GP subunit GP1 and support a multistep mechanism that explains the relative contributions of these enzymes to infection. CatB and CatB/CatL inhibitors diminish the multiplication of infectious EboV-Zaire in cultured cells and may merit investigation as anti-EboV drugs. PMID:15831716

  14. Impact of spatial dispersion, evolution, and selection on Ebola Zaire Virus epidemic waves

    PubMed Central

    Azarian, Taj; Lo Presti, Alessandra; Giovanetti, Marta; Cella, Eleonora; Rife, Brittany; Lai, Alessia; Zehender, Gianguglielmo; Ciccozzi, Massimo; Salemi, Marco

    2015-01-01

    Ebola virus Zaire (EBOV) has reemerged in Africa, emphasizing the global importance of this pathogen. Amidst the response to the current epidemic, several gaps in our knowledge of EBOV evolution are evident. Specifically, uncertainty has been raised regarding the potential emergence of more virulent viral variants through amino acid substitutions. Glycoprotein (GP), an essential component of the EBOV genome, is highly variable and a potential site for the occurrence of advantageous mutations. For this study, we reconstructed the evolutionary history of EBOV by analyzing 65 GP sequences from humans and great apes over diverse locations across epidemic waves between 1976 and 2014. We show that, although patterns of spatial dispersion throughout Africa varied, the evolution of the virus has largely been characterized by neutral genetic drift. Therefore, the radical emergence of more transmissible variants is unlikely, a positive finding, which is increasingly important on the verge of vaccine deployment. PMID:25973685

  15. The Ebola virus glycoprotein mediates entry via a non-classical dynamin-dependent macropinocytic pathway

    SciTech Connect

    Mulherkar, Nirupama [Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461 (United States); Raaben, Matthijs [Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115 (United States); Torre, Juan Carlos de la [Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037 (United States); Whelan, Sean P. [Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115 (United States); Chandran, Kartik, E-mail: kartik.chandran@einstein.yu.edu [Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461 (United States)

    2011-10-25

    Ebola virus (EBOV) has been reported to enter cultured cell lines via a dynamin-2-independent macropinocytic pathway or clathrin-mediated endocytosis. The route(s) of productive EBOV internalization into physiologically relevant cell types remain unexplored, and viral-host requirements for this process are incompletely understood. Here, we use electron microscopy and complementary chemical and genetic approaches to demonstrate that the viral glycoprotein, GP, induces macropinocytic uptake of viral particles into cells. GP's highly-glycosylated mucin domain is dispensable for virus-induced macropinocytosis, arguing that interactions between other sequences in GP and the host cell surface are responsible. Unexpectedly, we also found a requirement for the large GTPase dynamin-2, which is proposed to be dispensable for several types of macropinocytosis. Our results provide evidence that EBOV uses an atypical dynamin-dependent macropinocytosis-like entry pathway to enter Vero cells, adherent human peripheral blood-derived monocytes, and a mouse dendritic cell line.

  16. Occupational safety and health protections against Ebola virus disease.

    PubMed

    Ringen, Knut; Landrigan, Philip J; O Stull, Jeffrey; Duffy, Richard; Melius, James; McDiarmid, Melissa A

    2015-07-01

    Even as the Ebola epidemic is finally showing signs of remitting, controversy continues regarding the modes of disease transmission, the understanding of which necessarily dictates methods of prevention. The initial public health response to the epidemic was based on assumptions formed during previous outbreaks, and in the belief that transmission was restricted to direct "contact" with other infected patients. However, the current Ebola outbreak differed from previous experiences in its intensity of transmission, speed of spread, and fatality rate and was also particularly unforgiving on health workers occupationally infected. Even with these differences, however, other modes of transmission were not considered by public health authorities, thus denying both the hard-hit health worker populations and the wider public more protective guidance. International Labor Conventions require employers to provide a comprehensive safety program that anticipates work-related risks and specifies strategies for protection against them. Such a precautionary approach is recommended in future epidemic planning, especially where evidence regarding transmission is incomplete. Am. J. Ind. Med. 58:703-714, 2015. © 2015 Wiley Periodicals, Inc. PMID:25950864

  17. Antigenic Subversion: A Novel Mechanism of Host Immune Evasion by Ebola Virus

    PubMed Central

    Mohan, Gopi S.; Li, Wenfang; Ye, Ling; Compans, Richard W.; Yang, Chinglai

    2012-01-01

    In addition to its surface glycoprotein (GP1,2), Ebola virus (EBOV) directs the production of large quantities of a truncated glycoprotein isoform (sGP) that is secreted into the extracellular space. The generation of secreted antigens has been studied in several viruses and suggested as a mechanism of host immune evasion through absorption of antibodies and interference with antibody-mediated clearance. However such a role has not been conclusively determined for the Ebola virus sGP. In this study, we immunized mice with DNA constructs expressing GP1,2 and/or sGP, and demonstrate that sGP can efficiently compete for anti-GP12 antibodies, but only from mice that have been immunized by sGP. We term this phenomenon “antigenic subversion”, and propose a model whereby sGP redirects the host antibody response to focus on epitopes which it shares with membrane-bound GP1,2, thereby allowing it to absorb anti-GP1,2 antibodies. Unexpectedly, we found that sGP can also subvert a previously immunized host's anti-GP1,2 response resulting in strong cross-reactivity with sGP. This finding is particularly relevant to EBOV vaccinology since it underscores the importance of eliciting robust immunity that is sufficient to rapidly clear an infection before antigenic subversion can occur. Antigenic subversion represents a novel virus escape strategy that likely helps EBOV evade host immunity, and may represent an important obstacle to EBOV vaccine design. PMID:23271969

  18. The Role of Social Mobilization in Controlling Ebola Virus in Lofa County, Liberia

    PubMed Central

    Fast, Shannon M.; Mekaru, Sumiko; Brownstein, John S.; Postlethwaite, Timothy A.; Markuzon, Natasha

    2015-01-01

    The West Africa Ebola virus epidemic now appears to be coming to an end. In the proposed model, we simulate changes in population behavior that help to explain the observed transmission dynamics. We introduce an EVD transmission model accompanied by a model of social mobilization. The model was fit to Lofa County, Liberia through October 2014, using weekly counts of new cases reported by the US CDC. In simulation studies, we analyze the dynamics of the disease transmission with and without population behavior change, given the availability of beds in Ebola treatment units (ETUs) estimated from observed data. Only the model scenario that included individuals' behavioral change achieved a good fit to the observed case counts. Although the capacity of the Lofa County ETUs greatly increased in mid-August, our simulations show that the expansion was insufficient to alone control the outbreak. Modeling the entire outbreak without considering behavior change fit the data poorly, and extrapolating from early data without taking behavioral changes into account led to a prediction of exponential outbreak growth, contrary to the observed decline.  Education and awareness-induced behavior change in the population was instrumental in curtailing the Ebola outbreak in Lofa County and is likely playing an important role in stopping the West Africa epidemic altogether.

  19. Molecular Characterization of the First Ebola Virus Isolated in Italy, from a Health Care Worker Repatriated from Sierra Leone

    PubMed Central

    Castilletti, Concetta; Carletti, Fabrizio; Gruber, Cesare E. M.; Bordi, Licia; Lalle, Eleonora; Quartu, Serena; Meschi, Silvia; Lapa, Daniele; Colavita, Francesca; Chiappini, Roberta; Mazzarelli, Antonio; Marsella, Patrizia; Petrosillo, Nicola; Nicastri, Emanuele; Chillemi, Giovanni; Valentini, Alessio; Desideri, Alessandro; Di Caro, Antonino; Ippolito, Giuseppe

    2015-01-01

    Here, we report the complete genome sequence of an Ebola virus (EBOV) isolated from a health worker repatriated from Sierra Leone to Italy in November 2014. The sequence, clustering in clade 3 of the Sierra Leone sequences, was analyzed with respect to mutations possibly affecting diagnostic and therapeutic targets as well as virulence. PMID:26089420

  20. Molecular Characterization of the First Ebola Virus Isolated in Italy, from a Health Care Worker Repatriated from Sierra Leone.

    PubMed

    Castilletti, Concetta; Carletti, Fabrizio; Gruber, Cesare E M; Bordi, Licia; Lalle, Eleonora; Quartu, Serena; Meschi, Silvia; Lapa, Daniele; Colavita, Francesca; Chiappini, Roberta; Mazzarelli, Antonio; Marsella, Patrizia; Petrosillo, Nicola; Nicastri, Emanuele; Chillemi, Giovanni; Valentini, Alessio; Desideri, Alessandro; Di Caro, Antonino; Ippolito, Giuseppe; Capobianchi, Maria R

    2015-01-01

    Here, we report the complete genome sequence of an Ebola virus (EBOV) isolated from a health worker repatriated from Sierra Leone to Italy in November 2014. The sequence, clustering in clade 3 of the Sierra Leone sequences, was analyzed with respect to mutations possibly affecting diagnostic and therapeutic targets as well as virulence. PMID:26089420

  1. Proinflammatory response during Ebola virus infection of primate models: possible involvement of the tumor necrosis factor receptor superfamily

    Microsoft Academic Search

    Lisa E Hensley; Howard A Young; Peter B Jahrling; Thomas W Geisbert

    2002-01-01

    Ebola virus (EBOV) infections are characterized by dysregulation of normal host immune responses. Insight into the mechanism came from recent studies in nonhuman primates, which showed that EBOV infects cells of the mononuclear phagocyte system (MPS), resulting in apoptosis of bystander lymphocytes. In this study, we evaluated serum levels of cytokines\\/chemokines in EBOV-infected nonhuman primates, as possible correlates of this

  2. The Western Africa Ebola Virus Disease Epidemic Exhibits Both Global Exponential and Local Polynomial Growth Rates

    PubMed Central

    Chowell, Gerardo; Viboud, Cécile; Hyman, James M; Simonsen, Lone

    2015-01-01

    Background: While many infectious disease epidemics are initially characterized by an exponential growth in time, we show that district-level Ebola virus disease (EVD) outbreaks in West Africa follow slower polynomial-based growth kinetics over several generations of the disease. Methods: We analyzed epidemic growth patterns at three different spatial scales (regional, national, and subnational) of the Ebola virus disease epidemic in Guinea, Sierra Leone and Liberia by compiling publicly available weekly time series of reported EVD case numbers from the patient database available from the World Health Organization website for the period 05-Jan to 17-Dec 2014. Results: We found significant differences in the growth patterns of EVD cases at the scale of the country, district, and other subnational administrative divisions. The national cumulative curves of EVD cases in Guinea, Sierra Leone, and Liberia show periods of approximate exponential growth. In contrast, local epidemics are asynchronous and exhibit slow growth patterns during 3 or more EVD generations, which can be better approximated by a polynomial than an exponential function. Conclusions: The slower than expected growth pattern of local EVD outbreaks could result from a variety of factors, including behavior changes, success of control interventions, or intrinsic features of the disease such as a high level of clustering. Quantifying the contribution of each of these factors could help refine estimates of final epidemic size and the relative impact of different mitigation efforts in current and future EVD outbreaks. PMID:25685633

  3. Evaluation of Different Strategies for Post-Exposure Treatment of Ebola Virus Infection in Rodents

    PubMed Central

    Richardson, Jason S.; Wong, Gary; Pillet, Stéphane; Schindle, Samantha; Ennis, Jane; Turner, Jeffrey; Strong, James E.; Kobinger, Gary P.

    2012-01-01

    Zaire Ebola virus (ZEBOV) is a pathogen that causes severe hemorrhagic fever in humans and non-human primates. There are currently no licensed vaccines or approved treatments available against ZEBOV infections. The goal of this work was to evaluate different treatment strategies in conjunction with a replication deficient, recombinant human adenovirus serotype 5-based vaccine expressing the Zaire Ebola virus glycoprotein (Ad-CAGoptZGP) in Ebola infected mice and guinea pigs. Guinea pigs were treated with Ad-CAGoptZGP in combination with different treatment strategies after challenge with guinea pig adapted-ZEBOV (GA-ZEBOV). B10.BR mice were used to further characterize efficacy and immune responses following co-administration of Ad-CAGoptZGP with the most effective treatment: AdHu5 expressing recombinant IFN-? (hereafter termed DEF201) after challenge with a lethal dose of mouse adapted-ZEBOV (MA-ZEBOV). In mice, DEF201 treatment was able to elicit full protection against a lethal dose of MA-ZEBOV when administered 30 minutes after infection. In guinea pigs the Ad-CAGoptZGP and DEF201 combination therapy elicited full protection when treated 30 minutes post-exposure and were a superior treatment to Ad-CAGoptZGP supplemented with recombinant IFN-? protein. Further analysis of the immune response revealed that addition of DEF201 to Ad-CAGoptZGP enhances the resulting adaptive immune response against ZGP. The results highlight the importance of the innate immune response in the prevention of ZEBOV pathogenesis and support further development of the Ad-CAGoptZGP with DEF201 treatment combination for post-exposure therapy against ZEBOV infection. PMID:23205319

  4. An upstream open reading frame modulates ebola virus polymerase translation and virus replication.

    PubMed

    Shabman, Reed S; Hoenen, Thomas; Groseth, Allison; Jabado, Omar; Binning, Jennifer M; Amarasinghe, Gaya K; Feldmann, Heinz; Basler, Christopher F

    2013-01-01

    Ebolaviruses, highly lethal zoonotic pathogens, possess longer genomes than most other non-segmented negative-strand RNA viruses due in part to long 5' and 3' untranslated regions (UTRs) present in the seven viral transcriptional units. To date, specific functions have not been assigned to these UTRs. With reporter assays, we demonstrated that the Zaire ebolavirus (EBOV) 5'-UTRs lack internal ribosomal entry site function. However, the 5'-UTRs do differentially regulate cap-dependent translation when placed upstream of a GFP reporter gene. Most dramatically, the 5'-UTR derived from the viral polymerase (L) mRNA strongly suppressed translation of GFP compared to a ?-actin 5'-UTR. The L 5'-UTR is one of four viral genes to possess upstream AUGs (uAUGs), and ablation of each uAUG enhanced translation of the primary ORF (pORF), most dramatically in the case of the L 5'-UTR. The L uAUG was sufficient to initiate translation, is surrounded by a "weak" Kozak sequence and suppressed pORF translation in a position-dependent manner. Under conditions where eIF2? was phosphorylated, the presence of the uORF maintained translation of the L pORF, indicating that the uORF modulates L translation in response to cellular stress. To directly address the role of the L uAUG in virus replication, a recombinant EBOV was generated in which the L uAUG was mutated to UCG. Strikingly, mutating two nucleotides outside of previously-defined protein coding and cis-acting regulatory sequences attenuated virus growth to titers 10-100-fold lower than a wild-type virus in Vero and A549 cells. The mutant virus also exhibited decreased viral RNA synthesis as early as 6 hours post-infection and enhanced sensitivity to the stress inducer thapsigargin. Cumulatively, these data identify novel mechanisms by which EBOV regulates its polymerase expression, demonstrate their relevance to virus replication and identify a potential therapeutic target. PMID:23382680

  5. Antibody Quality and Protection from Lethal Ebola Virus Challenge in Nonhuman Primates Immunized with Rabies Virus Based Bivalent Vaccine

    PubMed Central

    Papaneri, Amy B.; Wirblich, Christoph; Feldmann, Friederike; Holbrook, Michael; Jahrling, Peter; Feldmann, Heinz; Schnell, Matthias J.

    2013-01-01

    We have previously described the generation of a novel Ebola virus (EBOV) vaccine platform based on (a) replication-competent rabies virus (RABV), (b) replication-deficient RABV, or (c) chemically inactivated RABV expressing EBOV glycoprotein (GP). Mouse studies demonstrated safety, immunogenicity, and protective efficacy of these live or inactivated RABV/EBOV vaccines. Here, we evaluated these vaccines in nonhuman primates. Our results indicate that all three vaccines do induce potent immune responses against both RABV and EBOV, while the protection of immunized animals against EBOV was largely dependent on the quality of humoral immune response against EBOV GP. We also determined if the induced antibodies against EBOV GP differ in their target, affinity, or the isotype. Our results show that IgG1-biased humoral responses as well as high levels of GP-specific antibodies were beneficial for the control of EBOV infection after immunization. These results further support the concept that a successful EBOV vaccine needs to induce strong antibodies against EBOV. We also showed that a dual vaccine against RABV and filoviruses is achievable; therefore addressing concerns for the marketability of this urgently needed vaccine. PMID:23737747

  6. Structural rearrangement of ebola virus VP40 begets multiple functions in the virus life cycle.

    PubMed

    Bornholdt, Zachary A; Noda, Takeshi; Abelson, Dafna M; Halfmann, Peter; Wood, Malcolm R; Kawaoka, Yoshihiro; Saphire, Erica Ollmann

    2013-08-15

    Proteins, particularly viral proteins, can be multifunctional, but the mechanisms behind multifunctionality are not fully understood. Here, we illustrate through multiple crystal structures, biochemistry, and cellular microscopy that VP40 rearranges into different structures, each with a distinct function required for the ebolavirus life cycle. A butterfly-shaped VP40 dimer traffics to the cellular membrane. Once there, electrostatic interactions trigger rearrangement of the polypeptide into a linear hexamer. These hexamers construct a multilayered, filamentous matrix structure that is critical for budding and resembles tomograms of authentic virions. A third structure of VP40, formed by a different rearrangement, is not involved in virus assembly but instead uniquely binds RNA to regulate viral transcription inside infected cells. These results provide a functional model for ebolavirus matrix assembly and the other roles of VP40 in the virus life cycle and demonstrate how a single wild-type, unmodified polypeptide can assemble into different structures for different functions. PMID:23953110

  7. Ebola virus disease and marburg disease in pregnancy: a review and management considerations for filovirus infection.

    PubMed

    Bebell, Lisa M; Riley, Laura E

    2015-06-01

    The largest-ever recorded outbreak of viral hemorrhagic fever is ongoing. As a result of the epidemic and rural nature of outbreaks, little is published about the Filovirus infections Ebola virus disease and Marburg disease in pregnancy. This review of viral hemorrhagic fever focusing on Marburg and Ebola uses knowledge of disease in nonpregnant individuals and pregnancy-specific data to inform management for pregnant women. Filovirus infection presentation is similar between pregnant and nonpregnant patients, although infections may be more severe in pregnancy. Although labeled as hemorrhagic fevers, Marburg and Ebola do not commonly cause gross bleeding and should be conceptualized as diseases of high gastrointestinal losses. Early, aggressive supportive care is the mainstay of Filovirus infection management with massive fluid resuscitation as the key management principle. Patients often require 5-10 L or more per day of intravenous or oral fluid to maintain circulating blood volume in the setting of ongoing gastrointestinal loss. Fluid shifts warrant aggressive monitoring and correction of potassium levels and acid-base disturbances to prevent life-threatening arrhythmias and metabolic complications. Regardless of maternal survival, fetal loss rates are nearly 100% in Filovirus infection, likely resulting from unchecked transplacental and hematogenous viral spread. High fetal loss rates support the placenta as a difficult-to-eradicate Filovirus infection reservoir. In conclusion, the management of Filovirus infection in pregnancy should focus on stabilizing the mother with intensive monitoring and aggressive fluid and electrolyte repletion as well as maintaining strict infection control to minimize transmission to others. PMID:26000499

  8. Ebola Virus Exploits a Monocyte Differentiation Program To Promote Its Entry

    PubMed Central

    Martinez, Osvaldo; Johnson, Joshua C.; Honko, Anna; Yen, Benjamin; Shabman, Reed S.; Hensley, Lisa E.; Olinger, Gene G.

    2013-01-01

    Antigen-presenting cells (APCs) are critical targets of Ebola virus (EBOV) infection in vivo. However, the susceptibility of monocytes to infection is controversial. Studies indicate productive monocyte infection, and yet monocytes are also reported to be resistant to EBOV GP-mediated entry. In contrast, monocyte-derived macrophages and dendritic cells are permissive for both EBOV entry and replication. Here, freshly isolated monocytes are demonstrated to indeed be refractory to EBOV entry. However, EBOV binds monocytes, and delayed entry occurs during monocyte differentiation. Cultured monocytes spontaneously downregulate the expression of viral entry restriction factors such as interferon-inducible transmembrane proteins, while upregulating the expression of critical EBOV entry factors cathepsin B and NPC1. Moreover, these processes are accelerated by EBOV infection. Finally, ectopic expression of NPC1 is sufficient to rescue entry into an undifferentiated, normally nonpermissive monocytic cell line. These results define the molecular basis for infection of APCs and suggest means to limit APC infection. PMID:23345511

  9. A Single Phosphorodiamidate Morpholino Oligomer Targeting VP24 Protects Rhesus Monkeys against Lethal Ebola Virus Infection

    PubMed Central

    Warren, Travis K.; Whitehouse, Chris A.; Wells, Jay; Welch, Lisa; Heald, Alison E.; Charleston, Jay S.; Sazani, Pete; Reid, St. Patrick; Iversen, Patrick L.

    2015-01-01

    ABSTRACT Ebola viruses (EBOV) cause severe disease in humans and nonhuman primates with high mortality rates and continue to emerge in new geographic locations, including several countries in West Africa, the site of a large ongoing outbreak. Phosphorodiamidate morpholino oligomers (PMOs) are synthetic antisense molecules that are able to target mRNAs in a sequence-specific fashion and suppress translation through steric hindrance. We previously showed that the use of PMOs targeting a combination of VP35 and VP24 protected rhesus monkeys from lethal EBOV infection. Surprisingly, the present study revealed that a PMOplus compound targeting VP24 alone was sufficient to confer protection from lethal EBOV infection but that a PMOplus targeting VP35 alone resulted in no protection. This study further substantiates recent data demonstrating that VP24 may be a key virulence factor encoded by EBOV and suggests that VP24 is a promising target for the development of effective anti-EBOV countermeasures. PMID:25670780

  10. Brief Report: Persistence of Ebola Virus in Ocular Fluid during Convalescence.

    PubMed

    2015-06-18

    Brief Report: Persistence of Ebola Virus in Ocular Fluid during Convalescence Original Article, N Engl J Med 2015;372:2423-2427. In the Case Report, the final paragraph (page 3) should have included, as the third sentence, "Continued clinical deterioration of the patient's left eye prompted the initiation of treatment with topical difluprednate (Alcon Laboratories), a 21-day course of oral favipiravir (MediVector), a periocular injection of triamcinolone, and a 10-week tapering course of oral prednisone." In the Discussion, the last sentence of the final paragraph (page 4) should have ended, ". . . and to identify effective treatment strategies for the clinical management of EVD complications," rather than, "and to develop strategies . . . ." Also, MediVector should have been included in the acknowledgements, as well as the following statement: "Favipiravir was provided by the Department of Defense Joint Project Manager Medical Countermeasure Systems." The article is correct in print and at NEJM.org. PMID:26030721

  11. Reconsidering the Ethical Permissibility of the Use of Unregistered Interventions against Ebola Virus Disease.

    PubMed

    Landry, Joshua T; Foreman, Thomas; Kekewich, Michael

    2015-07-01

    Ethical considerations for the use of unregistered interventions for Ebola virus disease have sparked considerable debate among academic and clinical ethicists. In August 2014 the World Health Organization (WHO) convened a panel of experts to discuss approaches to the outbreak in West Africa, with the goal of determining "whether it is ethical to use unregistered interventions with unknown adverse effects for possible treatment or prophylaxis". 1 The panel concluded that there would be an ethical imperative to provide such unregistered interventions if specific criteria could be met. This paper evaluates the WHO conclusion and argues that although it may be reasonable to provide unregistered interventions considering the circumstance, there is no clear ethical imperative to do so. PMID:26059962

  12. Ethical and practical considerations in providing critical care to patients with ebola virus disease.

    PubMed

    Torabi-Parizi, Parizad; Davey, Richard T; Suffredini, Anthony F; Chertow, Daniel S

    2015-06-01

    Infectious disease epidemics in the past have given rise to psychologic and emotional responses among health-care workers (HCWs), stemming from fear of infection during patient care. Early experiences in the AIDS epidemic provide an example where fear of contagion resulted in differential treatment of patients infected with HIV. However, with a deeper understanding of AIDS pathogenesis and treatment, fear and discrimination diminished. Parallels exist between early experiences with AIDS and the present outbreak of Ebola virus disease in West Africa, particularly regarding discussions of medical futility in seriously ill patients. We provide a historical perspective on HCWs' risk of infection during the provision of CPR, discuss physicians' duty to treat in the face of perceived or actual HCW risk, and, finally, present the protocols implemented at the National Institutes of Health to reduce HCW risk while providing lifesaving and life-sustaining care. PMID:25764372

  13. Digital Sensing and Sizing of Vesicular Stomatitis Virus Pseudotypes in Complex Media; A Model for Ebola and Marburg Detection

    PubMed Central

    Chinnala, Jyothsna; Goldberg, Bennett B.; Connor, John H.; Ünlü, M. Selim

    2015-01-01

    Rapid, sensitive, and direct label-free capture and characterization of nanoparticles from complex media such as blood or serum will broadly impact medicine and the life sciences. We demonstrate identification of virus particles in complex samples for replication-competent wild-type vesicular stomatitis virus (VSV), defective VSV, and Ebola- and Marburg-pseudotyped VSV with high sensitivity and specificity. Size discrimination of the imaged nanoparticles (virions) allows differentiation between modified viruses having different genome lengths and facilitates a reduction in the counting of non-specifically bound particles to achieve a limit-of-detection (LOD) of 5×103 pfu/mL for the Ebola and Marburg VSV pseudotypes. We demonstrate the simultaneous detection of multiple viruses in a single sample (composed of serum or whole blood) for screening applications and uncompromised detection capabilities in samples contaminated with high levels of bacteria. By employing affinity-based capture, size discrimination, and a “digital” detection scheme to count single virus particles, we show that a robust and sensitive virus/nanoparticle sensing assay can been established for targets in complex samples. The nanoparticle microscopy system is termed the Single Particle Interferometric Reflectance Imaging Sensor (SP-IRIS) and is capable of high-throughput and rapid sizing of large numbers of biological nanoparticles on an antibody microarray for research and diagnostic applications. PMID:24840765

  14. Social pathways for ebola virus disease in rural sierra leone, and some implications for containment.

    PubMed

    Richards, Paul; Amara, Joseph; Ferme, Mariane C; Kamara, Prince; Mokuwa, Esther; Sheriff, Amara Idara; Suluku, Roland; Voors, Maarten

    2015-04-01

    The current outbreak of Ebola Virus Disease in Upper West Africa is the largest ever recorded. Molecular evidence suggests spread has been almost exclusively through human-to-human contact. Social factors are thus clearly important to understand the epidemic and ways in which it might be stopped, but these factors have so far been little analyzed. The present paper focuses on Sierra Leone, and provides cross sectional data on the least understood part of the epidemic-the largely undocumented spread of Ebola in rural areas. Various forms of social networking in rural communities and their relevance for understanding pathways of transmission are described. Particular attention is paid to the relationship between marriage, funerals and land tenure. Funerals are known to be a high-risk factor for infection. It is suggested that more than a shift in awareness of risks will be needed to change local patterns of behavior, especially in regard to funerals, since these are central to the consolidation of community ties. A concluding discussion relates the information presented to plans for halting the disease. Local consultation and access are seen as major challenges to be addressed. PMID:25886400

  15. Global health security: the wider lessons from the west African Ebola virus disease epidemic.

    PubMed

    Heymann, David L; Chen, Lincoln; Takemi, Keizo; Fidler, David P; Tappero, Jordan W; Thomas, Mathew J; Kenyon, Thomas A; Frieden, Thomas R; Yach, Derek; Nishtar, Sania; Kalache, Alex; Olliaro, Piero L; Horby, Peter; Torreele, Els; Gostin, Lawrence O; Ndomondo-Sigonda, Margareth; Carpenter, Daniel; Rushton, Simon; Lillywhite, Louis; Devkota, Bhimsen; Koser, Khalid; Yates, Rob; Dhillon, Ranu S; Rannan-Eliya, Ravi P

    2015-05-01

    The Ebola virus disease outbreak in West Africa was unprecedented in both its scale and impact. Out of this human calamity has come renewed attention to global health security--its definition, meaning, and the practical implications for programmes and policy. For example, how does a government begin to strengthen its core public health capacities, as demanded by the International Health Regulations? What counts as a global health security concern? In the context of the governance of global health, including WHO reform, it will be important to distil lessons learned from the Ebola outbreak. The Lancet invited a group of respected global health practitioners to reflect on these lessons, to explore the idea of global health security, and to offer suggestions for next steps. Their contributions describe some of the major threats to individual and collective human health, as well as the values and recommendations that should be considered to counteract such threats in the future. Many different perspectives are proposed. Their common goal is a more sustainable and resilient society for human health and wellbeing. PMID:25987157

  16. Social Pathways for Ebola Virus Disease in Rural Sierra Leone, and Some Implications for Containment

    PubMed Central

    Richards, Paul; Amara, Joseph; Ferme, Mariane C.; Kamara, Prince; Mokuwa, Esther; Sheriff, Amara Idara; Suluku, Roland; Voors, Maarten

    2015-01-01

    The current outbreak of Ebola Virus Disease in Upper West Africa is the largest ever recorded. Molecular evidence suggests spread has been almost exclusively through human-to-human contact. Social factors are thus clearly important to understand the epidemic and ways in which it might be stopped, but these factors have so far been little analyzed. The present paper focuses on Sierra Leone, and provides cross sectional data on the least understood part of the epidemic—the largely undocumented spread of Ebola in rural areas. Various forms of social networking in rural communities and their relevance for understanding pathways of transmission are described. Particular attention is paid to the relationship between marriage, funerals and land tenure. Funerals are known to be a high-risk factor for infection. It is suggested that more than a shift in awareness of risks will be needed to change local patterns of behavior, especially in regard to funerals, since these are central to the consolidation of community ties. A concluding discussion relates the information presented to plans for halting the disease. Local consultation and access are seen as major challenges to be addressed. PMID:25886400

  17. Ebola virus envelope glycoprotein derived peptide in human Furin-bound state: computational studies.

    PubMed

    Omotuyi, I Olaposi

    2015-01-01

    Ebola virus (EboV) is currently ravaging West Africa with estimated case fatality rate of 52%. Currently, no drug treatment is available and immunoglobulin therapy is still at the rudimentary stage. For anti-EboV drug development, druggable viral and host protein targets, including human Furin are under intense investigation. Here, molecular dynamics simulation was performed on Apo-Furin, meta-guanidinomethyl-Phac-RVR-Amba-bound, and two EboV glycoprotein (GP) 494-TGGRRTRREA-503/Furin complexes (Accurate and one amino acid shift alignment). The results of the simulation established ligand-induced desolvation of Furin active site and structural compactness. Accurately aligned EboV-GP peptide exhibited a tighter binding mode with Furin and showed 1.5- and 3.0-fold MMPBSA binding free energy estimate compared with the displaced peptide and inhibitor, respectively. The difference in free energy was traced to the difference in contribution of threonine residues of the peptides. Furthermore, Furin subsites I conferred substrate specificity and ligand binding accuracy. Accurately aligned peptide trapped active site His194 side chain into gauche (-) (+60(o)) ?1-dihedral compared with gauche+ (-60(o)) in other biosystems while Asp153 is trapped in gauche+ (-60(o)) in ligand bound not Apo state. Ramachandran plot showed that the scissile Arg8 of the accurately aligned peptide showed ? conformation distribution as apposed to 310R, ?L, and 310L. Finally, the active site proximal Na(+) binding is dependent on substrate peptide occupancy of the active site but detaches in the absence of a ligand. In conclusion, Furin might represent candidate drug target for Ebola virus disease treatment via therapeutic target of the active site and Na(+) binding pocket. PMID:25347780

  18. Epitope-based peptide vaccine design and target site depiction against Ebola viruses: an immunoinformatics study.

    PubMed

    Khan, M A; Hossain, M U; Rakib-Uz-Zaman, S M; Morshed, M N

    2015-07-01

    Ebola viruses (EBOVs) have been identified as an emerging threat in recent year as it causes severe haemorrhagic fever in human. Epitope-based vaccine design for EBOVs remains a top priority because a mere progress has been made in this regard. Another reason is the lack of antiviral drug and licensed vaccine although there is a severe outbreak in Central Africa. In this study, we aimed to design an epitope-based vaccine that can trigger a significant immune response as well as to prognosticate inhibitor that can bind with potential drug target sites using various immunoinformatics and docking simulation tools. The capacity to induce both humoral and cell-mediated immunity by T cell and B cell was checked for the selected protein. The peptide region spanning 9 amino acids from 42 to 50 and the sequence TLASIGTAF were found as the most potential B and T cell epitopes, respectively. This peptide could interact with 12 HLAs and showed high population coverage up to 80.99%. Using molecular docking, the epitope was further appraised for binding against HLA molecules to verify the binding cleft interaction. In addition with this, the allergenicity of the epitopes was also evaluated. In the post-therapeutic strategy, docking study of predicted 3D structure identified suitable therapeutic inhibitor against targeted protein. However, this computational epitope-based peptide vaccine designing and target site prediction against EBOVs open up a new horizon which may be the prospective way in Ebola viruses research; the results require validation by in vitro and in vivo experiments. PMID:25857850

  19. Ebola virus disease, transmission risk to laboratory personnel, and pretransfusion testing.

    PubMed

    Katz, Louis M; Tobian, Aaron A R

    2014-12-01

    As Ebola virus has infected thousands of individuals in West Africa, there is growing concern about the appropriate response of hospitals in developed nations caring for patients and handling laboratory specimens for patients suspected of Ebola virus disease (EVD). Guidelines for caring for EVD patients are proliferating rapidly from national and state public health authorities, professional societies, and individual hospitals. It is no surprise that they differ from one another, and some very conservative recommendations call for suspension of routine laboratory testing, including pretransfusion testing. EVD is transmitted by direct contact with blood, secretions, organs, and other body fluids and not by airborne routes. Based on experimental and observational data, the US Centers for Disease Control and Prevention (CDC) recommends that clinicians follow contact and droplet precautions. Laboratory personnel are required to follow the blood-borne pathogen standard, especially the use of appropriate barriers consisting of gloves, gown, goggles, mask to cover nose and mouth, and plexiglass shield, where splashes of potentially infectious materials may be generated. Their recommendations are permissive of clinically appropriate laboratory testing, including pretransfusion testing, using barrier isolation precautions. Most individuals with suspected EVD will have a fever of another etiology, such as Plasmodium?falciparum malaria. We believe that forgoing all routine pretransfusion laboratory testing may result in a greater increase in poor clinical outcomes than any diminution in the risks to laboratory personnel will justify. It is imperative for all laboratory directors, working with institutional infection control and safety personnel, to evaluate their hospital policies for potentially infectious patients and provide a safe environment for their patients and employees. PMID:25403825

  20. Signaling through RIG-I and type I interferon receptor: Immune activation by Newcastle disease virus in man versus immune evasion by Ebola virus (Review).

    PubMed

    Schirrmacher, Volker

    2015-07-01

    In this review, two types of RNA viruses are compared with regard to the type I interferon (IFN) response in order to obtain a better understanding of the molecular mechanisms of immune activation or evasion. Upon human infection, both viruses exert either beneficial or detrimental effects. The Newcastle disease virus (NDV), is a type strain for avian paramyxoviruses, while the Ebola virus (EBOV), is a virus affecting primates. During evolution, both viruses specifically adapted to their respective hosts, acquiring sophisticated viral escape mechanisms. Two types of receptors play an important role in the life cycle of these two viruses: cytoplasmic retinoic acid?inducible gene I (RIG?I) and membrane expressed type I IFN receptor (IFNAR). In mouse and human cells, NDV is a strong inducer of the type I IFN response. The early phase of this is initiated by signaling through RIG?I and the late response by signaling through IFNAR. EBOV does not induce type I IFN responses in humans as it has viral proteins that specifically and strongly interfere with RIG?I and IFNAR signaling, as well as immune activation. In this review, we discuss whether the beneficial effects of one virus can be exploited in the fight against the detrimental effects of the other. PMID:25998621

  1. [Ebola virus disease in West Africa and Germany : Clinical presentation, management and practical experience with medevacuated patients in Germany].

    PubMed

    Schmiedel, Stefan; Kreuels, B

    2015-07-01

    Ebolaviruses are the causative pathogens of a severe form of viral haemorrhagic fever with cytokine induced shock and multi-organ failure and a high case fatality rate in humans (50-90?%, more than 70?% in the beginning of the current outbreak), designated Ebola haemorrhagic fever or Ebola virus disease (EVD). Ebola is endemic in regions of Central and West Africa. Ebolavirus Zaire (EBOV) is the most aggressive Ebola virus species and is causing the current epidemic. Currently, beginning in late 2013, an unprecedented epidemic with several thousand cases and deaths (as per WHO report 24.12.2014: 19,497 documented cases, 7588 death, 2352 cases in past 3 weeks) is unfolding in Guinea, Liberia and Sierra Leone, and spreading to other countries in Africa, Europe and the USA, where isolated cases have occurred. Ebola transmission occurs exclusively through direct contact with body fluids through mucosal surfaces, skin abrasions, or by parenteral introduction-an aerolised transmission has not been reported so far. Infections in healthcare personnel have not only occurred after needle stick injuries but also after unsafe doffing procedures of personal protection equipment (PPE). The protection of healthcare personnel caring for Ebola patients, therefore, requires that high standards in the use of PPE are mandatory. In high-income countries the management and treatment of EVD patients in specialized centres is recommended. Using negative pressure rooms and positive pressure suits may provide additional safety. Due to the high degree of training and monitoring needed to prevent occupational risks, treatment of EVD patients in non-specialized hospitals should not take place. PMID:25963641

  2. DNA Topoisomerase 1 Facilitates the Transcription and Replication of the Ebola Virus Genome

    PubMed Central

    Takahashi, Kei; Halfmann, Peter; Oyama, Masaaki; Kozuka-Hata, Hiroko

    2013-01-01

    Ebola virus (EBOV) protein L (EBOL) acts as a viral RNA-dependent RNA polymerase. To better understand the mechanisms underlying the transcription and replication of the EBOV genome, we sought to identify cellular factors involved in these processes via their coimmunoprecipitation with EBOL and by mass spectrometry. Of 65 candidate proteins identified, we focused on DNA topoisomerase 1 (TOP1), which localizes to the nucleus and unwinds helical DNA. We found that in the presence of EBOL, TOP1 colocalizes and interacts with EBOL in the cytoplasm, where transcription and replication of the EBOV genome occur. Knockdown of TOP1 markedly reduced virus replication and viral polymerase activity. We also found that the phosphodiester bridge-cleaving and recombination activities of TOP1 are required for the polymerase activity of EBOL. These results demonstrate that TOP1 is an important cellular factor for the transcription and replication of the EBOV genome and, as such, plays a key role in the EBOV life cycle. PMID:23658456

  3. DRBP76 Associates With Ebola Virus VP35 and Suppresses Viral Polymerase Function

    PubMed Central

    Shabman, Reed S.; Leung, Daisy W.; Johnson, Joshua; Glennon, Nicole; Gulcicek, Erol E.; Stone, Kathryn L.; Leung, Lawrence; Hensley, Lisa; Amarasinghe, Gaya K.

    2011-01-01

    The Zaire Ebola virus (EBOV) protein VP35 is multifunctional; it inhibits IFN-?/? production and functions as a cofactor of the viral RNA polymerase. Mass spectrometry identified the double stranded RNA binding protein 76 (DRBP76/NFAR-1/NF90) as a cellular factor that associates with the VP35 C-terminal interferon inhibitory domain (IID). DRBP76 is described to regulate host cell protein synthesis and play an important role in host defense. The VP35-IID-DRBP76 interaction required the addition of exogenous dsRNA, but full-length VP35 associated with DRBP76 in the absence of exogenous dsRNA. Cells infected with a Newcastle disease virus (NDV)–expressing VP35 redistributed DRBP76 from the nucleus to the cytoplasm, the compartment in which EBOV replicates. Overexpression of DRBP76 did not alter the ability of VP35 to inhibit type I IFN production but did impair the function of the EBOV transcription/replication complex. These data suggest that DRBP76, via its association with VP35, exerts an anti-EBOV function. PMID:21987769

  4. DNA Vaccines Expressing either the GP or NP Genes of Ebola Virus Protect Mice from Lethal Challenge

    Microsoft Academic Search

    Lorna Vanderzanden; Mike Bray; Deborah Fuller; Tim Roberts; David Custer; Kristin Spik; Peter Jahrling; John Huggins; Alan Schmaljohn; Connie Schmaljohn

    1998-01-01

    DNA vaccines expressing the envelope glycoprotein (GP) or nucleocapsid protein (NP) genes of Ebola virus were evaluated in adult, immunocompetent mice. The vaccines were delivered into the skin by particle bombardment of DNA-coated gold beads with thePowderJect-XRgene gun. Both vaccines elicited antibody responses as measured by ELISA and elicited cytotoxic T cell responses as measured by chromium release assays. From

  5. Shed GP of Ebola Virus Triggers Immune Activation and Increased Vascular Permeability

    PubMed Central

    Escudero-Pérez, Beatriz; Volchkova, Valentina A.; Dolnik, Olga; Lawrence, Philip; Volchkov, Viktor E.

    2014-01-01

    During Ebola virus (EBOV) infection a significant amount of surface glycoprotein GP is shed from infected cells in a soluble form due to cleavage by cellular metalloprotease TACE. Shed GP and non-structural secreted glycoprotein sGP, both expressed from the same GP gene, have been detected in the blood of human patients and experimentally infected animals. In this study we demonstrate that shed GP could play a particular role during EBOV infection. In effect it binds and activates non-infected dendritic cells and macrophages inducing the secretion of pro- and anti-inflammatory cytokines (TNF?, IL1?, IL6, IL8, IL12p40, and IL1-RA, IL10). Activation of these cells by shed GP correlates with the increase in surface expression of co-stimulatory molecules CD40, CD80, CD83 and CD86. Contrary to shed GP, secreted sGP activates neither DC nor macrophages while it could bind DCs. In this study, we show that shed GP activity is likely mediated through cellular toll-like receptor 4 (TLR4) and is dependent on GP glycosylation. Treatment of cells with anti-TLR4 antibody completely abolishes shed GP-induced activation of cells. We also demonstrate that shed GP activity is negated upon addition of mannose-binding sera lectin MBL, a molecule known to interact with sugar arrays present on the surface of different microorganisms. Furthermore, we highlight the ability of shed GP to affect endothelial cell function both directly and indirectly, demonstrating the interplay between shed GP, systemic cytokine release and increased vascular permeability. In conclusion, shed GP released from virus-infected cells could activate non-infected DCs and macrophages causing the massive release of pro- and anti-inflammatory cytokines and effect vascular permeability. These activities could be at the heart of the excessive and dysregulated inflammatory host reactions to infection and thus contribute to high virus pathogenicity. PMID:25412102

  6. Two Synthetic Antibodies that Recognize and Neutralize Distinct Proteolytic Forms of the Ebola Virus Envelope Glycoprotein

    PubMed Central

    Koellhoffer, Jayne F.; Chen, Gang; Sandesara, Rohini G.; Bale, Shridhar; Saphire, Erica Ollmann

    2013-01-01

    Ebola Virus (EBOV) is a highly pathogenic member of the family Filoviridae of viruses that causes severe hemorrhagic fever. Infection proceeds through fusion of the host cell and viral membranes, a process that is mediated by the viral envelope glycoprotein (GP). Following endosomal uptake, a key step in viral entry is the proteolytic cleavage of GP by host endosomal cysteine proteases. Cleavage exposes a binding site for the host cell receptor Niemann-Pick C1 (NPC1) and may induce conformational changes in GP leading to membrane fusion. However, the precise details of the structural changes in GP associated with proteolysis and the role of these changes in viral entry have not been established. Here, we have employed synthetic antibody technology to identify antibodies targeting EBOV GP prior to and following proteolysis (i.e. in the “uncleaved” [GPUNCL] and “cleaved” [GPCL] forms). We identified antibodies with distinct recognition profiles: FabCL bound preferentially to GPCL (EC50 = 1.7 nM), whereas FabUNCL bound specifically to GPUNCL (EC50 = 75 nM). Neutralization assays with GP-containing pseudotyped viruses indicated that these antibodies inhibited GPCL or GPUNCL mediated viral entry with specificity matching their recognition profiles (IC50: 87 nM for IgGCL; 1 ?M for FabUNCL). Competition ELISAs indicate that FabCL binds an epitope distinct from that of KZ52, a well-characterized EBOV GP antibody, and from that of the luminal domain of NPC1. The binding epitope of FabUNCL was also distinct from that of KZ52, suggesting that FabUNCL binds a novel neutralization epitope on GPUNCL. Furthermore, the neutralizing ability of FabCL suggests that there are targets on GPCL available for neutralization. This work showcases the applicability of synthetic antibody technology to the study of viral membrane fusion, and provides new tools for dissecting intermediates of EBOV entry. PMID:23111988

  7. Ebola Virus Outbreak among Wild Chimpanzees Living in a Rain Forest of Co^te Pierre Formenty, Christophe Boesch, Monique Wyers, World Health Organization (WHO), TaiF Forest Project, and Centre

    E-print Network

    S120 Ebola Virus Outbreak among Wild Chimpanzees Living in a Rain Forest of Co^te d'Ivoire Pierre, Paris, France An outbreak of Ebola in nature is described for the first time. During a few weeks. Laboratory procedures included histology, immunohistochemistry, bacteriology, and serology. Ebola

  8. Analyse d'chantillons de sang au CIRMF au Gabon, collects lors de l'pidmie de virus Ebola en RDC en 2007. ( CIRMF) Alors qu'une pidmie d'Ebola fait rage depuis mars 2014 en Afrique de l'Ouest,

    E-print Network

    Analyse d'échantillons de sang au CIRMF au Gabon, collectés lors de l'épidémie de virus Ebola en RDC en 2007. (© CIRMF) Alors qu'une épidémie d'Ebola fait rage depuis mars 2014 en Afrique de l. Les épidémies d'Ebola sévissent depuis plus de 30 ans en Afrique centrale. Depuis le premier cas

  9. A Highly Conserved GEQYQQLR Epitope Has Been Identified in the Nucleoprotein of Ebola Virus by Using an In Silico Approach

    PubMed Central

    Ali, Mohammad Tuhin; Islam, Md Ohedul

    2015-01-01

    Ebola virus (EBOV) is a deadly virus that has caused several fatal outbreaks. Recently it caused another outbreak and resulted in thousands afflicted cases. Effective and approved vaccine or therapeutic treatment against this virus is still absent. In this study, we aimed to predict B-cell epitopes from several EBOV encoded proteins which may aid in developing new antibody-based therapeutics or viral antigen detection method against this virus. Multiple sequence alignment (MSA) was performed for the identification of conserved region among glycoprotein (GP), nucleoprotein (NP), and viral structural proteins (VP40, VP35, and VP24) of EBOV. Next, different consensus immunogenic and conserved sites were predicted from the conserved region(s) using various computational tools which are available in Immune Epitope Database (IEDB). Among GP, NP, VP40, VP35, and VP30 protein, only NP gave a 100% conserved GEQYQQLR B-cell epitope that fulfills the ideal features of an effective B-cell epitope and could lead a way in the milieu of Ebola treatment. However, successful in vivo and in vitro studies are prerequisite to determine the actual potency of our predicted epitope and establishing it as a preventing medication against all the fatal strains of EBOV. PMID:25709646

  10. Evaluating Clinical Trial Designs for Investigational Treatments of Ebola Virus Disease

    PubMed Central

    Cooper, Ben S.; Boni, Maciej F.; Pan-ngum, Wirichada; Day, Nicholas P. J.; Horby, Peter W.; Olliaro, Piero; Lang, Trudie; White, Nicholas J.; White, Lisa J.; Whitehead, John

    2015-01-01

    Background Experimental treatments for Ebola virus disease (EVD) might reduce EVD mortality. There is uncertainty about the ability of different clinical trial designs to identify effective treatments, and about the feasibility of implementing individually randomised controlled trials during an Ebola epidemic. Methods and Findings A treatment evaluation programme for use in EVD was devised using a multi-stage approach (MSA) with two or three stages, including both non-randomised and randomised elements. The probabilities of rightly or wrongly recommending the experimental treatment, the required sample size, and the consequences for epidemic outcomes over 100 d under two epidemic scenarios were compared for the MSA, a sequential randomised controlled trial (SRCT) with up to 20 interim analyses, and, as a reference case, a conventional randomised controlled trial (RCT) without interim analyses. Assuming 50% 14-d survival in the population treated with the current standard of supportive care, all designs had similar probabilities of identifying effective treatments correctly, while the MSA was less likely to recommend treatments that were ineffective. The MSA led to a smaller number of cases receiving ineffective treatments and faster roll-out of highly effective treatments. For less effective treatments, the MSA had a high probability of including an RCT component, leading to a somewhat longer time to roll-out or rejection. Assuming 100 new EVD cases per day, the MSA led to between 6% and 15% greater reductions in epidemic mortality over the first 100 d for highly effective treatments compared to the SRCT. Both the MSA and SRCT led to substantially fewer deaths than a conventional RCT if the tested interventions were either highly effective or harmful. In the proposed MSA, the major threat to the validity of the results of the non-randomised components is that referral patterns, standard of care, or the virus itself may change during the study period in ways that affect mortality. Adverse events are also harder to quantify without a concurrent control group. Conclusions The MSA discards ineffective treatments quickly, while reliably providing evidence concerning effective treatments. The MSA is appropriate for the clinical evaluation of EVD treatments. PMID:25874579

  11. Evaluating Environmental Persistence and Disinfection of the Ebola Virus Makona Variant

    PubMed Central

    Cook, Bradley W. M.; Cutts, Todd A.; Nikiforuk, Aidan M.; Poliquin, Philip Guillaume; Court, Deborah A.; Strong, James E.; Theriault, Steven S.

    2015-01-01

    Background: The current disease outbreak caused by the Ebola virus Makona variant (EBOV/Mak) has led to unprecedented morbidity and lethality given its geographic reach and sustained transmission. Sodium hypochlorite and ethanol are well-accepted decontamination agents, however little published evidence supports the selection of appropriate concentrations and contact times. The present study addresses the environmental robustness of EBOV/Mak and evaluates the effectiveness of sodium hypochlorite and ethanol as disinfectants. Methods: EBOV/Mak was suspended in a simulated organic soil load and dried onto surfaces. Viability was measured at 1 hour, 24 hours, 72 hours, and 192 hours. For the evaluation of disinfectants, EBOV/Mak in a simulated organic soil was dried onto stainless steel carriers and disinfected with 0.01% (v/v), 0.1% (v/v), 0.5% (v/v) and 1% (v/v) sodium hypochlorite solutions or 67% (v/v) ethanol at contact times of 1, 5 or 10 minutes. Results: EBOV/Mak persisted longer on steel and plastic surfaces (192 hours) than cotton (<24 hours). Dilute sodium hypochlorite (0.01% and 0.1%) showed little antiviral action, whereas 0.5% and 1% sodium hypochlorite solutions demonstrated recoverable virus at one minute but sterilized surfaces in five minutes. Disinfection with 67% ethanol did not fully clear infectious virions from 3/9 carriers at 1 minute but sterilized all carriers at 5 and 10 minutes. Conclusions: Sodium hypochlorite and ethanol effectively decontaminate EBOV/Mak suspended in a simulated organic load; however, selection of concentration and contact time proves critical. PMID:25875372

  12. Monitoring of Persons with Risk for Exposure to Ebola Virus Disease - United States, November 3, 2014-March 8, 2015.

    PubMed

    Stehling-Ariza, Tasha; Fisher, Emily; Vagi, Sara; Fechter-Leggett, Ethan; Prudent, Natasha; Dott, Mary; Daley, Randolph; Avchen, Rachel Nonkin

    2015-07-01

    On October 27, 2014, CDC released guidance for monitoring and movement of persons with potential Ebola virus disease (Ebola) exposure in the United States. For persons with possible exposure to Ebola, this guidance recommended risk categorization, daily monitoring during the 21-day incubation period, and, for persons in selected risk categories, movement restrictions. The purpose of the guidance was to delineate methods for early identification of symptoms among persons at potential risk for Ebola so that they could be isolated, tested, and if necessary, treated to improve their chance of survival and reduce transmission. Within 7 days, all 50 states and two local jurisdictions (New York City [NYC] and the District of Columbia [DC]) had implemented the guidelines. During November 3, 2014-March 8, 2015, a total of 10,344 persons were monitored for up to 21 days with >99% complete monitoring. This public health response demonstrated the ability of state, territorial, and local health agencies to rapidly implement systems to effectively monitor thousands of persons over a sustained period. PMID:26135588

  13. High-throughput, luciferase-based reverse genetics systems for identifying inhibitors of Marburg and Ebola viruses.

    PubMed

    Uebelhoer, Luke S; Albariño, César G; McMullan, Laura K; Chakrabarti, Ayan K; Vincent, Joel P; Nichol, Stuart T; Towner, Jonathan S

    2014-06-01

    Marburg virus (MARV) and Ebola virus (EBOV), members of the family Filoviridae, represent a significant challenge to global public health. Currently, no licensed therapies exist to treat filovirus infections, which cause up to 90% mortality in human cases. To facilitate development of antivirals against these viruses, we established two distinct screening platforms based on MARV and EBOV reverse genetics systems that express secreted Gaussia luciferase (gLuc). The first platform is a mini-genome replicon to screen viral replication inhibitors using gLuc quantification in a BSL-2 setting. The second platform is complementary to the first and expresses gLuc as a reporter gene product encoded in recombinant infectious MARV and EBOV, thereby allowing for rapid quantification of viral growth during treatment with antiviral compounds. We characterized these viruses by comparing luciferase activity to virus production, and validated luciferase activity as an authentic real-time measure of viral growth. As proof of concept, we adapt both mini-genome and infectious virus platforms to high-throughput formats, and demonstrate efficacy of several antiviral compounds. We anticipate that both approaches will prove highly useful in the development of anti-filovirus therapies, as well as in basic research on the filovirus life cycle. PMID:24713118

  14. Structure of the Ebola virus glycoprotein bound to a human survivor antibody

    PubMed Central

    Lee, Jeffrey E.; Fusco, Marnie L.; Hessell, Ann J.; Oswald, Wendelien B.; Burton, Dennis R.; Saphire, Erica Ollmann

    2008-01-01

    Ebola virus (EBOV) entry requires the surface glycoprotein, GP, to initiate attachment and fusion of viral and host membranes. Here, we report the crystal structure of EBOV GP in its trimeric, pre-fusion conformation (GP1+GP2) bound to a neutralizing antibody, KZ52, derived from a human survivor of the 1995 Kikwit outbreak. Three GP1 viral attachment subunits assemble to form a chalice, cradled by the GP2 fusion subunits, while a novel glycan cap and projected mucin-like domain restrict access to the conserved receptor-binding site sequestered in the chalice bowl. The glycocalyx surrounding GP is likely central to immune evasion and may explain why survivors have insignificant neutralizing antibody titres. KZ52 recognizes a protein epitope at the chalice base where it clamps several regions of the pre-fusion GP2 to the N terminus of GP1. This structure now provides a template for unraveling the mechanism of EBOV GP-mediated fusion and for future immunotherapeutic development. PMID:18615077

  15. Estimating the Reproduction Number of Ebola Virus (EBOV) During the 2014 Outbreak in West Africa

    PubMed Central

    Althaus, Christian L.

    2014-01-01

    The 2014 Ebola virus (EBOV) outbreak in West Africa is the largest outbreak of the genus Ebolavirus to date. To better understand the spread of infection in the affected countries, it is crucial to know the number of secondary cases generated by an infected index case in the absence and presence of control measures, i.e., the basic and effective reproduction number. In this study, I describe the EBOV epidemic using an SEIR (susceptible-exposed-infectious-recovered) model and fit the model to the most recent reported data of infected cases and deaths in Guinea, Sierra Leone and Liberia. The maximum likelihood estimates of the basic reproduction number are 1.51 (95% confidence interval [CI]: 1.50-1.52) for Guinea, 2.53 (95% CI: 2.41-2.67) for Sierra Leone and 1.59 (95% CI: 1.57-1.60) for Liberia. The model indicates that in Guinea and Sierra Leone the effective reproduction number might have dropped to around unity by the end of May and July 2014, respectively. In Liberia, however, the model estimates no decline in the effective reproduction number by end-August 2014. This suggests that control efforts in Liberia need to be improved substantially in order to stop the current outbreak. PMID:25642364

  16. Structure of the Ebola Virus Glycoprotein Bound to An Antibody From a Human Survivor

    SciTech Connect

    Lee, J.E.; Fusco, M.L.; Hessell, A.J.; Oswald, W.B.; Burton, D.R.; Saphire, E.O.

    2009-05-20

    Ebola virus (EBOV) entry requires the surface glycoprotein (GP) to initiate attachment and fusion of viral and host membranes. Here we report the crystal structure of EBOV GP in its trimeric, pre-fusion conformation (GP1+GP2) bound to a neutralizing antibody, KZ52, derived from a human survivor of the 1995 Kikwit outbreak. Three GP1 viral attachment subunits assemble to form a chalice, cradled by the GP2 fusion subunits, while a novel glycan cap and projected mucin-like domain restrict access to the conserved receptor-binding site sequestered in the chalice bowl. The glycocalyx surrounding GP is likely central to immune evasion and may explain why survivors have insignificant neutralizing antibody titres. KZ52 recognizes a protein epitope at the chalice base where it clamps several regions of the pre-fusion GP2 to the amino terminus of GP1. This structure provides a template for unraveling the mechanism of EBOV GP-mediated fusion and for future immunotherapeutic development.

  17. Ebola virus disease outbreak in Nigeria: Transmission dynamics and rapid control.

    PubMed

    Althaus, C L; Low, N; Musa, E O; Shuaib, F; Gsteiger, S

    2015-06-01

    International air travel has already spread Ebola virus disease (EVD) to major cities as part of the unprecedented epidemic that started in Guinea in December 2013. An infected airline passenger arrived in Nigeria on July 20, 2014 and caused an outbreak in Lagos and then Port Harcourt. After a total of 20 reported cases, including 8 deaths, Nigeria was declared EVD free on October 20, 2014. We quantified the impact of early control measures in preventing further spread of EVD in Nigeria and calculated the risk that a single undetected case will cause a new outbreak. We fitted an EVD transmission model to data from the outbreak in Nigeria and estimated the reproduction number of the index case at 9.0 (95% confidence interval [CI]: 5.2-15.6). We also found that the net reproduction number fell below unity 15 days (95% CI: 11-21 days) after the arrival of the index case. Hence, our study illustrates the time window for successful containment of EVD outbreaks caused by infected air travelers. PMID:25979285

  18. Antibody-mediated neutralization of Ebola virus can occur by two distinct mechanisms

    SciTech Connect

    Shedlock, Devon J., E-mail: shedlock@mail.med.upenn.ed [Biodefense Research Section, Vaccine Research Center, National Institute for Allergy and Infectious Disease, National Institutes of Health, 40 Convent Drive, MSC 3005, Bethesda, MD 20814 (United States); Bailey, Michael A., E-mail: mike.bailey@taurigroup.co [Biodefense Research Section, Vaccine Research Center, National Institute for Allergy and Infectious Disease, National Institutes of Health, 40 Convent Drive, MSC 3005, Bethesda, MD 20814 (United States); Popernack, Paul M. [Biodefense Research Section, Vaccine Research Center, National Institute for Allergy and Infectious Disease, National Institutes of Health, 40 Convent Drive, MSC 3005, Bethesda, MD 20814 (United States); Cunningham, James M. [Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115 (United States); Burton, Dennis R. [Department of Immunology, Scripps Research Institute, La Jolla, CA 92037 (United States); Department of Molecular Biology, Scripps Research Institute, La Jolla, CA 92037 (United States); Sullivan, Nancy J., E-mail: nsullivan@nih.go [Biodefense Research Section, Vaccine Research Center, National Institute for Allergy and Infectious Disease, National Institutes of Health, 40 Convent Drive, MSC 3005, Bethesda, MD 20814 (United States)

    2010-06-05

    Human Ebola virus causes severe hemorrhagic fever disease with high mortality and there is no vaccine or treatment. Antibodies in survivors occur early, are sustained, and can delay infection when transferred into nonhuman primates. Monoclonal antibodies (mAbs) from survivors exhibit potent neutralizing activity in vitro and are protective in rodents. To better understand targets and mechanisms of neutralization, we investigated a panel of mAbs shown previously to react with the envelope glycoprotein (GP). While one non-neutralizing mAb recognized a GP epitope in the nonessential mucin-like domain, the rest were specific for GP1, were neutralizing, and could be further distinguished by reactivity with secreted GP. We show that survivor antibodies, human KZ52 and monkey JP3K11, were specific for conformation-dependent epitopes comprising residues in GP1 and GP2 and that neutralization occurred by two distinct mechanisms; KZ52 inhibited cathepsin cleavage of GP whereas JP3K11 recognized the cleaved, fusion-active form of GP.

  19. Epidemiological and Surveillance Response to Ebola Virus Disease Outbreak in Lofa County, Liberia (March-September, 2014); Lessons Learned.

    PubMed

    Kouadio, Koffi Isidore; Clement, Peter; Bolongei, Josephus; Tamba, Alpha; Gasasira, Alex Ntale; Warsame, Abdihamid; Okeibunor, Joseph Chukwudi; Ota, Martin Okechukwu; Tamba, Boima; Gumede, Nicksy; Shaba, Keith; Poy, Alain; Salla, Mbaye; Mihigo, Richard; Nshimirimana, Deo

    2015-01-01

    Ebola Virus Disease (EVD) outbreak was confirmed in Liberia on March 31st 2014. A response comprising of diverse expertise was mobilized and deployed to the country to contain transmission of Ebola and give relief to a people already impoverished from protracted civil war. This paper describes the epidemiological and surveillance response to the EVD outbreak in Lofa County in Liberia from March to September 2014. Five of the 6 districts of Lofa were affected. The most affected districts were Voinjama/Guardu Gbondi and Foya. By 26th September, 2014, a total of 619 cases, including 19.4% probable cases, 20.3% suspected cases and 44.2% confirmed cases were recorded by the Ebola Emergency Response Team (EERT) of Lofa County. Adults (20-50 years) were the most affected. Overall fatality rate was 53.3%.  Twenty two (22) cases were reported among the Health Care Workers with a fatality rate of 81.8%. Seventy eight percent (78%) of the contacts successfully completed 21 days follow-up while 134 (6.15%) that developed signs and symptoms of EVD were referred to the ETU in Foya. The contributions of the weak health systems as well as socio-cultural factors in fueling the epidemic are highlighted. Importantly, the lessons learnt including the positive impact of multi-sectorial and multidisciplinary and coordinated response led by the government and community.  Again, given that the spread of infectious disease can be considered a security threat every effort has to put in place to strengthen the health systems in developing countries including the International Health Regulation (IHR)'s core capacities. Key words:  Ebola virus disease, outbreak, epidemiology and surveillance, socio-cultural factors, health system, West Africa. PMID:26064783

  20. Epidemiological and Surveillance Response to Ebola Virus Disease Outbreak in Lofa County, Liberia (March-September, 2014); Lessons Learned

    PubMed Central

    Kouadio, Koffi Isidore; Clement, Peter; Bolongei, Josephus; Tamba, Alpha; Gasasira, Alex Ntale; Warsame, Abdihamid; Okeibunor, Joseph Chukwudi; Ota, Martin Okechukwu; Tamba, Boima; Gumede, Nicksy; Shaba, Keith; Poy, Alain; Salla, Mbaye; Mihigo, Richard; Nshimirimana, Deo

    2015-01-01

    Ebola Virus Disease (EVD) outbreak was confirmed in Liberia on March 31st 2014. A response comprising of diverse expertise was mobilized and deployed to the country to contain transmission of Ebola and give relief to a people already impoverished from protracted civil war. This paper describes the epidemiological and surveillance response to the EVD outbreak in Lofa County in Liberia from March to September 2014. Five of the 6 districts of Lofa were affected. The most affected districts were Voinjama/Guardu Gbondi and Foya. By 26th September, 2014, a total of 619 cases, including 19.4% probable cases, 20.3% suspected cases and 44.2% confirmed cases were recorded by the Ebola Emergency Response Team (EERT) of Lofa County. Adults (20-50 years) were the most affected. Overall fatality rate was 53.3%.  Twenty two (22) cases were reported among the Health Care Workers with a fatality rate of 81.8%. Seventy eight percent (78%) of the contacts successfully completed 21 days follow-up while 134 (6.15%) that developed signs and symptoms of EVD were referred to the ETU in Foya. The contributions of the weak health systems as well as socio-cultural factors in fueling the epidemic are highlighted. Importantly, the lessons learnt including the positive impact of multi-sectorial and multidisciplinary and coordinated response led by the government and community.  Again, given that the spread of infectious disease can be considered a security threat every effort has to put in place to strengthen the health systems in developing countries including the International Health Regulation (IHR)’s core capacities. Key words:  Ebola virus disease, outbreak, epidemiology and surveillance, socio-cultural factors, health system, West Africa. 

  1. [Epidemiology of Ebola virus disease and of other highly contagious, life-threatening diseases with low incidence in Germany].

    PubMed

    Ehlkes, L; Kreuels, B; Schwarz, N G; May, Jürgen

    2015-07-01

    Apart from sporadic exported cases, the occurrence of Ebola, Marburg and Lassa virus diseases is limited to the African continent. Crimean-Congo Hemorrhagic Fever occurs in Southeastern Europe but, so far, not in Germany. Other hemorrhagic fever disease-viruses occur in distinct regions in South America. Pulmonary plague is the bacterial infectious disease with the most contagious and lethal course and it is endemic to Madagascar and East Africa, but also occurs in other countries (e.g. India, USA). Monkey pox epidemics have occurred in remote areas of the Congo Basin. Such outbreaks could potentially become more common with the discontinuation of the cross-protective smallpox vaccination. The Severe Acute Respiratory Syndrome (SARS) that emerged in 2002/2003 is another pathogen with significant epidemic potential. Typical for these diseases is a natural circulation between reservoir animals in remote areas. Sporadic transmission to humans can occur through contact with an infected animal. Subsequent human-to-human transmission can lead to epidemics, such as the current outbreak of Ebola virus disease in West Africa. PMID:25997608

  2. Determination of Specific Antibody Responses to the Six Species of Ebola and Marburg Viruses by Multiplexed Protein Microarrays

    PubMed Central

    Kamata, Teddy; Natesan, Mohan; Warfield, Kelly; Aman, M. Javad

    2014-01-01

    Infectious hemorrhagic fevers caused by the Marburg and Ebola filoviruses result in human mortality rates of up to 90%, and there are no effective vaccines or therapeutics available for clinical use. The highly infectious and lethal nature of these viruses highlights the need for reliable and sensitive diagnostic methods. We assembled a protein microarray displaying nucleoprotein (NP), virion protein 40 (VP40), and glycoprotein (GP) antigens from isolates representing the six species of filoviruses for use as a surveillance and diagnostic platform. Using the microarrays, we examined serum antibody responses of rhesus macaques vaccinated with trivalent (GP, NP, and VP40) virus-like particles (VLP) prior to infection with the Marburg virus (MARV) (i.e., Marburg marburgvirus) or the Zaire virus (ZEBOV) (i.e., Zaire ebolavirus). The microarray-based assay detected a significant increase in antigen-specific IgG resulting from immunization, while a greater level of antibody responses resulted from challenge of the vaccinated animals with ZEBOV or MARV. Further, while antibody cross-reactivities were observed among NPs and VP40s of Ebola viruses, antibody recognition of GPs was very specific. The performance of mucin-like domain fragments of GP (GP mucin) expressed in Escherichia coli was compared to that of GP ectodomains produced in eukaryotic cells. Based on results with ZEBOV and MARV proteins, antibody recognition of GP mucins that were deficient in posttranslational modifications was comparable to that of the eukaryotic cell-expressed GP ectodomains in assay performance. We conclude that the described protein microarray may translate into a sensitive assay for diagnosis and serological surveillance of infections caused by multiple species of filoviruses. PMID:25230936

  3. Use of the Syrian Hamster as a New Model of Ebola Virus Disease and Other Viral Hemorrhagic Fevers

    PubMed Central

    Wahl-Jensen, Victoria; Bollinger, Laura; Safronetz, David; de Kok-Mercado, Fabian; Scott, Dana P.; Ebihara, Hideki

    2012-01-01

    Historically, mice and guinea pigs have been the rodent models of choice for therapeutic and prophylactic countermeasure testing against Ebola virus disease (EVD). Recently, hamsters have emerged as a novel animal model for the in vivo study of EVD. In this review, we discuss the history of the hamster as a research laboratory animal, as well as current benefits and challenges of this model. Availability of immunological reagents is addressed. Salient features of EVD in hamsters, including relevant pathology and coagulation parameters, are compared directly with the mouse, guinea pig and nonhuman primate models. PMID:23242370

  4. Mutations Abrogating VP35 Interaction with Double-Stranded RNA Render Ebola Virus Avirulent in Guinea Pigs

    SciTech Connect

    Prins, Kathleen C.; Delpeut, Sebastien; Leung, Daisy W.; Reynard, Olivier; Volchkova, Valentina A.; Reid, St. Patrick; Ramanan, Parameshwaran; Cárdenas, Washington B.; Amarasinghe, Gaya K.; Volchkov, Viktor E.; Basler, Christopher F. (CNRS-INSERM); (Mount Sinai Hospital); (LB-Ecuador); (Iowa State)

    2010-10-11

    Ebola virus (EBOV) protein VP35 is a double-stranded RNA (dsRNA) binding inhibitor of host interferon (IFN)-{alpha}/{beta} responses that also functions as a viral polymerase cofactor. Recent structural studies identified key features, including a central basic patch, required for VP35 dsRNA binding activity. To address the functional significance of these VP35 structural features for EBOV replication and pathogenesis, two point mutations, K319A/R322A, that abrogate VP35 dsRNA binding activity and severely impair its suppression of IFN-{alpha}/{beta} production were identified. Solution nuclear magnetic resonance (NMR) spectroscopy and X-ray crystallography reveal minimal structural perturbations in the K319A/R322A VP35 double mutant and suggest that loss of basic charge leads to altered function. Recombinant EBOVs encoding the mutant VP35 exhibit, relative to wild-type VP35 viruses, minimal growth attenuation in IFN-defective Vero cells but severe impairment in IFN-competent cells. In guinea pigs, the VP35 mutant virus revealed a complete loss of virulence. Strikingly, the VP35 mutant virus effectively immunized animals against subsequent wild-type EBOV challenge. These in vivo studies, using recombinant EBOV viruses, combined with the accompanying biochemical and structural analyses directly correlate VP35 dsRNA binding and IFN inhibition functions with viral pathogenesis. Moreover, these studies provide a framework for the development of antivirals targeting this critical EBOV virulence factor.

  5. Recombinant lentogenic Newcastle disease virus expressing Ebola virus GP infects cells independently of exogenous trypsin and uses macropinocytosis as the major pathway for cell entry

    PubMed Central

    2013-01-01

    Background Using reverse genetics, we generated a recombinant low-pathogenic LaSota strain Newcastle disease virus (NDV) expressing the glycoprotein (GP) of Ebola virus (EBOV), designated rLa-EBOVGP, and evaluated its biological characteristic in vivo and in vitro. Results The introduction and expression of the EBOV GP gene did not increase the virulence of the NDV vector in poultry or mice. EBOV GP was incorporated into the particle of the vector virus and the recombinant virus rLa-EBOVGP infected cells and spread within them independently of exogenous trypsin. rLa-EBOVGP is more resistant to NDV antiserum than the vector NDV and is moderately sensitive to EBOV GP antiserum. More importantly, infection with rLa-EBOVGP was markedly inhibited by IPA3, indicating that rLa-EBOVGP uses macropinocytosis as the major internalization pathway for cell entry. Conclusions The results demonstrate that EBOV GP in recombinant NDV particles functions independently to mediate the viral infection of the host cells and alters the cell-entry pathway. PMID:24209904

  6. [Multiple Ebola virus haemorrhagic fever outbreaks in Gabon, from October 2001 to April 2002].

    PubMed

    Nkoghe, D; Formenty, P; Leroy, E M; Nnegue, S; Edou, S Y Obame; Ba, J Iba; Allarangar, Y; Cabore, J; Bachy, C; Andraghetti, R; de Benoist, A C; Galanis, E; Rose, A; Bausch, D; Reynolds, M; Rollin, P; Choueibou, C; Shongo, R; Gergonne, B; Koné, L M; Yada, A; Roth, C; Mve, M Toung

    2005-09-01

    Outbreaks of Ebola virus haemorrhagic fever have been reported from 1994 to 1996 in the province of Ogooué Ivindo, a forest zone situated in the Northeast of Gabon. Each time, the great primates had been identified as the initial source of human infection. End of November 2001 a new alert came from this province, rapidly confirmed as a EVHV outbreak. The response was given by the Ministry of Health with the help of an international team under the aegis of WHO. An active monitoring system was implemented in the three districts hit by the epidemic (Zadié, Ivindo and Mpassa) to organize the detection of cases and their follow-up. A case definition has been set up, the suspected cases were isolated at hospital, at home or in lazarets and serological tests were performed. These tests consisted of the detection of antigen or specific IgG and the RT-PCR. A classification of cases was made according to the results of biological tests, clinical and epidemiological data. The contact subjects were kept watch over for 21 days. 65 cases were recorded among which 53 deaths. The first human case, a hunter died on the 28th of October 2001. The epidemic spreads over through family transmission and nosocomial contamination. Four distinct primary foci have been identified together with an isolated case situated in the South East of Gabon, 580 km away from the epicenter. Deaths happened within a delay of 6 days. The last death has been recorded on the 22nd of March 2002 and the end of the outbreak was declared on the 6th of May 2002. The epidemic spreads over the Gabon just next. Unexplained deaths of animals had been mentionned in the nearby forests as soon as August 2001: great primates and cephalophus. Samples taken from their carcasses confirmed a concomitant animal epidemic. PMID:16267965

  7. Comprehensive Functional Analysis of N-Linked Glycans on Ebola Virus GP1

    PubMed Central

    Lennemann, Nicholas J.; Rhein, Bethany A.; Ndungo, Esther; Chandran, Kartik; Qiu, Xiangguo; Maury, Wendy

    2014-01-01

    ABSTRACT Ebola virus (EBOV) entry requires the virion surface-associated glycoprotein (GP) that is composed of a trimer of heterodimers (GP1/GP2). The GP1 subunit contains two heavily glycosylated domains, the glycan cap and the mucin-like domain (MLD). The glycan cap contains only N-linked glycans, whereas the MLD contains both N- and O-linked glycans. Site-directed mutagenesis was performed on EBOV GP1 to systematically disrupt N-linked glycan sites to gain an understanding of their role in GP structure and function. All 15 N-glycosylation sites of EBOV GP1 could be removed without compromising the expression of GP. The loss of these 15 glycosylation sites significantly enhanced pseudovirion transduction in Vero cells, which correlated with an increase in protease sensitivity. Interestingly, exposing the receptor-binding domain (RBD) by removing the glycan shield did not allow interaction with the endosomal receptor, NPC1, indicating that the glycan cap/MLD domains mask RBD residues required for binding. The effects of the loss of GP1 N-linked glycans on Ca2+-dependent (C-type) lectin (CLEC)-dependent transduction were complex, and the effect was unique for each of the CLECs tested. Surprisingly, EBOV entry into murine peritoneal macrophages was independent of GP1 N-glycans, suggesting that CLEC-GP1 N-glycan interactions are not required for entry into this important primary cell. Finally, the removal of all GP1 N-glycans outside the MLD enhanced antiserum and antibody sensitivity. In total, our results provide evidence that the conserved N-linked glycans on the EBOV GP1 core protect GP from antibody neutralization despite the negative impact the glycans have on viral entry efficiency. PMID:24473128

  8. A multiagent filovirus DNA vaccine delivered by intramuscular electroporation completely protects mice from ebola and Marburg virus challenge

    PubMed Central

    Grant-Klein, Rebecca J.; Van Deusen, Nicole M.; Badger, Catherine V.; Hannaman, Drew; Dupuy, Lesley C.; Schmaljohn, Connie S.

    2012-01-01

    We evaluated the immunogenicity and protective efficacy of DNA vaccines expressing the codon-optimized envelope glycoprotein genes of Zaire ebolavirus, Sudan ebolavirus, and Marburg marburgvirus (Musoke and Ravn). Intramuscular or intradermal delivery of the vaccines in BALB/c mice was performed using the TriGrid™ electroporation device. Mice that received DNA vaccines against the individual viruses developed robust glycoprotein-specific antibody titers as determined by ELISA and survived lethal viral challenge with no display of clinical signs of infection. Survival curve analysis revealed there was a statistically significant increase in survival compared to the control groups for both the Ebola and Ravn virus challenges. These data suggest that further analysis of the immune responses generated in the mice and additional protection studies in nonhuman primates are warranted. PMID:22922764

  9. [Health Communication: Preventing the Spread of Ebola Virus Disease in the Portuguese Spoken African Countries - Methodology KISS & KEYWORDS].

    PubMed

    De Santiago, Isabel; Miguel, José Pereira; Antunes, Francisco

    2015-01-01

    In this work, Health Communication is considered as an important discipline in medicine and health sciences for his role as true determinant of health. We highlight their contribution to health promotion and disease prevention. Thus, the Health Communication Plan (PCS): Preventing the spread of Ebola virus disease in the Portuguese Speaking African Countries - KISS & KEYWORDS methodology is a tool that aims to minimize the risk of infection by Ebola virus in the Portuguese Speaking African Countries and also train for a general improvement of health conditions of the local populations. In the PCS design are especially considered the social and cultural contexts of the target populations, especially the customs, traditions and religion. Health Communication is considered as an Essential Function of Public Health and its main is to provide a population-based approach. The target of communication actions are population groups in addition to the individual communication, target-audiences are people without access to the media, in Guinea Bissau, Cape Verde and Sao Tome and Principe. Under the communication plan uses the methodology, models and practices both by media professionals as health. A proximity approach and cultural mediation, previously identified key facts, are defined objectives; outlines to the Plan in concrete and its implementation methodology (target-audience and following intervention, materials to be used and key-messages and partners to mobilize) following the World Health Organisation standards. PMID:26061502

  10. Evaluation of Signature Erosion in Ebola Virus Due to Genomic Drift and Its Impact on the Performance of Diagnostic Assays

    PubMed Central

    Sozhamannan, Shanmuga; Holland, Mitchell Y.; Hall, Adrienne T.; Negrón, Daniel A.; Ivancich, Mychal; Koehler, Jeffrey W.; Minogue, Timothy D.; Campbell, Catherine E.; Berger, Walter J.; Christopher, George W.; Goodwin, Bruce G.; Smith, Michael A.

    2015-01-01

    Genome sequence analyses of the 2014 Ebola Virus (EBOV) isolates revealed a potential problem with the diagnostic assays currently in use; i.e., drifting genomic profiles of the virus may affect the sensitivity or even produce false-negative results. We evaluated signature erosion in ebolavirus molecular assays using an in silico approach and found frequent potential false-negative and false-positive results. We further empirically evaluated many EBOV assays, under real time PCR conditions using EBOV Kikwit (1995) and Makona (2014) RNA templates. These results revealed differences in performance between assays but were comparable between the old and new EBOV templates. Using a whole genome approach and a novel algorithm, termed BioVelocity, we identified new signatures that are unique to each of EBOV, Sudan virus (SUDV), and Reston virus (RESTV). Interestingly, many of the current assay signatures do not fall within these regions, indicating a potential drawback in the past assay design strategies. The new signatures identified in this study may be evaluated with real-time reverse transcription PCR (rRT-PCR) assay development and validation. In addition, we discuss regulatory implications and timely availability to impact a rapidly evolving outbreak using existing but perhaps less than optimal assays versus redesign these assays for addressing genomic changes. PMID:26090727

  11. Evaluation of Signature Erosion in Ebola Virus Due to Genomic Drift and Its Impact on the Performance of Diagnostic Assays.

    PubMed

    Sozhamannan, Shanmuga; Holland, Mitchell Y; Hall, Adrienne T; Negrón, Daniel A; Ivancich, Mychal; Koehler, Jeffrey W; Minogue, Timothy D; Campbell, Catherine E; Berger, Walter J; Christopher, George W; Goodwin, Bruce G; Smith, Michael A

    2015-01-01

    Genome sequence analyses of the 2014 Ebola Virus (EBOV) isolates revealed a potential problem with the diagnostic assays currently in use; i.e., drifting genomic profiles of the virus may affect the sensitivity or even produce false-negative results. We evaluated signature erosion in ebolavirus molecular assays using an in silico approach and found frequent potential false-negative and false-positive results. We further empirically evaluated many EBOV assays, under real time PCR conditions using EBOV Kikwit (1995) and Makona (2014) RNA templates. These results revealed differences in performance between assays but were comparable between the old and new EBOV templates. Using a whole genome approach and a novel algorithm, termed BioVelocity, we identified new signatures that are unique to each of EBOV, Sudan virus (SUDV), and Reston virus (RESTV). Interestingly, many of the current assay signatures do not fall within these regions, indicating a potential drawback in the past assay design strategies. The new signatures identified in this study may be evaluated with real-time reverse transcription PCR (rRT-PCR) assay development and validation. In addition, we discuss regulatory implications and timely availability to impact a rapidly evolving outbreak using existing but perhaps less than optimal assays versus redesign these assays for addressing genomic changes. PMID:26090727

  12. Ebola Virus Glycoprotein Needs an Additional Trigger, beyond Proteolytic Priming for Membrane Fusion

    Microsoft Academic Search

    Shridhar Bale; Tong Liu; Sheng Li; Yuhao Wang; Dafna Abelson; Marnie Fusco; Virgil L. Woods; Erica Ollmann Saphire

    2011-01-01

    BackgroundEbolavirus belongs to the family filoviridae and causes severe hemorrhagic fever in humans with 50–90% lethality. Detailed understanding of how the viruses attach to and enter new host cells is critical to development of medical interventions. The virus displays a trimeric glycoprotein (GP1,2) on its surface that is solely responsible for membrane attachment, virus internalization and fusion. GP1,2 is expressed

  13. Ebola virus genome plasticity as a marker of its passaging history: a comparison of in vitro passaging to non-human primate infection.

    PubMed

    Kugelman, Jeffrey R; Lee, Michael S; Rossi, Cynthia A; McCarthy, Sarah E; Radoshitzky, Sheli R; Dye, John M; Hensley, Lisa E; Honko, Anna; Kuhn, Jens H; Jahrling, Peter B; Warren, Travis K; Whitehouse, Chris A; Bavari, Sina; Palacios, Gustavo

    2012-01-01

    To identify polymorphic sites that could be used as biomarkers of Ebola virus passage history, we repeatedly amplified Ebola virus (Kikwit variant) in vitro and in vivo and performed deep sequencing analysis of the complete genomes of the viral subpopulations. We then determined the sites undergoing selection during passage in Vero E6 cells. Four locations within the Ebola virus Kikwit genome were identified that together segregate cell culture-passaged virus and virus obtained from infected non-human primates. Three of the identified sites are located within the glycoprotein gene (GP) sequence: the poly-U (RNA editing) site at position 6925, as well as positions 6677, and 6179. One site was found in the VP24 gene at position 10833. In all cases, in vitro and in vivo, both populations (majority and minority variants) were maintained in the viral swarm, with rapid selections occurring after a few passages or infections. This analysis approach will be useful to differentiate whether filovirus stocks with unknown history have been passaged in cell culture and may support filovirus stock standardization for medical countermeasure development. PMID:23209706

  14. Lectin-Dependent Enhancement of Ebola Virus Infection via Soluble and Transmembrane C-type Lectin Receptors

    PubMed Central

    Lear, Calli; Chen, Li; Yantosca, L. Michael; Scully, Corinne; Sarraju, Ashish; Sokolovska, Anna; Zariffard, M. Reza; Eisen, Damon P.; Mungall, Bruce A.; Kotton, Darrell N.; Omari, Amel; Huang, I-Chueh; Farzan, Michael; Takahashi, Kazue; Stuart, Lynda; Stahl, Gregory L.; Ezekowitz, Alan B.; Spear, Gregory T.; Olinger, Gene G.; Schmidt, Emmett V.; Michelow, Ian C.

    2013-01-01

    Mannose-binding lectin (MBL) is a key soluble effector of the innate immune system that recognizes pathogen-specific surface glycans. Surprisingly, low-producing MBL genetic variants that may predispose children and immunocompromised individuals to infectious diseases are more common than would be expected in human populations. Since certain immune defense molecules, such as immunoglobulins, can be exploited by invasive pathogens, we hypothesized that MBL might also enhance infections in some circumstances. Consequently, the low and intermediate MBL levels commonly found in human populations might be the result of balancing selection. Using model infection systems with pseudotyped and authentic glycosylated viruses, we demonstrated that MBL indeed enhances infection of Ebola, Hendra, Nipah and West Nile viruses in low complement conditions. Mechanistic studies with Ebola virus (EBOV) glycoprotein pseudotyped lentiviruses confirmed that MBL binds to N-linked glycan epitopes on viral surfaces in a specific manner via the MBL carbohydrate recognition domain, which is necessary for enhanced infection. MBL mediates lipid-raft-dependent macropinocytosis of EBOV via a pathway that appears to require less actin or early endosomal processing compared with the filovirus canonical endocytic pathway. Using a validated RNA interference screen, we identified C1QBP (gC1qR) as a candidate surface receptor that mediates MBL-dependent enhancement of EBOV infection. We also identified dectin-2 (CLEC6A) as a potentially novel candidate attachment factor for EBOV. Our findings support the concept of an innate immune haplotype that represents critical interactions between MBL and complement component C4 genes and that may modify susceptibility or resistance to certain glycosylated pathogens. Therefore, higher levels of native or exogenous MBL could be deleterious in the setting of relative hypocomplementemia which can occur genetically or because of immunodepletion during active infections. Our findings confirm our hypothesis that the pressure of infectious diseases may have contributed in part to evolutionary selection of MBL mutant haplotypes. PMID:23573288

  15. Risk Factors Associated with Ebola and Marburg Viruses Seroprevalence in Blood Donors in the Republic of Congo

    PubMed Central

    Moyen, Nanikaly; Thirion, Laurence; Emmerich, Petra; Dzia-Lepfoundzou, Amelia; Richet, Hervé; Boehmann, Yannik; Dimi, Yannick; Gallian, Pierre; Gould, Ernest A.; Günther, Stephan; de Lamballerie, Xavier

    2015-01-01

    Background Ebola and Marburg viruses (family Filoviridae, genera Ebolavirus and Marburgvirus) cause haemorrhagic fevers in humans, often associated with high mortality rates. The presence of antibodies to Ebola virus (EBOV) and Marburg virus (MARV) has been reported in some African countries in individuals without a history of haemorrhagic fever. In this study, we present a MARV and EBOV seroprevalence study conducted amongst blood donors in the Republic of Congo and the analysis of risk factors for contact with EBOV. Methodology and Findings In 2011, we conducted a MARV and EBOV seroprevalence study amongst 809 blood donors recruited in rural (75; 9.3%) and urban (734; 90.7%) areas of the Republic of Congo. Serum titres of IgG antibodies to MARV and EBOV were assessed by indirect double-immunofluorescence microscopy. MARV seroprevalence was 0.5% (4 in 809) without any identified risk factors. Prevalence of IgG to EBOV was 2.5%, peaking at 4% in rural areas and in Pointe Noire. Independent risk factors identified by multivariate analysis were contact with bats and exposure to birds. Conclusions/Significance This MARV and EBOV serological survey performed in the Republic of Congo identifies a probable role for environmental determinants of exposure to EBOV. It highlights the requirement for extending our understanding of the ecological and epidemiological risk of bats (previously identified as a potential ecological reservoir) and birds as vectors of EBOV to humans, and characterising the protection potentially afforded by EBOV-specific antibodies as detected in blood donors. PMID:26047124

  16. Crystal structure of the C-terminal domain of Ebola virus VP30 reveals a role in transcription and nucleocapsid association

    PubMed Central

    Hartlieb, Bettina; Muziol, Tadeusz; Weissenhorn, Winfried; Becker, Stephan

    2007-01-01

    Transcription of the highly pathogenic Ebola virus depends on VP30, a nucleocapsid-associated Ebola virus-specific transcription factor. The transcription activator VP30 was shown to play an essential role in Ebola virus replication, most likely by stabilizing nascent mRNA. Here we present the crystal structure of the C-terminal domain (CTD) of VP30 (VP30CTD) at 2.0-? resolution. VP30CTD folds independently into a dimeric helical assembly. The VP30CTD dimers assemble into hexamers that are present in virions, by an oligomerization domain located in the N terminus of VP30. Mutagenesis of conserved charged amino acids on VP30CTD revealed that two regions, namely a basic cluster around Lys-180 and Glu-197, are required for nucleocapsid interaction. However, only mutagenesis of the basic cluster was shown to impair transcription activation, suggesting that both processes are regulated independently. The structure and the mutagenesis results reveal a potential pocket for small-molecule inhibitors that might prevent VP30 activity and thus virus propagation as it has been shown previously by peptides, which interfere with VP30 homooligomerization. PMID:17202263

  17. Crystal structure of the C-terminal domain of Ebola virus VP30 reveals a role in transcription and nucleocapsid association.

    PubMed

    Hartlieb, Bettina; Muziol, Tadeusz; Weissenhorn, Winfried; Becker, Stephan

    2007-01-01

    Transcription of the highly pathogenic Ebola virus depends on VP30, a nucleocapsid-associated Ebola virus-specific transcription factor. The transcription activator VP30 was shown to play an essential role in Ebola virus replication, most likely by stabilizing nascent mRNA. Here we present the crystal structure of the C-terminal domain (CTD) of VP30 (VP30(CTD)) at 2.0-A resolution. VP30(CTD) folds independently into a dimeric helical assembly. The VP30(CTD) dimers assemble into hexamers that are present in virions, by an oligomerization domain located in the N terminus of VP30. Mutagenesis of conserved charged amino acids on VP30(CTD) revealed that two regions, namely a basic cluster around Lys-180 and Glu-197, are required for nucleocapsid interaction. However, only mutagenesis of the basic cluster was shown to impair transcription activation, suggesting that both processes are regulated independently. The structure and the mutagenesis results reveal a potential pocket for small-molecule inhibitors that might prevent VP30 activity and thus virus propagation as it has been shown previously by peptides, which interfere with VP30 homooligomerization. PMID:17202263

  18. Involvement of viral envelope GP2 in Ebola virus entry into cells expressing the macrophage galactose-type C-type lectin

    SciTech Connect

    Usami, Katsuaki [Laboratory of Cancer Biology and Molecular Immunology, Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo 113-0033 (Japan)] [Laboratory of Cancer Biology and Molecular Immunology, Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo 113-0033 (Japan); Matsuno, Keita; Igarashi, Manabu [Department of Global Epidemiology, Hokkaido University Research Center for Zoonosis Control, Sapporo 001-0020 (Japan)] [Department of Global Epidemiology, Hokkaido University Research Center for Zoonosis Control, Sapporo 001-0020 (Japan); Denda-Nagai, Kaori [Laboratory of Cancer Biology and Molecular Immunology, Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo 113-0033 (Japan)] [Laboratory of Cancer Biology and Molecular Immunology, Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo 113-0033 (Japan); Takada, Ayato [Department of Global Epidemiology, Hokkaido University Research Center for Zoonosis Control, Sapporo 001-0020 (Japan)] [Department of Global Epidemiology, Hokkaido University Research Center for Zoonosis Control, Sapporo 001-0020 (Japan); Irimura, Tatsuro, E-mail: irimura@mol.f.u-tokyo.ac.jp [Laboratory of Cancer Biology and Molecular Immunology, Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo 113-0033 (Japan)] [Laboratory of Cancer Biology and Molecular Immunology, Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo 113-0033 (Japan)

    2011-04-01

    Highlights: {yields} Ebola virus infection is mediated by binding to and fusion with the target cells. {yields} Structural feature of the viral glycoprotein determines the infectivity. {yields} Surface C-type lectin, MGL, of macrophages and dendritic cells mediate the infection. {yields} GP2, one of glycoprotein subunits, plays an essential role in MGL-mediated infection. {yields} There is a critical amino acid residue involved in high infectivity. -- Abstract: Ebola virus (EBOV) infection is initiated by the interaction of the viral surface envelope glycoprotein (GP) with the binding sites on target cells. Differences in the mortality among different species of the Ebola viruses, i.e., Zaire ebolavirus (ZEBOV) and Reston ebolavirus (REBOV), correspond to the in vitro infectivity of the pseudo-typed virus constructed with the GPs in cells expressing macrophage galactose-type calcium-type lectin (MGL/CD301). Through mutagenesis of GP2, the transmembrane-anchored subunit of GP, we found that residues 502-527 of the GP2 sequence determined the different infectivity between VSV-ZEBOV GP and -REBOV GP in MGL/CD301-expressing cells and a histidine residue at position 516 of ZEBOV GP2 appeared essential in the differential infectivity. These findings may provide a clue to clarify a molecular basis of different pathogenicity among EBOV species.

  19. An intrinsically disordered peptide from Ebola virus VP35 controls viral RNA synthesis by modulating nucleoprotein-RNA interactions

    DOE PAGESBeta

    Leung, Daisy  W.; Borek, Dominika; Luthra, Priya; Binning, Jennifer  M.; Anantpadma, Manu; Liu, Gai; Harvey, Ian B.; Su, Zhaoming; Endlich-Frazier, Ariel; Pan, Juanli; et al

    2015-04-01

    During viral RNA synthesis, Ebola virus (EBOV) nucleoprotein (NP) alternates between an RNA-template-bound form and a template-free form to provide the viral polymerase access to the RNA template. In addition, newly synthesized NP must be prevented from indiscriminately binding to noncognate RNAs. Here, we investigate the molecular bases for these critical processes. We identify an intrinsically disordered peptide derived from EBOV VP35 (NPBP, residues 20–48) that binds NP with high affinity and specificity, inhibits NP oligomerization, and releases RNA from NP-RNA complexes in vitro. The structure of the NPBP/?NPNTD complex, solved to 3.7 Å resolution, reveals how NPBP peptide occludesmore »a large surface area that is important for NP-NP and NP-RNA interactions and for viral RNA synthesis. Together, our results identify a highly conserved viral interface that is important for EBOV replication and can be targeted for therapeutic development.« less

  20. Backs against the wall: novel and existing strategies used during the 2014-2015 Ebola virus outbreak.

    PubMed

    Wong, Gary; Kobinger, Gary P

    2015-07-01

    The 2014-2015 outbreak of Ebola virus (EBOV), originating from Guinea, is now responsible for the infection of >20,000 people in 9 countries. Whereas past filovirus outbreaks in sub-Saharan Africa have been rapidly brought under control with comparably few cases, this outbreak has been particularly resistant to containment efforts. Both the general population and primary health care workers have been affected by this outbreak, with hundreds of doctors and nurses being infected in the line of duty. In the absence of approved therapeutics, several caregivers have turned to investigational new drugs as well as experimental therapies in an effort to save lives. This review aims to summarize the candidates currently under consideration for postexposure use in infected patients during the largest EBOV outbreak in history. PMID:25972518

  1. Be-CoDiS: An epidemiological model to predict the risk of human diseases spread worldwide. Application to the 2014 Ebola Virus Disease epidemic

    E-print Network

    Benjamin, Ivorra; Diène, Ngom

    2014-01-01

    Ebola virus disease is a lethal human and primate disease that currently requires a particular attention from the national and international health authorities due to important outbreaks concurring in some Western African countries and possible spread to other continents, which has already occurred in the USA and Spain. Regarding the emergency of this situation, there is a need of development of decision tools to help the authorities to focus their efforts in important factors that can help to eradicate Ebola. Mathematical modeling and, more precisely, epidemiological modeling can help to predict the possible evolution of the Ebola outbreaks and to give some recommendations in the region to be prioritized for surveillance. In this work, we present a first formulation of a new spatial-temporal epidemiological model, called Be-CoDiS (Between-COuntries Disease Spread), based on the combination of a deterministic Individual-Based model (modelling the interaction between countries, considered as individual) for be...

  2. Ebola infection reported

    NSDL National Science Digital Library

    Sean Henahan

    1995-01-01

    This article describes cases and outbreaks of Ebola virus. The focus is on how little is known about Ebola and Marberg viruses, especially about how certain people survive those infections. Copyright 2005 Eisenhower National Clearinghouse

  3. Mutual antagonism between the Ebola virus VP35 protein and the RIG-I activator PACT determines infection outcome.

    PubMed

    Luthra, Priya; Ramanan, Parameshwaran; Mire, Chad E; Weisend, Carla; Tsuda, Yoshimi; Yen, Benjamin; Liu, Gai; Leung, Daisy W; Geisbert, Thomas W; Ebihara, Hideki; Amarasinghe, Gaya K; Basler, Christopher F

    2013-07-17

    The cytoplasmic pattern recognition receptor RIG-I is activated by viral RNA and induces type I IFN responses to control viral replication. The cellular dsRNA binding protein PACT can also activate RIG-I. To counteract innate antiviral responses, some viruses, including Ebola virus (EBOV), encode proteins that antagonize RIG-I signaling. Here, we show that EBOV VP35 inhibits PACT-induced RIG-I ATPase activity in a dose-dependent manner. The interaction of PACT with RIG-I is disrupted by wild-type VP35, but not by VP35 mutants that are unable to bind PACT. In addition, PACT-VP35 interaction impairs the association between VP35 and the viral polymerase, thereby diminishing viral RNA synthesis and modulating EBOV replication. PACT-deficient cells are defective in IFN induction and are insensitive to VP35 function. These data support a model in which the VP35-PACT interaction is mutually antagonistic and plays a fundamental role in determining the outcome of EBOV infection. PMID:23870315

  4. Ebola virus disease 2013-2014 outbreak in west Africa: an analysis of the epidemic spread and response.

    PubMed

    Cenciarelli, Orlando; Pietropaoli, Stefano; Malizia, Andrea; Carestia, Mariachiara; D'Amico, Fabrizio; Sassolini, Alessandro; Di Giovanni, Daniele; Rea, Silvia; Gabbarini, Valentina; Tamburrini, Annalaura; Palombi, Leonardo; Bellecci, Carlo; Gaudio, Pasquale

    2015-01-01

    The Ebola virus epidemic burst in West Africa in late 2013, started in Guinea, reached in a few months an alarming diffusion, actually involving several countries (Liberia, Sierra Leone, Nigeria, Senegal, and Mali). Guinea and Liberia, the first nations affected by the outbreak, have put in place measures to contain the spread, supported by international organizations; then they were followed by the other nations affected. In the present EVD outbreak, the geographical spread of the virus has followed a new route: the achievement of large urban areas at an early stage of the epidemic has led to an unprecedented diffusion, featuring the largest outbreak of EVD of all time. This has caused significant concerns all over the world: the potential reaching of far countries from endemic areas, mainly through fast transports, induced several countries to issue information documents and health supervision for individuals going to or coming from the areas at risk. In this paper the geographical spread of the epidemic was analyzed, assessing the sequential appearance of cases by geographic area, considering the increase in cases and mortality according to affected nations. The measures implemented by each government and international organizations to contain the outbreak, and their effectiveness, were also evaluated. PMID:25852754

  5. High-throughput virtual screening and docking studies of matrix protein vp40 of ebola virus

    PubMed Central

    Tamilvanan, Thangaraju; Hopper, Waheeta

    2013-01-01

    Ebolavirus, a member of the Filoviridae family of negative-sense RNA viruses, causes severe haemorrhagic fever leading up to 90% lethality. Ebolavirus matrix protein VP40 is involved in the virus assembly and budding process. The RNA binding pocket of VP40 is considered as the drug target site for structure based drug design. High Throughput Virtual Screening and molecular docking studies were employed to find the suitable inhibitors against VP40. Ten compounds showing good glide score and glide energy as well as interaction with specific amino acid residues were short listed as drug leads. These small molecule inhibitors could be potent inhibitors for VP40 matrix protein by blocking virus assembly and budding process. PMID:23559747

  6. The Central Structural Feature of the Membrane Fusion Protein Subunit from the Ebola Virus Glycoprotein is a Long Triple-Stranded Coiled Coil

    Microsoft Academic Search

    Winfried Weissenhorn; Lesley J. Calder; Stephen A. Wharton; John J. Skehel; Don C. Wiley

    1998-01-01

    The ectodomain of the Ebola virus Gp2 glycoprotein was solubilized with a trimeric, isoleucine zipper derived from GCN4 (pIIGCN4) in place of the hydrophobic fusion peptide at the N terminus. This chimeric molecule forms a trimeric, highly alpha -helical, and very thermostable molecule, as determined by chemical crosslinking and circular dichroism. Electron microscopy indicates that Gp2 folds into a rod-like

  7. Innovative Technological Approach to Ebola Virus Disease Outbreak Response in Nigeria Using the Open Data Kit and Form Hub Technology

    PubMed Central

    Nguku, Patrick; Waziri, Ndadilnasiya; Adewuyi, Peter; Adeoye, Olawunmi; Adeseye, Aderonke; Oguntimehin, Olukayode; Shuaib, Faisal

    2015-01-01

    The recent outbreak of Ebola Virus Disease (EVD) in West Africa has ravaged many lives. Effective containment of this outbreak relies on prompt and effective coordination and communication across various interventions; early detection and response being critical to successful control. The use of information and communications technology (ICT) in active surveillance has proved to be effective but its use in Ebola outbreak response has been limited. Due to the need for timeliness in reporting and communication for early discovery of new EVD cases and promptness in response; it became imperative to empower the response team members with technologies and solutions which would enable smooth and rapid data flow. The Open Data Kit and Form Hub technology were used in combination with the Dashboard technology and ArcGIS mapping for follow up of contacts, identification of cases, case investigation and management and also for strategic planning during the response. A remarkable improvement was recorded in the reporting of daily follow-up of contacts after the deployment of the integrated real time technology. The turnaround time between identification of symptomatic contacts and evacuation to the isolation facility and also for receipt of laboratory results was reduced and informed decisions could be taken by all concerned. Accountability in contact tracing was ensured by the use of a GPS enabled device. The use of innovative technologies in the response of the EVD outbreak in Nigeria contributed significantly to the prompt control of the outbreak and containment of the disease by providing a valuable platform for early warning and guiding early actions. PMID:26115402

  8. Ebola Virus Disease Outbreak in Isiro, Democratic Republic of the Congo, 2012: Signs and Symptoms, Management and Outcomes

    PubMed Central

    Kratz, Thomas; Roddy, Paul; Tshomba Oloma, Antoine; Jeffs, Benjamin; Pou Ciruelo, Diana; de la Rosa, Olimpia; Borchert, Matthias

    2015-01-01

    Data collected during the 2012 Ebola virus disease (EVD) epidemic in the Democratic Republic of the Congo were analysed for clinical signs, symptoms and case fatality of EVD caused by Bundibugyo virus (BDBV), establishment of differential diagnoses, description of medical treatment and evaluation of the quality of clinical documentation. In a quantitative observational prospective study, global epidemiological data from 52 patients (34 patients within the community, 18 patients treated in the Ebola Treatment Centre) were entered anonymously into a database, subsequently matched and analysed. Relevant findings include an over-representation of females among community EVD cases (85.3%) and of community EVD cases in the age group of 15-54 years (82.4%). All ETC patients had fever (55.6% of all 18 ETC patients during their hospital stay) or self-reported fever (88.2% upon admission) at some point of time during their illness. Major symptoms of ETC patients during hospital stay included asthenia (82.4%), anorexia (82.4%), myalgia (70.6%), sore throat/difficulty swallowing (70.6%), arthralgia (76.5%) and nausea (70.6%). Gastrointestinal signs and symptoms (nausea, diarrhoea, vomiting) (76.4%) as well as general pain (94.1%) were frequent in ETC patients. The median duration of EVD was 18 days, while the mean incubation period was 11.3 days. Differential diagnosis of EVD included malaria (28.3%), intestinal parasitosis (10.9%), and infectious syndrome (10.9%). There was also an important variation in clinical evolvement. Quality of documentation was adversely affected by the way patient file contents were transferred from inside to outside the high-risk zone, entailing a mean mismatch value of 27.3% between patient file contents inside vs. outside the high-risk zone. This study adds further description of EVD (frequently non-specific signs and symptoms, non frequent bleeding, a long incubation period, long duration of disease) and emphasizes the need for improving clinical monitoring and documentation in EVD outbreak settings. PMID:26107529

  9. Ebola Virus Disease Outbreak in Isiro, Democratic Republic of the Congo, 2012: Signs and Symptoms, Management and Outcomes.

    PubMed

    Kratz, Thomas; Roddy, Paul; Tshomba Oloma, Antoine; Jeffs, Benjamin; Pou Ciruelo, Diana; de la Rosa, Olimpia; Borchert, Matthias

    2015-01-01

    Data collected during the 2012 Ebola virus disease (EVD) epidemic in the Democratic Republic of the Congo were analysed for clinical signs, symptoms and case fatality of EVD caused by Bundibugyo virus (BDBV), establishment of differential diagnoses, description of medical treatment and evaluation of the quality of clinical documentation. In a quantitative observational prospective study, global epidemiological data from 52 patients (34 patients within the community, 18 patients treated in the Ebola Treatment Centre) were entered anonymously into a database, subsequently matched and analysed. Relevant findings include an over-representation of females among community EVD cases (85.3%) and of community EVD cases in the age group of 15-54 years (82.4%). All ETC patients had fever (55.6% of all 18 ETC patients during their hospital stay) or self-reported fever (88.2% upon admission) at some point of time during their illness. Major symptoms of ETC patients during hospital stay included asthenia (82.4%), anorexia (82.4%), myalgia (70.6%), sore throat/difficulty swallowing (70.6%), arthralgia (76.5%) and nausea (70.6%). Gastrointestinal signs and symptoms (nausea, diarrhoea, vomiting) (76.4%) as well as general pain (94.1%) were frequent in ETC patients. The median duration of EVD was 18 days, while the mean incubation period was 11.3 days. Differential diagnosis of EVD included malaria (28.3%), intestinal parasitosis (10.9%), and infectious syndrome (10.9%). There was also an important variation in clinical evolvement. Quality of documentation was adversely affected by the way patient file contents were transferred from inside to outside the high-risk zone, entailing a mean mismatch value of 27.3% between patient file contents inside vs. outside the high-risk zone. This study adds further description of EVD (frequently non-specific signs and symptoms, non frequent bleeding, a long incubation period, long duration of disease) and emphasizes the need for improving clinical monitoring and documentation in EVD outbreak settings. PMID:26107529

  10. Mapping overlapping functional elements embedded within the protein-coding regions of RNA viruses

    E-print Network

    Firth, Andrew E.

    2014-10-17

    with the potential to cause acute fatal disease in healthy adult humans are RNA viruses. Such viruses include influenza A virus (IAV), Ebola virus, ra- bies virus, SARS virus, MERS virus, Japanese encephali- tis virus, yellow fever virus, dengue virus, eastern equine...

  11. Characterization of the RNA Silencing Suppression Activity of the Ebola Virus VP35 Protein in Plants and Mammalian Cells

    PubMed Central

    Zhu, Yali; Cherukuri, Nil Celebi; Jackel, Jamie N.; Wu, Zetang; Crary, Monica; Buckley, Kenneth J.; Bisaro, David M.

    2012-01-01

    Ebola virus (EBOV) causes a lethal hemorrhagic fever for which there is no approved effective treatment or prevention strategy. EBOV VP35 is a virulence factor that blocks innate antiviral host responses, including the induction of and response to alpha/beta interferon. VP35 is also an RNA silencing suppressor (RSS). By inhibiting microRNA-directed silencing, mammalian virus RSSs have the capacity to alter the cellular environment to benefit replication. A reporter gene containing specific microRNA target sequences was used to demonstrate that prior expression of wild-type VP35 was able to block establishment of microRNA silencing in mammalian cells. In addition, wild-type VP35 C-terminal domain (CTD) protein fusions were shown to bind small interfering RNA (siRNA). Analysis of mutant proteins demonstrated that reporter activity in RSS assays did not correlate with their ability to antagonize double-stranded RNA (dsRNA)-activated protein kinase R (PKR) or bind siRNA. The results suggest that enhanced reporter activity in the presence of VP35 is a composite of nonspecific translational enhancement and silencing suppression. Moreover, most of the specific RSS activity in mammalian cells is RNA binding independent, consistent with VP35's proposed role in sequestering one or more silencing complex proteins. To examine RSS activity in a system without interferon, VP35 was tested in well-characterized plant silencing suppression assays. VP35 was shown to possess potent plant RSS activity, and the activities of mutant proteins correlated strongly, but not exclusively, with RNA binding ability. The results suggest the importance of VP35-protein interactions in blocking silencing in a system (mammalian) that cannot amplify dsRNA. PMID:22238300

  12. Multiple Cationic Amphiphiles Induce a Niemann-Pick C Phenotype and Inhibit Ebola Virus Entry and Infection

    PubMed Central

    Shoemaker, Charles J.; Schornberg, Kathryn L.; Delos, Sue E.; Scully, Corinne; Pajouhesh, Hassan; Olinger, Gene G.; Johansen, Lisa M.; White, Judith M.

    2013-01-01

    Ebola virus (EBOV) is an enveloped RNA virus that causes hemorrhagic fever in humans and non-human primates. Infection requires internalization from the cell surface and trafficking to a late endocytic compartment, where viral fusion occurs, providing a conduit for the viral genome to enter the cytoplasm and initiate replication. In a concurrent study, we identified clomiphene as a potent inhibitor of EBOV entry. Here, we screened eleven inhibitors that target the same biosynthetic pathway as clomiphene. From this screen we identified six compounds, including U18666A, that block EBOV infection (IC50 1.6 to 8.0 µM) at a late stage of entry. Intriguingly, all six are cationic amphiphiles that share additional chemical features. U18666A induces phenotypes, including cholesterol accumulation in endosomes, associated with defects in Niemann–Pick C1 protein (NPC1), a late endosomal and lysosomal protein required for EBOV entry. We tested and found that all six EBOV entry inhibitors from our screen induced cholesterol accumulation. We further showed that higher concentrations of cationic amphiphiles are required to inhibit EBOV entry into cells that overexpress NPC1 than parental cells, supporting the contention that they inhibit EBOV entry in an NPC1-dependent manner. A previously reported inhibitor, compound 3.47, inhibits EBOV entry by blocking binding of the EBOV glycoprotein to NPC1. None of the cationic amphiphiles tested had this effect. Hence, multiple cationic amphiphiles (including several FDA approved agents) inhibit EBOV entry in an NPC1-dependent fashion, but by a mechanism distinct from that of compound 3.47. Our findings suggest that there are minimally two ways of perturbing NPC1-dependent pathways that can block EBOV entry, increasing the attractiveness of NPC1 as an anti-filoviral therapeutic target. PMID:23441171

  13. Emerging Viruses

    NSDL National Science Digital Library

    Lee, Amy.

    Emerging viruses are those "whose incidence in humans has increased in the past 2 decades or threatens to increase in the near future." This week's Topic in Depth focuses on sites related to viruses, particularly those that are considered "emerging."The first site (1) is an essay by Alison Jacobson of the University of Capetown that discusses some emerging and potentially emerging viruses, along with factors that contribute to the threat. From a US government interagency working group, the second report (2) focuses on the responses to infectious disease outbreaks, including drugs, vaccines, and government response. A World Health Organization site (3) highlights recent reports of infectious disease, archived by date and by disease. This ThinkQuest site (4) gives a basic introduction to viruses and how they cause infections. An online virology tutorial (5) by Ed Rybicki of the University of Cape Town serves as a lesson on the basics of virology for a more advanced student. The next two sites focus on the specifics of selected viruses. From the Institute for Molecular Virology (6) comes a resource on Marburg and Ebola viruses, and from the National Biological Information Infrastructure (7) is a site on West Nile Virus. The last resource (8) is a scholarly journal from the Centers for Disease Control that presents some of the latest scientific research on emerging diseases.

  14. Camouflage and misdirection: the full-on assault of ebola virus disease.

    PubMed

    Misasi, John; Sullivan, Nancy J

    2014-10-23

    Ebolaviruses cause a severe hemorrhagic fever syndrome that is rapidly fatal to humans and nonhuman primates. Ebola protein interactions with host cellular proteins disrupt type I and type II interferon responses, RNAi antiviral responses, antigen presentation, T-cell-dependent B cell responses, humoral antibodies, and cell-mediated immunity. This multifaceted approach to evasion and suppression of innate and adaptive immune responses in their target hosts leads to the severe immune dysregulation and "cytokine storm" that is characteristic of fatal ebolavirus infection. Here, we highlight some of the processes by which Ebola interacts with its mammalian hosts to evade antiviral defenses. PMID:25417101

  15. The development of a protocol for post-mortem management of Ebola virus disease in the setting of developed countries.

    PubMed

    Leditschke, Jodie; Rose, Toby; Cordner, Stephen; Woodford, Noel; Pollanen, Michael

    2015-06-01

    The management of the recent Ebola virus disease (EVD) epidemic continues to pose currently insuperable challenges to health care providers in the resource-deprived countries of West Africa. In an age where air travel facilitates rapid movement of people between countries and continents, there is an urgent requirement for health systems around the globe to develop management strategies and protocols in the event that EVD cases are suspected or confirmed. Departments of forensic pathology play an important, and underestimated, role in public health service delivery, particularly at times of novel infectious disease emergence. This role can include disease identification, characterization, and notification, as well as close engagement with agencies responsible for disease surveillance and treatment provision. A mass outbreak of EVD in the Western world is considered highly unlikely; however, there is clear responsibility on departments of forensic pathology to develop protocols for rapid assessment of sporadic or suspected cases while ensuring the health and safety of mortuary and pathology personnel. The Ontario Forensic Pathology Service and the Victorian Institute of Forensic Medicine have collaborated on the development of a protocol for management of EVD cases presenting at a scene or in the mortuary. It is hoped that this trans-national, inter-departmental exercise will serve as a model for future co-operative endeavors. The protocol has been distributed to forensic pathology departments around Australia and may be modified to accommodate local resource capabilities. PMID:25616524

  16. A retrospective and prospective analysis of the west African Ebola virus disease epidemic: robust national health systems at the foundation and an empowered WHO at the apex.

    PubMed

    Gostin, Lawrence O; Friedman, Eric A

    2015-05-01

    The Ebola virus disease outbreak in west Africa is pivotal for the worldwide health system. Just as the depth of the crisis ultimately spurred an unprecedented response, the failures of leadership suggest the need for innovative reforms. Such reforms would transform the existing worldwide health system architecture into a purposeful, organised system with an empowered, highly capable WHO at its apex and enduring, equitable national health systems at its foundation. It would be designed not only to provide security against epidemic threats, but also to meet everyday health needs, thus realising the right to health. This retrospective and prospective analysis offers a template for these reforms, responding to the profound harms posed by fragile national health systems, delays in the international response, deficient resource mobilisation, ill defined responsibilities, and insufficient coordination. The scope of the reforms should address failures in the Ebola response, and entrenched weaknesses that enabled the epidemic to reach its heights. PMID:25987158

  17. Antiviral therapies against Ebola and other emerging viral diseases using existing medicines that block virus entry

    PubMed Central

    Long, Jason; Wright, Edward; Molesti, Eleonora; Temperton, Nigel; Barclay, Wendy

    2015-01-01

    Emerging viral diseases pose a threat to the global population as intervention strategies are mainly limited to basic containment due to the lack of efficacious and approved vaccines and antiviral drugs. The former was the only available intervention when the current unprecedented Ebolavirus (EBOV) outbreak in West Africa began. Prior to this, the development of EBOV vaccines and anti-viral therapies required time and resources that were not available. Therefore, focus has turned to re-purposing of existing, licenced medicines that may limit the morbidity and mortality rates of EBOV and could be used immediately. Here we test three such medicines and measure their ability to inhibit pseudotype viruses (PVs) of two EBOV species, Marburg virus (MARV) and avian influenza H5 (FLU-H5). We confirm the ability of chloroquine (CQ) to inhibit viral entry in a pH specific manner. The commonly used proton pump inhibitors, Omeprazole and Esomeprazole were also able to inhibit entry of all PVs tested but at higher drug concentrations than may be achieved in vivo. We propose CQ as a priority candidate to consider for treatment of EBOV.

  18. Marburg virus-like particles protect guinea pigs from lethal Marburg virus infection

    Microsoft Academic Search

    Kelly L Warfield; Dana L Swenson; Diane L Negley; Alan L Schmaljohn; M. Javad Aman; Sina Bavari

    2004-01-01

    Ongoing outbreaks of filoviruses in Africa and concerns about their use in bioterrorism attacks have led to intense efforts to find safe and effective vaccines to prevent the high mortality associated with these viruses. We previously reported the generation of virus-like particles (VLPs) for the filoviruses, Marburg (MARV) and Ebola (EBOV) virus, and that vaccinating mice with Ebola VLPs (eVLPs)

  19. Modeling the 2014 Ebola Virus Epidemic – Agent-Based Simulations, Temporal Analysis and Future Predictions for Liberia and Sierra Leone

    PubMed Central

    Siettos, Constantinos; Anastassopoulou, Cleo; Russo, Lucia; Grigoras, Christos; Mylonakis, Eleftherios

    2015-01-01

    We developed an agent-based model to investigate the epidemic dynamics of Ebola virus disease (EVD) in Liberia and Sierra Leone from May 27 to December 21, 2014. The dynamics of the agent-based simulator evolve on small-world transmission networks of sizes equal to the population of each country, with adjustable densities to account for the effects of public health intervention policies and individual behavioral responses to the evolving epidemic. Based on time series of the official case counts from the World Health Organization (WHO), we provide estimates for key epidemiological variables by employing the so-called Equation-Free approach. The underlying transmission networks were characterized by rather random structures in the two countries with densities decreasing by ~19% from the early (May 27-early August) to the last period (mid October-December 21). Our estimates for the values of key epidemiological variables, such as the mean time to death, recovery and the case fatality rate, are very close to the ones reported by the WHO Ebola response team during the early period of the epidemic (until September 14) that were calculated based on clinical data. Specifically, regarding the effective reproductive number Re, our analysis suggests that until mid October, Re was above 2.3 in both countries; from mid October to December 21, Re dropped well below unity in Liberia, indicating a saturation of the epidemic, while in Sierra Leone it was around 1.9, indicating an ongoing epidemic. Accordingly, a ten-week projection from December 21 estimated that the epidemic will fade out in Liberia in early March; in contrast, our results flashed a note of caution for Sierra Leone since the cumulative number of cases could reach as high as 18,000, and the number of deaths might exceed 5,000, by early March 2015. However, by processing the reported data of the very last period (December 21, 2014-January 18, 2015), we obtained more optimistic estimates indicative of a remission of the epidemic in Sierra Leone, as reflected by the derived Re (~0.82, 95% CI: 0.81-0.83).

  20. Inhibition of Ebola Virus Infection: Identification of Niemann-Pick C1 as the Target by Optimization of a Chemical Probe

    PubMed Central

    2012-01-01

    A high-throughput screen identified adamantane dipeptide 1 as an inhibitor of Ebola virus (EboV) infection. Hit-to-lead optimization to determine the structure–activity relationship (SAR) identified the more potent EboV inhibitor 2 and a photoaffinity labeling agent 3. These antiviral compounds were employed to identify the target as Niemann-Pick C1 (NPC1), a host protein that binds the EboV glycoprotein and is essential for infection. These studies establish NPC1 as a promising target for antiviral therapy. PMID:23526644

  1. Ebola virus in West Africa: waiting for the owl of Minerva.

    PubMed

    Upshur, Ross E G

    2014-12-01

    The evolving Ebola epidemic in West Africa is unprecedented in its size and scope, requiring the rapid mobilization of resources. It is too early to determine all of the ethical challenges associated with the outbreak, but these should be monitored closely. Two issues that can be discussed are (1) the decision to implement and evaluate unregistered agents to determine therapeutic or prophylactic safety and efficacy and (2) the justification behind this decision. In this paper, I argue that it is not compassionate use that justifies this decision and suggest three lines of reasoning to support the decision. PMID:25294651

  2. A tribute to Sheik Humarr Khan and all the healthcare workers in West Africa who have sacrificed in the fight against Ebola virus disease: Mae we hush.

    PubMed

    Bausch, Daniel G; Bangura, James; Garry, Robert F; Goba, Augustine; Grant, Donald S; Jacquerioz, Frederique A; McLellan, Susan L; Jalloh, Simbirie; Moses, Lina M; Schieffelin, John S

    2014-11-01

    The Kenema Government Hospital Lassa Fever Ward in Sierra Leone, directed since 2005 by Dr. Sheikh Humarr Khan, is the only medical unit in the world devoted exclusively to patient care and research of a viral hemorrhagic fever. When Ebola virus disease unexpectedly appeared in West Africa in late 2013 and eventually spread to Kenema, Khan and his fellow healthcare workers remained at their posts, providing care to patients with this devastating illness. Khan and the chief nurse, Mbalu Fonnie, became infected and died at the end of July, a fate that they have sadly shared with more than ten other healthcare workers in Kenema and hundreds across the region. This article pays tribute to Sheik Humarr Khan, Mbalu Fonnie and all the healthcare workers who have acquired Ebola virus disease while fighting the epidemic in West Africa. Besides the emotional losses, the death of so many skilled and experienced healthcare workers will severely impair health care and research in affected regions, which can only be restored through dedicated, long-term programs. PMID:25196533

  3. Middletown, Connecticut 06459 Ebola Travel Advisory

    E-print Network

    Devoto, Stephen H.

    Middletown, Connecticut 06459 Ebola Travel Advisory The devastating outbreak of the Ebola virus in West Africa has caused pain and suffering on an almost that region. Even though this topic has receded from the headlines, Ebola remains

  4. Could pharmacological curtailment of the RhoA/Rho-kinase pathway reverse the endothelial barrier dysfunction associated with Ebola virus infection?

    PubMed

    Eisa-Beygi, Shahram; Wen, Xiao-Yan

    2015-02-01

    Activation of the RhoA/Rho-kinase (ROCK) pathway induces endothelial barrier dysfunction and increased vascular permeability, which is a hallmark of various life-threatening vascular pathologies. Therapeutic approaches aimed at inhibiting the RhoA/ROCK pathway have proven effective in the attenuation of vascular leakage observed in animal models of endotoxin-induced lung injury/sepsis, edema, autoimmune disorders, and stroke. These findings suggest that treatments targeting the ROCK pathway might be of benefit in the management of the Ebola virus disease (EVD), which is characterized by severe vascular leak, likely involving pro-inflammatory cytokines, such as tumor necrosis factor-alpha, released from virus-infected macrophages. In this paper, we review evidence from in vivo and in vitro models of vascular leakage, suggesting that the RhoA/ROCK pathway is an important therapeutic target for the reversal of the vascular permeability defects associated with EVD. Future studies should explore the efficacy of pharmacological inhibition of RhoA/ROCK pathway on reversing the endothelial barrier dysfunction in animal models of EVD and other hemorrhagic fever virus infections as part of an adjunctive therapy. Such experimental studies should focus, in particular, on the small molecule fasudil (HA-1077), a derivative of isoquinoline, which is a safe and clinically approved inhibitor of ROCK, making it an excellent candidate in this context. PMID:25512227

  5. Emerging intracellular receptors for hemorrhagic fever viruses.

    PubMed

    Jae, Lucas T; Brummelkamp, Thijn R

    2015-07-01

    Ebola virus and Lassa virus belong to different virus families that can cause viral hemorrhagic fever, a life-threatening disease in humans with limited treatment options. To infect a target cell, Ebola and Lassa viruses engage receptors at the cell surface and are subsequently shuttled into the endosomal compartment. Upon arrival in late endosomes/lysosomes, the viruses trigger membrane fusion to release their genome into the cytoplasm. Although contact sites at the cell surface were recognized for Ebola virus and Lassa virus, it was postulated that Ebola virus requires a critical receptor inside the cell. Recent screens for host factors identified such internal receptors for both viruses: Niemann-Pick disease type C1 protein (NPC1) for Ebola virus and lysosome-associated membrane protein 1 (LAMP1) for Lassa virus. A cellular trigger is needed to permit binding of the viral envelope protein to these intracellular receptors. This 'receptor switch' represents a previously unnoticed step in virus entry with implications for host-pathogen interactions and viral tropism. PMID:26004032

  6. A novel immunohistochemical assay for the detection of Ebola virus in skin: implications for diagnosis, spread, and surveillance of Ebola hemorrhagic fever. Commission de Lutte contre les Epidémies à Kikwit.

    PubMed

    Zaki, S R; Shieh, W J; Greer, P W; Goldsmith, C S; Ferebee, T; Katshitshi, J; Tshioko, F K; Bwaka, M A; Swanepoel, R; Calain, P; Khan, A S; Lloyd, E; Rollin, P E; Ksiazek, T G; Peters, C J

    1999-02-01

    Laboratory diagnosis of Ebola hemorrhagic fever (EHF) is currently performed by virus isolation and serology and can be done only in a few high-containment laboratories worldwide. In 1995, during the EHF outbreak in the Democratic Republic of Congo, the possibility of using immunohistochemistry (IHC) testing of formalin-fixed postmortem skin specimens was investigated as an alternative diagnostic method for EHF. Fourteen of 19 cases of suspected EHF met the surveillance definition for EHF and were positive by IHC. IHC, serologic, and virus isolation results were concordant for all EHF and non-EHF cases. IHC and electron microscopic examination showed that endothelial cells, mononuclear phagocytes, and hepatocytes are main targets of infection, and IHC showed an association of cellular damage with viral infection. The finding of abundant viral antigens and particles in the skin of EHF patients suggests an epidemiologic role for contact transmission. IHC testing of formalin-fixed skin specimens is a safe, sensitive, and specific method for laboratory diagnosis of EHF and should be useful for EHF surveillance and prevention. PMID:9988163

  7. Comparison of routes for achieving parenteral access with a focus on the management of patients with Ebola virus disease

    PubMed Central

    Ker, Katharine; Tansley, Gavin; Beecher, Deirdre; Perner, Anders; Shakur, Haleema; Harris, Tim; Roberts, Ian

    2015-01-01

    Background Dehydration is an important cause of death in patients with Ebola virus disease (EVD). Parenteral fluids are often required in patients with fluid requirements in excess of their oral intake. The peripheral intravenous route is the most commonly used method of parenteral access, but inserting and maintaining an intravenous line can be challenging in the context of EVD. Therefore it is important to consider the advantages and disadvantages of different routes for achieving parenteral access (e.g. intravenous, intraosseous, subcutaneous and intraperitoneal). Objectives To compare the reliability, ease of use and speed of insertion of different parenteral access methods. Search methods We ran the search on 17 November 2014. We searched the Cochrane Injuries Group's Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library), Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations, Ovid MEDLINE(R) Daily, Ovid MEDLINE(R) and Ovid OLDMEDLINE(R), Embase Classic + Embase (OvidSP), CINAHL (EBSCOhost), clinicaltrials.gov and screened reference lists. Selection criteria Randomised controlled trials comparing different parenteral routes for the infusion of fluids or medication. Data collection and analysis Two review authors examined the titles and abstracts of records obtained by searching the electronic databases to determine eligibility. Two review authors extracted data from the included trials and assessed the risk of bias. Outcome measures of interest were success of insertion; time required for insertion; number of insertion attempts; number of dislodgements; time period with functional access; local site reactions; clinicians' perception of ease of administration; needlestick injury to healthcare workers; patients' discomfort; and mortality. For trials involving the administration of fluids we also collected data on the volume of fluid infused, changes in serum electrolytes and markers of renal function. We rated the quality of the evidence as 'high', 'moderate', 'low' or 'very low' according to the GRADE approach for the following outcomes: success of insertion, time required for insertion, number of dislodgements, volume of fluid infused and needlestick injuries. Main results We included 17 trials involving 885 participants. Parenteral access was used to infuse fluids in 11 trials and medications in six trials. None of the trials involved patients with EVD. Intravenous and intraosseous access was compared in four trials; intravenous and subcutaneous access in 11; peripheral intravenous and intraperitoneal access in one; saphenous vein cutdown and intraosseous access in one; and intraperitoneal with subcutaneous access in one. All of the trials assessing the intravenous method involved peripheral intravenous access. We judged few trials to be at low risk of bias for any of the assessed domains. Compared to the intraosseous group, patients in the intravenous group were more likely to experience an insertion failure (risk ratio (RR) 3.89, 95% confidence interval (CI) 2.39 to 6.33; n = 242; GRADE rating: low). We did not pool data for time to insertion but estimates from the trials suggest that inserting intravenous access takes longer (GRADE rating: moderate). Clinicians judged the intravenous route to be easier to insert (RR 0.15, 95% CI 0.04 to 0.61; n = 182). A larger volume of fluids was infused via the intravenous route (GRADE rating: moderate). There was no evidence of a difference between the two routes for any other outcomes, including adverse events. Compared to the subcutaneous group, patients in the intravenous group were more likely to experience an insertion failure (RR 14.79, 95% CI 2.87 to 76.08; n = 238; GRADE rating: moderate) and dislodgement of the device (RR 3.78, 95% CI 1.16 to 12.34; n = 67; GRADE rating: low). Clinicians also judged the intravenous route as being more difficult to insert and patients were more likely to be agitated in the intravenous group. Patients in the intravenous group were more likely to develop a local infection and phlebitis,

  8. Ebola haemorrhagic fever

    PubMed Central

    Feldmann, Heinz; Geisbert, Thomas W

    2012-01-01

    Ebola viruses are the causative agents of a severe form of viral haemorrhagic fever in man, designated Ebola haemorrhagic fever, and are endemic in regions of central Africa. The exception is the species Reston Ebola virus, which has not been associated with human disease and is found in the Philippines. Ebola virus constitutes an important local public health threat in Africa, with a worldwide effect through imported infections and through the fear of misuse for biological terrorism. Ebola virus is thought to also have a detrimental effect on the great ape population in Africa. Case-fatality rates of the African species in man are as high as 90%, with no prophylaxis or treatment available. Ebola virus infections are characterised by immune suppression and a systemic inflammatory response that causes impairment of the vascular, coagulation, and immune systems, leading to multiorgan failure and shock, and thus, in some ways, resembling septic shock. PMID:21084112

  9. Peptides derived from HIV-1, HIV-2, Ebola virus, SARS coronavirus and coronavirus 229E exhibit high affinity binding to the formyl peptide receptor

    PubMed Central

    Mills, John S.

    2007-01-01

    Peptides derived from the membrane proximal region of fusion proteins of human immunodeficiency viruses 1 and 2, Coronavirus 229 E, severe acute respiratory syndrome coronavirus and Ebola virus were all potent antagonists of the formyl peptide receptor expressed in Chinese hamster ovary cells. Binding of viral peptides was affected by the naturally occurring polymorphisms at residues 190 and 192, which are located at second extracellular loop-transmembrane helix 5 interface. Substitution of R190 with W190 enhanced the affinity for a severe acute respiratory syndrome coronavirus peptide 6 fold but reduced the affinity for N-formyl-Nle–Leu-Phe by 2.5 fold. A 12 mer peptide derived from coronavirus 229E (ETYIKPWWVWL) was the most potent antagonist of the formyl peptide receptor W190 with a Ki of 230 nM. Fluorescently labeled ETYIKPWWVWL was effectively internalized by all three variants with EC50 of ~25 nM. An HKU-1 coronavirus peptide, MYVKWPWYVWL, was a potent antagonist but N-formyl-MYVKWPWYVWL was a potent agonist. ETYIKPWWVWL did not stimulate GTP?S binding but inhibited the stimulation by formyl-NleLeuPhe. It also blocked ? arrestin translocation and receptor downregulation induced by formyl-Nle–Leu–Phe. This indicates that formyl peptide receptor may be important in viral infections and that variations in its sequence among individuals may affect their likelihood of viral and bacterial infections. PMID:16842982

  10. Ebola virus VP35 induces high-level production of recombinant TPL-2-ABIN-2-NF-?B1 p105 complex in co-transfected HEK-293 cells.

    PubMed

    Gantke, Thorsten; Boussouf, Sabrina; Janzen, Julia; Morrice, Nicholas A; Howell, Steven; Mühlberger, Elke; Ley, Steven C

    2013-06-01

    Activation of PKR (double-stranded-RNA-dependent protein kinase) by DNA plasmids decreases translation, and limits the amount of recombinant protein produced by transiently transfected HEK (human embryonic kidney)-293 cells. Co-expression with Ebola virus VP35 (virus protein 35), which blocked plasmid activation of PKR, substantially increased production of recombinant TPL-2 (tumour progression locus 2)-ABIN-2 [A20-binding inhibitor of NF-?B (nuclear factor ?B) 2]-NF-?B1 p105 complex. VP35 also increased expression of other co-transfected proteins, suggesting that VP35 could be employed generally to boost recombinant protein production by HEK-293 cells. PMID:23557442

  11. 2005 Nature Publishing Group Step by step for Ebola entry

    E-print Network

    Chandran, Kartik

    © 2005 Nature Publishing Group VI ROLOGY Step by step for Ebola entry In a recent paper, Chandran (CatL) in Ebola virus infection. Ebola virus (EboV) causes out- breaks of rapidly fatal haemorrhagicL is functionally equivalenttobindingofHIVgp120to CD4/co-receptor. With no effective therapeutics for Ebola

  12. A Mutation in the Ebola Virus Envelope Glycoprotein Restricts Viral Entry in a Host Species- and Cell-Type-Specific Manner

    PubMed Central

    Ndungo, Esther; Tantral, Lee; Miller, Emily Happy; Leung, Lawrence W.; Chandran, Kartik

    2013-01-01

    Zaire Ebola virus (EBOV) is a zoonotic pathogen that causes severe hemorrhagic fever in humans. A single viral glycoprotein (GP) mediates viral attachment and entry. Here, virus-like particle (VLP)-based entry assays demonstrate that a GP mutant, GP-F88A, which is defective for entry into a variety of human cell types, including antigen-presenting cells (APCs), such as macrophages and dendritic cells, can mediate viral entry into mouse CD11b+ APCs. Like that of wild-type GP (GP-wt), GP-F88A-mediated entry occurs via a macropinocytosis-related pathway and requires endosomal cysteine proteases and an intact fusion peptide. Several additional hydrophobic residues lie in close proximity to GP-F88, including L111, I113, L122, and F225. GP mutants in which these residues are mutated to alanine displayed preferential and often impaired entry into several cell types, although not in a species-specific manner. Niemann-Pick C1 (NPC1) protein is an essential filovirus receptor that binds directly to GP. Overexpression of NPC1 was recently demonstrated to rescue GP-F88A-mediated entry. A quantitative enzyme-linked immunosorbent assay (ELISA) demonstrated that while the F88A mutation impairs GP binding to human NPC1 by 10-fold, it has little impact on GP binding to mouse NPC1. Interestingly, not all mouse macrophage cell lines permit GP-F88A entry. The IC-21 cell line was permissive, whereas RAW 264.7 cells were not. Quantitative reverse transcription (RT)-PCR assays demonstrate higher NPC1 levels in GP-F88A permissive IC-21 cells and mouse peritoneal macrophages than in RAW 264.7 cells. Cumulatively, these studies suggest an important role for NPC1 in the differential entry of GP-F88A into mouse versus human APCs. PMID:23302883

  13. Foodborne viruses

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Testing for human pathogenic viruses in foods represents a formidable task requiring the extraction, concentration, and assay of a host of viruses from a wide range of food matrices. The enteric viruses, particularly genogroup I and II (GI and GII) noroviruses and hepatitis A virus, are the princip...

  14. The landscape configuration of zoonotic transmission of Ebola virus disease in West and Central Africa: interaction between population density and vegetation cover

    PubMed Central

    Haseeb, MA

    2015-01-01

    Ebola virus disease (EVD) is an emerging infectious disease of zoonotic origin that has been responsible for high mortality and significant social disruption in West and Central Africa. Zoonotic transmission of EVD requires contact between susceptible human hosts and the reservoir species for Ebolaviruses, which are believed to be fruit bats. Nevertheless, features of the landscape that may facilitate such points of contact have not yet been adequately identified. Nor have spatial dependencies between zoonotic EVD transmission and landscape structures been delineated. This investigation sought to describe the spatial relationship between zoonotic EVD transmission events, or spillovers, and population density and vegetation cover. An inhomogeneous Poisson process model was fitted to all precisely geolocated zoonotic transmissions of EVD in West and Central Africa. Population density was strongly associated with spillover; however, there was significant interaction between population density and green vegetation cover. In areas of very low population density, increasing vegetation cover was associated with a decrease in risk of zoonotic transmission, but as population density increased in a given area, increasing vegetation cover was associated with increased risk of zoonotic transmission. This study showed that the spatial dependencies of Ebolavirus spillover were associated with the distribution of population density and vegetation cover in the landscape, even after controlling for climate and altitude. While this is an observational study, and thus precludes direct causal inference, the findings do highlight areas that may be at risk for zoonotic EVD transmission based on the spatial configuration of important features of the landscape. PMID:25648654

  15. Computer viruses

    Microsoft Academic Search

    S. R. Subramanya; N. Lakshminarasimhan

    2001-01-01

    Computer viruses have been around since the mid 1980s. Over 40,000 different viruses have been cataloged so far and the number of viruses is increasing dramatically. The damage they cause is estimated to be several billions of U.S. dollars per year. Most often, the origin of the virus is difficult to trace. Various kinds of anti-virus software have been developed

  16. Bat flight and zoonotic viruses

    USGS Publications Warehouse

    O'Shea, Thomas; Cryan, Paul M.; Cunningham, Andrew A.; Fooks, Anthony R.; Hayman, David T.S.; Luis, Angela D.; Peel, Alison J.; Plowright, Raina K.; Wood, James L.N.

    2014-01-01

    Bats are sources of high viral diversity and high-profile zoonotic viruses worldwide. Although apparently not pathogenic in their reservoir hosts, some viruses from bats severely affect other mammals, including humans. Examples include severe acute respiratory syndrome coronaviruses, Ebola and Marburg viruses, and Nipah and Hendra viruses. Factors underlying high viral diversity in bats are the subject of speculation. We hypothesize that flight, a factor common to all bats but to no other mammals, provides an intensive selective force for coexistence with viral parasites through a daily cycle that elevates metabolism and body temperature analogous to the febrile response in other mammals. On an evolutionary scale, this host–virus interaction might have resulted in the large diversity of zoonotic viruses in bats, possibly through bat viruses adapting to be more tolerant of the fever response and less virulent to their natural hosts.

  17. Ebola Hemorrhagic Fever: Signs and Symptoms

    MedlinePLUS

    ... Guidance Waste Management Survivability of Ebola Virus in Medical Waste Handling Ebola-Associated Waste Emergency Services Emergency Department Guidance Emergency Department Preparedness Training EMS Systems and 9-1-1 Answering Points Air ... of Pediatric Patients Hospitals Infection Control ...

  18. Inhibitors of cellular kinases with broad-spectrum antiviral activity for hemorrhagic fever viruses.

    PubMed

    Mohr, Emma L; McMullan, Laura K; Lo, Michael K; Spengler, Jessica R; Bergeron, Éric; Albariño, César G; Shrivastava-Ranjan, Punya; Chiang, Cheng-Feng; Nichol, Stuart T; Spiropoulou, Christina F; Flint, Mike

    2015-08-01

    Host cell kinases are important for the replication of a number of hemorrhagic fever viruses. We tested a panel of kinase inhibitors for their ability to block the replication of multiple hemorrhagic fever viruses. OSU-03012 inhibited the replication of Lassa, Ebola, Marburg and Nipah viruses, whereas BIBX 1382 dihydrochloride inhibited Lassa, Ebola and Marburg viruses. BIBX 1382 blocked both Lassa and Ebola virus glycoprotein-dependent cell entry. These compounds may be used as tools to understand conserved virus-host interactions, and implicate host cell kinases that may be targets for broad spectrum therapeutic intervention. PMID:25986249

  19. Oncolytic Viruses

    Microsoft Academic Search

    John Nemunaitis

    1999-01-01

    Viruses capable of inducing lysis of malignant cells through theirreplication process are known as ``oncolytic'' viruses. Clinicaltrials in oncology have been performed with oncolytic viruses fornearly fifty years. Both systemic and intratumoral routes ofadministration have been explored. Toxicity has generally beenlimited to injection site pain, transient fever and tumor necrosis.Responses with early crude materials were usually short induration; however, recent

  20. Virus Maturation

    PubMed Central

    Veesler, David; Johnson, John E.

    2013-01-01

    We examined virus maturation of selected non-enveloped and enveloped ssRNA viruses; retroviruses; bacteriophages and herpes virus. Processes associated with maturation in the RNA viruses range from subtle (noda and picornaviruses) to dramatic (tetraviruses and togaviruses). The elaborate assembly and maturation pathway of HIV is discussed in contrast to the less sophisticated but highly efficient processes associated with togaviruses. Bacteriophage assembly and maturation are discussed in general terms with specific examples chosen for emphasis. Finally the herpes viruses are compared with bacteriophages. The data support divergent evolution of noda, picorna and tetraviruses from a common ancestor and divergent evolution of alpha and flaviviruses from a common ancestor. Likewise, bacteriophages and herpes viruses almost certainly share a common ancestor in their evolution. Comparing all the viruses, we conclude that maturation is a convergent process that is required to solve conflicting requirements in biological dynamics and function. PMID:22404678

  1. Virus Membrane Fusion Proteins: Biological Machines that Undergo a Metamorphosis

    Microsoft Academic Search

    Rebecca Ellis Dutch; Theodore S. Jardetzky; Robert A. Lamb

    2000-01-01

    Fusion proteins from a group of widely disparate viruses, including the paramyxovirus F protein, the HIV and SIV gp160 proteins, the retroviral Env protein, the Ebola virus Gp, and the influenza virus haemagglutinin, share a number of common features. All contain multiple glycosylation sites, and must be trimeric and undergo proteolytic cleavage to be fusogenically active. Subsequent to proteolytic cleavage,

  2. Datasets: Phylogenetic assessment of filoviruses: how many lineages of Marburg virus?

    E-print Network

    Peterson, A. Townsend; Holder, Mark T.

    2012-06-08

    Filoviruses have to date been considered as consisting of one diverse genus (Ebola viruses) and one undifferentiated genus (Marburg virus). We reconsider this idea by means of detailed phylogenetic analyses of sequence ...

  3. Discovery of a Novel Compound with Anti-Venezuelan Equine Encephalitis Virus Activity That Targets the Nonstructural Protein 2

    E-print Network

    Chung, Dong-Hoon; Jonsson, Colleen B.; Tower, Nichole A.; Chu, Yong-Kyu; Sahin, Ergin; Golden, Jennifer E.; Noah, James W.; Schroeder, Chad E.; Stosky, Julie B.; Sosa, Melinda; Cramer, Daniel E.; McKellip, Sara N.; Rasmussen, Lynn; White, E. Lucile; Schmaljohn, Connie S.; Julander, Justin G.; Smith, Jeffery M.; Filone, Claire Marie; Connor, John H.; Sakurai, Yasuteru; Davey, Robert A.

    2014-06-26

    EEEV .20 Togaviridae New World alphavirus WEEV 10 Togaviridae Old World alphavirus CHIKV .50 Filoviridae Ebola virus (Zaire)-GFP .10 Paramyxoviridae RSV .50 Poxviridae VACV-LREV .20 Rhabdoviridae VSV-EGFP .20 * IC50 measured in a cell-based CPE assay (m... moderate activity (IC50 of 10 mM), respectively. Chikungunya virus, an Old World alphavirus, was not inhibited by CID15997213. No antiviral activity was observed against Ebola virus (Zaire), vesicular stomatitis virus, vaccinia virus (western reserve...

  4. Obesity Virus

    NSDL National Science Digital Library

    Science Update (AAAS; )

    2007-06-12

    Obesity has many causes, but there is growing evidence that common viruses may contribute to the condition in some people. Recently, Nikhil Dhurandhar and his colleagues at the Pennington Biomedical Research Center infected human stem cells with Ad-36, a common virus known to be associated with obesity in humans. They found that the cells they exposed to the virus accumulated a much higher amount of fat than uninfected cells.

  5. Ebola Not Mutating Beyond 'Normal' Rate, Scientists Say

    MedlinePLUS

    Ebola Not Mutating Beyond 'Normal' Rate, Scientists Say New genetic information aids planning for future outbreaks To ... WEDNESDAY, May 13, 2015 (HealthDay News) -- The deadly Ebola virus has continued to mutate during the West ...

  6. Phytophthora viruses.

    PubMed

    Cai, Guohong; Hillman, Bradley I

    2013-01-01

    Phytophthora sp. is a genus in the oomycetes, which are similar to filamentous fungi in morphology and habitat, but phylogenetically more closely related to brown algae and diatoms and fall in the kingdom Stramenopila. In the past few years, several viruses have been characterized in Phytophthora species, including four viruses from Phytophthora infestans, the late blight pathogen, and an endornavirus from an unnamed Phytophthora species from Douglas fir. Studies on Phytophthora viruses have revealed several interesting systems. Phytophthora infestans RNA virus 1 (PiRV-1) and PiRV-2 are likely the first members of two new virus families; studies on PiRV-3 support the establishment of a new virus genus that is not affiliated with established virus families; PiRV-4 is a member of Narnaviridae, most likely in the genus Narnavirus; and Phytophthora endornavirus 1 (PEV1) was the first nonplant endornavirus at the time of reporting. Viral capsids have not been found in any of the above-mentioned viruses. PiRV-1 demonstrated a unique genome organization that requires further examination, and PiRV-2 may have played a role in late blight resurgence in 1980s-1990s. PMID:23498912

  7. Diseases Caused by Viruses

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The symptoms, causal agents, epidemiology and management of important virus diseases in chickpea and lentil crops were reviewed in depth. The virus diseases include.Alflafa mosaic virus, Cucumber mosaiv virus, Faba bean necrotic yellows virus, Pea enation mosaic virus, Pea seed-borne mosaci virus,...

  8. Ethical issues in the response to Ebola virus disease in US emergency departments: a position paper of the American College of Emergency Physicians, the Emergency Nurses Association and the Society for Academic Emergency Medicine.

    PubMed

    Venkat, Arvind; Wolf, Lisa; Geiderman, Joel M; Asher, Shellie L; Marco, Catherine A; McGreevy, Jolion; Derse, Arthur R; Otten, Edward J; Jesus, John E; Kreitzer, Natalie P; Escalante, Monica; Levine, Adam C

    2015-03-01

    The 2014 outbreak of Ebola Virus Disease (EVD) in West Africa has presented a significant public health crisis to the international health community and challenged US emergency departments to prepare for patients with a disease of exceeding rarity in developed nations. With the presentation of patients with Ebola to US acute care facilities, ethical questions have been raised in both the press and medical literature as to how US emergency departments, emergency physicians, emergency nurses and other stakeholders in the healthcare system should approach the current epidemic and its potential for spread in the domestic environment. To address these concerns, the American College of Emergency Physicians, the Emergency Nurses Association and the Society for Academic Emergency Medicine developed this joint position paper to provide guidance to US emergency physicians, emergency nurses and other stakeholders in the healthcare system on how to approach the ethical dilemmas posed by the outbreak of EVD. This paper will address areas of immediate and potential ethical concern to US emergency departments in how they approach preparation for and management of potential patients with EVD. PMID:25770003

  9. Ethical issues in the response to ebola virus disease in United States emergency departments: a position paper of the american college of emergency physicians, the emergency nurses association, and the society for academic emergency medicine.

    PubMed

    Venkat, Arvind; Asher, Shellie L; Wolf, Lisa; Geiderman, Joel M; Marco, Catherine A; McGreevy, Jolion; Derse, Arthur R; Otten, Edward J; Jesus, John E; Kreitzer, Natalie P; Escalante, Monica; Levine, Adam C

    2015-05-01

    The 2014 outbreak of Ebola virus disease (EVD) in West Africa has presented a significant public health crisis to the international health community and challenged U.S. emergency departments (EDs) to prepare for patients with a disease of exceeding rarity in developed nations. With the presentation of patients with Ebola to U.S. acute care facilities, ethical questions have been raised in both the press and medical literature as to how U.S. EDs, emergency physicians (EPs), emergency nurses, and other stakeholders in the health care system should approach the current epidemic and its potential for spread in the domestic environment. To address these concerns, the American College of Emergency Physicians, the Emergency Nurses Association, and the Society for Academic Emergency Medicine developed this joint position paper to provide guidance to U.S. EPs, emergency nurses, and other stakeholders in the health care system on how to approach the ethical dilemmas posed by the outbreak of EVD. This paper will address areas of immediate and potential ethical concern to U.S. EDs in how they approach preparation for and management of potential patients with EVD. PMID:25903144

  10. Mathematical Modeling the Zoonotic and Vector Transmission Dynamics of West Nile virus as They Relate to Human Morbidity and Mortality 

    E-print Network

    Laine, Christopher Glen

    2014-12-04

    , spongiform encephalopathy, is variant 2 Creutzfeldt-Jakob disease. Bacterial diseases include anthrax, salmonellosis, and plague. Viral diseases include Ebola hemorrhagic fever, smallpox, and West Nile virus (WNV). Viruses transmitted...

  11. Mathematical Modeling the Zoonotic and Vector Transmission Dynamics of West Nile virus as They Relate to Human Morbidity and Mortality

    E-print Network

    Laine, Christopher Glen

    2014-12-04

    , spongiform encephalopathy, is variant 2 Creutzfeldt-Jakob disease. Bacterial diseases include anthrax, salmonellosis, and plague. Viral diseases include Ebola hemorrhagic fever, smallpox, and West Nile virus (WNV). Viruses transmitted...

  12. HIV virus

    NSDL National Science Digital Library

    Carl Henderson (National Institutes of Health; )

    2005-12-09

    HIV is a virus that can be transmitted through fluids exchanged in sexual activity. HIV eventually causes AIDS. AIDS patients have compromised immune systems and they eventually die from diseases that healthy humans would normally fight off very easily.

  13. Calf w/ Virus 

    E-print Network

    Unknown

    2011-08-17

    ). One of the best animal models of MS is the demyelination induced by Theiler's virus. The early events that occur during Theiler's virus infection are crucial in the effective clearance of virus from the CNS. Failure to clear virus results...

  14. Computer viruses

    SciTech Connect

    Cohen, F.B.

    1986-01-01

    This thesis investigates a recently discovered vulnerability in computer systems which opens the possibility that a single individual with an average user's knowledge could cause widespread damage to information residing in computer networks. This vulnerability is due to a transitive integrity corrupting mechanism called a computer virus which causes corrupted information to spread from program to program. Experiments have shown that a virus can spread at an alarmingly rapid rate from user to user, from system to system, and from network to network, even when the best-availability security techniques are properly used. Formal definitions of self-replication, evolution, viruses, and protection mechanisms are used to prove that any system that allows sharing, general functionality, and transitivity of information flow cannot completely prevent viral attack. Computational aspects of viruses are examined, and several undecidable problems are shown. It is demonstrated that a virus may evolve so as to generate any computable sequence. Protection mechanisms are explored, and the design of computer networks that prevent both illicit modification and dissemination of information are given. Administration and protection of information networks based on partial orderings are examined, and probably correct automated administrative assistance is introduced.

  15. Computer Viruses

    Microsoft Academic Search

    Robyn P. Weems

    1998-01-01

    This paper presents a description of the major characteristics of disk and network borne viruses for the convenience of library and archival systems administrators. It includes a brief history of the use of destructive software by computer hackers, noting some of the early and more recent forms of attack, and suggests that computer languages newly developed for use with the

  16. Computer viruses

    Microsoft Academic Search

    Frederick B. Cohen

    1986-01-01

    This thesis investigates a recently discovered vulnerability in computer systems which opens the possibility that a single individual with an average user's knowledge could cause widespread damage to information residing in computer networks. This vulnerability is due to a transitive integrity corrupting mechanism called a computer virus which causes corrupted information to spread from program to program. Experiments have shown

  17. Computer viruses

    Microsoft Academic Search

    C. E. Pelaez; John Bowles

    1991-01-01

    This paper presents an overview of the main categories of malicious programs known as Trojan horses, viruses, bacteria, worms, and logic bombs. The focus is on their general behavior and the properties seen in their implementations rather than the ultimate effects or their intended destructive behavior. Possible preventive measures are also discussed

  18. Meeting the Challenge of Developing Drugs for Ebola

    E-print Network

    Gleeson, Joseph G.

    Meeting the Challenge of Developing Drugs for Ebola and Other Neglected Tropical Diseases James Mc million dollars) 5 years5 years #12;Ebola Virus: Major Outbreaks New York Times, October 13, 2013 (Data Deaths Total 8031 Cases 3865 Deaths ew York Times, Updated October 8, 2014 #12;Ebola Cases as of October

  19. Analysis of Ebola Glycoprotein Sequences from Strains of Varying Lethality

    E-print Network

    Analysis of Ebola Glycoprotein Sequences from Strains of Varying Lethality Biochem 218 Spring 2002 Tammy Doukas tdoukas@stanford.edu I. Background and Significance Ebola hemorrhagic fever is a disease in humans, chimpanzees, and monkeys, caused by infection with Ebola virus, and associated with high

  20. Exploring computer viruses

    Microsoft Academic Search

    R. Davis

    1988-01-01

    The author presents some thoughts on viruses and explores the anatomy of a sample computer virus. He details, using C language programs, some of the fundamental parts associated with viruses and how these viruses can be detected. It is concluded that the final decision for virus control rests with risk management. It is suggested that, at the very least, contingency

  1. METHODOLOGY Open Access Virus replicon particle based Chikungunya virus

    E-print Network

    Boyer, Edmond

    METHODOLOGY Open Access Virus replicon particle based Chikungunya virus neutralization assay using Mareike Kümmerer1* Abstract Background: Chikungunya virus (CHIKV) has been responsible for large epidemic antibodies without the need of using infectious CHIKV. Keywords: Chikungunya virus, Virus replicon particles

  2. Plant Virus Metagenomics: Advances in Virus Discovery.

    PubMed

    Roossinck, Marilyn J; Martin, Darren P; Roumagnac, Philippe

    2015-06-01

    In recent years plant viruses have been detected from many environments, including domestic and wild plants and interfaces between these systems-aquatic sources, feces of various animals, and insects. A variety of methods have been employed to study plant virus biodiversity, including enrichment for virus-like particles or virus-specific RNA or DNA, or the extraction of total nucleic acids, followed by next-generation deep sequencing and bioinformatic analyses. All of the methods have some shortcomings, but taken together these studies reveal our surprising lack of knowledge about plant viruses and point to the need for more comprehensive studies. In addition, many new viruses have been discovered, with most virus infections in wild plants appearing asymptomatic, suggesting that virus disease may be a byproduct of domestication. For plant pathologists these studies are providing useful tools to detect viruses, and perhaps to predict future problems that could threaten cultivated plants. PMID:26056847

  3. Dengue Virus

    Microsoft Academic Search

    Greg Smith

    \\u000a Dengue Virus (DENV) diagnosis can be performed by isolation of DENV from blood or autopsy samples; demonstration of a four-fold\\u000a or greater rise in reciprocal IgG or IgM antibody titres to one or more DENV in paired serum samples (acute and convascent);\\u000a use of the newer rapid diagnostic test kit (also differentiates between primary and secondary dengue infections – these

  4. Virus Movement Maintains Local Virus Population Diversity

    SciTech Connect

    J. Snyder; B. Wiedenheft; M. Lavin; F. Roberto; J. Spuhler; A. Ortmann; T. Douglas; M. Young

    2007-11-01

    Viruses are the largest reservoir of genetic material on the planet, yet little is known about the population dynamics of any virus within its natural environment. Over a 2-year period, we monitored the diversity of two archaeal viruses found in hot springs within Yellowstone National Park (YNP). Both temporal phylogeny and neutral biodiversity models reveal that virus diversity in these local environments is not being maintained by mutation but rather by high rates of immigration from a globally distributed metacommunity. These results indicate that geographically isolated hot springs are readily able to exchange viruses. The importance of virus movement is supported by the detection of virus particles in air samples collected over YNP hot springs and by their detection in metacommunity sequencing projects conducted in the Sargasso Sea. Rapid rates of virus movement are not expected to be unique to these archaeal viruses but rather a common feature among virus metacommunities. The finding that virus immigration rather than mutation can dominate community structure has significant implications for understanding virus circulation and the role that viruses play in ecology and evolution by providing a reservoir of mobile genetic material.

  5. [Characterization of Marburg virus morphology].

    PubMed

    Song, Jing-Dong; Qu, Jian-Guo; Hong, Tao

    2014-05-01

    Ebola virus (EBOV) and Marburg virus (MARV) belong to the family Filoviridae. Filoviruses cause severe filovirus hemorrhagic fever (FHF) in humans, with high case fatality rates, and represent potential agents for bioterrorism and biological weapons. It is necessary to keep surveillance of filoviruses, even though there is no report of their isolation and patients in China so far. To characterize MARV morphology, the Lake Victoria marburgvirus--Leiden was stained negatively and observed under a transmission electron microscope which is one of important detection methods for filoviruses in emergencies and bioterrorism. MARV showed pleomorphism, with filamentous, rod-shaped, cobra-like, spherical, and branch-shaped particles of uniform diameter but different lengths. Pleomorphism of negatively stained MARV is summarized in this article, so as to provide useful information for possible electron microscopic identification of filoviruses in China. PMID:25118385

  6. EBOLA IN THE NEWS (UPDATED 10-17-14) The likelihood of the arrival of someone at the University of Rochester with hemorrhagic fever

    E-print Network

    EBOLA IN THE NEWS (UPDATED 10-17-14) The likelihood of the arrival of someone at the University of Rochester with hemorrhagic fever due to Ebola virus disease is very low. The potential for transmission in the United States outside healthcare settings is also very low. However, the continued spread of Ebola virus

  7. Clinical manifestations and case management of Ebola haemorrhagic fever caused by a newly identified virus strain, Bundibugyo, Uganda, 2007-2008.

    PubMed

    Roddy, Paul; Howard, Natasha; Van Kerkhove, Maria D; Lutwama, Julius; Wamala, Joseph; Yoti, Zabulon; Colebunders, Robert; Palma, Pedro Pablo; Sterk, Esther; Jeffs, Benjamin; Van Herp, Michel; Borchert, Matthias

    2012-01-01

    A confirmed Ebola haemorrhagic fever (EHF) outbreak in Bundibugyo, Uganda, November 2007-February 2008, was caused by a putative new species (Bundibugyo ebolavirus). It included 93 putative cases, 56 laboratory-confirmed cases, and 37 deaths (CFR?=?25%). Study objectives are to describe clinical manifestations and case management for 26 hospitalised laboratory-confirmed EHF patients. Clinical findings are congruous with previously reported EHF infections. The most frequently experienced symptoms were non-bloody diarrhoea (81%), severe headache (81%), and asthenia (77%). Seven patients reported or were observed with haemorrhagic symptoms, six of whom died. Ebola care remains difficult due to the resource-poor setting of outbreaks and the infection-control procedures required. However, quality data collection is essential to evaluate case definitions and therapeutic interventions, and needs improvement in future epidemics. Organizations usually involved in EHF case management have a particular responsibility in this respect. PMID:23285243

  8. Viruses and Virus Diseases of Rubus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Rubus species are propagated vegetatively and are subject to infection by viruses during development, propagation and fruit production stages. Reports of initial detection and symptoms of more than 30 viruses, virus-like diseases and phytoplasmas affecting Rubus spp. have been reviewed more than 20 ...

  9. Characterization of uncultivable bat influenza virus using a replicative synthetic virus.

    PubMed

    Zhou, Bin; Ma, Jingjiao; Liu, Qinfang; Bawa, Bhupinder; Wang, Wei; Shabman, Reed S; Duff, Michael; Lee, Jinhwa; Lang, Yuekun; Cao, Nan; Nagy, Abdou; Lin, Xudong; Stockwell, Timothy B; Richt, Juergen A; Wentworth, David E; Ma, Wenjun

    2014-10-01

    Bats harbor many viruses, which are periodically transmitted to humans resulting in outbreaks of disease (e.g., Ebola, SARS-CoV). Recently, influenza virus-like sequences were identified in bats; however, the viruses could not be cultured. This discovery aroused great interest in understanding the evolutionary history and pandemic potential of bat-influenza. Using synthetic genomics, we were unable to rescue the wild type bat virus, but could rescue a modified bat-influenza virus that had the HA and NA coding regions replaced with those of A/PR/8/1934 (H1N1). This modified bat-influenza virus replicated efficiently in vitro and in mice, resulting in severe disease. Additional studies using a bat-influenza virus that had the HA and NA of A/swine/Texas/4199-2/1998 (H3N2) showed that the PR8 HA and NA contributed to the pathogenicity in mice. Unlike other influenza viruses, engineering truncations hypothesized to reduce interferon antagonism into the NS1 protein didn't attenuate bat-influenza. In contrast, substitution of a putative virulence mutation from the bat-influenza PB2 significantly attenuated the virus in mice and introduction of a putative virulence mutation increased its pathogenicity. Mini-genome replication studies and virus reassortment experiments demonstrated that bat-influenza has very limited genetic and protein compatibility with Type A or Type B influenza viruses, yet it readily reassorts with another divergent bat-influenza virus, suggesting that the bat-influenza lineage may represent a new Genus/Species within the Orthomyxoviridae family. Collectively, our data indicate that the bat-influenza viruses recently identified are authentic viruses that pose little, if any, pandemic threat to humans; however, they provide new insights into the evolution and basic biology of influenza viruses. PMID:25275541

  10. Ebola therapy protects severely ill monkeys

    PubMed Central

    GEISBERT, THOMAS W.

    2015-01-01

    A blend of three monoclonal antibodies has completely protected monkeys against a lethal dose of Ebola virus. Unlike other post-infection therapies, the treatment works even at advanced stages of the disease. PMID:25171470

  11. More Dangerous Ebola Strain Unlikely, Study Shows

    MedlinePLUS

    More Dangerous Ebola Strain Unlikely, Study Shows Researchers compared virus samples that were 9 months apart, and found normal mutating rate ... 26, 2015 THURSDAY, March 26, 2015 (HealthDay News) -- Ebola likely won't mutate into a strain that ...

  12. Arthropods as a source of new RNA viruses.

    PubMed

    Bichaud, L; de Lamballerie, X; Alkan, C; Izri, A; Gould, E A; Charrel, R N

    2014-12-01

    The discovery and development of methods for isolation, characterisation and taxonomy of viruses represents an important milestone in the study, treatment and control of virus diseases during the 20th century. Indeed, by the late-1950s, it was becoming common belief that most human and veterinary pathogenic viruses had been discovered. However, at that time, knowledge of the impact of improved commercial transportation, urbanisation and deforestation, on disease emergence, was in its infancy. From the late 1960s onwards viruses, such as hepatitis virus (A, B and C) hantavirus, HIV, Marburg virus, Ebola virus and many others began to emerge and it became apparent that the world was changing, at least in terms of virus epidemiology, largely due to the influence of anthropological activities. Subsequently, with the improvement of molecular biotechnologies, for amplification of viral RNA, genome sequencing and proteomic analysis the arsenal of available tools for virus discovery and genetic characterization opened up new and exciting possibilities for virological discovery. Many recently identified but "unclassified" viruses are now being allocated to existing genera or families based on whole genome sequencing, bioinformatic and phylogenetic analysis. New species, genera and families are also being created following the guidelines of the International Committee for the Taxonomy of Viruses. Many of these newly discovered viruses are vectored by arthropods (arboviruses) and possess an RNA genome. This brief review will focus largely on the discovery of new arthropod-borne viruses. PMID:25239874

  13. EBOLA IN THE NEWS (UPDATED 8-15-14 AND 9-3-14) The likelihood of the arrival of someone at the University of Rochester with hemorrhagic fever

    E-print Network

    Portman, Douglas

    EBOLA IN THE NEWS (UPDATED 8-15-14 AND 9-3-14) The likelihood of the arrival of someone at the University of Rochester with hemorrhagic fever due to Ebola virus disease is very low. The potential for transmission in the United States is even lower. However, the continued spread of Ebola virus infection

  14. The nature of measles virus

    Microsoft Academic Search

    J. G. Atherton; K. S. K. Lain

    1965-01-01

    Summary Observations of the effect of halogen derivatives of deoxyuridine, known to affect the synthesis of deoxyviruses (DNA-containing viruses) show that measles virus replication is unaffected. This suggests that measles virus is a ribovirus (RNA-containing virus).

  15. Molecular evolution of primate immunodeficiency viruses and hepatitis delta virus

    Microsoft Academic Search

    Julia Samuilovna Krushkal

    1996-01-01

    Primate immunodeficiency viruses, or lentiviruses (HIV-1, HIV-2, and SIV), and hepatitis delta virus (HDV) are RNA viruses characterized by rapid evolution. Infection by primate immunodeficiency viruses usually results in the development of acquired immunodeficiency syndrome (AIDS) in humans and AIDS-like illnesses in Asian macaques. Similarly, hepatitis delta virus infection causes hepatitis and liver cancer in humans. These viruses are heterogeneous

  16. Viruses and cancer

    SciTech Connect

    Rigby, P.W.J.; Wilkie, N.M.

    1985-01-01

    This book contains 14 selections. Some of the titles are: Immortalising gene(s) encoded by Epstein-Barr Virus; Adenovirus genes involved in transformation. What determines the oncogenic phenotype.; Oncogenesis by mouse mammary tumour virus; and Transforming ras genes.

  17. The use of pseudotypes to study viruses, virus sero-epidemiology and vaccination.

    PubMed

    Bentley, Emma M; Mather, Stuart T; Temperton, Nigel J

    2015-06-12

    The globalization of the world's economies, accompanied by increasing international travel, changing climates, altered human behaviour and demographics is leading to the emergence of different viral diseases, many of which are highly pathogenic and hence are considered of great public and animal health importance. To undertake basic research and therapeutic development, many of these viruses require handling by highly trained staff in BSL-3/4 facilities not readily available to the majority of the global R&D community. In order to circumvent the enhanced biosafety requirement, the development of non-pathogenic, replication-defective pseudotyped viruses is an effective and established solution to permit the study of many aspects of virus biology in a low containment biosafety level (BSL)-1/2 laboratory. Under the spectre of the unfolding Ebola crisis, this timely conference (the second to be organised by the Viral Pseudotype Unit, www.viralpseudotypeunit.info*) discusses the recent advances in pseudotype technology and how it is revolutionizing the study of important human and animal pathogens (human and avian influenza viruses, rabies/lyssaviruses, HIV, Marburg and Ebola viruses). Key topics addressed in this conference include the exploitation of pseudotypes for serology and serosurveillance, immunogenicity testing of current and next-generation vaccines and new pseudotype assay formats (multiplexing, kit development). *The first pseudotype-focused Euroscicon conference organised by the Viral Pseudotype Unit was recently reviewed [1]. PMID:25936665

  18. Transcriptional slippage in the positive-sense RNA virus family Potyviridae

    E-print Network

    Olspert, Allan; Chung, Betty Y.-W.; Atkins, John F.; Carr, John P.; Firth, Andrew E.

    2015-01-01

    of 41 P3N-PIPO. The slippage efficiency is ~2% in Turnip mosaic virus and slippage is inhibited by 42 mutations in the GAAAAAA sequence. While utilization of transcriptional slippage is well-known 43 in negative-sense RNA viruses such as Ebola, mumps... SG, Mahy BW, Peters CJ, Nichol ST (1996) The virion glycoproteins of 528 Ebola viruses are encoded in two reading frames and are expressed through transcriptional 529 editing. Proc Natl Acad Sci U S A 93: 3602-3607 530 28. Volchkova VA, Dolnik O...

  19. BOVINE VIRAL DIARRHEA VIRUSES

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bovine viral diarrhea virus (BVDV) is an umbrella term for two species of viruses, BVDV1 and BVDV2, within the Pestivirus genus of the Flavivirus family. BVDV viruses are further subclassified as cytopathic and noncytopathic based on their activity in cultured epithelial cells. Noncytopathic BVDV p...

  20. Ecology of prokaryotic viruses

    Microsoft Academic Search

    Markus G Weinbauer

    2004-01-01

    The finding that total viral abundance is higher than total prokaryotic abundance and that a significant fraction of the prokaryotic community is infected with phages in aquatic systems has stimulated research on the ecology of prokaryotic viruses and their role in ecosystems. This review treats the ecology of prokaryotic viruses (`phages') in marine, freshwater and soil systems from a `virus

  1. MAIZE FINE STREAK VIRUS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The report outlines the salient features of maize fine streak virus (MFSV) including a general description of the causal virus species, virion properties, genome description, the relationship of the virus to other taxa, biological properties of the disease and agronomic aspects of the disease. Maize...

  2. Chikungunya Virus, Cameroon, 2006

    Microsoft Academic Search

    Christophe N. Peyrefi; Dominique Rousset; Boris A. M. Pastorino; Regis Pouillot; Maël Bessaud; Fabienne Tock; Helene Mansaray; Olivier L. Merle; Aurelie M. Pascual; Christophe Paupy; Aurelia Vessiere; Patrice Imbert; Jean-Paul Durand; Hugues J. Tolou; Marc Grandadam

    2007-01-01

    We report the isolation of chikungunya virus from a pa- tient during an outbreak of a denguelike syndrome in Cam- eroon in 2006. The virus was phylogenetically grouped in the Democratic Republic of the Congo cluster, indicating a continuous circulation of a genetically similar chikungunya virus population during 6 years in Central Africa.

  3. VIRUSES IN WASTEWATER

    EPA Science Inventory

    Viruses of animals, plants, and bacteria abound in sewage and receiving waters. Their ecological impact has, for the most part, gone unheeded except as it relates to viruses from human sources. Viruses present at levels infective to man have been recovered from waters used for re...

  4. Encephalitis Virus, Kyrgyzstan

    E-print Network

    Baker, Robert J.

    Tick-Borne Encephalitis Virus, Kyrgyzstan Benjamin J. Briggs, Barry Atkinson, Donna M. Czechowski-borne encephalitis virus (TBEV) is an emerging pathogen in Europe and Asia. We investigated TBEV in Kyrgyzstan reported. Tick-borne encephalitis virus (TBEV) is a flavivirus in the family Flaviviridae. The TBEV

  5. Prevalence and Transmission of Honeybee Viruses

    Microsoft Academic Search

    Y. P. Chen; J. S. Pettis; A. Collins; M. F. Feldlaufer

    2006-01-01

    Transmission mechanisms of six honeybee viruses, including acute bee paralysis virus (ABPV), black queen cell virus (BQCV), chronic bee paralysis virus (CBPV), deformed wing virus (DWV), Kashmir bee virus (KBV), and sacbrood bee virus (SBV), in honey bee colonies were investigated by reverse transcription-PCR (RT-PCR) methods. The virus status of individual queens was evaluated by examining the presence of viruses

  6. The viral transmembrane superfamily: possible divergence of Arenavirus and Filovirus glycoproteins from a common RNA virus ancestor

    Microsoft Academic Search

    William R. Gallaher; Christopher DiSimone; Michael J. Buchmeier

    2001-01-01

    BACKGROUND: Recent studies of viral entry proteins from influenza, measles, human immunodeficiency virus, type 1 (HIV-1), and Ebola virus have shown, first with molecular modeling, and then X-ray crystallographic or other biophysical studies, that these disparate viruses share a coiled-coil type of entry protein. RESULTS: Structural models of the transmembrane glycoproteins (GP-2) of the Arenaviruses, lymphochoriomeningitis virus (LCMV) and Lassa

  7. Ebola Hemorrhagic Fever and the Current State of Vaccine Development

    PubMed Central

    Hong, Joo Eun; Hong, Kee-Jong; Choi, Woo Young; Lee, Won-Ja; Choi, Yeon Hwa; Jeong, Chung-Hyeon; Cho, Kwang-il

    2014-01-01

    Current Ebola virus outbreak in West Africa already reached the total number of 1,323 including 729 deaths by July 31st. the fatality is around 55% in the southeastern area of Guinea, Sierra Leone, Liberia, and Nigeria. The number of patients with Ebola Hemorrhagic Fever (EHF) was continuously increasing even though the any effective therapeutics or vaccines has not been developed yet. The Ebola virus in Guinea showed 98% homology with Zaire Ebola Virus. Study of the pathogenesis of Ebola virus infection and assess of the various candidates of vaccine have been tried for a long time, especially in United States and some European countries. Even though the attenuated live vaccine and DNA vaccine containing Ebola viral genes were tested and showed efficacy in chimpanzees, those candidates still need clinical tests requiring much longer time than the preclinical development to be approved for the practical treatment. It can be expected to eradicate Ebola virus by a safe and efficient vaccine development similar to the case of smallpox virus which was extinguished from the world by the variola vaccine. PMID:25562048

  8. Viruses of asparagus.

    PubMed

    Tomassoli, Laura; Tiberini, Antonio; Vetten, Heinrich-Josef

    2012-01-01

    The current knowledge on viruses infecting asparagus (Asparagus officinalis) is reviewed. Over half a century, nine virus species belonging to the genera Ilarvirus, Cucumovirus, Nepovirus, Tobamovirus, Potexvirus, and Potyvirus have been found in this crop. The potyvirus Asparagus virus 1 (AV1) and the ilarvirus Asparagus virus 2 (AV2) are widespread and negatively affect the economic life of asparagus crops reducing yield and increasing the susceptibility to biotic and abiotic stress. The main properties and epidemiology of AV1 and AV2 as well as diagnostic techniques for their detection and identification are described. Minor viruses and control are briefly outlined. PMID:22682173

  9. Serodiagnosis for tumor viruses.

    PubMed

    Morrison, Brian J; Labo, Nazzarena; Miley, Wendell J; Whitby, Denise

    2015-04-01

    The known human tumor viruses include the DNA viruses Epstein-Barr virus (EBV), Kaposi sarcoma herpesvirus (KSHV), Merkel cell polyomavirus (MCPyV), human papillomavirus (HPV), and hepatitis B virus (BV). RNA tumor viruses include human T-cell lymphotrophic virus type 1 (HTLV-1) and hepatitis C virus (HCV). The serological identification of antigens/antibodies in serum is a rapidly progressing field with utility for both scientists and clinicians. Serology is useful for conducting seroepidemiology studies and to inform on the pathogenesis and host immune response to a particular viral agent. Clinically, serology is useful for diagnosing current or past infection and for aiding in clinical management decisions. Serology is useful for screening blood donations for infectious agents and for monitoring the outcome of vaccination against these viruses. Serodiagnosis of human tumor viruses has improved in recent years with increased specificity and sensitivity of the assays, as well as reductions in cost and the ability to assess multiple antibody/antigens in single assays. Serodiagnosis of tumor viruses plays an important role in our understanding of the prevalence and transmission of these viruses and ultimately in the ability to develop treatments/preventions for these globally important diseases. PMID:25843726

  10. Readability of Ebola Information on Websites of Public Health Agencies, United States, United Kingdom, Canada, Australia, and Europe

    PubMed Central

    Spanoudakis, Elpiniki; Holmes, Alison H.

    2015-01-01

    Public involvement in efforts to control the current Ebola virus disease epidemic requires understandable information. We reviewed the readability of Ebola information from public health agencies in non–Ebola-affected areas. A substantial proportion of citizens would have difficulty understanding existing information, which would potentially hinder effective health-seeking behaviors. PMID:26079313

  11. Readability of Ebola Information on Websites of Public Health Agencies, United States, United Kingdom, Canada, Australia, and Europe.

    PubMed

    Castro-Sánchez, Enrique; Spanoudakis, Elpiniki; Holmes, Alison H

    2015-07-01

    Public involvement in efforts to control the current Ebola virus disease epidemic requires understandable information. We reviewed the readability of Ebola information from public health agencies in non-Ebola-affected areas. A substantial proportion of citizens would have difficulty understanding existing information, which would potentially hinder effective health-seeking behaviors. PMID:26079313

  12. Lipids of Archaeal Viruses

    PubMed Central

    Roine, Elina; Bamford, Dennis H.

    2012-01-01

    Archaeal viruses represent one of the least known territory of the viral universe and even less is known about their lipids. Based on the current knowledge, however, it seems that, as in other viruses, archaeal viral lipids are mostly incorporated into membranes that reside either as outer envelopes or membranes inside an icosahedral capsid. Mechanisms for the membrane acquisition seem to be similar to those of viruses infecting other host organisms. There are indications that also some proteins of archaeal viruses are lipid modified. Further studies on the characterization of lipids in archaeal viruses as well as on their role in virion assembly and infectivity require not only highly purified viral material but also, for example, constant evaluation of the adaptability of emerging technologies for their analysis. Biological membranes contain proteins and membranes of archaeal viruses are not an exception. Archaeal viruses as relatively simple systems can be used as excellent tools for studying the lipid protein interactions in archaeal membranes. PMID:23049284

  13. VIRUS AND VIRUS-LIKE DISEASES OF CITRUS IN EPIRUS

    Microsoft Academic Search

    L. Barbarossa; G. Loconsole; C. Vovlas

    2007-01-01

    SUMMARY In 2005 a survey was conducted in the main citrus- growing areas of Epirus. Commercial groves and nurs- eries were inspected for symptoms of virus and virus- like diseases and a total of 123 samples were collected. Molecular hybridisation was used to test for Citrus tris- teza virus (CTV), Citrus psorosis virus (CPsV), Citrus in- fectious variegation virus (CVV),

  14. Simian hemorrhagic fever virus infection of rhesus macaques as a model of viral hemorrhagic fever: Clinical characterization and risk factors for severe disease

    Microsoft Academic Search

    Reed F. Johnson; Lori E. Dodd; Srikanth Yellayi; Wenjuan Gu; Jennifer A. Cann; Catherine Jett; John G. Bernbaum; Dan R. Ragland; Marisa St. Claire; Russell Byrum; Jason Paragas; Joseph E. Blaney; Peter B. Jahrling

    2011-01-01

    Simian Hemorrhagic Fever Virus (SHFV) has caused sporadic outbreaks of hemorrhagic fevers in macaques at primate research facilities. SHFV is a BSL-2 pathogen that has not been linked to human disease; as such, investigation of SHFV pathogenesis in non-human primates (NHPs) could serve as a model for hemorrhagic fever viruses such as Ebola, Marburg, and Lassa viruses. Here we describe

  15. Other Viruses and Viruslike Agents

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The diseases reported under 'Virus and Virus-like Agents' in the first volume of this compendium, with the exception of Cherry rasp leaf virus and Rubus chinese seed-borne virus, should be considered oddities since there are no known type isolates available for these reported viruses. Without a po...

  16. RNA Viruses Infecting Pest Insects

    Technology Transfer Automated Retrieval System (TEKTRAN)

    RNA viruses are viruses whose genetic material is ribonucleic acid (RNA). RNA viruses may be double or single-stranded based on the type of RNA they contain. Single-stranded RNA viruses can be further grouped into negative sense or positive-sense viruses according to the polarity of their RNA. Fur...

  17. Investigating the zoonotic origin of the West African Ebola epidemic

    PubMed Central

    Marí Saéz, Almudena; Weiss, Sabrina; Nowak, Kathrin; Lapeyre, Vincent; Zimmermann, Fee; Düx, Ariane; Kühl, Hjalmar S; Kaba, Moussa; Regnaut, Sebastien; Merkel, Kevin; Sachse, Andreas; Thiesen, Ulla; Villányi, Lili; Boesch, Christophe; Dabrowski, Piotr W; Radoni?, Aleksandar; Nitsche, Andreas; Leendertz, Siv Aina J; Petterson, Stefan; Becker, Stephan; Krähling, Verena; Couacy-Hymann, Emmanuel; Akoua-Koffi, Chantal; Weber, Natalie; Schaade, Lars; Fahr, Jakob; Borchert, Matthias; Gogarten, Jan F; Calvignac-Spencer, Sébastien; Leendertz, Fabian H

    2015-01-01

    The severe Ebola virus disease epidemic occurring in West Africa stems from a single zoonotic transmission event to a 2-year-old boy in Meliandou, Guinea. We investigated the zoonotic origins of the epidemic using wildlife surveys, interviews, and molecular analyses of bat and environmental samples. We found no evidence for a concurrent outbreak in larger wildlife. Exposure to fruit bats is common in the region, but the index case may have been infected by playing in a hollow tree housing a colony of insectivorous free-tailed bats (Mops condylurus). Bats in this family have previously been discussed as potential sources for Ebola virus outbreaks, and experimental data have shown that this species can survive experimental infection. These analyses expand the range of possible Ebola virus sources to include insectivorous bats and reiterate the importance of broader sampling efforts for understanding Ebola virus ecology. PMID:25550396

  18. Investigating the zoonotic origin of the West African Ebola epidemic.

    PubMed

    Marí Saéz, Almudena; Weiss, Sabrina; Nowak, Kathrin; Lapeyre, Vincent; Zimmermann, Fee; Düx, Ariane; Kühl, Hjalmar S; Kaba, Moussa; Regnaut, Sebastien; Merkel, Kevin; Sachse, Andreas; Thiesen, Ulla; Villányi, Lili; Boesch, Christophe; Dabrowski, Piotr W; Radoni?, Aleksandar; Nitsche, Andreas; Leendertz, Siv Aina J; Petterson, Stefan; Becker, Stephan; Krähling, Verena; Couacy-Hymann, Emmanuel; Akoua-Koffi, Chantal; Weber, Natalie; Schaade, Lars; Fahr, Jakob; Borchert, Matthias; Gogarten, Jan F; Calvignac-Spencer, Sébastien; Leendertz, Fabian H

    2015-01-01

    The severe Ebola virus disease epidemic occurring in West Africa stems from a single zoonotic transmission event to a 2-year-old boy in Meliandou, Guinea. We investigated the zoonotic origins of the epidemic using wildlife surveys, interviews, and molecular analyses of bat and environmental samples. We found no evidence for a concurrent outbreak in larger wildlife. Exposure to fruit bats is common in the region, but the index case may have been infected by playing in a hollow tree housing a colony of insectivorous free-tailed bats (Mops condylurus). Bats in this family have previously been discussed as potential sources for Ebola virus outbreaks, and experimental data have shown that this species can survive experimental infection. These analyses expand the range of possible Ebola virus sources to include insectivorous bats and reiterate the importance of broader sampling efforts for understanding Ebola virus ecology. PMID:25550396

  19. Viruses in Antarctic lakes

    NASA Technical Reports Server (NTRS)

    Kepner, R. L. Jr; Wharton, R. A. Jr; Suttle, C. A.; Wharton RA, J. r. (Principal Investigator)

    1998-01-01

    Water samples collected from four perennially ice-covered Antarctic lakes during the austral summer of 1996-1997 contained high densities of extracellular viruses. Many of these viruses were found to be morphologically similar to double-stranded DNA viruses that are known to infect algae and protozoa. These constitute the first observations of viruses in perennially ice-covered polar lakes. The abundance of planktonic viruses and data suggesting substantial production potential (relative to bacteria] secondary and photosynthetic primary production) indicate that viral lysis may be a major factor in the regulation of microbial populations in these extreme environments. Furthermore, we suggest that Antarctic lakes may be a reservoir of previously undescribed viruses that possess novel biological and biochemical characteristics.

  20. Cell transformation by viruses

    Microsoft Academic Search

    Joseph L. Melnick; Janet S. Butel; Satvir S. Tevethia; Nilambar Biswal; Matilda Benyesh-Melnick

    1971-01-01

    Summary  This paper describes some current work pertaining to transformation of cells by oncogenic viruses.\\u000a \\u000a Part I includes: (1) the effect of a deoxyribonucleic acid (DNA) tumor virus (SV40) on the antigenic characteristics of transformed\\u000a cells; (2) in vitro and in vivo methods of detecting virus-specific surface antigens; (3) the role that the host cell may\\u000a play in the expression of

  1. Virus entry paradigms

    Microsoft Academic Search

    Manjula Kalia; Shahid Jameel

    Viruses, despite being relatively simple in structure and composition, have evolved to exploit complex cellular processes\\u000a for their replication in the host cell. After binding to their specific receptor on the cell surface, viruses (or viral genomes)\\u000a have to enter cells to initiate a productive infection. Though the entry processes of many enveloped viruses is well understood,\\u000a that of most

  2. Wheat Streak Mosaic Virus 

    E-print Network

    Morgan, Gaylon

    2005-01-26

    . Infected wheat plants normally are stunted, with leaves mottled and streaked in green-yellow, parallel and discontinuous patterns (Fig. 1). This disease?s negative impact varies from year to year depending on its severity and distribution...; in the Southern Great Plains states, crop losses due to WSMV exceed $30 million in some years but are in- significant in others. High Plains Virus High Plains Virus (HPV), occasionally called High Plains Disease, is a relatively new virus identified...

  3. Water system virus detection

    NASA Technical Reports Server (NTRS)

    Fraser, A. S.; Wells, A. F.; Tenoso, H. J.

    1975-01-01

    A monitoring system developed to test the capability of a water recovery system to reject the passage of viruses into the recovered water is described. A nonpathogenic marker virus, bacteriophage F2, is fed into the process stream before the recovery unit and the reclaimed water is assayed for its presence. Detection of the marker virus consists of two major components, concentration and isolation of the marker virus, and detection of the marker virus. The concentration system involves adsorption of virus to cellulose acetate filters in the presence of trivalent cations and low pH with subsequent desorption of the virus using volumes of high pH buffer. The detection of the virus is performed by a passive immune agglutination test utilizing specially prepared polystyrene particles. An engineering preliminary design was performed as a parallel effort to the laboratory development of the marker virus test system. Engineering schematics and drawings of a fully functional laboratory prototype capable of zero-G operation are presented. The instrument consists of reagent pump/metering system, reagent storage containers, a filter concentrator, an incubation/detector system, and an electronic readout and control system.

  4. CDC: West Nile Virus

    NSDL National Science Digital Library

    This Web site contains the most recent West Nile virus data from the Centers for Disease Control. The main features include a 2003 Human Case Count and updated maps representing the spread of the virus. A downloadable document outlines the CDC's West Nile virus surveillance and control program, which involves weekly data collection for wild birds, sentinel chicken flocks, human cases, veterinary cases, and mosquito surveillance. The site also provides links to general information about the virus, from the ecology and virology of West Nile to epidemiological and laboratory issues.

  5. Critical Role for the Cysteines Flanking the Internal Fusion Peptide of Avian Sarcoma\\/Leukosis Virus Envelope Glycoprotein

    Microsoft Academic Search

    S. E. Delos; J. M. White

    2000-01-01

    The transmembrane subunit (TM) of the envelope glycoprotein (Env) of the oncovirus avian sarcoma\\/ leukosis virus (ASLV) contains an internal fusion peptide flanked by two cysteines (C9 and C45). These cysteines, as well as an analogous pair in the Ebola virus GP glycoprotein, are predicted to be joined by a disulfide bond. To examine the importance of these cysteines, we

  6. Communiqu de presse | 13 novembre 2014 L'Afrique de l'Ouest est touche, depuis mars 2014, par la plus grave pidmie d'Ebola jamais observe.

    E-print Network

    , par la plus grave épidémie d'Ebola jamais observée. Le 12 novembre 2014, l'Organisation mondiale de la'étudiants, en participant à des enseignements de niveau Master et doctorat. Pour en savoir plus. Epidémie d'Ebola et pratiques relatives à la maladie à virus Ebola et aux mesures préventives au Bénin (EBBEN) et en

  7. Ebola Outbreak Killed 5000 Gorillas

    Microsoft Academic Search

    Magdalena Bermejo; José Domingo Rodríguez-Teijeiro; Germán Illera; Alex Barroso; Carles Vilà; Peter D. Walsh

    2006-01-01

    Over the past decade, the Zaire strain of Ebola virus (ZEBOV) has repeatedly emerged in Gabon and Congo. Each human outbreak has been accompanied by reports of gorilla and chimpanzee carcasses in neighboring forests, but both the extent of ape mortality and the causal role of ZEBOV have been hotly debated. Here, we present data suggesting that in 2002 and

  8. Newcastle disease virus (velogens)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Newcastle disease virus (NDV) is also known as avian paramyxovirus serotype-1 (APMV-1). While all NDV are referred to as APMV-1 and are of one serotype, only infections with virulent NDV (vNDV) cause Newcastle disease (ND). Newcastle disease virus strains are defined as virulent if they 1) have th...

  9. Lettuce Necrotic Yellows Virus

    Microsoft Academic Search

    L. L. Stubbs; R. G. GROGAN

    1963-01-01

    A DESTRUCTIVE virus disease of lettuce, causing extensive crop losses sometimes as high as 100 per cent, was recognized in Victoria in 1954 as being distinct from the lettuce mosaic disease. Until 1959, however, all attempts to transmit the virus to lettuce with aphids which commonly infest lettuce, with thrips, leaf-hoppers and sap inoculation methods were unsuccessful. In that year

  10. Papaya ringspot virus (Potyviridae)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Papaya ringspot virus, a member of the family Potyviridae, is single stranded RNA plant virus with a monocistronic genome of about 10,326 nucleotides that is expressed via a large polyprotein subsequently cleaved into functional proteins. It causes severe damage on cucurbit crops such as squash and...

  11. Papaya Ringspot Virus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The term papaya ringspot virus (PRSV) was coined by Jensen in 1949, to describe a papaya disease in Hawaii. Later work showed that diseases such as papaya mosaic and watermelon mosaic virus-1 were caused by PRSV. The primary host range of PRSV is papaya and cucurbits, with Chenopium amaranticolor ...

  12. Human Papilloma Virus Infections

    PubMed Central

    Wright, V. Cecil

    1989-01-01

    Genital warts are believed to be caused by human papilloma viruses and to be sexually transmitted. The viruses are classified by DNA types, which appear to cause different types of disease. The choice of treatment, and usually its success rate, vary according to the type of disease and its location. PMID:21248973

  13. DETECTING VIRUSES IN WATER

    EPA Science Inventory

    This article, which reviews the subject of detecting viruses in water, encompasses two topics. he first topic consists of methods used for concentrating viruses from large volumes of water into smaller, more manageable volumes. he second topic consists of assay methods used for e...

  14. Towards synthetic viruses

    Microsoft Academic Search

    Guy Zuber; Emmanuel Dauty; Marc Nothisen; Pascale Belguise; Jean-Paul Behr

    2001-01-01

    Gene delivery is too complex to be performed with a single carrier molecule. Synthetic multicomponent vectors are being designed that mimic key properties of viruses. Some solutions, such as diverting cell-anchoring molecules or the endogenous nuclear import machinery from their normal function, are directly copied from bacteria and viruses. Some other solutions are original ones: monomolecular genome condensation via detergent

  15. Biological versus computer viruses

    Microsoft Academic Search

    Daniel GUINIER

    1989-01-01

    To understand biological viruses, some notions of the fundamental knowledge of the structure of DNA, the genetic code, the biosynthesis of proteins, the transcription, replication and transfer processes,... are presented so as to give an idea as to how the genetic information is decrypted by biological mechanisms and consequently, how viruses work.A computer \\

  16. Virus separation using membranes.

    PubMed

    Grein, Tanja A; Michalsky, Ronald; Czermak, Peter

    2014-01-01

    Industrial manufacturing of cell culture-derived viruses or virus-like particles for gene therapy or vaccine production are complex multistep processes. In addition to the bioreactor, such processes require a multitude of downstream unit operations for product separation, concentration, or purification. Similarly, before a biopharmaceutical product can enter the market, removal or inactivation of potential viral contamination has to be demonstrated. Given the complexity of biological solutions and the high standards on composition and purity of biopharmaceuticals, downstream processing is the bottleneck in many biotechnological production trains. Membrane-based filtration can be an economically attractive and efficient technology for virus separation. Viral clearance, for instance, of up to seven orders of magnitude has been reported for state of the art polymeric membranes under best conditions.This chapter summarizes the fundamentals of virus ultrafiltration, diafiltration, or purification with adsorptive membranes. In lieu of an impractical universally applicable protocol for virus filtration, application of these principles is demonstrated with two examples. The chapter provides detailed methods for production, concentration, purification, and removal of a rod-shaped baculovirus (Autographa californica M nucleopolyhedrovirus, about 40 × 300 nm in size, a potential vector for gene therapy, and an industrially important protein expression system) or a spherical parvovirus (minute virus of mice, 22-26 nm in size, a model virus for virus clearance validation studies). PMID:24297430

  17. Equine Arteritis Virus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    03. Nidovirales : 03.004. Arteriviridae : 03.004.0. {03.004.0. unknown} : 03.004.0.01. Arterivirus : 03.004.0.01.001. Equine arteritis virus will be published online. The article details the phenotypic and genotypic makeup of equine arteritis virus (EAV), and summarizes its biological properties....

  18. Rift Valley Fever Virus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Rift Valley fever virus (RVFV) is a mosquito-transmitted virus or arbovirus that is endemic in sub-Saharan Africa. In the last decade, Rift Valley fever (RVF) outbreaks have resulted in loss of human and animal life, as well as had significant economic impact. The disease in livestock is primarily a...

  19. Cutthroat Trout Virus

    USGS Multimedia Gallery

    Electron micrograph of the cutthroat trout virus (CTV) showing the small, round virions of approximately 30 nanometers in diameter containing a single-stranded RNA genome. CTV, whose genome was first characterized by USGS researchers, is being used in research into the human virus Hepatitis E....

  20. Characterization and identification of two virus diseases of spinach in South Texas 

    E-print Network

    Adams, Edward Blair

    1979-01-01

    mosaic virus Beet western yellows virus Beet yellows virus Broad bean wilt virus Carnation ring spot virus Clover yellow mosaic virus Cucumber green mottle mosaic virus Cucumber mosaic virus Lettuce mosaic virus Radish mosaic virus Raspberry...

  1. Replication of Sendai Virus

    PubMed Central

    Blair, Carol D.; Robinson, William S.

    1970-01-01

    Chick embryo fibroblast cultures infected with Sendai virus were incubated with 3H-uridine in the presence of actinomycin D beginning at 18 hr after infection. The 35 and 18S virus-specific ribonucleic acid (RNA) components were found in a ribonuclease-sensitive form in the cell and appeared to be associated with polyribosomes. Newly synthesized 57S viral RNA was rapidly coated with protein to form intracellular viral nucleocapsid, and no 57S RNA was found “free” (ribonucleasesensitive) in the 2,000 × g supernatant fraction of disrupted cells. The nucleocapsid from detergent-disrupted Sendai virus and that from disrupted cells were indistinguishable in ultrastructure and buoyant density, and neither was found to be infectious or have hemagglutinating activity. Kinetic studies of nucleocapsid and virus formation indicated a relative block in conversion of viral nucleocapsid to complete enveloped virus in these cells, resulting in accumulation of large amounts of nucleocapsid in the cell cytoplasm. Images PMID:4315961

  2. VIROLOGY: Rafting with Ebola

    NSDL National Science Digital Library

    Eric O. Freed (National Institutes of Health; National Institute of Allergy and Infectious Diseases)

    2002-04-12

    Access to the article is free, however registration and sign-in are required: Lipid rafts are microdomains in the cell plasma membrane that are enriched in cholesterol, saturated fatty acids, and certain proteins. In a Perspective, Freed discusses new work published elsewhere showing that filoviruses, including the deadly human pathogens Ebola and Marburg, use these lipid rafts to infect host cells and to assemble new virus particles.

  3. Is The Virus Problem Getting Worse?

    Microsoft Academic Search

    Jan Hruska

    2001-01-01

    The number of known viruses exceeded 50?000 in August 2000. The vast majority of those (74%) are parasitic viruses (attacking executables), second most populous are macro viruses (19%) and 7% are boot sector viruses. In May 2000, 88% of infections reported to Sophos were due to macro viruses, 9% were parasitic viruses and only 3% were boot sector viruses. Note

  4. Understanding virus filtration membrane performance

    Microsoft Academic Search

    S. Ranil Wickramasinghe; Emily D. Stump; David L. Grzenia; Scott M. Husson; John Pellegrino

    2010-01-01

    Virus filtration membranes are used to obtain virus clearance during the purification of biopharmaceutical products. These direct flow (also referred to as dead end or normal flow) filtration membranes are designed to reject virus particles and yield >98% product recovery for proteins less than 170kDa. Virus filtration feed streams generally have high purity and high product concentrations. Decrease in permeate

  5. Realms of the Viruses Online

    ERIC Educational Resources Information Center

    Liu, Dennis

    2007-01-01

    Viruses have evolved strategies for infecting all taxa, but most viruses are highly specific about their cellular host. In humans, viruses cause diverse diseases, from chronic but benign warts, to acute and deadly hemorrhagic fever. Viruses have entertaining names like Zucchini Yellow Mosaic, Semliki Forest, Coxsackie, and the original terminator,…

  6. Citrus Virus Symptoms in Sardinia

    Microsoft Academic Search

    A. Bruno

    1964-01-01

    SARDINIA was believed to be a virus-free citrus region until Boselli1 first noted a disorder showing symptoms commonly referred to as the psorosis virus complex. Following this, the main citrus areas of the Island have been surveyed with the view of recognizing and recording virus or virus-like manifestations.

  7. Virus-PEDOT Biocomposite Films

    PubMed Central

    Donavan, Keith C.; Arter, Jessica A.

    2012-01-01

    Virus-poly(3,4-ethylenedioxythiophene) (virus-PEDOT) biocomposite films are prepared by electropolymerizing 3,4-ethylenedioxythiophene (EDOT) in aqueous electrolytes containing 12 mM LiClO4 and the bacteriophage M13. The concentration of virus in these solutions, [virus]soln, is varied from 3 nM to 15 nM. A quartz crystal microbalance is used to directly measure the total mass of the biocomposite film during its electrodeposition. In combination with a measurement of the electrodeposition charge, the mass of the virus incorporated into the film is calculated. These data show that concentration of the M13 within the electropolymerized film, [virus]film, increases linearly with [virus]soln. The incorporation of virus particles into the PEDOT film from solution is efficient, resulting in a concentration ratio: [virus]film:[virus]soln ?450. Virus incorporation into the PEDOT causes roughening of the film topography that is observed using scanning electron microscopy and atomic force microscopy (AFM). The electrical conductivity of the virus-PEDOT film, measured perpendicular to the plane of the film using conductive tip AFM, decreases linearly with virus loading, from 270 ?S/cm for pure PE-DOT films to 50 ?S/cm for films containing 100 ?M virus. The presence on the virus surface of displayed affinity peptides did not significantly influence the efficiency of incorporation into virus-PEDOT biocomposite films. PMID:22856875

  8. Development of novel entry inhibitors targeting emerging viruses

    PubMed Central

    Zhou, Yanchen; Simmons, Graham

    2013-01-01

    Emerging viral diseases pose a unique risk to public health, and thus there is a need to develop therapies. A current focus of funding agencies, and hence research, is the development of broad-spectrum antivirals, and in particular, those targeting common cellular pathways. The scope of this article is to review screening strategies and recent advances in this area, with a particular emphasis on antivirals targeting the step of viral entry for emerging lipid-enveloped viruses such as Ebola virus and SARS-coronavirus. PMID:23199399

  9. Viruses isolated from Panamanian sloths.

    PubMed

    Seymour, C; Peralta, P H; Montgomery, G G

    1983-11-01

    Seven virus strains were isolated in Vero cells from whole blood samples from 80 wild-caught sloths, Bradypus variegatus and Choloepus hoffmanni, from Central Panamá. Four strains of at least two different serotypes are related to Changuinola virus; two of these were associated with prolonged or recrudescent viremias. One strain is an antigenic subtype of Punta Toro virus, and another, described here as Bradypus-4 virus, is a new, antigenically ungrouped virus. A second new virus from sloths, Utive virus, forms an antigenic complex within the Simbu serogroup with Utinga and Pintupo viruses. Tests on sequential plasma samples from radio-marked free-ranging sloths and from recently captured animals maintained in captivity showed that both species develop neutralizing antibodies following naturally acquired virus infections. Antibodies against the Changuinola and Simbu serogroup viruses are widespread in both sloth species and are especially prevalent in Choloepus, but are virtually absent in all other wild vertebrate species tested. PMID:6316795

  10. Targeted Transduction Patterns in the Mouse Brain by Lentivirus Vectors Pseudotyped with VSV, Ebola, Mokola, LCMV, or MuLV Envelope Proteins

    Microsoft Academic Search

    Deborah J. Watson; Gary P. Kobinger; Marco A. Passini; James M. Wilson; John H. Wolfe

    2002-01-01

    Lentiviral vectors have proven to be promising tools for transduction of central nervous system (CNS) cells in vivo and in vitro. In this study, CNS transduction patterns of lentiviral vectors pseudotyped with envelope glycoproteins from Ebola virus, murine leukemia virus (MuLV), lymphocytic choriomeningitis virus (LCMV), or the rabies-related Mokola virus were compared to a vector pseudotyped with the vesicular stomatitis

  11. Towards synthetic viruses.

    PubMed

    Zuber, G; Dauty, E; Nothisen, M; Belguise, P; Behr, J P

    2001-11-19

    Gene delivery is too complex to be performed with a single carrier molecule. Synthetic multicomponent vectors are being designed that mimic key properties of viruses. Some solutions, such as diverting cell-anchoring molecules or the endogenous nuclear import machinery from their normal function, are directly copied from bacteria and viruses. Some other solutions are original ones: monomolecular genome condensation via detergent dimerization or endosome disruption by the proton sponge effect are not exploited by natural cell invaders. All these components, however, still have to be assembled into a unique supramolecular system, an 'artificial virus'. PMID:11718949

  12. [Grapevine viruses in Tunisia].

    PubMed

    Acheche, H; Fattouch, S; M'Hirsi, S; Marzouki, N; Marrakchi, M

    1998-01-01

    Tunisian grapevine culture is affected by many viruses caused by some phytovirus belonging to nepovirus, closterovirus and trichovirus groups. The present work deal with the economically important viroses identified in tunisian grapevines. We present here the development methods to detect these viruses in propagating material. The important viruses biologically, biochemically, serologically and using molecular techniques, characterised are: GFLV, GLRaV3 and GVB. The genetic polymorphism analysis was also carried and tunisian isolates were compared to previously described ones in literature. PMID:14666749

  13. Ebola: a review for emergency providers.

    PubMed

    Torres, Mercedes; Hansen, Karen N; Jerrard, David

    2015-05-01

    Filoviruses, including Ebola virus, are associated with outbreaks of severe febrile illness with high fatality rates in humans. The 2014 outbreak of Ebola virus in West Africa is by far the largest outbreak in history and the first to spread to highly populated urban areas. The potential for such an epidemic to spread beyond Africa through international travel has raised concern in the world community as well as in American and international health agencies. This article presents background information, personal and public protective strategies, and treatment recommendations for emergency physicians. PMID:26065304

  14. TIM-family Proteins Promote Infection of Multiple Enveloped Viruses through Virion-associated Phosphatidylserine

    PubMed Central

    Jemielity, Stephanie; Wang, Jinyize J.; Chan, Ying Kai; Ahmed, Asim A.; Li, Wenhui; Monahan, Sheena; Bu, Xia; Farzan, Michael; Freeman, Gordon J.; Umetsu, Dale T.; DeKruyff, Rosemarie H.; Choe, Hyeryun

    2013-01-01

    Human T-cell Immunoglobulin and Mucin-domain containing proteins (TIM1, 3, and 4) specifically bind phosphatidylserine (PS). TIM1 has been proposed to serve as a cellular receptor for hepatitis A virus and Ebola virus and as an entry factor for dengue virus. Here we show that TIM1 promotes infection of retroviruses and virus-like particles (VLPs) pseudotyped with a range of viral entry proteins, in particular those from the filovirus, flavivirus, New World arenavirus and alphavirus families. TIM1 also robustly enhanced the infection of replication-competent viruses from the same families, including dengue, Tacaribe, Sindbis and Ross River viruses. All interactions between TIM1 and pseudoviruses or VLPs were PS-mediated, as demonstrated with liposome blocking and TIM1 mutagenesis experiments. In addition, other PS-binding proteins, such as Axl and TIM4, promoted infection similarly to TIM1. Finally, the blocking of PS receptors on macrophages inhibited the entry of Ebola VLPs, suggesting that PS receptors can contribute to infection in physiologically relevant cells. Notably, infection mediated by the entry proteins of Lassa fever virus, influenza A virus and SARS coronavirus was largely unaffected by TIM1 expression. Taken together our data show that TIM1 and related PS-binding proteins promote infection of diverse families of enveloped viruses, and may therefore be useful targets for broad-spectrum antiviral therapies. PMID:23555248

  15. Virus Chapter: Iflaviridae

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The iflaviruses comprise viruses isolated from arthropod species of agricultural importance. All members of iflaviruses have a genome arrangement similar to the picornaviruses, ootyviruses, and secoviruses. However, phylogenetic analysis using the RNA-dependent RNA polymerase region showed that th...

  16. What's West Nile Virus?

    MedlinePLUS

    ... discovered all the way back in 1937 in Africa, the West Nile virus probably didn't make ... Foundation, iStock, Getty Images, Corbis, Veer, Science Photo Library, Science Source Images, Shutterstock, and Clipart.com

  17. The dengue viruses.

    PubMed Central

    Henchal, E A; Putnak, J R

    1990-01-01

    Dengue, a major public health problem throughout subtropical and tropical regions, is an acute infectious disease characterized by biphasic fever, headache, pain in various parts of the body, prostration, rash, lymphadenopathy, and leukopenia. In more severe or complicated dengue, patients present with a severe febrile illness characterized by abnormalities of hemostasis and increased vascular permeability, which in some instances results in a hypovolemic shock. Four distinct serotypes of the dengue virus (dengue-1, dengue-2, dengue-3, and dengue-4) exist, with numerous virus strains found worldwide. Molecular cloning methods have led to a greater understanding of the structure of the RNA genome and definition of virus-specific structural and nonstructural proteins. Progress towards producing safe, effective dengue virus vaccines, a goal for over 45 years, has been made. Images PMID:2224837

  18. Avoiding Computer Viruses.

    ERIC Educational Resources Information Center

    Rowe, Joyce; And Others

    1989-01-01

    The threat of computer sabotage is a real concern to business teachers and others responsible for academic computer facilities. Teachers can minimize the possibility. Eight suggestions for avoiding computer viruses are given. (JOW)

  19. Sexually transmitted viruses.

    PubMed Central

    Rapp, F.

    1989-01-01

    Human viruses known to be spread by sexual contact include herpes simplex viruses (HSV), papillomaviruses (HPV), human immunodeficiency virus (HIV), hepatitis B virus, and cytomegalovirus. Infections with the first three (HSV, HPV, and HIV) have reached epidemic proportions and pose global health concerns. Most of what we know about these human pathogens has been learned only recently, owing to the advent of DNA technologies and advances in culture techniques. In fact, our awareness of one virally transmitted venereal disease, acquired immunodeficiency syndrome, dates to the early 1980s. This paper touches on various aspects of the biology, pathogenesis, clinical manifestations, and, where applicable, oncogenicity of these agents, as well as current treatments and vaccine initiatives. PMID:2549736

  20. VIRUS instrument enclosures

    NASA Astrophysics Data System (ADS)

    Prochaska, T.; Allen, R.; Mondrik, N.; Rheault, J. P.; Sauseda, M.; Boster, E.; James, M.; Rodriguez-Patino, M.; Torres, G.; Ham, J.; Cook, E.; Baker, D.; DePoy, Darren L.; Marshall, Jennifer L.; Hill, G. J.; Perry, D.; Savage, R. D.; Good, J. M.; Vattiat, Brian L.

    2014-08-01

    The Visible Integral-Field Replicable Unit Spectrograph (VIRUS) instrument will be installed at the Hobby-Eberly Telescope† in the near future. The instrument will be housed in two enclosures that are mounted adjacent to the telescope, via the VIRUS Support Structure (VSS). We have designed the enclosures to support and protect the instrument, to enable servicing of the instrument, and to cool the instrument appropriately while not adversely affecting the dome environment. The system uses simple HVAC air handling techniques in conjunction with thermoelectric and standard glycol heat exchangers to provide efficient heat removal. The enclosures also provide power and data transfer to and from each VIRUS unit, liquid nitrogen cooling to the detectors, and environmental monitoring of the instrument and dome environments. In this paper, we describe the design and fabrication of the VIRUS enclosures and their subsystems.

  1. Powassan (POW) Virus Basics

    MedlinePLUS

    ... attachment time needed to transmit the virus. When spending time in wooded or brushy habitat in north ... and woods, and doing thorough tick checks after spending time in the woods. These precautions are most ...

  2. West Nile Virus

    MedlinePLUS

    ... for Parents for Kids for Teens Teens Home Body Mind Sexual Health Food & Fitness Diseases & Conditions Infections Q&A School & Jobs Drugs & Alcohol Staying Safe Recipes En Español ... Image West Nile Virus KidsHealth > Teens > Infections > Bacterial & ...

  3. Wheat Streak Mosaic Virus

    E-print Network

    Morgan, Gaylon

    2005-01-26

    Virus First discovered in Nebraska in 1922, wheat streak mosaic virus (WSMV) remains a threat today across most of the U.S. Central Plains. WSMV affects spring wheat, barley, corn, triticale, rye and numerous other annual and perennial grasses... have tre- mendous reproductive capability, enabling large populations to build. The mite is most active during warm weather, with temperatures of 75-80 degrees F optimum for reproduction. Mites require a living grass host to survive the summer; sum...

  4. Dengue Virus Diagnostics

    Microsoft Academic Search

    Evgeni Eltzov; Danit Atias; Levi Gheber; Robert S. Marks

    \\u000a Dengue fever (DF) is an emerging arborviral disease caused by infection with dengue virus (DENV) which has emerged as the\\u000a most important vector-borne viral disease in tropical areas and it continues to expand geographically. The four serotypes\\u000a of DENV that cause human disease are transmitted by Aedes mosquitoes. Expansion in geographic distribution of both viruses\\u000a and mosquito vectors, has led

  5. Origins of Viruses

    NSDL National Science Digital Library

    Ed Rybicki

    This page is part of a site created as a supplement for an introduction to virology course for second year microbiology students. It includes discussions on the origins of viruses as well as how they might have evolved. There are several links to pertinent conceptial matter such as basics on the different types of viruses as well as a link to the course home page.

  6. Hepatitis B virus infection.

    PubMed

    Trépo, Christian; Chan, Henry L Y; Lok, Anna

    2014-12-01

    Hepatitis B virus infection is a major public health problem worldwide; roughly 30% of the world's population show serological evidence of current or past infection. Hepatitis B virus is a partly double-stranded DNA virus with several serological markers: HBsAg and anti-HBs, HBeAg and anti-HBe, and anti-HBc IgM and IgG. It is transmitted through contact with infected blood and semen. A safe and effective vaccine has been available since 1981, and, although variable, the implementation of universal vaccination in infants has resulted in a sharp decline in prevalence. Hepatitis B virus is not cytopathic; both liver damage and viral control--and therefore clinical outcome--depend on the complex interplay between virus replication and host immune response. Overall, as much as 40% of men and 15% of women with perinatally acquired hepatitis B virus infection will die of liver cirrhosis or hepatocellular carcinoma. In addition to decreasing hepatic inflammation, long-term antiviral treatment can reverse cirrhosis and reduce hepatocellular carcinoma. Development of new therapies that can improve HBsAg clearance and virological cure is warranted. PMID:24954675

  7. Tick-borne viruses*

    PubMed Central

    Work, Telford H.

    1963-01-01

    More than 150 arthropod-borne viruses are now recognized, and over 50 of these are known to produce human infections and disease. Among these viruses are those of the tick-borne Russian spring-summer complex, which is etiologically involved in a wide variety of human diseases of varying severity. The eight antigenically different members of this complex so far known are Russian spring-summer encephalitis, louping-ill, Central European encephalitis, Omsk haemorrhagic fever, Kyasanur Forest disease, Langat, Negishi and Powassan viruses. In his review of the problems posed by these viruses and of research on them, the author points out that, while this complex is distributed around the globe in the temperate zone of the northern hemisphere, the only serious tick-borne virus disease known in the tropics is Kyasanur Forest disease. It is probable, however, that there are other, unrecognized tick-borne viruses in the tropical areas of Asia, Africa and America of importance to human health, and that these will be brought to light as virological studies of diseases of now obscure etiology are pursued. PMID:14043753

  8. Ebola death toll rises in Africa with at least 14 nurses among the dead.

    PubMed

    Duffin, Christian

    2014-08-19

    At least 14 nurses are among 80 healthcare workers who have died from an outbreak of the Ebola virus spreading across West Africa, declared an international public health emergency last week by the World Health Organization (WHO). PMID:25116521

  9. Multiple virus infections in the honey bee and genome divergence of honey bee viruses

    Microsoft Academic Search

    Yanping Chen; Yan Zhao; John Hammond; Hei-ti Hsu; Jay Evans; Mark Feldlaufer

    2004-01-01

    Using uniplex RT-PCR we screened honey bee colonies for the presence of several bee viruses, including black queen cell virus (BQCV), deformed wing virus (DWV), Kashmir bee virus (KBV), and sacbrood virus (SBV), and described the detection of mixed virus infections in bees from these colonies. We report for the first time that individual bees can harbor four viruses simultaneously.

  10. Immunology of hepatitis B virus and hepatitis C virus infection

    Microsoft Academic Search

    Michelina Nascimbeni; Barbara Rehermann

    2005-01-01

    More than 500 million people worldwide are persistently infected with the hepatitis B virus (HBV) and\\/or hepatitis C virus (HCV) and are at risk of developing chronic liver disease, cirrhosis and hepatocellular carcinoma. Despite many common features in the pathogenesis of HBV- and HCV-related liver disease, these viruses markedly differ in their virological properties and in their immune escape and

  11. Glycyrrhizic acid inhibits virus growth and inactivates virus particles.

    PubMed

    Pompei, R; Flore, O; Marccialis, M A; Pani, A; Loddo, B

    1979-10-25

    Screening investigations in antiviral action of plant extracts have revealed that a component of Glycyrrhiza glabra roots, found to be glycyrrhizie acid, is active against viruses. We report here that this drug inhibits growth and cytopathology of several unrelated DNA and RNA viruses, while not affecting cell activity and ability to replicate. In addition, glycyrrhizic acid inactivates herpes simplex virus particles irreversibly. PMID:233133

  12. Chicken anemia virus.

    PubMed

    Schat, K A

    2009-01-01

    Chicken anemia virus (CAV), the only member of the genus Gyrovirus of the Circoviridae, is a ubiquitous pathogen of chickens and has a worldwide distribution. CAV shares some similarities with Torque teno virus (TTV) and Torque teno mini virus (TTMV) such as coding for a protein inducing apoptosis and a protein with a dual-specificity phosphatase. In contrast to TTV, the genome of CAV is highly conserved. Another important difference is that CAV can be isolated in cell culture. CAV produces a single polycistronic messenger RNA (mRNA), which is translated into three proteins. The promoter-enhancer region has four direct repeats resembling estrogen response elements. Transcription is enhanced by estrogen and repressed by at least two other transcription factors, one of which is COUP-TF1. A remarkable feature of CAV is that the virus can remain latent in gonadal tissues in the presence or absence of virus-neutralizing antibodies. In contrast to TTV, CAV can cause clinical disease and subclinical immunosuppression especially affecting CD8+ T lymphocytes. Clinical disease is associated with infection in newly hatched chicks lacking maternal antibodies or older chickens with a compromised humoral immune response. PMID:19230563

  13. Research on computer virus database management system

    NASA Astrophysics Data System (ADS)

    Qi, Guoquan

    2011-12-01

    The growing proliferation of computer viruses becomes the lethal threat and research focus of the security of network information. While new virus is emerging, the number of viruses is growing, virus classification increasing complex. Virus naming because of agencies' capture time differences can not be unified. Although each agency has its own virus database, the communication between each other lacks, or virus information is incomplete, or a small number of sample information. This paper introduces the current construction status of the virus database at home and abroad, analyzes how to standardize and complete description of virus characteristics, and then gives the information integrity, storage security and manageable computer virus database design scheme.

  14. Phylogenetic assessment of filoviruses: how many lineages of Marburg virus?

    PubMed Central

    Peterson, A Townsend; Holder, Mark T

    2012-01-01

    Filoviruses have to date been considered as consisting of one diverse genus (Ebola viruses) and one undifferentiated genus (Marburg virus). We reconsider this idea by means of detailed phylogenetic analyses of sequence data available for the Filoviridae: using coalescent simulations, we ascertain that two Marburg isolates (termed the “RAVN” strain) represent a quite-distinct lineage that should be considered in studies of biogeography and host associations, and may merit recognition at the level of species. In contrast, filovirus isolates recently obtained from bat tissues are not distinct from previously known strains, and should be considered as drawn from the same population. Implications for understanding the transmission geography and host associations of these viruses are discussed. PMID:22957185

  15. [Marburg and Ebola hemorrhagic fevers--pathogens, epidemiology and therapy].

    PubMed

    Stock, Ingo

    2014-09-01

    Marburg and Ebola hemorrhagic fevers are severe, systemic viral diseases affecting humans and non-human primates. They are characterized by multiple symptoms such as hemorrhages, fever, headache, muscle and abdominal pain, chills, sore throat, nausea, vomiting and diarrhea. Elevated liver-associated enzyme levels and coagulopathy are also associated with these diseases. Marburg and Ebola hemorrhagic fevers are caused by (Lake victoria) Marburg virus and different species of Ebola viruses, respectively. They are enveloped, single-stranded RNA viruses and belong to the family of filoviridae. Case fatality rates of filovirus disease outbreaks are among the highest reported for any human pathogen, ranging from 25 to 90% or more. Outbreaks of Marburg and Ebola hemorrhagic fever occur in certain regions of equatorial Africa at irregular intervals. Since 2000, the number of outbreaks has increased. In 2014, the biggest outbreak of a filovirus-induced hemorrhagic fever that has been documented so far occurred from March to July 2014 in Guinea, Sierra Leone, Liberia and Nigeria. The outbreak was caused by a new variant of Zaire Ebola-Virus, affected more than 2600 people (stated 20 August) and was associated with case-fatality rates of up to 67% (Guinea). Treatment of Marburg and Ebola hemorrhagic fevers is symptomatic and supportive, licensed antiviral agents are currently not available. Recently, BCX4430, a promising synthetic adenosine analogue with high in vitro and in vivo activity against filoviruses and other RNA viruses, has been described. BCX4430 inhibits viral RNA polymerase activity and protects cynomolgus macaques from Marburg virus infection when administered as late as 48 hours after infection. Nucleic acid-based products, recombinant vaccines and antibodies appear to be less suitable for the treatment of Marburg and Ebola hemorrhagic fevers. PMID:25282746

  16. Mosquitoborne Viruses, Czech Republic, 2002

    PubMed Central

    Zeman, Petr; Halouzka, Ji?í; Ju?icová, Zina; Š?oví?ková, Eva; Bálková, Helena; Šikutová, Silvie; Rudolf, Ivo

    2005-01-01

    Specimens from residents (n = 497) of an area affected by the 2002 flood were examined serologically for mosquitoborne viruses. Antibodies were detected against Tahyna (16%), Sindbis (1%), and Batai (0.2%) viruses, but not West Nile virus. An examination of paired serum samples showed 1 Tahyna bunyavirus (California group) infection. PMID:15705333

  17. CAN CRYPTOGRAPHY PREVENT COMPUTER VIRUSES?

    Microsoft Academic Search

    John F Morar; David M Chess

    2000-01-01

    The relationship between cryptography and virus prevention is anything but simple. Since the beginning of the computer virus problem, people have proposed solutions involving some form of cryptography; but cryptography plays only a minor role in the solutions we actually use today. Encryption can also make virus prevention more difficult, by providing viral hiding places inside the objects that it

  18. An introduction to computer viruses

    SciTech Connect

    Brown, D.R.

    1992-03-01

    This report on computer viruses is based upon a thesis written for the Master of Science degree in Computer Science from the University of Tennessee in December 1989 by David R. Brown. This thesis is entitled An Analysis of Computer Virus Construction, Proliferation, and Control and is available through the University of Tennessee Library. This paper contains an overview of the computer virus arena that can help the reader to evaluate the threat that computer viruses pose. The extent of this threat can only be determined by evaluating many different factors. These factors include the relative ease with which a computer virus can be written, the motivation involved in writing a computer virus, the damage and overhead incurred by infected systems, and the legal implications of computer viruses, among others. Based upon the research, the development of a computer virus seems to require more persistence than technical expertise. This is a frightening proclamation to the computing community. The education of computer professionals to the dangers that viruses pose to the welfare of the computing industry as a whole is stressed as a means of inhibiting the current proliferation of computer virus programs. Recommendations are made to assist computer users in preventing infection by computer viruses. These recommendations support solid general computer security practices as a means of combating computer viruses.

  19. Viruses and viral proteins

    PubMed Central

    Verdaguer, Nuria; Ferrero, Diego; Murthy, Mathur R. N.

    2014-01-01

    For more than 30 years X-ray crystallography has been by far the most powerful approach for determining the structures of viruses and viral proteins at atomic resolution. The information provided by these structures, which covers many important aspects of the viral life cycle such as cell-receptor recognition, viral entry, nucleic acid transfer and genome replication, has extensively enriched our vision of the virus world. Many of the structures available correspond to potential targets for antiviral drugs against important human pathogens. This article provides an overview of the current knowledge of different structural aspects of the above-mentioned processes. PMID:25485129

  20. Soilborne viruses: advances in virus movement, virus induced gene silencing, and engineered resistance

    Microsoft Academic Search

    Jeanmarie Verchot-Lubicz

    2003-01-01

    Until recently soilborne plant viruses were considered important only because they are causative agents for agricultural diseases. In recent years, soilborne plant viruses have played a significant role in advancing research into mechanisms of plasmodesmata transport, gene silencing, and engineered resistance to plant pathogens. Three different mechanisms by which viruses move through plasmodesmata have been identified using dianthoviruses, nepoviruses, and

  1. Viruses and disease: emerging concepts for prevention, diagnosis and treatment.

    PubMed

    Herrington, C S; Coates, P J; Duprex, W P

    2015-01-01

    Viruses cause a wide range of human diseases, ranging from acute self-resolving conditions to acute fatal diseases. Effects that arise long after the primary infection can also increase the propensity for chronic conditions or lead to the development of cancer. Recent advances in the fields of virology and pathology have been fundamental in improving our understanding of viral pathogenesis, in providing improved vaccination strategies and in developing newer, more effective treatments for patients worldwide. The reviews assembled here focus on the interface between virology and pathology and encompass aspects of both the clinical pathology of viral disease and the underlying disease mechanisms. Articles on emerging diseases caused by Ebola virus, Marburg virus, coronaviruses such as SARS and MERS, Nipah virus and noroviruses are followed by reviews of enteroviruses, HIV infection, measles, mumps, human respiratory syncytial virus (RSV), influenza, cytomegalovirus (CMV) and varicella zoster virus (VZV). The issue concludes with a series of articles reviewing the relationship between viruses and cancer, including the role played by Epstein-Barr virus (EBV) in the pathogenesis of lymphoma and carcinoma; how human papillomaviruses (HPVs) are involved in the development of skin cancer; the involvement of hepatitis B virus infection in hepatocellular carcinoma; and the mechanisms by which Kaposi's sarcoma-associated herpesvirus (KSHV) leads to Kaposi's sarcoma. We hope that this collection of articles will be of interest to a wide range of scientists and clinicians at a time when there is a renaissance in the appreciation of the power of pathology as virologists dissect the processes of disease. PMID:25366544

  2. Host genetic diversity enables Ebola hemorrhagic fever pathogenesis and resistance.

    PubMed

    Rasmussen, Angela L; Okumura, Atsushi; Ferris, Martin T; Green, Richard; Feldmann, Friederike; Kelly, Sara M; Scott, Dana P; Safronetz, David; Haddock, Elaine; LaCasse, Rachel; Thomas, Matthew J; Sova, Pavel; Carter, Victoria S; Weiss, Jeffrey M; Miller, Darla R; Shaw, Ginger D; Korth, Marcus J; Heise, Mark T; Baric, Ralph S; de Villena, Fernando Pardo-Manuel; Feldmann, Heinz; Katze, Michael G

    2014-11-21

    Existing mouse models of lethal Ebola virus infection do not reproduce hallmark symptoms of Ebola hemorrhagic fever, neither delayed blood coagulation and disseminated intravascular coagulation nor death from shock, thus restricting pathogenesis studies to nonhuman primates. Here we show that mice from the Collaborative Cross panel of recombinant inbred mice exhibit distinct disease phenotypes after mouse-adapted Ebola virus infection. Phenotypes range from complete resistance to lethal disease to severe hemorrhagic fever characterized by prolonged coagulation times and 100% mortality. Inflammatory signaling was associated with vascular permeability and endothelial activation, and resistance to lethal infection arose by induction of lymphocyte differentiation and cellular adhesion, probably mediated by the susceptibility allele Tek. These data indicate that genetic background determines susceptibility to Ebola hemorrhagic fever. PMID:25359852

  3. Lessons learned from hospital ebola preparation.

    PubMed

    Morgan, Daniel J; Braun, Barbara; Milstone, Aaron M; Anderson, Deverick; Lautenbach, Ebbing; Safdar, Nasia; Drees, Marci; Meddings, Jennifer; Linkin, Darren R; Croft, Lindsay D; Pineles, Lisa; Diekema, Daniel J; Harris, Anthony D

    2015-06-01

    BACKGROUND Hospital Ebola preparation is underway in the United States and other countries; however, the best approach and resources involved are unknown. OBJECTIVE To examine costs and challenges associated with hospital Ebola preparation by means of a survey of Society for Healthcare Epidemiology of America (SHEA) members. DESIGN Electronic survey of infection prevention experts. RESULTS A total of 257 members completed the survey (221 US, 36 international) representing institutions in 41 US states, the District of Columbia, and 18 countries. The 221 US respondents represented 158 (43.1%) of 367 major medical centers that have SHEA members and included 21 (60%) of 35 institutions recently defined by the US Centers for Disease Control and Prevention as Ebola virus disease treatment centers. From October 13 through October 19, 2014, Ebola consumed 80% of hospital epidemiology time and only 30% of routine infection prevention activities were completed. Routine care was delayed in 27% of hospitals evaluating patients for Ebola. LIMITATIONS Convenience sample of SHEA members with a moderate response rate. CONCLUSIONS Hospital Ebola preparations required extraordinary resources, which were diverted from routine infection prevention activities. Patients being evaluated for Ebola faced delays and potential limitations in management of other diseases that are more common in travelers returning from West Africa. Infect Control Hosp Epidemiol 2015;00(0): 1-5. PMID:25994323

  4. Toscana Virus in Spain

    Microsoft Academic Search

    Sara Sanbonmatsu-Gámez; Mercedes Pérez-Ruiz; Ximena Collao; María Paz Sánchez-Seco; Francisco Morillas-Márquez; Manuel de la Rosa-Fraile; José María Navarro-Marí; Antonio Tenorio

    2005-01-01

    Toscana virus (TOSV, Phlebovirus, family Bunya- viridae) infection is one of the most prevalent arboviruses in Spain. Within the objectives of a multidisciplinary network, a study on the epidemiology of TOSV was conducted in Granada, in southern Spain. The overall seroprevalence rate was 24.9%, significantly increasing with age. TOSV was detected in 3 of 103 sandfly pools by viral culture

  5. From Shakespeare to Viruses

    ScienceCinema

    Sung-Hou Kim

    2010-01-08

    Berkeley Lab scientists have created a unique new tool for analyzing and comparing long sets of data, be it the genomes of mammals or viruses, or the works of Shakespeare. The results of the Shakespeare analysis surprised scholars with their accuracy

  6. Virus Chapter: Dicistrovidae

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The Dicistroviridae family comprises viruses infecting both beneficial arthropods such as honey bees and shrimp and insect pests of medical and agricultural importance. During the last five years, advances in sequencing and phylogenetic analysis have led to the discovery and identification of sever...

  7. Cache Valley virus.

    PubMed

    Edwards, J F

    1994-11-01

    Cache Valley Virus (CVV) is a causative agent of a mosquito-borne disease syndrome of sheep and, possibly, of all ruminants, characterized by embryonic and fetal death, stillbirths, and multiple congenital malformations. CVV is endemic in Canada, Mexico, and the United States. Several related Bunyaviruses also may play a role in syndromes of congenital malformations and embryonic losses in North America. PMID:7728634

  8. Human Viruses and Cancer

    PubMed Central

    Morales-Sánchez, Abigail; Fuentes-Pananá, Ezequiel M.

    2014-01-01

    The first human tumor virus was discovered in the middle of the last century by Anthony Epstein, Bert Achong and Yvonne Barr in African pediatric patients with Burkitt’s lymphoma. To date, seven viruses -EBV, KSHV, high-risk HPV, MCPV, HBV, HCV and HTLV1- have been consistently linked to different types of human cancer, and infections are estimated to account for up to 20% of all cancer cases worldwide. Viral oncogenic mechanisms generally include: generation of genomic instability, increase in the rate of cell proliferation, resistance to apoptosis, alterations in DNA repair mechanisms and cell polarity changes, which often coexist with evasion mechanisms of the antiviral immune response. Viral agents also indirectly contribute to the development of cancer mainly through immunosuppression or chronic inflammation, but also through chronic antigenic stimulation. There is also evidence that viruses can modulate the malignant properties of an established tumor. In the present work, causation criteria for viruses and cancer will be described, as well as the viral agents that comply with these criteria in human tumors, their epidemiological and biological characteristics, the molecular mechanisms by which they induce cellular transformation and their associated cancers. PMID:25341666

  9. Viruses and autophagy

    PubMed Central

    Kudchodkar, Sagar B.; Levine, Beth

    2010-01-01

    SUMMARY Autophagy is an evolutionarily conserved intracellular process by which bulk cytoplasm is enveloped inside a double-membraned vesicle and shuttled to lysosomes for degradation. Within the last 15 years, the genes necessary for the execution of autophagy have been identified and the number of tools for studying this process has grown. Autophagy is essential for tissue homeostasis and development and defective autophagy is associated with a number of diseases. As intracellular parasites, during the course of an infection, viruses encounter autophagy and interact with the proteins that execute this process. Autophagy and/or autophagy genes likely play both anti-viral and proviral roles in the life cycles and pathogenesis of many different virus families. With respect to anti-viral roles, the autophagy proteins function in targeting viral components or virions for lysosomal degradation in a process termed xenophagy, and they also play a role in the initiation of innate and adaptive immune system responses to viral infections. Consistent with this anti-viral role of host autophagy, some viruses encode virulence factors that interact with the host autophagy machinery and block the execution of autophagy. In contrast, other viruses appear to utilise components of the autophagic machinery to foster their own intracellular growth or non-lytic cellular egress. As the details of the role(s) of autophagy in viral pathogenesis become clearer, new anti-viral therapies could be developed to inhibit the beneficial and enhance the destructive aspects of autophagy on the viral life cycle. PMID:19750559

  10. VIRUS PERSISTENCE IN GROUNDWATER

    EPA Science Inventory

    The purpose of the study was to determine whether measurable chemical and physical factors correlate with virus survival in groundwater. Groundwater samples were obtained from 11 sites throughout the United States. Water temperature was measured at the time of collection. Several...

  11. Molecular epidemiology of respiratory viruses in virus-induced asthma

    PubMed Central

    Ishioka, Taisei; Noda, Masahiro; Kozawa, Kunihisa; Kimura, Hirokazu

    2013-01-01

    Acute respiratory illness (ARI) due to various viruses is not only the most common cause of upper respiratory infection in humans but is also a major cause of morbidity and mortality, leading to diseases such as bronchiolitis and pneumonia. Previous studies have shown that respiratory syncytial virus (RSV), human rhinovirus (HRV), human metapneumovirus (HMPV), human parainfluenza virus (HPIV), and human enterovirus infections may be associated with virus-induced asthma. For example, it has been suggested that HRV infection is detected in the acute exacerbation of asthma and infection is prolonged. Thus it is believed that the main etiological cause of asthma is ARI viruses. Furthermore, the number of asthma patients in most industrial countries has greatly increased, resulting in a morbidity rate of around 10-15% of the population. However, the relationships between viral infections, host immune response, and host factors in the pathophysiology of asthma remain unclear. To gain a better understanding of the epidemiology of virus-induced asthma, it is important to assess both the characteristics of the viruses and the host defense mechanisms. Molecular epidemiology enables us to understand the pathogenesis of microorganisms by identifying specific pathways, molecules, and genes that influence the risk of developing a disease. However, the epidemiology of various respiratory viruses associated with virus-induced asthma is not fully understood. Therefore, in this article, we review molecular epidemiological studies of RSV, HRV, HPIV, and HMPV infection associated with virus-induced asthma. PMID:24062735

  12. Polyadenylic acid in Visna virus RNA.

    PubMed

    Gillespie, D; Takemoto, K; Robert, M; Gallo, R C

    1973-03-30

    Visna virus 70S RNA contains long stretches of polyadenylic acid [poly(A)]. The homogeneity in length of poly(4) regions is observed in 70S RNA from visna virus and all RNA tumor viruses tested, and not with other types of RNA. By this criterion visna virus resembles RNA tumor viruses. PMID:4631425

  13. The temporal program of peripheral blood gene expression in the response of non-human primates to Ebola hemorrhagic fever

    E-print Network

    Rubins, Kathleen H

    Background: Infection with Ebola virus (EBOV) causes a fulminant and often fatal hemorrhagic fever. In order to improve our understanding of EBOV pathogenesis and EBOV-host interactions, we examined the molecular features ...

  14. GB virus-C infection in patients infected with the human immunodeficiency virus

    Microsoft Academic Search

    Hans L Tillmann; Michael P Manns

    2001-01-01

    Hepatitis virus infections are frequent in patients suffering from HIV infection due to similar transmission routes of these viruses. In addition, hepatitis virus infections lead to impaired survival in HIV positive patients. The recently discovered flavivirus GB virus C (alias Hepatitis G Virus) was initially believed to be another hepatitis virus. While there is still some minor discussion whether GB

  15. Heparan Sulfate-Mediated Binding of Infectious Dengue Virus Type 2 and Yellow Fever Virus

    Microsoft Academic Search

    Raphaële Germi; Jean-Marc Crance; Daniel Garin; Josette Guimet; Hugues Lortat-Jacob; Rob W. H. Ruigrok; Jean-Pierre Zarski; Emmanuel Drouet

    2002-01-01

    Dengue virus type 2 and Yellow fever virus are arthropod-borne flaviviruses causing hemorrhagic fever in humans. Identification of virus receptors is important in understanding flavivirus pathogenesis. The aim of this work was to study the role of cellular heparan sulfate in the adsorption of infectious Yellow fever and Dengue type 2 viruses. Virus attachment was assessed by adsorbing virus to

  16. Detection of sweet potato viruses in Yunnan and genetic diversity analysis of the common viruses

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Two hundred seventy-nine samples with virus-like symptoms collected from 16 regions in Yunnan Province were tested by RT-PCR/PCR using virus-specific primers for 8 sweet potato viruses. Six viruses, Sweet potato chlorotic fleck virus (SPCFV), Sweet Potato feathery mottle virus (SPFMV), Sweet potato ...

  17. Virus diseases of Solanum laciniatum Ait. in New Zealand

    Microsoft Academic Search

    A. D. Thomson

    1976-01-01

    Cucumber mosaic virus, potato virus Y, potato virus X, tobacco mosaic virus, and tomato spotted wilt virus were identified in Solatium laciniatum Ait. Cucumber mosaic virus induced the most severe symptoms, including mottle and narrowing of the leaf lamina. Infection of crops with cucumber mosaic virus varied from 0–70% (mean of seven crops 25%), and potato virus Y from 0–48%

  18. PREVALENCE AND TRANSMISSION ROUTES OF HONEY BEE VIRUSES

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Transmission mechanisms of six viruses including acute bee paralysis virus (ABPV), black queen cell virus (BQCV), chronic bee paralysis virus (CBPV), deformed wing virus (DWV), Kashmir bee virus (KBV), and sacbrood bee virus (SBV) in honey bee colonies were investigated by RT-PCR methods. The virus...

  19. Durability of a vesicular stomatitis virus-based marburg virus vaccine in nonhuman primates.

    PubMed

    Mire, Chad E; Geisbert, Joan B; Agans, Krystle N; Satterfield, Benjamin A; Versteeg, Krista M; Fritz, Elizabeth A; Feldmann, Heinz; Hensley, Lisa E; Geisbert, Thomas W

    2014-01-01

    The filoviruses, Marburg virus (MARV) and Ebola virus, causes severe hemorrhagic fever with high mortality in humans and nonhuman primates. A promising filovirus vaccine under development is based on a recombinant vesicular stomatitis virus (rVSV) that expresses individual filovirus glycoproteins (GPs) in place of the VSV glycoprotein (G). These vaccines have shown 100% efficacy against filovirus infection in nonhuman primates when challenge occurs 28-35 days after a single injection immunization. Here, we examined the ability of a rVSV MARV-GP vaccine to provide protection when challenge occurs more than a year after vaccination. Cynomolgus macaques were immunized with rVSV-MARV-GP and challenged with MARV approximately 14 months after vaccination. Immunization resulted in the vaccine cohort of six animals having anti-MARV GP IgG throughout the pre-challenge period. Following MARV challenge none of the vaccinated animals showed any signs of clinical disease or viremia and all were completely protected from MARV infection. Two unvaccinated control animals exhibited signs consistent with MARV infection and both succumbed. Importantly, these data are the first to show 100% protective efficacy against any high dose filovirus challenge beyond 8 weeks after final vaccination. These findings demonstrate the durability of VSV-based filovirus vaccines. PMID:24759889

  20. Durability of a Vesicular Stomatitis Virus-Based Marburg Virus Vaccine in Nonhuman Primates

    PubMed Central

    Mire, Chad E.; Geisbert, Joan B.; Agans, Krystle N.; Satterfield, Benjamin A.; Versteeg, Krista M.; Fritz, Elizabeth A.; Feldmann, Heinz; Hensley, Lisa E.; Geisbert, Thomas W.

    2014-01-01

    The filoviruses, Marburg virus (MARV) and Ebola virus, causes severe hemorrhagic fever with high mortality in humans and nonhuman primates. A promising filovirus vaccine under development is based on a recombinant vesicular stomatitis virus (rVSV) that expresses individual filovirus glycoproteins (GPs) in place of the VSV glycoprotein (G). These vaccines have shown 100% efficacy against filovirus infection in nonhuman primates when challenge occurs 28–35 days after a single injection immunization. Here, we examined the ability of a rVSV MARV-GP vaccine to provide protection when challenge occurs more than a year after vaccination. Cynomolgus macaques were immunized with rVSV-MARV-GP and challenged with MARV approximately 14 months after vaccination. Immunization resulted in the vaccine cohort of six animals having anti-MARV GP IgG throughout the pre-challenge period. Following MARV challenge none of the vaccinated animals showed any signs of clinical disease or viremia and all were completely protected from MARV infection. Two unvaccinated control animals exhibited signs consistent with MARV infection and both succumbed. Importantly, these data are the first to show 100% protective efficacy against any high dose filovirus challenge beyond 8 weeks after final vaccination. These findings demonstrate the durability of VSV-based filovirus vaccines. PMID:24759889

  1. Ebola active monitoring system for travelers returning from West Africa—Georgia, 2014-2015.

    PubMed

    Parham, Mary; Edison, Laura; Soetebier, Karl; Feldpausch, Amanda; Kunkes, Audrey; Smith, Wendy; Guffey, Taylor; Fetherolf, Romana; Sanlis, Kathryn; Gabel, Julie; Cowell, Alex; Drenzek, Cherie

    2015-04-10

    The Ebola virus disease (Ebola) epidemic in West Africa has so far produced approximately 25,000 cases, more than 40 times the number in any previously documented Ebola outbreak. Because of the risk for imported disease from infected travelers, in October 2014 CDC recommended that all travelers to the United States from Ebola-affected countries receive enhanced entry screening and postarrival active monitoring for Ebola signs or symptoms until 21 days after their departure from an Ebola-affected country. The state of Georgia began its active monitoring program on October 25, 2014. The Georgia Department of Public Health (DPH) modified its existing, web-based electronic notifiable disease reporting system to create an Ebola Active Monitoring System (EAMS). DPH staff members developed EAMS from conceptualization to implementation in 6 days. In accordance with CDC recommendations, "low (but not zero) risk" travelers are required to report their daily health status to DPH, and the EAMS dashboard enables DPH epidemiologists to track symptoms and compliance with active monitoring. Through March 31, 2015, DPH monitored 1,070 travelers, and 699 (65%) used their EAMS traveler login instead of telephone or e-mail to report their health status. Medical evaluations were performed on 30 travelers, of whom three were tested for Ebola. EAMS has enabled two epidemiologists to monitor approximately 100 travelers daily, and to rapidly respond to travelers reporting signs and symptoms of potential Ebola virus infection. Similar electronic tracking systems might be useful for other jurisdictions. PMID:25856255

  2. Phage Displayed Peptides to Avian H5N1 Virus Distinguished the Virus from Other Viruses

    PubMed Central

    Qin, Chengfeng; Ren, Xiaofeng

    2011-01-01

    The purpose of the current study was to identify potential ligands and develop a novel diagnostic test to highly pathogenic avian influenza A virus (HPAI), subtype H5N1 viruses using phage display technology. The H5N1 viruses were used as an immobilized target in a biopanning process using a 12-mer phage display random peptide library. After five rounds of panning, three phages expressing peptides HAWDPIPARDPF, AAWHLIVALAPN or ATSHLHVRLPSK had a specific binding activity to H5N1 viruses were isolated. Putative binding motifs to H5N1 viruses were identified by DNA sequencing. In terms of the minimum quantity of viruses, the phage-based ELISA was better than antiserum-based ELISA and a manual, semi-quantitative endpoint RT-PCR for detecting H5N1 viruses. More importantly, the selected phages bearing the specific peptides to H5N1 viruses were capable of differentiating this virus from other avian viruses in enzyme-linked immunosorbent assays. PMID:21887228

  3. The Global Virus Network: Challenging chikungunya.

    PubMed

    McSweegan, Edward; Weaver, Scott C; Lecuit, Marc; Frieman, Matthew; Morrison, Thomas E; Hrynkow, Sharon

    2015-08-01

    The recent spread of chikungunya virus to the Western Hemisphere, together with the ongoing Ebola epidemic in West Africa, have highlighted the importance of international collaboration in the detection and management of disease outbreaks. In response to this need, the Global Virus Network (GVN) was formed in 2011. The GVN is a coalition of leading medical virologists in 34 affiliated laboratories in 24 countries, who collaborate to share their resources and expertise. The GVN supports research, promotes training for young scientists, serves as a technical resource for governments, businesses and international organizations, facilitates international scientific cooperation, and advocates for funding and evidence-based public policies. In response to the spread of chikungunya, the GVN formed a task force to identify research gaps and opportunities, including models of infection and disease, candidate vaccines and antivirals, epidemiology and vector control measures. Its members also serve as authoritative sources of information for the public, press, and policy-makers. This article forms part of a symposium in Antiviral Research on "Chikungunya discovers the New World". PMID:26071007

  4. Virus-encoded superantigens.

    PubMed Central

    Huber, B T; Hsu, P N; Sutkowski, N

    1996-01-01

    Superantigens are microbial agents that have a strong effect on the immune response of the host. Their initial target is the T lymphocyte, but a whole cascade of immunological reactions ensues. It is thought that the microbe engages the immune system of the host to its own advantage, to facilitate persistent infection and/or transmission. In this review, we discuss in detail the structure and function of the superantigen encoded by the murine mammary tumor virus, a B-type retrovirus which is the causative agent of mammary carcinoma. We will also outline what has more recently become known about superantigen activity associated with two human herpesviruses, cytomegalovirus and Epstein-Barr virus. It is likely that we have only uncovered the tip of the iceberg in our discovery of microbial superantigens, and we predict a flood of new information on this topic shortly. PMID:8840782

  5. Mechanisms of Virus Assembly

    NASA Astrophysics Data System (ADS)

    Perlmutter, Jason D.; Hagan, Michael F.

    2015-04-01

    Viruses are nanoscale entities containing a nucleic acid genome encased in a protein shell called a capsid and in some cases are surrounded by a lipid bilayer membrane. This review summarizes the physics that govern the processes by which capsids assemble within their host cells and in vitro. We describe the thermodynamics and kinetics for the assembly of protein subunits into icosahedral capsid shells and how these are modified in cases in which the capsid assembles around a nucleic acid or on a lipid bilayer. We present experimental and theoretical techniques used to characterize capsid assembly, and we highlight aspects of virus assembly that are likely to receive significant attention in the near future.

  6. Canine respiratory viruses.

    PubMed

    Buonavoglia, Canio; Martella, Vito

    2007-01-01

    Acute contagious respiratory disease (kennel cough) is commonly described in dogs worldwide. The disease appears to be multifactorial and a number of viral and bacterial pathogens have been reported as potential aetiological agents, including canine parainfluenza virus, canine adenovirus and Bordetella bronchiseptica, as well as mycoplasmas, Streptococcus equi subsp. zooepidemicus, canine herpesvirus and reovirus-1,-2 and -3. Enhancement of pathogenicity by multiple infections can result in more severe clinical forms. In addition, acute respiratory diseases associated with infection by influenza A virus, and group I and II coronaviruses, have been described recently in dogs. Host species shifts and tropism changes are likely responsible for the onset of these new pathogens. The importance of the viral agents in the kennel cough complex is discussed. PMID:17296161

  7. The encephalomyocarditis virus

    PubMed Central

    Carocci, Margot; Bakkali-Kassimi, Labib

    2012-01-01

    The encephalomyocarditis virus (EMCV) is a small non-enveloped single-strand RNA virus, the causative agent of not only myocarditis and encephalitis, but also neurological diseases, reproductive disorders and diabetes in many mammalian species. EMCV pathogenesis appears to be viral strain- and host-specific, and a better understanding of EMCV virulence factors is increasingly required. Indeed, EMCV is often used as a model for diabetes and viral myocarditis, and is also widely used in immunology as a double-stranded RNA stimulus in the study of Toll-like as well as cytosolic receptors. However, EMCV virulence and properties have often been neglected. Moreover, EMCV is able to infect humans albeit with a low morbidity. Progress on xenografts, such as pig heart transplantation in humans, has raised safety concerns that need to be explored. In this review we will highlight the biology of EMCV and all known and potential virulence factors. PMID:22722247

  8. Measles Virus Receptors

    Microsoft Academic Search

    Y. Yanagi; M. Takeda; S. Ohno; T. Hashiguchi

    Measles virus (MV) has two envelope glycoproteins, the hemagglutinin (H) and fusion protein, which are responsible for attachment\\u000a and membrane fusion, respectively. Signaling lymphocyte activation molecule (SLAM, also called CD150), a membrane glycoprotein\\u000a expressed on immune cells, acts as the principal cellular receptor for MV, accounting for its lymphotropism and immunosuppressive\\u000a nature. MV also infects polarized epithelial cells via an

  9. Chikungunya Virus Infection

    Microsoft Academic Search

    Fabrice Simon; Emilie Javelle; Manuela Oliver; Isabelle Leparc-Goffart; Catherine Marimoutou

    2011-01-01

    Chikungunya virus (CHIKV) is an alphavirus transmitted by mosquitoes, mostly Aedes aegypti and Aedes albopictus. After half a century of focal outbreaks of acute febrile polyarthralgia in Africa and Asia, the disease unexpectedly spread\\u000a in the past decade with large outbreaks in Africa and around the Indian Ocean and rare autochthonous transmission in temperate\\u000a areas. This emergence brought new insights

  10. Molecular studies of avian leukosis virus 

    E-print Network

    Mozisek, Blayne Myron

    2007-04-25

    leukosis virus (ALV), Rous sarcoma virus (RSV), mouse mammary tumor virus (MMTV), and murine leukemia virus (MLV). These viruses were the subject of intense study due to their propensity to form neoplastic disease in their host organisms. Investigations... into the mechanisms by which these viruses were able to cause tumors eventually led to the discovery and development of the oncogene theory of tumorigenesis: the elucidation of oncogenes within their viral genomes or their interaction with host oncogenes following...

  11. Trigger events: enviroclimatic coupling of Ebola hemorrhagic fever outbreaks

    NASA Technical Reports Server (NTRS)

    Pinzon, Jorge E.; Wilson, James M.; Tucker, Compton J.; Arthur, Ray; Jahrling, Peter B.; Formenty, Pierre

    2004-01-01

    We use spatially continuous satellite data as a correlate of precipitation within tropical Africa and show that the majority of documented Ebola hemorrhagic fever outbreaks were closely associated with sharply drier conditions at the end of the rainy season. We propose that these trigger events may enhance transmission of Ebola virus from its cryptic reservoir to humans. These findings suggest specific directions to help understand the sylvatic cycle of the virus and may provide early warning tools to detect possible future outbreaks of this enigmatic disease.

  12. Nuclear entry of DNA viruses

    PubMed Central

    Fay, Nikta; Panté, Nelly

    2015-01-01

    DNA viruses undertake their replication within the cell nucleus, and therefore they must first deliver their genome into the nucleus of their host cells. Thus, trafficking across the nuclear envelope is at the basis of DNA virus infections. Nuclear transport of molecules with diameters up to 39 nm is a tightly regulated process that occurs through the nuclear pore complex (NPC). Due to the enormous diversity of virus size and structure, each virus has developed its own strategy for entering the nucleus of their host cells, with no two strategies alike. For example, baculoviruses target their DNA-containing capsid to the NPC and subsequently enter the nucleus intact, while the hepatitis B virus capsid crosses the NPC but disassembles at the nuclear side of the NPC. For other viruses such as herpes simplex virus and adenovirus, although both dock at the NPC, they have each developed a distinct mechanism for the subsequent delivery of their genome into the nucleus. Remarkably, other DNA viruses, such as parvoviruses and human papillomaviruses, access the nucleus through an NPC-independent mechanism. This review discusses our current understanding of the mechanisms used by DNA viruses to deliver their genome into the nucleus, and further presents the experimental evidence for such mechanisms.

  13. Nuclear entry of DNA viruses.

    PubMed

    Fay, Nikta; Panté, Nelly

    2015-01-01

    DNA viruses undertake their replication within the cell nucleus, and therefore they must first deliver their genome into the nucleus of their host cells. Thus, trafficking across the nuclear envelope is at the basis of DNA virus infections. Nuclear transport of molecules with diameters up to 39 nm is a tightly regulated process that occurs through the nuclear pore complex (NPC). Due to the enormous diversity of virus size and structure, each virus has developed its own strategy for entering the nucleus of their host cells, with no two strategies alike. For example, baculoviruses target their DNA-containing capsid to the NPC and subsequently enter the nucleus intact, while the hepatitis B virus capsid crosses the NPC but disassembles at the nuclear side of the NPC. For other viruses such as herpes simplex virus and adenovirus, although both dock at the NPC, they have each developed a distinct mechanism for the subsequent delivery of their genome into the nucleus. Remarkably, other DNA viruses, such as parvoviruses and human papillomaviruses, access the nucleus through an NPC-independent mechanism. This review discusses our current understanding of the mechanisms used by DNA viruses to deliver their genome into the nucleus, and further presents the experimental evidence for such mechanisms. PMID:26029198

  14. Limits in virus filtration capability? Impact of virus quality and spike level on virus removal with xenotropic murine leukemia virus.

    PubMed

    Roush, David J; Myrold, Adam; Burnham, Michael S; And, Joseph V; Hughes, Joseph V

    2015-01-01

    Virus filtration (VF) is a key step in an overall viral clearance process since it has been demonstrated to effectively clear a wide range of mammalian viruses with a log reduction value (LRV)?>?4. The potential to achieve higher LRV from virus retentive filters has historically been examined using bacteriophage surrogates, which commonly demonstrated a potential of?>?9 LRV when using high titer spikes (e.g. 10(10) PFU/mL). However, as the filter loading increases, one typically experiences significant decreases in performance and LRV. The 9 LRV value is markedly higher than the current expected range of 4-5 LRV when utilizing mammalian retroviruses on virus removal filters (Miesegaes et al., Dev Biol (Basel) 2010;133:3-101). Recent values have been reported in the literature (Stuckey et al., Biotech Progr 2014;30:79-85) of LRV in excess of 6 for PPV and XMuLV although this result appears to be atypical. LRV for VF with therapeutic proteins could be limited by several factors including process limits (flux decay, load matrix), virus spike level and the analytical methods used for virus detection (i.e. the Limits of Quantitation), as well as the virus spike quality. Research was conducted using the Xenotropic-Murine Leukemia Virus (XMuLV) for its direct relevance to the most commonly cited document, the International Conference of Harmonization (ICH) Q5A (International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use, Geneva, Switzerland, 1999) for viral safety evaluations. A unique aspect of this work is the independent evaluation of the impact of retrovirus quality and virus spike level on VF performance and LRV. The VF studies used XMuLV preparations purified by either ultracentrifugation (Ultra 1) or by chromatographic processes that yielded a more highly purified virus stock (Ultra 2). Two monoclonal antibodies (Mabs) with markedly different filtration characteristics and with similar levels of aggregate (<1.5%) were evaluated with the Ultra 1 and Ultra 2 virus preparations utilizing the Planova 20 N, a small virus removal filter. Impurities in the virus preparation ultimately limited filter loading as measured by determining the volumetric loading condition where 75% flux decay is observed versus initial conditions (V75). This observation occurred with both Mabs with the difference in virus purity more pronounced when very high spike levels were used (>5 vol/vol %). Significant differences were seen for the process performance over a number of lots of the less-pure Ultra 1 virus preparations. Experiments utilizing a developmental lot of the chromatographic purified XMuLV (Ultra 2 Development lot) that had elevated levels of host cell residuals (vs. the final Ultra 2 preparations) suggest that these contaminant residuals can impact virus filter fouling, even if the virus prep is essentially monodisperse. Process studies utilizing an Ultra 2 virus with substantially less host cell residuals and highly monodispersed virus particles demonstrated superior performance and an LRV in excess of 7.7 log10 . A model was constructed demonstrating the linear dependence of filtration flux versus filter loading which can be used to predict the V75 for a range of virus spike levels conditions using this highly purified virus. Fine tuning the virus spike level with this model can ultimately maximize the LRV for the virus filter step, essentially adding the LRV equivalent of another process step (i.e. protein A or CEX chromatography). PMID:25395156

  15. Computer virus information update CIAC-2301

    SciTech Connect

    Orvis, W.J.

    1994-01-15

    While CIAC periodically issues bulletins about specific computer viruses, these bulletins do not cover all the computer viruses that affect desktop computers. The purpose of this document is to identify most of the known viruses for the MS-DOS and Macintosh platforms and give an overview of the effects of each virus. The authors also include information on some windows, Atari, and Amiga viruses. This document is revised periodically as new virus information becomes available. This document replaces all earlier versions of the CIAC Computer virus Information Update. The date on the front cover indicates date on which the information in this document was extracted from CIAC`s Virus database.

  16. Tomato chlorosis virus and Tomato infectious chlorosis virus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This presentation will help consultants, growers, and other practitioners in the Southern and Western Regions of the US, as well as Mexico and the Caribbean identify and manage Tomato infectious chlorosis virus (TICV) and Tomato chlorosis virus (ToCV) in tomato. Information will directly benefit cr...

  17. Lactate dehydrogenase-elevating virus: an ideal persistent virus?

    Microsoft Academic Search

    Peter G. W. Plagemann; Raymond R. R. Rowland; Chen Even; Kay S. Faaberg

    1995-01-01

    LDV contradicts all commonly held views about mechanisms of virus persistence, namely that persistence is primarily associated with noncytopathic viruses, or the selection of immune escape variants or other mutants, or a decrease in expression of certain viral proteins by infected cells, or replication in “immune-privileged sites”, or a general suppression of the host immune system, etc. [1, 2, 5,

  18. Bovine virus diarrhoea virus - strategic decisions for diagnosis and control

    Microsoft Academic Search

    Joe Brownlie; Ian Thompson; Andrew Curwen

    2000-01-01

    IN the 15 years since the last In Practice article on bovine virus diarrhoea virus (BVDV) (Brownlie 1985), there has been an explosion in the understanding of the molecular mechanisms of viral replication and mutation, especially those related to biotypic variation. Hand in hand has come a greater understanding of the importance of BVDV as a primary pathogen of cattle,

  19. Group 2 Vaccinia Virus, Brazil

    PubMed Central

    Assis, Felipe Lopes; Borges, Iara Apolinario; Ferreira, Paulo César Peregrino; Bonjardim, Cláudio Antônio; Trindade, Giliane de Souza; Lobato, Zélia Inês Portela; Guedes, Maria Isabel Maldonado; Mesquita, Vaz; Kroon, Erna Geessien

    2012-01-01

    In 2011, vaccinia virus caused an outbreak of bovine vaccinia, affecting dairy cattle and dairy workers in Brazil. Genetic and phenotypic analyses identified this isolate as distinct from others recently identified, thereby reinforcing the hypothesis that different vaccinia virus strains co-circulate in Brazil. PMID:23171598

  20. INTERACTIONS OF VIRUS AND HOST

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bovine viral diarrhea virus (BVDV) is an ubiquitous pathogen of ruminants, found worldwide that is often associated with severe economic losses. Understanding these viruses, particularly at the cellular and molecular levels, is important to develop new vaccination and treatment strategies for produc...

  1. West Nile Virus and Wildlife

    Microsoft Academic Search

    Peter P. Marra; Sean Griffing; Carolee Caffrey; A. Marm Kilpatrick; Robert McLean; Christopher Brand; Emi Saito; Alan P. Dupuis; Laura Kramer; Robert Novak

    2004-01-01

    West Nile virus (WNV) has spread rapidly across North America, resulting in human deaths and in the deaths of untold numbers of birds, mammals, and reptiles. The virus has reached Central America and the Caribbean and may spread to Hawaii and South America. Although tens of thousands of birds have died, and studies of some bird species show local declines,

  2. Hepatitis C Virus and Cardiomyopathy

    Microsoft Academic Search

    Akira Matsumori

    2000-01-01

    The importance of hepatitis C virus infection has been recently noted in patients with hypertrophic cardiomyopathy or dilated cardiomyopathy. In a collaborative research project of the Committees for the Study of Idiopathic Cardiomyopathy, hepatitis C virus antibody was found in 74 of 697 patients (10.65) with hypertrophic cardiomyopathy and in 42 of 663 patients (6.3%) with dilated cardiomyopathy; these prevalences

  3. Human viruses: discovery and emergence

    PubMed Central

    Woolhouse, Mark; Scott, Fiona; Hudson, Zoe; Howey, Richard; Chase-Topping, Margo

    2012-01-01

    There are 219 virus species that are known to be able to infect humans. The first of these to be discovered was yellow fever virus in 1901, and three to four new species are still being found every year. Extrapolation of the discovery curve suggests that there is still a substantial pool of undiscovered human virus species, although an apparent slow-down in the rate of discovery of species from different families may indicate bounds to the potential range of diversity. More than two-thirds of human viruses can also infect non-human hosts, mainly mammals, and sometimes birds. Many specialist human viruses also have mammalian or avian origins. Indeed, a substantial proportion of mammalian viruses may be capable of crossing the species barrier into humans, although only around half of these are capable of being transmitted by humans and around half again of transmitting well enough to cause major outbreaks. A few possible predictors of species jumps can be identified, including the use of phylogenetically conserved cell receptors. It seems almost inevitable that new human viruses will continue to emerge, mainly from other mammals and birds, for the foreseeable future. For this reason, an effective global surveillance system for novel viruses is needed. PMID:22966141

  4. TOTAL CULTURABLE VIRUS QUANTAL ASSAY

    EPA Science Inventory

    This chapter describes a quantal method for assaying culturable human enteric viruses from water matrices. The assay differs from the plaque assay described in Chapter 10 (December 1987 Revision) in that it is based upon the direct microscopic viewing of cells for virus-induced ...

  5. Swine Influenza Virus: Emerging Understandings

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Introduction: In March-April 2009, a novel pandemic H1N1 emerged in the human population in North America [1]. The gene constellation of the emerging virus was demonstrated to be a combination of genes from swine influenza A viruses (SIV) of North American and Eurasian lineages that had never before...

  6. Dynamic models for computer viruses

    Microsoft Academic Search

    Jose R. C. Piqueira; Adolfo A. De Vasconcelos; Carlos E. C. J. Gabriel; Vanessa O. Araujo

    2008-01-01

    Computer viruses are an important risk to computational systems endangering either corporations of all sizes or personal computers used for domestic applications. Here, classical epidemiological models for disease propagation are adapted to computer networks and, by using simple systems identification techniques a model called SAIC (Susceptible, Antidotal, Infectious, Contaminated) is developed. Real data about computer viruses are used to validate

  7. Computer viruses: a quantitative analysis

    Microsoft Academic Search

    A. Coulthard; T. A. Vuori

    2002-01-01

    This paper provides interesting insights for anti-virus research, as it reflects a period of rapid uptake in the application of the Internet and the use of e-mail for business purposes. The purpose of the research is to provide independent justification of the growing prevalence of computer virus incidents over the past five years, and identify patterns in the frequency and

  8. Mathematical models on computer viruses

    Microsoft Academic Search

    Bimal Kumar Mishra; Dinesh Saini

    2007-01-01

    An attempt has been made to develop mathematical models on computer viruses infecting the system under different conditions. Mathematical model 1 discusses the situation to find the probability that at any time t how many software components are infected by virus, assuming the recovery rate and proportion of un-infected population receiving infection per unit time does not change with time.

  9. Computer Viruses as Artificial Life

    Microsoft Academic Search

    Eugene H. Spafford

    1994-01-01

    There has been considerable interest in computer viruses since they first appeared in 1981, and especially in the past few years as they have reached epidemic numbers in many per- sonal computer environments. Viruses have been written about as a security problem, as a social problem, and as a possible means of performing useful tasks in a distributed computing environment.

  10. Oropouche Virus Isolation, Southeast Brazil

    PubMed Central

    Martins, Lívia Carício; Rodrigues, Sueli Guerreiro; Chiang, Jannifer Oliveira; Azevedo, Raimunda do Socorro da Silva; Travassos da Rosa, Amelia P.A.; Vasconcelos, Pedro Fernando da Costa

    2005-01-01

    An Oropouche virus strain was isolated from a novel host (Callithrix sp.) in Arinos, Minas Gerais State, southeastern Brazil. The virus was identified by complement fixation test and confirmed by reverse transcription–polymerase chain reaction. Phylogenetic analysis identified this strain as a genotype III isolate previously recognized only in Panama. PMID:16318707

  11. Defining Life: The Virus Viewpoint

    NASA Astrophysics Data System (ADS)

    Forterre, Patrick

    2010-04-01

    Are viruses alive? Until very recently, answering this question was often negative and viruses were not considered in discussions on the origin and definition of life. This situation is rapidly changing, following several discoveries that have modified our vision of viruses. It has been recognized that viruses have played (and still play) a major innovative role in the evolution of cellular organisms. New definitions of viruses have been proposed and their position in the universal tree of life is actively discussed. Viruses are no more confused with their virions, but can be viewed as complex living entities that transform the infected cell into a novel organism—the virus—producing virions. I suggest here to define life (an historical process) as the mode of existence of ribosome encoding organisms (cells) and capsid encoding organisms (viruses) and their ancestors. I propose to define an organism as an ensemble of integrated organs (molecular or cellular) producing individuals evolving through natural selection. The origin of life on our planet would correspond to the establishment of the first organism corresponding to this definition.

  12. Pathogenic pseudorabies virus, China, 2012.

    PubMed

    Yu, Xiuling; Zhou, Zhi; Hu, Dongmei; Zhang, Qian; Han, Tao; Li, Xiaoxia; Gu, Xiaoxue; Yuan, Lin; Zhang, Shuo; Wang, Baoyue; Qu, Ping; Liu, Jinhua; Zhai, Xinyan; Tian, Kegong

    2014-01-01

    In 2012, an unprecedented large-scale outbreak of disease in pigs in China caused great economic losses to the swine industry. Isolates from pseudorabies virus epidemics in swine herds were characterized. Evidence confirmed that the pathogenic pseudorabies virus was the etiologic agent of this epidemic. PMID:24377462

  13. Pathogenic Pseudorabies Virus, China, 2012

    PubMed Central

    Yu, Xiuling; Zhou, Zhi; Hu, Dongmei; Zhang, Qian; Han, Tao; Li, Xiaoxia; Gu, Xiaoxue; Yuan, Lin; Zhang, Shuo; Wang, Baoyue; Qu, Ping; Liu, Jinhua; Zhai, Xinyan

    2014-01-01

    In 2012, an unprecedented large-scale outbreak of disease in pigs in China caused great economic losses to the swine industry. Isolates from pseudorabies virus epidemics in swine herds were characterized. Evidence confirmed that the pathogenic pseudorabies virus was the etiologic agent of this epidemic. PMID:24377462

  14. How Viruses Enter Animal Cells

    Microsoft Academic Search

    Alicia E. Smith; Ari Helenius

    2004-01-01

    Viruses replicate within living cells and use the cellular machinery for the synthesis of their genome and other components. To gain access, they have evolved a variety of elegant mechanisms to deliver their genes and accessory proteins into the host cell. Many animal viruses take advantage of endocytic pathways and rely on the cell to guide them through a complex

  15. Marine Viruses: Truth or Dare

    NASA Astrophysics Data System (ADS)

    Breitbart, Mya

    2012-01-01

    Over the past two decades, marine virology has progressed from a curiosity to an intensely studied topic of critical importance to oceanography. At concentrations of approximately 10 million viruses per milliliter of surface seawater, viruses are the most abundant biological entities in the oceans. The majority of these viruses are phages (viruses that infect bacteria). Through lysing their bacterial hosts, marine phages control bacterial abundance, affect community composition, and impact global biogeochemical cycles. In addition, phages influence their hosts through selection for resistance, horizontal gene transfer, and manipulation of bacterial metabolism. Recent work has also demonstrated that marine phages are extremely diverse and can carry a variety of auxiliary metabolic genes encoding critical ecological functions. This review is structured as a scientific "truth or dare," revealing several well-established "truths" about marine viruses and presenting a few "dares" for the research community to undertake in future studies.

  16. Vaccinia virus in postvaccinal encephalitis.

    PubMed

    Gurvich, E B; Vilesova, I S

    1983-03-01

    Results of virological examination of 239 samples taken from 84 children with neurological complications after smallpox vaccination are described. In postvaccinal encephalitis, vaccinia virus was isolated from blood, cerebrospinal fluid and pharyngeal secretions of 23 out of 40 children (57.5%) as well as from autopsy specimens sampled between 10-35 days after vaccination. During the acute period of disease, virus was detected in 17 out of 31 (54.2%) cerebrospinal fluid specimens. In 3 postvaccinal encephalitis cases the virus was present in brain and in a case of encephalomyelitis--in the spinal cord. These results confirmed the participation of vaccinia virus in the pathogenesis of postvaccinal encephalitis. The pathogenicity of vaccinia virus may be manifested only under a changed reactivity of the vaccinated host. PMID:6135334

  17. Co-infections with Chikungunya Virus and Dengue Virus in Delhi, India

    PubMed Central

    Chahar, Harendra S.; Bharaj, Preeti; Dar, Lalit; Guleria, Randeep; Kabra, Sushil K.

    2009-01-01

    Aedes aegypti mosquitoes are common vectors for dengue virus and chikungunya virus. In areas where both viruses cocirculate, they can be transmitted together. During a dengue outbreak in Delhi in 2006, 17 of 69 serum samples were positive for chikungunya virus by reverse transcription–PCR; 6 samples were positive for both viruses. PMID:19624923

  18. Genome Sequence of Bivens Arm Virus, a Tibrovirus Belonging to the Species Tibrogargan virus (Mononegavirales: Rhabdoviridae)

    PubMed Central

    Hensley, Lisa E.

    2015-01-01

    The new rhabdoviral genus Tibrovirus currently has two members, Coastal Plains virus and Tibrogargan virus. Here, we report the coding-complete genome sequence of a putative member of this genus, Bivens Arm virus. A genomic comparison reveals Bivens Arm virus to be closely related to, but distinct from, Tibrogargan virus. PMID:25792044

  19. IInoculate your computer with Symantec AntiVirus, for free! Welchia virus? Blaster

    E-print Network

    IInoculate your computer with Symantec AntiVirus, for free! Welchia virus? Blaster virus? PC all students, faculty and staff can get a free copy. Computer viruses on campus are no laughing matter. Last Symantec AntiVirus managed version from the "Computing Essentials 2004" CD or download it from http

  20. Infectious vaccinia virus recombinants that express hepatitis B virus surface antigen

    NASA Astrophysics Data System (ADS)

    Smith, Geoffrey L.; Mackett, Michael; Moss, Bernard

    1983-04-01

    Potential live vaccines against hepatitis B virus have been produced. The coding sequence for hepatitis B virus surface antigen (HBsAg) has been inserted into the vaccinia virus genome under control of vaccinia virus early promoters. Cells infected with these vaccinia virus recombinants synthesize and excrete HBsAg and vaccinated rabbits rapidly produce antibodies to HBsAg.

  1. A single vertebrate DNA virus protein disarms invertebrate immunity to RNA virus infection

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Virus-host interactions drive a remarkable diversity of immune responses and countermeasures. While investigating virus-invertebrate host interactions we found that two RNA viruses with broad host ranges, vesicular stomatitis virus (VSV) and Sindbis virus (SINV), were unable to infect certain Lepido...

  2. Immunogenicity of combination DNA vaccines for Rift Valley fever virus, tick-borne encephalitis virus, Hantaan virus, and Crimean Congo hemorrhagic fever virus

    Microsoft Academic Search

    Kristin Spik; Amy Shurtleff; Anita K. McElroy; Mary C. Guttieri; Jay W. Hooper; Connie Schmaljohn

    2006-01-01

    DNA vaccines for Rift Valley fever virus (RVFV), Crimean Congo hemorrhagic fever virus (CCHFV), tick-borne encephalitis virus (TBEV), and Hantaan virus (HTNV), were tested in mice alone or in various combinations. The bunyavirus vaccines (RVFV, CCHFV, and HTNV) expressed Gn and Gc genes, and the flavivirus vaccine (TBEV) expressed the preM and E genes. All vaccines were delivered by gene

  3. Biologically Inspired Defenses Against Computer Viruses

    Microsoft Academic Search

    Jeffrey O. Kephart; Gregory B. Sorkin; William C. Arnold; David M. Chess; Gerald Tesauro; Steve R. White

    1995-01-01

    Today's anti-virus technology, based largely on analysis of existing viruses by human experts, is just barely able to keep pace with the more than three new computer viruses that are writ­ ten daily. In a few years, intelligent agents nav­ igating through highly connected networks are likely to form an extremely fertile medium for a new breed of viruses. At

  4. Modeling Computer Viruses MSc Thesis (Afstudeerscriptie)

    E-print Network

    Amsterdam, University of

    Modeling Computer Viruses MSc Thesis (Afstudeerscriptie) written by Luite Menno Pieter van Zelst About half a year ago, Alban Ponse, my thesis supervisor, suggested that the topic of `computer viruses indus- try and the creators of computer viruses. After all, the anti-virus industry stands to lose a lot

  5. Hepatitis E Virus Infection

    PubMed Central

    Dalton, Harry R.; Abravanel, Florence; Izopet, Jacques

    2014-01-01

    SUMMARY Hepatitis E virus (HEV) infection is a worldwide disease. An improved understanding of the natural history of HEV infection has been achieved within the last decade. Several reservoirs and transmission modes have been identified. Hepatitis E is an underdiagnosed disease, in part due to the use of serological assays with low sensitivity. However, diagnostic tools, including nucleic acid-based tests, have been improved. The epidemiology and clinical features of hepatitis E differ between developing and developed countries. HEV infection is usually an acute self-limiting disease, but in developed countries it causes chronic infection with rapidly progressive cirrhosis in organ transplant recipients, patients with hematological malignancy requiring chemotherapy, and individuals with HIV. HEV also causes extrahepatic manifestations, including a number of neurological syndromes and renal injury. Acute infection usually requires no treatment, but chronic infection should be treated by reducing immunosuppression in transplant patients and/or the use of antiviral therapy. In this comprehensive review, we summarize the current knowledge about the virus itself, as well as the epidemiology, diagnostics, natural history, and management of HEV infection in developing and developed countries. PMID:24396139

  6. Virus interactions with human signal transduction pathways.

    PubMed

    Zhao, Zhongming; Xia, Junfeng; Tastan, Oznur; Singh, Irtisha; Kshirsagar, Meghana; Carbonell, Jaime; Klein-Seetharaman, Judith

    2011-01-01

    Viruses depend on their hosts at every stage of their life cycles and must therefore communicate with them via Protein-Protein Interactions (PPIs). To investigate the mechanisms of communication by different viruses, we overlay reported pairwise human-virus PPIs on human signalling pathways. Of 671 pathways obtained from NCI and Reactome databases, 355 are potentially targeted by at least one virus. The majority of pathways are linked to more than one virus. We find evidence supporting the hypothesis that viruses often interact with different proteins depending on the targeted pathway. Pathway analysis indicates overrepresentation of some pathways targeted by viruses. The merged network of the most statistically significant pathways shows several centrally located proteins, which are also hub proteins. Generally, hub proteins are targeted more frequently by viruses. Numerous proteins in virus-targeted pathways are known drug targets, suggesting that these might be exploited as potential new approaches to treatments against multiple viruses. PMID:21330695

  7. Monitoring Exposure to Ebola and Health of U.S. Military Personnel Deployed in Support of Ebola Control Efforts - Liberia, October 25, 2014-February 27, 2015.

    PubMed

    Cardile, Anthony P; Murray, Clinton K; Littell, Christopher T; Shah, Neel J; Fandre, Matthew N; Drinkwater, Dennis C; Markelz, Brian P; Vento, Todd J

    2015-07-01

    In response to the unprecedented Ebola virus disease (Ebola) outbreak in West Africa, the U.S. government deployed approximately 2,500 military personnel to support the government of Liberia. Their primary missions were to construct Ebola treatment units (ETUs), train health care workers to staff ETUs, and provide laboratory testing capacity for Ebola. Service members were explicitly prohibited from engaging in activities that could result in close contact with an Ebola-infected patient or coming in contact with the remains of persons who had died from unknown causes. Military units performed twice-daily monitoring of temperature and review of exposures and symptoms ("unit monitoring") on all persons throughout deployment, exit screening at the time of departure from Liberia, and post-deployment monitoring for 21 days at segregated, controlled monitoring areas on U.S. military installations. A total of 32 persons developed a fever during deployment from October 25, 2014, through February 27, 2015; none had a known Ebola exposure or developed Ebola infection. Monitoring of all deployed service members revealed no Ebola exposures or infections. Given their activity restrictions and comprehensive monitoring while deployed to Liberia, U.S. military personnel constitute a unique population with a lower risk for Ebola exposure compared with those working in the country without such measures. PMID:26135589

  8. Modelling the evolution of the influenza virus

    E-print Network

    Burke, David

    2008-06-27

    CamGrid: High Throughput Computing in Science dfb21@cam.ac.uk Dr David Burke Antigenic Cartography Group Department of Zoology University of Cambridge 25th June 2008 Modelling the evolution of the influenza virus Antigenic variation of viruses... Antigenically Stable Pathogens Antigenically Variable Pathogens Smallpox Measles Tuberculosis Mumps Tetanus Influenza Virus Malaria HIV Dengue The Influenza Virus Annually, 'flu infects 7-14% of the population (400-800 million people globally ) Virus...

  9. An optofluidic nanoplasmonic biosensor for direct detection of live viruses from biological media.

    PubMed

    Yanik, Ahmet A; Huang, Min; Kamohara, Osami; Artar, Alp; Geisbert, Thomas W; Connor, John H; Altug, Hatice

    2010-12-01

    Fast and sensitive virus detection techniques, which can be rapidly deployed at multiple sites, are essential to prevent and control future epidemics and bioterrorism threats. In this Letter, we demonstrate a label-free optofluidic nanoplasmonic sensor that can directly detect intact viruses from biological media at clinically relevant concentrations with little to no sample preparation. Our sensing platform is based on an extraordinary light transmission effect in plasmonic nanoholes and utilizes group-specific antibodies for highly divergent strains of rapidly evolving viruses. So far, the questions remain for the possible limitations of this technique for virus detection, as the penetration depths of the surface plasmon polaritons are comparable to the dimensions of the pathogens. Here, we demonstrate detection and recognition of small enveloped RNA viruses (vesicular stomatitis virus and pseudotyped Ebola) as well as large enveloped DNA viruses (vaccinia virus) within a dynamic range spanning 3 orders of magnitude. Our platform, by enabling high signal to noise measurements without any mechanical or optical isolation, opens up opportunities for detection of a broad range of pathogens in typical biology laboratory settings. PMID:21053965

  10. SARS and West Nile Virus

    Microsoft Academic Search

    Mark B. Loeb

    Clinical presentation of SARS is nonspecific; the important clinical findings in West Nile virus infection are those associated\\u000a with neurological complications.\\u000a \\u000a Rapid and accurate diagnosis of SARS and West Nile virus infection remains an important clinical challenge.\\u000a \\u000a \\u000a Older adults are at higher risk of complications, including death from SARS and West Nile virus.\\u000a \\u000a \\u000a At present, there is no effective therapy

  11. DC-SIGN and DC-SIGNR Bind Ebola Glycoproteins and Enhance Infection of Macrophages and Endothelial Cells

    Microsoft Academic Search

    Graham Simmons; Jacqueline D. Reeves; Case C. Grogan; Luk H. Vandenberghe; Frédéric Baribaud; J. Charles Whitbeck; Emily Burke; Michael J. Buchmeier; Elizabeth J. Soilleux; James L. Riley; Robert W. Doms; Paul Bates; Stefan Pöhlmann

    2003-01-01

    Ebola virus exhibits a broad cellular tropism in vitro. In humans and animal models, virus is found in most tissues and organs during the latter stages of infection. In contrast, a more restricted cell and tissue tropism is exhibited early in infection where macrophages, liver, lymph node, and spleen are major initial targets. This indicates that cellular factors other than

  12. Respiratory Viruses Other than Influenza Virus: Impact and Therapeutic Advances

    PubMed Central

    Nichols, W. Garrett; Peck Campbell, Angela J.; Boeckh, Michael

    2008-01-01

    Summary: Though several antivirals have been developed and marketed to treat influenza virus infections, the development of antiviral agents with clinical activity against other respiratory viruses has been more problematic. Here we review the epidemiology of respiratory viral infections in immunocompetent and immunocompromised hosts, examine the evidence surrounding the currently available antivirals for respiratory viral infections other than influenza, highlight those that are in the pipeline, and discuss the hurdles for development of such agents. PMID:18400797

  13. Gene homology between orf virus and smallpox variola virus.

    PubMed

    Mercer, A A; Fraser, K M; Esposito, J J

    1996-01-01

    About 47% identity was observed between the deduced amino acid sequences of a protein encoded by a gene of the parapoxvirus orf virus (OV) strain NZ2 and a 6 kDa protein of unknown function reported to be produced by an open reading frame expressed early after infection by the orthopoxvirus Western Reserve vaccinia virus (VAC); the open reading frame is absent from VAC strain Copenhagen. Examination of sequences reported for variola virus (VAR) strains Bangladesh, India, Congo- 1970, Somalia- 1977 and Garcia- 1966 revealed each encoded a correlate 58 amino acid protein. The open reading frame was not reported in the original analyses of these sequences because a lower limit of 60 amino acids was used to identify potential encoded proteins. Inspection of partial reading frames reported for cowpox virus (CWV) and ectromelia virus (EMV) suggested that these viruses might also code for a correlate of the VAC WR protein. DNA sequencing of cloned fragments of CWV and EMV confirmed that both these orthopoxviruses encode closely related, full length variants of the VAC and VAR open reading frames. The OV homologue is coded in the OV strain NZ2 BamHI-E fragment E2L open reading frame, which we reported is transcribed early postinfection; moreover, analysis of an NZ2 variant showed E2L was absent, indicating that E2L, like the VAC cognate, is nonessential for virus replication in cell culture. The parapoxvirus and orthopoxvirus correlates have about 20% amino acid sequence resemblance to African swine fever virus DNA binding protein p10, suggesting an ancestral relation of genes. PMID:8972571

  14. Oncolytic virus therapy using genetically engineered herpes simplex viruses

    Microsoft Academic Search

    Tomoki Todo

    2002-01-01

    An increasing number of oncolytic virus vectors has been developed lately for cancer therapy. Herpes simplex virus type 1\\u000a (HSV-1) vectors are particularly useful, because they can be genetically engineered to replicate and spread highly selectively\\u000a in tumor cells and can also express multiple foreign transgenes. These vectors can manifest cytopathic effect in a wide variety\\u000a of tumor types without

  15. Rice Yellow Mottle Virus, an RNA Plant Virus, Evolves as Rapidly as Most RNA Animal Viruses? †

    PubMed Central

    Fargette, D.; Pinel, A.; Rakotomalala, M.; Sangu, E.; Traoré, O.; Sérémé, D.; Sorho, F.; Issaka, S.; Hébrard, E.; Séré, Y.; Kanyeka, Z.; Konaté, G.

    2008-01-01

    The rate of evolution of an RNA plant virus has never been estimated using temporally spaced sequence data, by contrast to the information available on an increasing range of animal viruses. Accordingly, the evolution rate of Rice yellow mottle virus (RYMV) was calculated from sequences of the coat protein gene of isolates collected from rice over a 40-year period in different parts of Africa. The evolution rate of RYMV was estimated by pairwise distance linear regression on five phylogeographically defined groups comprising a total of 135 isolates. It was further assessed from 253 isolates collected all over Africa by Bayesian coalescent methods under strict and relaxed molecular clock models and under constant size and skyline population genetic models. Consistent estimates of the evolution rate between 4 × 10?4 and 8 × 10?4 nucleotides (nt)/site/year were obtained whatever method and model were applied. The synonymous evolution rate was between 8 × 10?4 and 11 × 10?4 nt/site/year. The overall and synonymous evolution rates of RYMV were within the range of the rates of 50 RNA animal viruses, below the average but above the distribution median. Experimentally, in host change studies, substitutions accumulated at an even higher rate. The results show that an RNA plant virus such as RYMV evolves as rapidly as most RNA animal viruses. Knowledge of the molecular clock of plant viruses provides methods for testing a wide range of biological hypotheses. PMID:18199644

  16. Adeno-associated virus: from defective virus to effective vector

    PubMed Central

    Gonçalves, Manuel AFV

    2005-01-01

    The initial discovery of adeno-associated virus (AAV) mixed with adenovirus particles was not a fortuitous one but rather an expression of AAV biology. Indeed, as it came to be known, in addition to the unavoidable host cell, AAV typically needs a so-called helper virus such as adenovirus to replicate. Since the AAV life cycle revolves around another unrelated virus it was dubbed a satellite virus. However, the structural simplicity plus the defective and non-pathogenic character of this satellite virus caused recombinant forms to acquire centre-stage prominence in the current constellation of vectors for human gene therapy. In the present review, issues related to the development of recombinant AAV (rAAV) vectors, from the general principle to production methods, tropism modifications and other emerging technologies are discussed. In addition, the accumulating knowledge regarding the mechanisms of rAAV genome transduction and persistence is reviewed. The topics on rAAV vectorology are supplemented with information on the parental virus biology with an emphasis on aspects that directly impact on vector design and performance such as genome replication, genetic structure, and host cell entry. PMID:15877812

  17. Role of murine leukemia virus nucleocapsid protein in virus assembly.

    PubMed

    Muriaux, Delphine; Costes, Sylvain; Nagashima, Kunio; Mirro, Jane; Cho, Ed; Lockett, Stephen; Rein, Alan

    2004-11-01

    The retroviral nucleocapsid protein (NC) originates by cleavage of the Gag polyprotein. It is highly basic and contains one or two zinc fingers. Mutations in either the basic residues or the zinc fingers can affect several events of the virus life cycle. They frequently prevent the specific packaging of the viral RNA, affect reverse transcription, and impair virion assembly. In this work, we explore the role of NC in murine leukemia virus (MLV) particle assembly and release. A panel of NC mutants, including mutants of the zinc finger and of a basic region, as well as truncations of the NC domain of Gag, were studied. Several of these mutations dramatically reduce the release of virus particles. A mutant completely lacking the NC domain is apparently incapable of assembling into particles, although its Gag protein is still targeted to the plasma membrane. By electron microscopy on thin sections of virus-producing cells, we observed that some NC mutants exhibit various stages of budding defects at the plasma membrane and have aberrant particle morphology; electron micrographs of cells expressing some of these mutants are strikingly similar to those of cells expressing "late-domain" mutants. However, the defects of NC mutants with respect to virus release and infectivity could be complemented by an MLV lacking the p12 domain. Therefore, the functions of NC in virus budding and infectivity are completely distinct from viral late-domain function. PMID:15507624

  18. Role of Murine Leukemia Virus Nucleocapsid Protein in Virus Assembly

    PubMed Central

    Muriaux, Delphine; Costes, Sylvain; Nagashima, Kunio; Mirro, Jane; Cho, Ed; Lockett, Stephen; Rein, Alan

    2004-01-01

    The retroviral nucleocapsid protein (NC) originates by cleavage of the Gag polyprotein. It is highly basic and contains one or two zinc fingers. Mutations in either the basic residues or the zinc fingers can affect several events of the virus life cycle. They frequently prevent the specific packaging of the viral RNA, affect reverse transcription, and impair virion assembly. In this work, we explore the role of NC in murine leukemia virus (MLV) particle assembly and release. A panel of NC mutants, including mutants of the zinc finger and of a basic region, as well as truncations of the NC domain of Gag, were studied. Several of these mutations dramatically reduce the release of virus particles. A mutant completely lacking the NC domain is apparently incapable of assembling into particles, although its Gag protein is still targeted to the plasma membrane. By electron microscopy on thin sections of virus-producing cells, we observed that some NC mutants exhibit various stages of budding defects at the plasma membrane and have aberrant particle morphology; electron micrographs of cells expressing some of these mutants are strikingly similar to those of cells expressing “late-domain” mutants. However, the defects of NC mutants with respect to virus release and infectivity could be complemented by an MLV lacking the p12 domain. Therefore, the functions of NC in virus budding and infectivity are completely distinct from viral late-domain function. PMID:15507624

  19. Human immunodeficiency virus endocrinopathy

    PubMed Central

    Sinha, Uma; Sengupta, Nilanjan; Mukhopadhyay, Prasanta; Roy, Keshab Sinha

    2011-01-01

    Human immunodeficiency virus (HIV) endocrinopathy encompasses a broad spectrum of disorders. Almost all the endocrine organs are virtually affected by HIV infection. HIV can directly alter glandular function. More commonly secondary endocrine dysfunction occurs due to opportunistic infections and neoplasms in immunocompromised state. The complex interaction between HIV infection and endocrine system may be manifested as subtle biochemical and hormonal perturbation to overt glandular failure. Antiretroviral therapy as well as other essential medications often result in adverse endocrinal consequences. Apart from adrenal insufficiency, hypogonadism, diabetes and bone loss, AIDS wasting syndrome and HIV lipodystrophy need special reference. Endocrinal evaluation should proceed as in other patients with suspected endocrine dysfunction. Available treatment options have been shown to improve quality of life and long-term mortality in AIDS patients. PMID:22028995

  20. Lactate dehydrogenase-elevating virus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This book chapter describes the taxonomic classification of Lactate dehydrogenase-elevating virus (LDV). Included are: host, genome, classification, morphology, physicochemical and physical properties, nucleic acid, proteins, lipids, carbohydrates, geographic range, phylogenetic properties, biologic...