Sample records for virus ebola virus

  1. Understanding ebola virus transmission.

    PubMed

    Judson, Seth; Prescott, Joseph; Munster, Vincent

    2015-02-01

    An unprecedented number of Ebola virus infections among healthcare workers and patients have raised questions about our understanding of Ebola virus transmission. Here, we explore different routes of Ebola virus transmission between people, summarizing the known epidemiological and experimental data. From this data, we expose important gaps in Ebola virus research pertinent to outbreak situations. We further propose experiments and methods of data collection that will enable scientists to fill these voids in our knowledge about the transmission of Ebola virus. PMID:25654239

  2. Ebola virus disease epidemic.

    PubMed

    Phillips, Jennan A

    2014-11-01

    The Ebola virus disease epidemic now constitutes an international public health emergency. Occupational and environmental health nurses can collaborate with international colleagues to halt Ebola virus transmission within Africa, protect workers from exposures, and prevent another pandemic. [Workplace Health Saf 2014;62(11):484.]. PMID:25373029

  3. 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

  4. Ebola virus antibodies in fruit bats, bangladesh.

    PubMed

    Olival, Kevin J; Islam, Ariful; Yu, Meng; Anthony, Simon J; Epstein, Jonathan H; Khan, Shahneaz Ali; Khan, Salah Uddin; Crameri, Gary; Wang, Lin-Fa; Lipkin, W Ian; Luby, Stephen P; Daszak, Peter

    2013-02-01

    To determine geographic range for Ebola virus, we tested 276 bats in Bangladesh. Five (3.5%) bats were positive for antibodies against Ebola Zaire and Reston viruses; no virus was detected by PCR. These bats might be a reservoir for Ebola or Ebola-like viruses, and extend the range of filoviruses to mainland Asia. PMID:23343532

  5. [Ebola virus disease].

    PubMed

    Karwowska, Kornelia

    2015-01-01

    Ebola virus disease is a zoonosis causing high mortality epidemics in both human and animal populations. The virus belongs to the Filoviride family. It is composed of a single-strand of RNA. Morbidity foci appear in sub-Saharan Africa. The most probable reservoir are fruit bats, which are local delicacy. The most common route of infection is via mucosa or damaged skin. The spread of disease is rapid due to dietary habits, funeral rites and the insufficient supply of disposable equipment in hospitals. The incubation period of the disease ranges from 2 to 21 days. The beginning is abrupt, dominated by influenza-like symptoms. The disease is staggering with the predominant multi-organ failure and shock. Present-day epidemic symptoms from digestive system in the form of vomiting and diarrhoea are dominant. Currently, the research on vaccine and experimental drug is in progress. The virus is damaged by standard disinfectants used in health care units. Epidemic, which broke out in February 2014, caused by the most dangerous type Zaire, is the greatest of the existing. Morbidity and mortality is underestimated due to numerous unreported cases. PMID:25763588

  6. Ebola Virus Antibody Prevalence in Dogs

    E-print Network

    Human Risk; Loïs Allela; Olivier Bourry; Régis Pouillot; André Délicat; Brice Kumulungui; Pierre Rouquet; Jean-paul Gonzalez; Eric M. Leroy

    observed that several dogs were highly exposed to Ebola virus by eating infected dead animals. To examine whether these animals became infected with Ebola virus, we sampled 439 dogs and screened them by Ebola virus–specific immunoglobulin (Ig) G assay, antigen detection, and viral polymerase chain

  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. Ebola Virus Disease

    MedlinePLUS

    ... survival. There is as yet no licensed treatment proven to neutralise the virus but a range of ... symptoms, improves survival. There is as yet no proven treatment available for EVD. However, a range of ...

  10. 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.

  11. Ebola virus disease

    MedlinePLUS

    ... monkeys, and chimpanzees). The 2014 Ebola outbreak in West Africa is the largest in history. About 70% of ... One case occurred in a man traveling from West Africa to Texas. He died from the disease. Two ...

  12. Ebola virus: questions, answers, and more questions.

    PubMed

    Brizendine, Kyle D

    2014-12-01

    Ebola virus causes a hemorrhagic fever with a high case-fatality rate. Treatment remains supportive although a variety of specific treatments are still in the early stages of investigation. This report reviews the clinical virology of Ebola virus, the reported proposed treatments, and the current outbreak. PMID:25452350

  13. DISPATCHES Ebola Virus Antibodies in Fruit Bats, Bangladesh

    E-print Network

    Kevin J. Olival; Ariful Islam; Meng Yu; Simon J. Anthony; Jonathan H. Epstein; Shahneaz Ali Khan; Salah Uddin Khan; Gary Crameri; Lin-fa Wang; W. Ian Lipkin; Stephen P. Luby; Peter Daszak; Ebola Virus; Lloviu Ebola Virus

    To determine geographic range for Ebola virus, we tested 276 bats in Bangladesh. Five (3.5%) bats were positive for antibodies against Ebola Zaire and Reston viruses; no virus was detected by PCR. These bats might be a reservoir for Ebola or Ebola-like viruses, and extend the range of filoviruses

  14. [Ebola virus disease].

    PubMed

    Grünewald, Th

    2014-12-01

    The current Ebola outbreak in Western Africa differs from previous ones due to its extent. Serious shortcomings in the on-site management in Africa are obvious. In addition to the situation in the countries affected media and medical interests also focus on detection and management of imported cases in Germany. From the experience with such patients already treated in Germany the existing medical concepts have been updated and expanded. This overview addresses not only the latest clinical knowledge and epidemiological developments but also outlines the key measures as well as the practical procedure when there is a suspected case. PMID:25423458

  15. 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

  16. The Ebola virus epidemic: Preparation, not panic.

    PubMed

    Borchardt, Roy A

    2015-02-01

    The largest-ever outbreak and first epidemic of Ebola virus disease is affecting several West African countries. Early symptoms of Ebola can mimic those of other tropical diseases. In a world of rapid global travel, physician assistants need to be capable of identifying patients at greatest risk for developing Ebola. Clinicians also should be familiar with associated symptoms, diagnosis, and treatment considerations. PMID:25565023

  17. 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

  18. 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

  19. Cutaneous manifestations of the ebola virus.

    PubMed

    Blattner, Collin M; Mortazie, Michael B; Murase, Jenny E

    2015-01-01

    The current Ebola outbreak has drawn attention to the virus in the medical community. Zaire ebolavirus, more commonly known as 'the Ebola virus,' is a level 4-security agent in the Filoviridae family. The main cutaneous finding of Ebola is a nonspecific maculopapular rash that appears between day four and six of disease. Patients have "ghost-like" features, and the rash initially presents on the upper arms, flexor forearms, and upper legs, sometimes in a centripetal fashion. Skin biopsy, immunohistochemistry, ELISA, and electron microscopy can help provide early diagnosis and conceivably prevent spread if proper precautionary measures are in place. PMID:25780982

  20. Ebola virus disease: history, epidemiology and outbreaks.

    PubMed

    Weyer, Jacqueline; Grobbelaar, Antoinette; Blumberg, Lucille

    2015-05-01

    Over the past 40 years, sporadic Ebola virus disease (EVD) outbreaks have occurred mostly in the central African region. In March 2014, an outbreak of EVD was recognized in Guinea which would become the most significant outbreak of haemorrhagic fever in Africa to date. The outbreak started in Guinea and rapidly spread to Liberia and Sierra Leone, claiming thousands of lives. Many questions still remain regarding the ecology of Ebola viruses, but it is believed that contact with infected bushmeat is an important risk factor for initial spill over of the virus into the human population. At present, there is still no registered prophylaxis or curative biologicals against EVD. PMID:25896751

  1. Comprehensive Analysis of Ebola Virus GP1 in Viral Entry

    Microsoft Academic Search

    Balaji Manicassamy; Jizhen Wang; Haiqing Jiang; Lijun Rong

    2005-01-01

    Ebola virus infection is initiated by interactions between the viral glycoprotein GP1 and its cognate recep- tor(s), but little is known about the structure and function of GP1 in viral entry, partly due to the concern about safety when working with the live Ebola virus and the difficulty of manipulating the RNA genome of Ebola virus. In this study, we

  2. 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

  3. Ebola Virus: Immune Mechanisms of Protection and Vaccine Development

    Microsoft Academic Search

    Adeline M. Nyamathi; John L. Fahey; Heather Sands; Adrian M. Casillas

    2003-01-01

    Vaccination is one of our most powerful antiviral strategies. Despite the emergence of deadly viruses such as Ebola virus, vaccination efforts have focused mainly on childhood communicable diseases. Although Ebola virus was once believed to be limited to isolated outbreaks in distant lands, forces of globalization potentiate outbreaks anywhere in the world through incidental transmission. Moreover, since this virus has

  4. Treatment of Ebola Virus Infection with Antibodies from Reconvalescent Donors

    PubMed Central

    2015-01-01

    Clinical evidence suggests that antibodies from reconvalescent donors (persons who have recovered from infection) may be effective in the treatment of Ebola virus infection. Administration of this treatment to Ebola virus–infected patients while preventing the transmission of other pathogenic viruses may be best accomplished by use of virus-inactivated reconvalescent plasma. PMID:25695274

  5. Treatment of ebola virus infection with antibodies from reconvalescent donors.

    PubMed

    Kreil, Thomas R

    2015-03-01

    Clinical evidence suggests that antibodies from reconvalescent donors (persons who have recovered from infection) may be effective in the treatment of Ebola virus infection. Administration of this treatment to Ebola virus-infected patients while preventing the transmission of other pathogenic viruses may be best accomplished by use of virus-inactivated reconvalescent plasma. PMID:25695274

  6. A System for Functional Analysis of Ebola Virus Glycoprotein

    Microsoft Academic Search

    Ayato Takada; Clinton Robison; Hideo Goto; Anthony Sanchez; K. Gopal Murti; Michael A. Whitt; Yoshihiro Kawaoka

    1997-01-01

    Ebola virus causes hemorrhagic fever in humans and nonhuman primates, resulting in mortality rates of up to 90%. Studies of this virus have been hampered by its extraordinary pathogenicity, which requires biosafety level 4 containment. To circumvent this problem, we developed a novel complementation system for functional analysis of Ebola virus glycoproteins. It relies on a recombinant vesicular stomatitis virus

  7. Ebola virus: a clear and present danger.

    PubMed

    Burd, Eileen M

    2015-01-01

    An epidemic of Ebola virus disease is occurring in Western Africa on a scale not seen before, particularly in the countries of Guinea, Liberia, and Sierra Leone. The continued spread is facilitated by insufficient medical facilities, poor sanitation, travel, and unsafe burial practices. Several patients diagnosed with Ebola virus disease in Africa have been evacuated to the United States for treatment, and several other patients have been diagnosed in the United States. It is important for laboratories to be aware of available tests, especially those granted emergency use authorization, as hospitals prepare protocols for the diagnosis and management of high-risk patients. PMID:25392362

  8. Ebola virus-like particles protect from lethal Ebola virus infection

    Microsoft Academic Search

    Kelly L. Warfield; Catharine M. Bosio; Brent C. Welcher; Emily M. Deal; Mansour Mohamadzadeh; Alan Schmaljohn; M. Javad Aman; Sina Bavari

    2003-01-01

    The filovirus Ebola causes hemorrhagic fever with 70-80% human mortality. High case-fatality rates, as well as known aerosol infectivity, make Ebola virus a potential global health threat and possible biological warfare agent. Development of an effective vaccine for use in natural outbreaks, response to biological attack, and protection of laboratory workers is a higher national priority than ever before. Coexpression

  9. 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

  10. 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

  11. Covalent Modifications of the Ebola Virus Glycoprotein

    Microsoft Academic Search

    Scott A. Jeffers; David Avram Sanders; Anthony Sanchez

    2002-01-01

    The role of covalent modifications of the Ebola virus glycoprotein (GP) and the significance of the sequence identity between filovirus and avian retrovirus GPs were investigated through biochemical and functional analyses of mutant GPs. The expression and processing of mutant GPs with altered N-linked glycosylation, substitutions for conserved cysteine residues, or a deletion in the region of O-linked glycosylation were

  12. Genetic Changes to Ebola Virus Challenge Treatment Efforts

    MedlinePLUS

    ... this page, please enable JavaScript. Genetic Changes to Ebola Virus Challenge Treatment Efforts Researchers need to be ... Preidt Tuesday, January 20, 2015 Related MedlinePlus Pages Ebola Genes and Gene Therapy TUESDAY, Jan. 20, 2015 ( ...

  13. 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

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

    PubMed Central

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

    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 nonhuman primates infected with an Ebola virus lacking the furin recognition sequence compared to those infected with wild-type virus. We conclude that glycoprotein cleavage by subtilisin-like endoproteases is not critical for Ebola virus infectivity and virulence in nonhuman primates. PMID:17229700

  15. The Origin and Evolution of Ebola and Marburg Viruses

    E-print Network

    Takashi Gojoborp

    Molecular evolutionary analyses for Ebola and Marburg viruses were conducted with the aim of elucidating evo-lutionary features of these viruses. In particular, the rate of nonsynonymous substitutions for the glycoprotein gene of Ebola virus was estimated to be, on the average, 3.6 X 1O-5 per site

  16. Successful Topical Respiratory Tract Immunization of Primates against Ebola Virus

    Microsoft Academic Search

    Alexander Bukreyev; Pierre E. Rollin; Mallory K. Tate; Lijuan Yang; Sherif R. Zaki; Wun-Ju Shieh; Brian R. Murphy; Peter L. Collins; Anthony Sanchez

    2007-01-01

    Ebola virus causes outbreaks of severe viral hemorrhagic fever with high mortality in humans. The virus is highly contagious and can be transmitted by contact and by the aerosol route. These features make Ebola virus a potential weapon for bioterrorism and biological warfare. Therefore, a vaccine that induces both systemic and local immune responses in the respiratory tract would be

  17. Infectivity-Enhancing Antibodies to Ebola Virus Glycoprotein

    Microsoft Academic Search

    AYATO TAKADA; SHINJI WATANABE; KATSUNORI OKAZAKI; HIROSHI KIDA; Y. Kawaoka

    2001-01-01

    Ebola virus causes severe hemorrhagic fever in primates, resulting in mortality rates of up to 100%, yet there are no satisfactory biologic explanations for this extreme virulence. Here we show that antisera produced by DNA immunization with a plasmid encoding the surface glycoprotein (GP) of the Zaire strain of Ebola virus enhances the infectivity of vesicular stomatitis virus pseudotyped with

  18. Antibody-Dependent Enhancement of Ebola Virus Infection

    PubMed Central

    Takada, Ayato; Feldmann, Heinz; Ksiazek, Thomas G.; Kawaoka, Yoshihiro

    2003-01-01

    Most strains of Ebola virus cause a rapidly fatal hemorrhagic disease in humans, yet there are still no biologic explanations that adequately account for the extreme virulence of these emerging pathogens. Here we show that Ebola Zaire virus infection in humans induces antibodies that enhance viral infectivity. Plasma or serum from convalescing patients enhanced the infection of primate kidney cells by the Zaire virus, and this enhancement was mediated by antibodies to the viral glycoprotein and by complement component C1q. Our results suggest a novel mechanism of antibody-dependent enhancement of Ebola virus infection, one that would account for the dire outcome of Ebola outbreaks in human populations. PMID:12805454

  19. Development of vaccines for prevention of Ebola virus infection.

    PubMed

    Ye, Ling; Yang, Chinglai

    2015-02-01

    Ebola virus infection causes severe hemorrhagic fevers with high fatality rates up to 90% in humans, for which no effective treatment is currently available. The ongoing Ebola outbreak in West Africa that has caused over 14,000 human infections and over 5000 deaths underscores its serious threat to the public health. While licensed vaccines against Ebola virus infection are still not available, a number of vaccine approaches have been developed and shown to protect against lethal Ebola virus infection in animal models. This review aims to summarize the advancement of different strategies for Ebola vaccine development with a focus on the discussion of their protective efficacies and possible limitations. In addition, the development of animal models for efficacy evaluation of Ebola vaccines and the mechanism of immune protection against Ebola virus infection are also discussed. PMID:25526819

  20. Ebola virus. Two-pore channels control Ebola virus host cell entry and are drug targets for disease treatment.

    PubMed

    Sakurai, Yasuteru; Kolokoltsov, Andrey A; Chen, Cheng-Chang; Tidwell, Michael W; Bauta, William E; Klugbauer, Norbert; Grimm, Christian; Wahl-Schott, Christian; Biel, Martin; Davey, Robert A

    2015-02-27

    Ebola virus causes sporadic outbreaks of lethal hemorrhagic fever in humans, but there is no currently approved therapy. Cells take up Ebola virus by macropinocytosis, followed by trafficking through endosomal vesicles. However, few factors controlling endosomal virus movement are known. Here we find that Ebola virus entry into host cells requires the endosomal calcium channels called two-pore channels (TPCs). Disrupting TPC function by gene knockout, small interfering RNAs, or small-molecule inhibitors halted virus trafficking and prevented infection. Tetrandrine, the most potent small molecule that we tested, inhibited infection of human macrophages, the primary target of Ebola virus in vivo, and also showed therapeutic efficacy in mice. Therefore, TPC proteins play a key role in Ebola virus infection and may be effective targets for antiviral therapy. PMID:25722412

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

    MedlinePLUS

    ... sharing features on this page, please enable JavaScript. Ebola Virus Evolving, But Isn't Getting Deadlier, Study ... Preidt Tuesday, April 14, 2015 Related MedlinePlus Page Ebola TUESDAY, April 14, 2015 (HealthDay News) -- The Ebola ...

  2. Ebola outbreak in Western Africa 2014: what is going on with Ebola virus?

    PubMed Central

    2015-01-01

    The 2014 outbreak of Ebola virus disease (EVD) in West Africa, caused by Ebola virus (Zaire Ebola virus species), is the largest outbreak of EVD in history. It cause hemorrhagic fever in human and nonhuman primates with high mortality rate up to 90% and can be transmitted by direct contact with blood, body fluids, skin of EVD patients or persons who have died of EVD. As of December 17, 2014, 450 healthcare personnel are known to have been infected with Ebola, of whom 244 died. For development of Ebola vaccine and treatment are highly difficult due to its dangerous and accessibility that requires biosafety level 4 (BSL-4) to conduct experiment. Also there is no specific vaccine and treatment for Ebola virus; however, many candidate vaccines and antiviral-drugs such as ZMapp and TKM-Ebola are being developed for Ebola virus disease. In this review, we focus on the epidemiology of 2014 outbreak of Ebola virus and candidate agent for preventing and curing from Ebola virus. PMID:25648530

  3. Protective efficacy of neutralizing antibodies against Ebola virus infection

    Microsoft Academic Search

    Ayato Takada; Hideki Ebihara; Steven Jones; Heinz Feldmann; Yoshihiro Kawaoka

    2007-01-01

    Ebola virus causes lethal hemorrhagic fever in humans and nonhuman primates, but no effective antiviral compounds are available for the treatment of this infection. The surface glycoprotein (GP) of Ebola virus is an important target of neutralizing antibodies. Although passive transfer of GP-specific antibodies has been evaluated in mouse and guinea pig models, protection was achieved only by treatment shortly

  4. Antibody-Dependent Enhancement of Ebola Virus Infection

    Microsoft Academic Search

    Ayato Takada; Heinz Feldmann; Thomas G. Ksiazek; Yoshihiro Kawaoka

    2003-01-01

    Most strains of Ebola virus cause a rapidly fatal hemorrhagic disease in humans, yet there are still no biologic explanations that adequately account for the extreme virulence of these emerging pathogens. Here we show that Ebola Zaire virus infection in humans induces antibodies that enhance viral infectivity. Plasma or serum from convalescing patients enhanced the infection of primate kidney cells

  5. 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

  6. Persistent Infection with Ebola Virus under Conditions of Partial Immunity

    Microsoft Academic Search

    Manisha Gupta; Siddhartha Mahanty; Patricia Greer; Jonathan S. Towner; Wun-Ju Shieh; Sherif R. Zaki; Rafi Ahmed; Pierre E. Rollin

    2004-01-01

    Ebola hemorrhagic fever in humans is associated with high mortality; however, some infected hosts clear the virus and recover. The mechanisms by which this occurs and the correlates of protective immunity are not well defined. Using a mouse model, we determined the role of the immune system in clearance of and protection against Ebola virus. All CD8 T-cell-deficient mice succumbed

  7. Ebola virus infection modeling and identifiability problems

    PubMed Central

    Nguyen, Van Kinh; Binder, Sebastian C.; Boianelli, Alessandro; Meyer-Hermann, Michael; Hernandez-Vargas, Esteban A.

    2015-01-01

    The recent outbreaks of Ebola virus (EBOV) infections have underlined the impact of the virus as a major threat for human health. Due to the high biosafety classification of EBOV (level 4), basic research is very limited. Therefore, the development of new avenues of thinking to advance quantitative comprehension of the virus and its interaction with the host cells is urgently needed to tackle this lethal disease. Mathematical modeling of the EBOV dynamics can be instrumental to interpret Ebola infection kinetics on quantitative grounds. To the best of our knowledge, a mathematical modeling approach to unravel the interaction between EBOV and the host cells is still missing. In this paper, a mathematical model based on differential equations is used to represent the basic interactions between EBOV and wild-type Vero cells in vitro. Parameter sets that represent infectivity of pathogens are estimated for EBOV infection and compared with influenza virus infection kinetics. The average infecting time of wild-type Vero cells by EBOV is slower than in influenza infection. Simulation results suggest that the slow infecting time of EBOV could be compensated by its efficient replication. This study reveals several identifiability problems and what kind of experiments are necessary to advance the quantification of EBOV infection. A first mathematical approach of EBOV dynamics and the estimation of standard parameters in viral infections kinetics is the key contribution of this work, paving the way for future modeling works on EBOV infection.

  8. Ebola virus disease: preparedness in Japan.

    PubMed

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

    2015-02-01

    ABSTRACT 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. (Disaster Med Public Health Preparedness. 2014;0:1-5). PMID:25399765

  9. Update: ebola virus disease epidemic - west Africa, january 2015.

    PubMed

    2015-02-01

    CDC is assisting ministries of health and working with other organizations to end the ongoing epidemic of Ebola virus disease (Ebola) in West Africa. The updated data in this report were compiled from situation reports from the Guinea Interministerial Committee for Response Against the Ebola Virus, the Liberia Ministry of Health and Social Welfare, the Sierra Leone Ministry of Health and Sanitation, and the World Health Organization. PMID:25654613

  10. Update: ebola virus disease epidemic - west Africa, february 2015.

    PubMed

    2015-02-27

    CDC is assisting ministries of health and working with other organizations to end the ongoing epidemic of Ebola virus disease (Ebola) in West Africa. The updated data in this report were compiled from situation reports from the Guinea Interministerial Committee for Response Against the Ebola Virus, the Liberia Ministry of Health and Social Welfare, the Sierra Leone Ministry of Health and Sanitation, and the World Health Organization. PMID:25719681

  11. A reconstituted replication and transcription system for Ebola virus Reston and comparison with Ebola virus Zaire

    Microsoft Academic Search

    Yannik Boehmann; Sven Enterlein; Anke Randolf; Elke Mühlberger

    2005-01-01

    The only known filovirus, which presumably is not pathogenic for humans, is Ebola virus (EBOV) Reston. When EBOV Reston and the highly pathogenic EBOV Zaire were grown in cell culture, comparison of the replication kinetics showed a clear growth impairment of EBOV Reston, indicating that the replication cycle of EBOV Reston might be delayed. In addition, the cytopathic effect caused

  12. Analysis of Linear B-Cell Epitopes of the Nucleoprotein of Ebola Virus That Distinguish Ebola Virus Subtypes

    Microsoft Academic Search

    Masahiro Niikura; Tetsuro Ikegami; Masayuki Saijo; Takeshi Kurata; Ichiro Kurane; Shigeru Morikawa

    2003-01-01

    Ebola virus consists of four genetically distinguishable subtypes. We developed monoclonal antibodies (MAbs) to the nucleoprotein (NP) of Ebola virus Zaire subtype and analyzed their cross-reactivities to the Reston and Sudan subtypes. We further determined the epitopes recognized by these MAbs. Three MAbs reacted with the three major subtypes and recognized a fragment containing 110 amino acids (aa) at the

  13. Reidentification of Ebola Virus E718 and ME as Ebola Virus/H.sapiens-tc/COD/1976/Yambuku-Ecran

    PubMed Central

    Lofts, Loreen L.; Kugelman, Jeffrey R.; Smither, Sophie J.; Lever, Mark S.; van der Groen, Guido; Johnson, Karl M.; Radoshitzky, Sheli R.; Bavari, Sina; Jahrling, Peter B.; Towner, Jonathan S.; Nichol, Stuart T.; Palacios, Gustavo

    2014-01-01

    Ebola virus (EBOV) was discovered in 1976 around Yambuku, Zaire. A lack of nomenclature standards resulted in a variety of designations for each isolate, leading to confusion in the literature and databases. We sequenced the genome of isolate E718/ME/Ecran and unified the various designations under Ebola virus/H.sapiens-tc/COD/1976/Yambuku-Ecran. PMID:25414499

  14. 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

  15. 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

  16. Proteolysis of the Ebola Virus Glycoproteins Enhances Virus Binding and Infectivity

    Microsoft Academic Search

    Rachel L. Kaletsky; Graham Simmons; Paul Bates

    2007-01-01

    Cellular cathepsins are required for Ebola virus infection and are believed to proteolytically process the Ebola virus glycoprotein (GP) during entry. However, the significance of cathepsin cleavage during infection remains unclear. Here we demonstrate a role for cathepsin L (CatL) cleavage of Ebola virus GP in the generation of a stable 18-kDa GP1 viral intermediate that exhibits increased binding to

  17. Infection and Activation of Monocytes by Marburg and Ebola Viruses

    Microsoft Academic Search

    UTE STROHER; ELMAR WEST; HARALD BUGANY; HANS-DIETER KLENK; HANS-JOACHIM SCHNITTLER; HEINZ FELDMANN

    2001-01-01

    In this study we investigated the effects of Marburg virus and Ebola virus (species Zaire and Reston) infections on freshly isolated suspended monocytes in comparison to adherent macrophages under culture conditions. Our data showed that monocytes are permissive for both filoviruses. As is the case in macrophages, infection resulted in the activation of monocytes which was largely independent of virus

  18. Immunopathology of highly virulent pathogens: insights from Ebola virus

    Microsoft Academic Search

    Carisa A Zampieri; Nancy J Sullivan; Gary J Nabel

    2007-01-01

    Ebola virus is a highly virulent pathogen capable of inducing a frequently lethal hemorrhagic fever syndrome. Accumulating evidence indicates that the virus actively subverts both innate and adaptive immune responses and triggers harmful inflammatory responses as it inflicts direct tissue damage. The host immune system is ultimately overwhelmed by a combination of inflammatory factors and virus-induced cell damage, particularly in

  19. 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

  20. Ebola virus (EBOV) infection: Therapeutic strategies.

    PubMed

    De Clercq, Erik

    2015-01-01

    Within less than a year after its epidemic started (in December 2013) in Guinea, Ebola virus (EBOV), a member of the filoviridae, has spread over a number of West-African countries (Guinea, Sierra Leone and Liberia) and gained allures that have been unprecedented except by human immunodeficiency virus (HIV). Although EBOV is highly contagious and transmitted by direct contact with body fluids, it could be counteracted by the adequate chemoprophylactic and -therapeutic interventions: vaccines, antibodies, siRNAs (small interfering RNAs), interferons and chemical substances, i.e. neplanocin A derivatives (i.e. 3-deazaneplanocin A), BCX4430, favipiravir (T-705), endoplasmic reticulum (ER) ?-glucosidase inhibitors and a variety of compounds that have been found to inhibit EBOV infection blocking viral entry or by a mode of action that still has to be resolved. Much has to be learned from the mechanism of action of the compounds active against VSV (vesicular stomatitis virus), a virus belonging to the rhabdoviridae, that in its mode of replication could be exemplary for the replication of filoviridae. PMID:25481298

  1. 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

  2. Recombinant Vesicular Stomatitis Virus–Based Vaccines Against Ebola and Marburg Virus Infections

    PubMed Central

    Feldmann, Heinz

    2011-01-01

    The filoviruses, Marburg virus and Ebola virus, cause severe hemorrhagic fever with a high mortality rate in humans and nonhuman primates. Among the most-promising filovirus vaccines under development is a system based on recombinant vesicular stomatitis virus (rVSV) that expresses a single filovirus glycoprotein (GP) in place of the VSV glycoprotein (G). Importantly, a single injection of blended rVSV-based filovirus vaccines was shown to completely protect nonhuman primates against Marburg virus and 3 different species of Ebola virus. These rVSV-based vaccines have also shown utility when administered as a postexposure treatment against filovirus infections, and a rVSV-based Ebola virus vaccine was recently used to treat a potential laboratory exposure. Here, we review the history of rVSV-based vaccines and pivotal animal studies showing their utility in combating Ebola and Marburg virus infections. PMID:21987744

  3. 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

  4. Ebola virus vaccines: an overview of current approaches.

    PubMed

    Marzi, Andrea; Feldmann, Heinz

    2014-04-01

    Ebola hemorrhagic fever is one of the most fatal viral diseases worldwide affecting humans and nonhuman primates. Although infections only occur frequently in Central Africa, the virus has the potential to spread globally and is classified as a category A pathogen that could be misused as a bioterrorism agent. As of today there is no vaccine or treatment licensed to counteract Ebola virus infections. DNA, subunit and several viral vector approaches, replicating and non-replicating, have been tested as potential vaccine platforms and their protective efficacy has been evaluated in nonhuman primate models for Ebola virus infections, which closely resemble disease progression in humans. Though these vaccine platforms seem to confer protection through different mechanisms, several of them are efficacious against lethal disease in nonhuman primates attesting that vaccination against Ebola virus infections is feasible. PMID:24575870

  5. Reemerging Sudan Ebola Virus Disease in Uganda, 2011

    PubMed Central

    Shoemaker, Trevor; Balinandi, Stephen; Campbell, Shelley; Wamala, Joseph Francis; McMullan, Laura K.; Downing, Robert; Lutwama, Julius; Mbidde, Edward; Ströher, Ute; Rollin, Pierre E.; Nichol, Stuart T.

    2012-01-01

    Two large outbreaks of Ebola hemorrhagic fever occurred in Uganda in 2000 and 2007. In May 2011, we identified a single case of Sudan Ebola virus disease in Luwero District. The establishment of a permanent in-country laboratory and cooperation between international public health entities facilitated rapid outbreak response and control activities. PMID:22931687

  6. The natural history of Ebola virus in Africa

    Microsoft Academic Search

    Xavier Pourrut; Brice Kumulungui; Tatiana Wittmann; Ghislain Moussavou; André Délicat; Philippe Yaba; Dieudonné Nkoghe; Jean-Paul Gonzalez; Eric Maurice Leroy

    2005-01-01

    Several countries spanning the equatorial forest regions of Africa have had outbreaks of Ebola hemorrhagic fever over the last three decades. This article is an overview of the many published investigations of how Ebola virus circulates in its natural environment, focusing on the viral reservoir, susceptible animal species, environmental conditions favoring inter-species transmission, and how the infection is transmitted to

  7. 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

  8. 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

  9. 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

  10. Disease modeling for Ebola and Marburg viruses

    PubMed Central

    Bente, Dennis; Gren, Jason; Strong, James E.; Feldmann, Heinz

    2009-01-01

    The filoviruses Ebola and Marburg are zoonotic agents that are classified as both biosafety level 4 and category A list pathogens. These viruses are pathogenic in humans and cause isolated infections or epidemics of viral hemorrhagic fever, mainly in Central Africa. Their natural reservoir has not been definitely identified, but certain species of African bat have been associated with Ebola and Marburg infections. Currently, there are no licensed options available for either treatment or prophylaxis. Different animal models have been developed for filoviruses including mouse, guinea pig and nonhuman primates. The ‘gold standard’ animal models for pathogenesis, treatment and vaccine studies are rhesus and cynomolgus macaques. This article provides a brief overview of the clinical picture and the pathology/pathogenesis of human filovirus infections. The current animal model options are discussed and compared with regard to their value in different applications. In general, the small animal models, in particular the mouse, are the most feasible for high biocontainment facilities and they offer the most options for research owing to the greater availability of immunologic and genetic tools. However, their mimicry of the human diseases as well as their predictive value for therapeutic efficacy in primates is limited, thereby making them, at best, valuable initial screening tools for pathophysiology, treatment and vaccine studies. PMID:19132113

  11. Update: Ebola virus disease epidemic--West Africa, November 2014.

    PubMed

    2014-11-21

    CDC is assisting ministries of health and working with other organizations to end the ongoing epidemic of Ebola virus disease (Ebola) in West Africa. The updated data in this report were compiled from situation reports from the Guinea Interministerial Committee for Response Against the Ebola Virus and the World Health Organization, the Liberia Ministry of Health and Social Welfare, and the Sierra Leone Ministry of Health and Sanitation. Total case counts include all suspected, probable, and confirmed cases, which are defined similarly by each country. These data reflect reported cases, which make up an unknown proportion of all cases, and reporting delays that vary from country to country. PMID:25412064

  12. Ebola GP-Specific Monoclonal Antibodies Protect Mice and Guinea Pigs from Lethal Ebola Virus Infection

    Microsoft Academic Search

    Xiangguo Qiu; Lisa Fernando; P. Leno Melito; Jonathan Audet; Heinz Feldmann; Gary Kobinger; Judie B. Alimonti; Steven M. Jones

    2012-01-01

    Ebola virus (EBOV) causes acute hemorrhagic fever in humans and non-human primates with mortality rates up to 90%. So far there are no effective treatments available. This study evaluates the protective efficacy of 8 monoclonal antibodies (MAbs) against Ebola glycoprotein in mice and guinea pigs. Immunocompetent mice or guinea pigs were given MAbs i.p. in various doses individually or as

  13. Genome structure of Ebola virus subtype Reston: differences among Ebola subtypes

    Microsoft Academic Search

    T. Ikegami; A. B. Calaor; M. E. Miranda; M. Niikura; M. Saijo; I. Kurane; Y. Yoshikawa; S. Morikawa

    2001-01-01

    Summary.  ?We determined the complete genome sequence of Ebola virus subtype Reston (EBO-R) in the Philippines in 1996. The deduced\\u000a transcriptional signals were highly conserved among Ebola viruses except for the stop signal of L genes. The intergenic regions\\u000a were composed of 4 to 7 nucleotides, and of 2 characteristic overlaps and a long intergenic region. The glycoprotein (GP)\\u000a had several

  14. Ebola virus: Melatonin as a readily available treatment option.

    PubMed

    Anderson, George; Maes, Michael; Markus, Regina P; Rodriguez, Moses

    2015-04-01

    There is currently an urgent need for a viable, cheap, and readily available treatment for the Ebola virus outbreak in West Africa. Here, it is proposed that melatonin may have significant utility in helping the management of this outbreak. Optimizing natural killer (NK) cell responses seems crucial to surviving Ebola virus infection. Melatonin increases NK cell cytotoxicity significantly, suggesting efficacy in managing the Ebola virus. Under conditions of challenge, melatonin increases heme oxygenase-1 (HO-1), which inhibits Ebola virus replication. Melatonin also has protective effects in cases of septic shock, which, although bacterial, has similar end-point presentations involving blood vessel leakage. Melatonin's effects on haemorrhage are mediated primarily by a decrease in pro-inflammatory cytokines. By optimizing the appropriate immune response, melatonin is likely to afford protection to those at high risk of Ebola viral infection, as well as having direct impacts on the course of infection per se. Although no direct data pertain to the utility of melatonin in the management of the Ebola virus, convergent bodies of data suggest its utility, which is reviewed in this article. J. Med. Virol. 87:537-543, 2015. © 2015 Wiley Periodicals, Inc. PMID:25611054

  15. 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).

  16. 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

  17. Implication of a retrovirus-like glycoprotein peptide in the immunopathogenesis of Ebola and Marburg viruses

    Microsoft Academic Search

    Kavitha Yaddanapudi; Gustavo Palacios; Jonathan S. Towner; Ivy Chen; Carlos A. Sariol; Stuart T. Nichol; W. Ian Lipkin

    2006-01-01

    Ebola and Marburg viruses can cause hemorrhagic fever (HF) outbreaks with high mortality in primates. Whereas Marburg (MARV), Ebola Zaire (ZEBOV), and Ebola Sudan (SEBOV) viruses are patho- genic in humans, apes, and monkeys, Ebola Reston (REBOV) is pathogenic only in monkeys (1-3). Early immunosuppression may contribute to pathogenesis by facilitating viral replication (4 - 6). Lymphocyte deple- tion, intravascular

  18. How Ebola virus counters the interferon system.

    PubMed

    Kühl, A; Pöhlmann, S

    2012-09-01

    Zoonotic transmission of Ebola virus (EBOV) to humans causes a severe haemorrhagic fever in afflicted individuals with high case-fatality rates. Neither vaccines nor therapeutics are at present available to combat EBOV infection, making the virus a potential threat to public health. To devise antiviral strategies, it is important to understand which components of the immune system could be effective against EBOV infection. The interferon (IFN) system constitutes a key innate defence against viral infections and prevents development of lethal disease in mice infected with EBOV strains not adapted to this host. Recent research revealed that expression of the host cell IFN-inducible transmembrane proteins 1-3 (IFITM1-3) and tetherin is induced by IFN and restricts EBOV infection, at least in cell culture model systems. IFITMs, tetherin and other effector molecules of the IFN system could thus pose a potent barrier against EBOV spread in humans. However, EBOV interferes with signalling events required for human cells to express these proteins. Here, we will review the strategies employed by EBOV to fight the IFN system, and we will discuss how IFITM proteins and tetherin inhibit EBOV infection. PMID:22958256

  19. Experimental inoculation of plants and animals with Ebola virus.

    PubMed Central

    Swanepoel, R.; Leman, P. A.; Burt, F. J.; Zachariades, N. A.; Braack, L. E.; Ksiazek, T. G.; Rollin, P. E.; Zaki, S. R.; Peters, C. J.

    1996-01-01

    Thirty-three varieties of 24 species of plants and 19 species of vertebrates and invertebrates were experimentally inoculated with Ebola Zaire virus. Fruit and insectivorous bats supported replication and circulation of high titers of virus without necessarily becoming ill; deaths occurred only among bats that had not adapted to the diet fed in the laboratory. PMID:8969248

  20. Effective Binding of a Phosphatidylserine-Targeting Antibody to Ebola Virus Infected Cells and Purified Virions

    PubMed Central

    Dowall, S. D.; Graham, V. A.; Corbin-Lickfett, K.; Empig, C.; Schlunegger, K.; Bruce, C. B.; Easterbrook, L.; Hewson, R.

    2015-01-01

    Ebola virus is responsible for causing severe hemorrhagic fevers, with case fatality rates of up to 90%. Currently, no antiviral or vaccine is licensed against Ebola virus. A phosphatidylserine-targeting antibody (PGN401, bavituximab) has previously been shown to have broad-spectrum antiviral activity. Here, we demonstrate that PGN401 specifically binds to Ebola virus and recognizes infected cells. Our study provides the first evidence of phosphatidylserine-targeting antibody reactivity against Ebola virus. PMID:25815346

  1. Effective binding of a phosphatidylserine-targeting antibody to ebola virus infected cells and purified virions.

    PubMed

    Dowall, S D; Graham, V A; Corbin-Lickfett, K; Empig, C; Schlunegger, K; Bruce, C B; Easterbrook, L; Hewson, R

    2015-01-01

    Ebola virus is responsible for causing severe hemorrhagic fevers, with case fatality rates of up to 90%. Currently, no antiviral or vaccine is licensed against Ebola virus. A phosphatidylserine-targeting antibody (PGN401, bavituximab) has previously been shown to have broad-spectrum antiviral activity. Here, we demonstrate that PGN401 specifically binds to Ebola virus and recognizes infected cells. Our study provides the first evidence of phosphatidylserine-targeting antibody reactivity against Ebola virus. PMID:25815346

  2. Human Ebola virus infection results in substantial immune activation.

    PubMed

    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

    2015-04-14

    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. Release of cellular proteases into the acidic extracellular milieu exacerbates Ebola virus-induced cell damage

    Microsoft Academic Search

    Laura G. Barrientos; Pierre E. Rollin

    2007-01-01

    Ebola virus is highly cytopathic through mechanisms that are largely unknown. We present evidence that progressive acidification of the extracellular milieu by Ebola virus-infected cells combined with reduced levels of natural cysteine protease inhibitor makes the cells vulnerable to uncontrolled proteolysis of extracellular matrix components by released active endosomal cathepsins, thereby exacerbating Ebola virus-induced cell destruction. The cell surface microenvironment

  5. 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

  6. 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

  7. Vesicular stomatitis virus-based vaccines against Lassa and Ebola viruses.

    PubMed

    Marzi, Andrea; Feldmann, Friederike; Geisbert, Thomas W; Feldmann, Heinz; Safronetz, David

    2015-02-01

    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

  8. 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

  9. Production of Novel Ebola Virus-Like Particles from cDNAs: an Alternative to Ebola Virus Generation by Reverse Genetics

    PubMed Central

    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 103 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

  10. Safety of Recombinant VSV-Ebola Virus Vaccine Vector in Pigs.

    PubMed

    de Wit, Emmie; Marzi, Andrea; Bushmaker, Trenton; Brining, Doug; Scott, Dana; Richt, Juergen A; Geisbert, Thomas W; Feldmann, Heinz

    2015-04-01

    The ongoing Ebola outbreak in West Africa has resulted in fast-track development of vaccine candidates. We tested a vesicular stomatitis virus vector expressing Ebola virus glycoprotein for safety in pigs. Inoculation did not cause disease and vaccine virus shedding was minimal, which indicated that the vaccine virus does not pose a risk of dissemination in pigs. PMID:25811738

  11. Safety of Recombinant VSV–Ebola Virus Vaccine Vector in Pigs

    PubMed Central

    de Wit, Emmie; Marzi, Andrea; Bushmaker, Trenton; Brining, Doug; Scott, Dana; Richt, Juergen A.; Geisbert, Thomas W.

    2015-01-01

    The ongoing Ebola outbreak in West Africa has resulted in fast-track development of vaccine candidates. We tested a vesicular stomatitis virus vector expressing Ebola virus glycoprotein for safety in pigs. Inoculation did not cause disease and vaccine virus shedding was minimal, which indicated that the vaccine virus does not pose a risk of dissemination in pigs. PMID:25811738

  12. 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

  13. 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. (Disaster Med Public Health Preparedness. 2014;0:1-3). PMID:25544306

  14. 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

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

    Microsoft Academic Search

    Alexander Bukreyev; Andrea Marzi; Friederike Feldmann; Liqun Zhang; Lijuan Yang; Jerrold M. Ward; David W. Dorward; Raymond J. Pickles; Brian R. Murphy; Heinz Feldmann; Peter L. Collins

    2009-01-01

    We generated a new live-attenuated vaccine against Ebola virus (EBOV) based on a chimeric virus HPIV3\\/?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

  16. 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

  17. Role of natural killer cells in innate protection against lethal Ebola virus infection

    Microsoft Academic Search

    Kelly L. Warfield; Jeremy G. Perkins; Dana L. Swenson; Emily M. Deal; Catharine M. Bosio; M. Javad Aman; Wayne M. Yokoyama; Howard A. Young; Sina Bavari

    2004-01-01

    Ebola virus is a highly lethal human pathogen and is rapidly driving many wild primate popula- tions toward extinction. Several lines of evidence suggest that innate, nonspecific host factors are potentially critical for survival after Ebola virus infection. Here, we show that nonreplicating Ebola virus-like particles (VLPs), containing the glycoprotein (GP) and matrix protein virus pro- tein (VP)40, administered 1-3

  18. Phosphoinositide3 Kinase-Akt Pathway Controls Cellular Entry of Ebola Virus

    Microsoft Academic Search

    Mohammad F. Saeed; Andrey A. Kolokoltsov; Alexander N. Freiberg; Michael R. Holbrook; Robert A. Davey

    2008-01-01

    The phosphoinositide-3 kinase (PI3K) pathway regulates diverse cellular activities related to cell growth, migration, survival, and vesicular trafficking. It is known that Ebola virus requires endocytosis to establish an infection. However, the cellular signals that mediate this uptake were unknown for Ebola virus as well as many other viruses. Here, the involvement of PI3K in Ebola virus entry was studied.

  19. Role of Natural Killer Cells in Innate Protection against Lethal Ebola Virus Infection

    E-print Network

    Kelly L. Warfield; Jeremy G. Perkins; Dana L. Swenson; Emily M. Deal; Catharine M. Bosio; M. Javad Aman; Wayne M. Yokoyama; Howard A. Young; Sina Bavari

    Ebola virus is a highly lethal human pathogen and is rapidly driving many wild primate populations toward extinction. Several lines of evidence suggest that innate, nonspecific host factors are potentially critical for survival after Ebola virus infection. Here, we show that nonreplicating Ebola

  20. 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

  1. 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

  2. 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

  3. The Marburg Virus 3' Noncoding Region Structurally and Functionally Differs from That of Ebola Virus

    Microsoft Academic Search

    Sven Enterlein; Kristina M. Schmidt; Michael Schumann; Dominik Conrad; Verena Krahling; Judith Olejnik; Elke Muhlberger

    2009-01-01

    We have previously shown that the first transcription start signal (TSS) of Zaire Ebola virus (ZEBOV) is involved in formation of an RNA secondary structure regulating VP30-dependent transcription activation. Interestingly, transcription of Marburg virus (MARV) minigenomes occurs independently of VP30. In this study, we analyzed the structure of the MARV 3 noncoding region and its influence on VP30 necessity. Secondary

  4. Marburg Virus Evades Interferon Responses by a Mechanism Distinct from Ebola Virus

    Microsoft Academic Search

    Charalampos Valmas; Melanie N. Grosch; Michael Schümann; Judith Olejnik; Osvaldo Martinez; Sonja M. Best; Verena Krähling; Christopher F. Basler; Elke Mühlberger

    2010-01-01

    Previous studies have demonstrated that Marburg viruses (MARV) and Ebola viruses (EBOV) inhibit interferon (IFN)-?\\/? signaling but utilize different mechanisms. EBOV inhibits IFN signaling via its VP24 protein which blocks the nuclear accumulation of tyrosine phosphorylated STAT1. In contrast, MARV infection inhibits IFN?\\/? induced tyrosine phosphorylation of STAT1 and STAT2. MARV infection is now demonstrated to inhibit not only IFN?\\/?

  5. 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 ...

  6. 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

  7. Nurses leading the fight against ebola virus disease.

    PubMed

    Sagar, Priscilla L

    2015-05-01

    The current Ebola crisis has sparked worldwide reaction of panic and disbelief in its wake as it decimated communities in West Africa, particularly in Guinea, Liberia, and Sierra Leone, including its health care workers. This article affirms the crucial role nurses play in maintaining health and preventing diseases, connects the devastating havoc of the Ebola virus disease to another issue of nursing shortage in underdeveloped countries, and asserts the key leadership nurses play in protecting the communities they serve while maintaining their safety and those of other health care workers. Nurses must actively seek a place at the table, as echoed by the American Academy of Nursing and American Nurses Association and the American Nurses Association, when decisions are being made regarding Ebola virus disease: at care settings, in the board room, and at federal, state, and local levels. PMID:25712149

  8. Professional development implications of Ebola virus disease education: part I.

    PubMed

    Smith, Elaine L; Kerner, Robert L; Schindler, Jaclyn S; DeVoe, Barbara

    2015-01-01

    This article is the first in a two-part series that explores how one large, integrated health care system swiftly responded to the emerging threat of Ebola virus disease. In this first article, the context and initial steps in planning staff education and training are outlined. PMID:25647314

  9. Professional development implications of Ebola virus disease education: part II.

    PubMed

    Smith, Elaine L; Kerner, Robert L; Schindler, Jaclyn S; DeVoe, Barbara

    2015-02-01

    This article is the second in a two-part series that explores how one large, integrated health care system swiftly responded to the emerging threat of Ebola virus disease. In this second article, the educational and training activities that were developed are described. PMID:25633300

  10. Small molecules with antiviral activity against the Ebola virus

    PubMed Central

    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

  11. 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

  12. Role of Ebola Virus VP30 in Transcription Reinitiation

    Microsoft Academic Search

    M. J. Martinez; Nadine Biedenkopf; Valentina Volchkova; Bettina Hartlieb; Nathalie Alazard-Dany; Olivier Reynard; Stephan Becker; Viktor Volchkov

    2008-01-01

    VP30 is a phosphoprotein essential for the initiation of Ebola virus transcription. In this work, we have studied the effect of mutations in VP30 phosphorylation sites on the ebolavirus replication cycle by using a reverse genetics system. We demonstrate that VP30 is involved in reinitiation of gene transcription and that this activity is affected by mutations at the phosphorylation sites.

  13. 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

  14. Ebola Virus VP30 Is an RNA Binding Protein

    Microsoft Academic Search

    Sinu P. John; Tan Wang; Scott Steffen; Sonia Longhi; Connie S. Schmaljohn; Colleen B. Jonsson

    2007-01-01

    The Ebola virus (EBOV) genome encodes for several proteins that are necessary and sufficient for replication and transcription of the viral RNAs in vitro; NP, VP30, VP35, and L. VP30 acts in trans with an RNA secondary structure upstream of the first transcriptional start site to modulate transcription. Using a bioinformatics approach, we identified a region within the N terminus

  15. RNA Polymerase I-Driven Minigenome System for Ebola Viruses

    Microsoft Academic Search

    Allison Groseth; Heinz Feldmann; Steven Theriault; Gulsah Mehmetoglu; Ramon Flick

    2005-01-01

    In general, Ebola viruses are well known for their ability to cause severe hemorrhagic fever in both human and nonhuman primates. However, despite substantial sequence homology to other members of the family Filoviridae, Reston ebolavirus displays reduced pathogenicity for nonhuman primates and has never been demonstrated to cause clinical disease in humans, despite its ability to cause infection. In order

  16. A Replicating Cytomegalovirus-Based Vaccine Encoding a Single Ebola Virus Nucleoprotein CTL Epitope Confers Protection against Ebola Virus

    Microsoft Academic Search

    Yoshimi Tsuda; Patrizia Caposio; Christopher J. Parkins; Sara Botto; Ilhem Messaoudi; Luka Cicin-Sain; Heinz Feldmann; Michael A. Jarvis

    2011-01-01

    BackgroundHuman outbreaks of Ebola virus (EBOV) are a serious human health concern in Central Africa. Great apes (gorillas\\/chimpanzees) are an important source of EBOV transmission to humans due to increased hunting of wildlife including the ‘bush-meat’ trade. Cytomegalovirus (CMV) is an highly immunogenic virus that has shown recent utility as a vaccine platform. CMV-based vaccines also have the unique potential

  17. 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

  18. Enhanced Protection against Ebola Virus Mediated by an Improved Adenovirus-Based Vaccine

    Microsoft Academic Search

    Jason S. Richardson; Michel K. Yao; Kaylie N. Tran; Maria A. Croyle; James E. Strong; Heinz Feldmann; Gary P. Kobinger; Olivier Schwartz

    2009-01-01

    BackgroundThe Ebola virus is transmitted by direct contact with bodily fluids of infected individuals, eliciting death rates as high as 90% among infected humans. Currently, replication defective adenovirus-based Ebola vaccine is being studied in a phase I clinical trial. Another Ebola vaccine, based on an attenuated vesicular stomatitis virus has shown efficacy in post-exposure treatment of nonhuman primates to Ebola

  19. 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.

  20. Cell Adhesion Promotes Ebola Virus Envelope Glycoprotein-Mediated Binding and Infection

    Microsoft Academic Search

    Derek Dube; Kathryn L. Schornberg; Tzanko S. Stantchev; Matthew I. Bonaparte; Sue E. Delos; Amy H. Bouton; Christopher C. Broder; Judith M. White

    2008-01-01

    Ebola virus infects a wide variety of adherent cell types, while nonadherent cells are found to be refractory. To explore this correlation, we compared the ability of pairs of related adherent and nonadherent cells to bind a recombinant Ebola virus receptor binding domain (EboV RBD) and to be infected with Ebola virus glyco- protein (GP)-pseudotyped particles. Both human 293F and

  1. 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.

  2. 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.

  3. 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

  4. Emergency Medical Services Public Health Implications and Interim Guidance for the Ebola Virus in the United States

    E-print Network

    McCoy, Christopher E.; Lotfipour, Shahram; Chakravarthy, Bharath; Schultz, Carl; Barton, Erik

    2014-01-01

    the arrival of Ebola to the U.S. , policies, protocols, andEbola Virus professionals, hospitals and emergency medical services (EMS) administrators, medial directors, and policypolicies for monitoring and managing EMS personnel potentially exposed to Ebola.

  5. 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

  6. Identification of Protective Epitopes on Ebola Virus Glycoprotein at the Single Amino Acid Level by Using Recombinant Vesicular Stomatitis Viruses

    Microsoft Academic Search

    Ayato Takada; Heinz Feldmann; Ute Stroeher; Mike Bray; Shinji Watanabe; Hiroshi Ito; Martha McGregor; Yoshihiro Kawaoka

    2003-01-01

    Ebola virus causes lethal hemorrhagic fever in humans, but currently there are no effective vaccines or antiviral compounds for this infectious disease. Passive transfer of monoclonal antibodies (MAbs) protects mice from lethal Ebola virus infection (J. A. Wilson, M. Hevey, R. Bakken, S. Guest, M. Bray, A. L. Schmaljohn, and M. K. Hart, Science 287:1664-1666, 2000). However, the epitopes responsible

  7. 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

  8. A case of Ebola virus infection.

    PubMed Central

    Emond, R T; Evans, B; Bowen, E T; Lloyd, G

    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 was mild and may have been modified by treatment with human interferon and convalescent serum. Convalescence was protracted; there was evidence of bone-marrow depression and virus was excreted in low titre for some weeks. Recovery was complete. Infection was contained by barrier-nursing techniques using a negative-pressure plastic isolator and infection did not spread to attendant staff or to the community. PMID:890413

  9. Drug targets in infections with Ebola and Marburg viruses.

    PubMed

    Gene, Olinger G; Julia, Biggins E; Vanessa, Melanson R; Victoria, Wahl-Jensen; Thomas, Geisbert W; Lisa, Hensley E

    2009-04-01

    The development of antiviral drugs for Ebola and Marburg viruses has been slow. To date, beyond supportive care, no effective treatments, prophylactic measures, therapies, or vaccines are approved to treat or prevent filovirus infections. In this review, we examine the current treatments available to administer care for filovirus infection, the potential therapeutic targets that can be used for filovirus drug development, and the various drug targeting techniques used against filoviruses. PMID:19275706

  10. 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

  11. Potential for large outbreaks of Ebola virus disease.

    PubMed

    Camacho, A; Kucharski, A J; Funk, S; Breman, J; Piot, P; Edmunds, W J

    2014-12-01

    Outbreaks of Ebola virus can cause substantial morbidity and mortality in affected regions. The largest outbreak of Ebola to date is currently underway in West Africa, with 3944 cases reported as of 5th September 2014. To develop a better understanding of Ebola transmission dynamics, we revisited data from the first known Ebola outbreak, which occurred in 1976 in Zaire (now Democratic Republic of Congo). By fitting a mathematical model to time series stratified by disease onset, outcome and source of infection, we were able to estimate several epidemiological quantities that have previously proved challenging to measure, including the contribution of hospital and community infection to transmission. We found evidence that transmission decreased considerably before the closure of the hospital, suggesting that the decline of the outbreak was most likely the result of changes in host behaviour. Our analysis suggests that the person-to-person reproduction number was 1.34 (95% CI: 0.92-2.11) in the early part of the outbreak. Using stochastic simulations we demonstrate that the same epidemiological conditions that were present in 1976 could have generated a large outbreak purely by chance. At the same time, the relatively high person-to-person basic reproduction number suggests that Ebola would have been difficult to control through hospital-based infection control measures alone. PMID:25480136

  12. Potential for large outbreaks of Ebola virus disease

    PubMed Central

    Camacho, A.; Kucharski, A.J.; Funk, S.; Breman, J.; Piot, P.; Edmunds, W.J.

    2014-01-01

    Outbreaks of Ebola virus can cause substantial morbidity and mortality in affected regions. The largest outbreak of Ebola to date is currently underway in West Africa, with 3944 cases reported as of 5th September 2014. To develop a better understanding of Ebola transmission dynamics, we revisited data from the first known Ebola outbreak, which occurred in 1976 in Zaire (now Democratic Republic of Congo). By fitting a mathematical model to time series stratified by disease onset, outcome and source of infection, we were able to estimate several epidemiological quantities that have previously proved challenging to measure, including the contribution of hospital and community infection to transmission. We found evidence that transmission decreased considerably before the closure of the hospital, suggesting that the decline of the outbreak was most likely the result of changes in host behaviour. Our analysis suggests that the person-to-person reproduction number was 1.34 (95% CI: 0.92–2.11) in the early part of the outbreak. Using stochastic simulations we demonstrate that the same epidemiological conditions that were present in 1976 could have generated a large outbreak purely by chance. At the same time, the relatively high person-to-person basic reproduction number suggests that Ebola would have been difficult to control through hospital-based infection control measures alone. PMID:25480136

  13. Isolation and phylogenetic characterization of Ebola viruses causing different outbreaks in Gabon.

    PubMed Central

    Georges-Courbot, M. C.; Sanchez, A.; Lu, C. Y.; Baize, S.; Leroy, E.; Lansout-Soukate, J.; Tévi-Bénissan, C.; Georges, A. J.; Trappier, S. G.; Zaki, S. R.; Swanepoel, R.; Leman, P. A.; Rollin, P. E.; Peters, C. J.; Nichol, S. T.; Ksiazek, T. G.

    1997-01-01

    Three outbreaks of Ebola hemorrhagic fever have recently occurred in Gabon. Virus has been isolated from clinical materials from all three outbreaks, and nucleotide sequence analysis of the glycoprotein gene of the isolates and virus present in clinical samples has been carried out. These data indicate that each of the three outbreaks should be considered an independent emergence of a different Ebola virus of the Zaire subtype. As in earlier Ebola virus outbreaks, no genetic variability was detected between virus samples taken during an individual outbreak. PMID:9126445

  14. Current knowledge on lower virulence of Reston Ebola virus (in French: Connaissances actuelles sur la moindre virulence du virus Ebola Reston)

    Microsoft Academic Search

    Shigeru Morikawa; Masayuki Saijo; Ichiro Kurane

    2007-01-01

    Ebola viruses (EBOV) and Marburg virus belong to the family Filoviridae, order Mononegavirales. The genus Ebolavirus consists of four species: Zaire ebolavirus (ZEBOV), Sudan ebolavirus (SEBOV), Ivory Coast ebolavirus (ICEBOV) and Reston ebolavirus (REBOV). Three species of ebolaviruses, ZEBOV, SEBOV, ICEBOV, and Marburg virus are known to be extremely pathogenic in primates and humans and cause severe hemorrhagic fever leading

  15. Development and Evaluation of a Fluorogenic 5 Nuclease Assay To Detect and Differentiate between Ebola Virus Subtypes Zaire and Sudan

    Microsoft Academic Search

    TAMMY R. GIBB; DAVID A. NORWOOD; NEAL WOOLLEN; ERIK A. HENCHAL; Fort Detrick

    2001-01-01

    The ability to rapidly recognize Ebola virus infections is critical to quickly limit further spread of the disease. A rapid, sensitive, and specific laboratory diagnostic test is needed to confirm outbreaks of Ebola virus infection and to distinguish it from other diseases that can cause similar clinical symptoms. A one-tube reverse transcription-PCR assay for the identification of Ebola virus subtype

  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. Role of Ebola Virus Secreted Glycoproteins and Virus-Like Particles in Activation of Human Macrophages

    Microsoft Academic Search

    Victoria Wahl-Jensen; Sabine K. Kurz; Paul R. Hazelton; Hans-Joachim Schnittler; Ute Stroher; Dennis R. Burton; Heinz Feldmann

    2005-01-01

    Ebola virus, a member of the family Filoviridae, causes one of the most severe forms of viral hemorrhagic fever. In the terminal stages of disease, symptoms progress to hypotension, coagulation disorders, and hemorrhages, and there is prominent involvement of the mononuclear phagocytic and reticuloendothelial systems. Cells of the mononuclear phagocytic system are primary target cells and producers of inflammatory mediators.

  18. BRIEF REPORT High-Dose Mannose-Binding Lectin Therapy for Ebola Virus Infection

    E-print Network

    Ian C. Michelow; Calli Lear; Corinne Scully; Laura I. Prugar; B. Longley; L. Michael Yantosca; Xin Ji; Marshall Karpel; Matthew Brudner; Kazue Takahashi; Gregory T. Spear; R. Alan; B. Ezekowitz; Emmett V. Schmidt; Department Of Pediatrics

    2010-01-01

    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>7fold above average human levels survived otherwise fatal Ebola virus infections and became immune to

  19. LEPTOSPIROSIS AND EBOLA VIRUS INFECTION IN FIVE GOLD-PANNING VILLAGES IN NORTHEASTERN GABON

    E-print Network

    Eric Bertherat; Andre Renaut; Rene Nabias; Guy Dubreuil; Marie-claude Georges-courbot

    Abstract. An exhaustive epidemiologic and serologic survey was carried out in five gold-panning villages situated in northeastern Gabon to estimate the degree of exposure of to leptospirosis and Ebola virus. The seroprevalence was 15.7 % for leptospirosis and 10.2 % for Ebola virus. Sixty years

  20. Production and characterization of monoclonal antibodies against different epitopes of Ebola virus antigens

    Microsoft Academic Search

    Soraya Shahhosseini; Dipankar Das; Xiangguo Qiu; Heinz Feldmann; Steven M. Jones; Mavanur R Suresh

    2007-01-01

    Ebola virus (EBOV) causes hemorrhagic fever in humans and nonhuman primates with up to 90% mortality rate. In this study, Ebola virus like particles (EVLPs) and the aglycosyl subfragment of glycoprotein (GP(1) subfragment D) were used to generate monoclonal antibodies (MAbs) against different epitopes of the viral antigens. Such MAbs could be useful in diagnostics and potential therapeutics of viral

  1. 996. Development of an siRNA Based Therapy for Ebola Virus Infection

    Microsoft Academic Search

    Thomas W. Geisbert; Lisa E. Hensley; Kristopher M. Curtis; Joan B. Geisbert; Kathleen M. Daddario; Elliott Kagan; Amy C. H. Lee; Lorne Palmer; Lloyd Jeffs; Ian MacLachlan

    2005-01-01

    Ebola virus infection causes a severe and frequently fatal hemorrhagic fever that is refractory to treatment with currently available antiviral therapeutics. Ebola and the related Marburg virus are of concern as potential bioweapon (BW) threats since they have the potential for aerosol dissemination and weaponization. RNA interference (RNAi) represents a powerful, naturally occurring biological strategy for inhibition of gene expression

  2. Ebola Virus Selectively Inhibits Responses to Interferons, but Not to Interleukin1b, in Endothelial Cells

    Microsoft Academic Search

    BRIAN H. HARCOURT; ANTHONY SANCHEZ; MARGARET K. OFFERMANN

    1999-01-01

    Ebola virus infection is highly lethal and leads to severe immunosuppression. In this study, we demonstrate that infection of human umbilical vein endothelial cells (HUVECs) with Ebola virus Zaire (EZ) suppressed basal expression of the major histocompatibility complex class I (MHC I) family of proteins and inhibited the induction of multiple genes by alpha interferon (IFN-a) and IFN-g, including those

  3. Ebola virus infection in guinea pigs: presumable role of granulomatous inflammation in pathogenesis

    Microsoft Academic Search

    E. Ryabchikova; L. Kolesnikova; M. Smolina; V. Tkachev; L. Pereboeva; S. Baranova; A. Grazhdantseva; Y. Rassadkin

    1996-01-01

    Summary An approach combining virology with light and electron microscopy was used to study the organs of guinea pigs during nine serial passages of Ebola virus, strain Zaire. It was observed that the wild type of Ebola virus causes severe granulomatous inflammation in the liver and reproduces in the cells of the mononuclear phagocyte system (MPS). Based on morphological characterization,

  4. Characterization of the L gene and 5« trailer region of Ebola virus

    Microsoft Academic Search

    Viktor E. Volchkov; Valentina A. Volchkova; Alexandr A. Chepurnov; Vladimir M. Blinov; Olga Dolnik; Sergej V. Netesov; Heinz Feldmann

    1999-01-01

    The nucleotide sequences of the L gene and 5« trailer region of Ebola virus strain Mayinga (subtype Zaire) have been determined, thus completing the sequence of the Ebola virus genome. The putative transcription start signal of the L gene was identical to the determined 5« terminus of the L mRNA (5« GAGGAAGAUUAA) and showed a high degree of similarity to

  5. A DNA Vaccine for Ebola Virus Is Safe and Immunogenic in a Phase I Clinical Trial

    Microsoft Academic Search

    Julie E. Martin; Nancy J. Sullivan; Mary E. Enama; Ingelise J. Gordon; Mario Roederer; Richard A. Koup; Robert T. Bailer; Bimal K. Chakrabarti; Michael A. Bailey; Phillip L. Gomez; Charla A. Andrews; Zoe Moodie; Lin Gu; Judith A. Stein; Gary J. Nabel; Barney S. Graham

    2006-01-01

    Ebola viruses represent a class of filoviruses that causes severe hemorrhagic fever with high mortality. Recognized first in 1976 in the Democratic Republic of Congo, outbreaks continue to occur in equatorial Africa. A safe and effective Ebola virus vaccine is needed because of its continued emergence and its potential for use for biodefense. We report the safety and immunogenicity of

  6. 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

  7. 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

  8. Complete Genome Sequences of Three Ebola Virus Isolates from the 2014 Outbreak in West Africa

    PubMed Central

    Groseth, A.; Feldmann, F.; Marzi, A.; Ebihara, H.; Kobinger, G.; Günther, S.

    2014-01-01

    Here, we report the complete genome sequences, including the genome termini, of three Ebola virus isolates (species Zaire ebolavirus) originating from Guinea that are now being widely used in laboratories in North America for research regarding West African Ebola viruses. PMID:25523781

  9. 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

  10. 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

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

    PubMed Central

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

    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 Ebola virus with an altered furin recognition motif in the glycoprotein (GP). When expressed in cells, the GP of the wild type, but not of the mutant, virus was cleaved into GP1 and GP2. Although posttranslational furin-mediated cleavage of GP was thought to be an essential step in Ebola virus infection, generation of a viable mutant Ebola virus lacking a furin recognition motif in the GP cleavage site demonstrates that GP cleavage is not essential for replication of Ebola virus in cell culture. PMID:11739705

  12. Host IQGAP1 and Ebola Virus VP40 Interactions Facilitate Virus-Like Particle Egress

    PubMed Central

    Lu, Jianhong; Qu, Yonggang; Liu, Yuliang; Jambusaria, Rakesh; Han, Ziying; Ruthel, Gordon; Freedman, Bruce D.

    2013-01-01

    We have identified host IQGAP1 as an interacting partner for Ebola virus (EBOV) VP40, and its expression is required for EBOV VP40 virus-like particle (VLP) budding. IQGAP1 is involved in actin cytoskeletal remodeling during cell migration and formation of filopodia. The physical interaction and the functional requirement for IQGAP1 in EBOV VP40 VLP egress link virus budding to the cytoskeletal remodeling machinery. Consequently, this interaction represents a novel target for development of therapeutics to block budding and transmission of filoviruses. PMID:23637409

  13. Management of pregnant women infected with Ebola virus in a treatment centre in Guinea, June 2014.

    PubMed

    Baggi, F M; Taybi, A; Kurth, A; Van Herp, M; Di Caro, A; Wölfel, R; Günther, S; Decroo, T; Declerck, H; Jonckheere, S

    2014-01-01

    We report two cases of confirmed Ebola virus disease in pregnant women, who presented at the Médecins Sans Frontières Ebola treatment centre in Guéckédou. Despite the very high risk of death, both pregnant women survived. In both cases the critical decision was made to induce vaginal delivery. We raise a number of considerations regarding the management of Ebola virus-infected pregnant women, including the place of amniocentesis and induced delivery, and whether certain invasive medical acts are justified. PMID:25523968

  14. A Serological Survey of Ebola Virus Infection in Central African Nonhuman Primates

    Microsoft Academic Search

    P. Telfer; B. Kumulungui; P. Yaba; P. Rouquet; P. Roques; E. Nerrienet

    2004-01-01

    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

  15. Phosphoinositide-3 Kinase-Akt Pathway Controls Cellular Entry of Ebola Virus

    PubMed Central

    Saeed, Mohammad F.; Kolokoltsov, Andrey A.; Freiberg, Alexander N.; Holbrook, Michael R.; Davey, Robert A.

    2008-01-01

    The phosphoinositide-3 kinase (PI3K) pathway regulates diverse cellular activities related to cell growth, migration, survival, and vesicular trafficking. It is known that Ebola virus requires endocytosis to establish an infection. However, the cellular signals that mediate this uptake were unknown for Ebola virus as well as many other viruses. Here, the involvement of PI3K in Ebola virus entry was studied. A novel and critical role of the PI3K signaling pathway was demonstrated in cell entry of Zaire Ebola virus (ZEBOV). Inhibitors of PI3K and Akt significantly reduced infection by ZEBOV at an early step during the replication cycle. Furthermore, phosphorylation of Akt-1 was induced shortly after exposure of cells to radiation-inactivated ZEBOV, indicating that the virus actively induces the PI3K pathway and that replication was not required for this induction. Subsequent use of pseudotyped Ebola virus and/or Ebola virus-like particles, in a novel virus entry assay, provided evidence that activity of PI3K/Akt is required at the virus entry step. Class 1A PI3Ks appear to play a predominant role in regulating ZEBOV entry, and Rac1 is a key downstream effector in this regulatory cascade. Confocal imaging of fluorescently labeled ZEBOV indicated that inhibition of PI3K, Akt, or Rac1 disrupted normal uptake of virus particles into cells and resulted in aberrant accumulation of virus into a cytosolic compartment that was non-permissive for membrane fusion. We conclude that PI3K-mediated signaling plays an important role in regulating vesicular trafficking of ZEBOV necessary for cell entry. Disruption of this signaling leads to inappropriate trafficking within the cell and a block in steps leading to membrane fusion. These findings extend our current understanding of Ebola virus entry mechanism and may help in devising useful new strategies for treatment of Ebola virus infection. PMID:18769720

  16. Evaluation in Nonhuman Primates of Vaccines against Ebola Virus

    PubMed Central

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

    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 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

  17. Prospects for immunisation against Marburg and Ebola viruses

    PubMed Central

    Geisbert, Thomas W.; Bausch, Daniel G.; Feldmann, Heinz

    2012-01-01

    SUMMARY For more than 30 years the filoviruses, Marburg virus and Ebola virus, have been associated with periodic outbreaks of hemorrhagic fever that produce severe and often fatal disease. The filoviruses are endemic primarily in resource-poor regions in Central Africa and are also potential agents of bioterrorism. Although no vaccines or antiviral drugs for Marburg or Ebola are currently available, remarkable progress has been made over the last decade in developing candidate preventive vaccines against filoviruses in nonhuman primate models. Due to the generally remote locations of filovirus outbreaks, a single-injection vaccine is desirable. Among the prospective vaccines that have shown efficacy in nonhuman primate models of filoviral hemorrhagic fever, two candidates, one based on a replication-defective adenovirus serotype 5 and the other on a recombinant VSV (rVSV), were shown to provide complete protection to nonhuman primates when administered as a single injection. The rVSV-based vaccine has also shown utility when administered for postexposure prophylaxis against filovirus infections. A VSV-based Ebola vaccine was recently used to manage a potential laboratory exposure. PMID:20658513

  18. Single-Injection Vaccine Protects Nonhuman Primates against Infection with Marburg Virus and Three Species of Ebola Virus

    Microsoft Academic Search

    Thomas W. Geisbert; Joan B. Geisbert; Anders Leung; Kathleen M. Daddario-DiCaprio; Lisa E. Hensley; Allen Grolla; Heinz Feldmann

    2009-01-01

    The filoviruses Marburg virus and Ebola virus cause severe hemorrhagic fever with high mortality in humans and nonhuman primates. Among the most promising filovirus vaccines under development is a system based on recombinant vesicular stomatitis virus (VSV) that expresses a single filovirus glycoprotein (GP) in place of the VSV glycoprotein (G). Here, we performed a proof-of-concept study in order to

  19. 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

  20. Therapy of Ebola and Marburg virus infections

    Microsoft Academic Search

    Mike Bray

    The filoviruses, Marburg and Ebola, cause fulminant hemorrhagic fever in humans and nonhuman primates. The agents replicate to high titer in macrophages and dendritic cells, suppressing type I interferon responses, and disseminate to these and other cell types in tissues throughout the body, causing extensive necrosis and inducing an intense systemic inflammatory response resembling septic shock. Effective therapies are urgently

  1. 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

  2. Ebola virus disease: roles and considerations for pharmacists.

    PubMed

    Guarascio, Anthony J; Faust, Andrew C; Sheperd, Lyndsay; O'Donnell, Lauren A

    2015-02-01

    Ebola virus disease (EVD) poses significant clinical care implications for pharmacists. Emergency preparedness efforts should be undertaken to ensure vital response to EVD. Pharmacists should consider factors such as enhanced use of resources for front-line EVD patient care along with procurement of investigational medications. Appropriate and timely preparation, distribution, and administration of treatment for patients with EVD in the setting of substantial critical illness as well as infection control measures are essential. Aggressive supportive care and early, goal-directed therapy are cornerstones of therapy, whereas investigational treatments for EVD will likely play a larger, more well-defined role as future clinical trials are conducted. PMID:25429092

  3. 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

  4. Serological Evidence of Ebola Virus Infection in Indonesian Orangutans

    PubMed Central

    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

  5. Application of real-time PCR for testing antiviral compounds against Lassa virus, SARS coronavirus and Ebola virus in vitro

    Microsoft Academic Search

    Stephan Günther; Marcel Asper; Christina Röser; Luciano K. S. Luna; Christian Drosten; Beate Becker-Ziaja; Peter Borowski; Huan-Ming Chen; Ramachandra S. Hosmane

    2004-01-01

    This report describes the application of real-time PCR for testing antivirals against highly pathogenic viruses such as Lassa virus, SARS coronavirus and Ebola virus. The test combines classical cell culture with a quantitative real-time PCR read-out. The assay for Lassa virus was validated with ribavirin, which showed an IC50 of 9?g\\/ml. Small-scale screening identified a class of imidazole nucleoside\\/nucleotide analogues

  6. 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

  7. 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

  8. 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

  9. Virtual screen for repurposing approved and experimental drugs for candidate inhibitors of EBOLA virus infection

    PubMed Central

    Veljkovic, Veljko; Loiseau, Philippe M.; Figadere, Bruno; Glisic, Sanja; Veljkovic, Nevena; Perovic, Vladimir R.; Cavanaugh, David P.; Branch, Donald R.

    2015-01-01

    The ongoing Ebola virus epidemic has presented numerous challenges with respect to control and treatment because there are no approved drugs or vaccines for the Ebola virus disease (EVD). Herein is proposed simple theoretical criterion for fast virtual screening of molecular libraries for candidate inhibitors of Ebola virus infection. We performed a repurposing screen of 6438 drugs from DrugBank using this criterion and selected 267 approved and 382 experimental drugs as candidates for treatment of EVD including 15 anti-malarial drugs and 32 antibiotics. An open source Web server allowing screening of molecular libraries for candidate drugs for treatment of EVD was also established. PMID:25717373

  10. Virtual screen for repurposing approved and experimental drugs for candidate inhibitors of EBOLA virus infection.

    PubMed

    Veljkovic, Veljko; Loiseau, Philippe M; Figadere, Bruno; Glisic, Sanja; Veljkovic, Nevena; Perovic, Vladimir R; Cavanaugh, David P; Branch, Donald R

    2015-01-01

    The ongoing Ebola virus epidemic has presented numerous challenges with respect to control and treatment because there are no approved drugs or vaccines for the Ebola virus disease (EVD). Herein is proposed simple theoretical criterion for fast virtual screening of molecular libraries for candidate inhibitors of Ebola virus infection. We performed a repurposing screen of 6438 drugs from DrugBank using this criterion and selected 267 approved and 382 experimental drugs as candidates for treatment of EVD including 15 anti-malarial drugs and 32 antibiotics. An open source Web server allowing screening of molecular libraries for candidate drugs for treatment of EVD was also established. PMID:25717373

  11. A paramyxovirus-vectored intranasal vaccine against Ebola virus is immunogenic in vector-immune animals

    Microsoft Academic Search

    Lijuan Yang; Anthony Sanchez; Jerrold M. Ward; Brian R. Murphy; Peter L. Collins; Alexander Bukreyev

    2008-01-01

    Ebola virus (EBOV) causes outbreaks of a highly lethal hemorrhagic fever in humans. The virus can be transmitted by direct contact as well as by aerosol and is considered a potential bioweapon. Because direct immunization of the respiratory tract should be particularly effective against infection of mucosal surfaces, we previously developed an intranasal vaccine based on replication-competent human parainfluenza virus

  12. 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-?

  13. 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

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

    PubMed Central

    Pigott, David M; Golding, Nick; Mylne, Adrian; Huang, Zhi; Henry, Andrew J; Weiss, Daniel J; Brady, Oliver J; Kraemer, Moritz UG; 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. DOI: http://dx.doi.org/10.7554/eLife.04395.001 PMID:25201877

  15. Euthanasia Assessment in Ebola Virus Infected Nonhuman Primates

    PubMed Central

    Warren, Travis K.; Trefry, John C.; Marko, Shannon T.; Chance, Taylor B.; Wells, Jay B.; Pratt, William D.; Johnson, Joshua C.; Mucker, Eric M.; Norris, Sarah L.; Chappell, Mark; Dye, John M.; Honko, Anna N.

    2014-01-01

    Multiple products are being developed for use against filoviral infections. Efficacy for these products will likely be demonstrated in nonhuman primate models of filoviral disease to satisfy licensure requirements under the Animal Rule, or to supplement human data. Typically, the endpoint for efficacy assessment will be survival following challenge; however, there exists no standardized approach for assessing the health or euthanasia criteria for filovirus-exposed nonhuman primates. Consideration of objective criteria is important to (a) ensure test subjects are euthanized without unnecessary distress; (b) enhance the likelihood that animals exhibiting mild or moderate signs of disease are not prematurely euthanized; (c) minimize the occurrence of spontaneous deaths and loss of end-stage samples; (d) enhance the reproducibility of experiments between different researchers; and (e) provide a defensible rationale for euthanasia decisions that withstands regulatory scrutiny. Historic records were compiled for 58 surviving and non-surviving monkeys exposed to Ebola virus at the US Army Medical Research Institute of Infectious Diseases. Clinical pathology parameters were statistically analyzed and those exhibiting predicative value for survival are reported. These findings may be useful for standardization of objective euthanasia assessments in rhesus monkeys exposed to Ebola virus and may serve as a useful approach for other standardization efforts. PMID:25421892

  16. 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

  17. Euthanasia assessment in ebola virus infected nonhuman primates.

    PubMed

    Warren, Travis K; Trefry, John C; Marko, Shannon T; Chance, Taylor B; Wells, Jay B; Pratt, William D; Johnson, Joshua C; Mucker, Eric M; Norris, Sarah L; Chappell, Mark; Dye, John M; Honko, Anna N

    2014-11-01

    Multiple products are being developed for use against filoviral infections. Efficacy for these products will likely be demonstrated in nonhuman primate models of filoviral disease to satisfy licensure requirements under the Animal Rule, or to supplement human data. Typically, the endpoint for efficacy assessment will be survival following challenge; however, there exists no standardized approach for assessing the health or euthanasia criteria for filovirus-exposed nonhuman primates. Consideration of objective criteria is important to (a) ensure test subjects are euthanized without unnecessary distress; (b) enhance the likelihood that animals exhibiting mild or moderate signs of disease are not prematurely euthanized; (c) minimize the occurrence of spontaneous deaths and loss of end-stage samples; (d) enhance the reproducibility of experiments between different researchers; and (e) provide a defensible rationale for euthanasia decisions that withstands regulatory scrutiny. Historic records were compiled for 58 surviving and non-surviving monkeys exposed to Ebola virus at the US Army Medical Research Institute of Infectious Diseases. Clinical pathology parameters were statistically analyzed and those exhibiting predicative value for survival are reported. These findings may be useful for standardization of objective euthanasia assessments in rhesus monkeys exposed to Ebola virus and may serve as a useful approach for other standardization efforts. PMID:25421892

  18. The Cytoprotective Enzyme Heme Oxygenase-1 Suppresses Ebola Virus Replication

    PubMed Central

    Hill-Batorski, Lindsay; Halfmann, Peter; Neumann, Gabriele

    2013-01-01

    Ebola virus (EBOV) is the causative agent of a severe hemorrhagic fever in humans with reported case fatality rates as high as 90%. There are currently no licensed vaccines or antiviral therapeutics to combat EBOV infections. Heme oxygenase-1 (HO-1), an enzyme that catalyzes the rate-limiting step in heme degradation, has antioxidative properties and protects cells from various stresses. Activated HO-1 was recently shown to have antiviral activity, potently inhibiting the replication of viruses such as hepatitis C virus and human immunodeficiency virus. However, the effect of HO-1 activation on EBOV replication remains unknown. To determine whether the upregulation of HO-1 attenuates EBOV replication, we treated cells with cobalt protoporphyrin (CoPP), a selective HO-1 inducer, and assessed its effects on EBOV replication. We found that CoPP treatment, pre- and postinfection, significantly suppressed EBOV replication in a manner dependent upon HO-1 upregulation and activity. In addition, stable overexpression of HO-1 significantly attenuated EBOV growth. Although the exact mechanism behind the antiviral properties of HO-1 remains to be elucidated, our data show that HO-1 upregulation does not attenuate EBOV entry or budding but specifically targets EBOV transcription/replication. Therefore, modulation of the cellular enzyme HO-1 may represent a novel therapeutic strategy against EBOV infection. PMID:24109237

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

    PubMed

    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

  20. A systems view and lessons from the ongoing Ebola Virus Disease (EVD) outbreak in West Africa.

    PubMed

    Agyepong, I A

    2014-09-01

    This article analyses the on-going (2014) Ebola Virus Disease (EVD) outbreak in West Africa from a systems perspective; and draws out lessons for West Africa in general and Ghana in particular. PMID:25709128

  1. 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

  2. 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

  3. 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

  4. Commentary Reemergence of Ebola Virus in Africa Members of the family Filoviridae, which currently

    E-print Network

    Consists Of Ebola; Marburg Viruses

    severe and often fatal hemorrhagic fevers in humans and nonhuman primates. The recent isolation and identification of a new Ebola virus from a single nonfatal human case in Côte d’Ivoire (1) and the more recent outbreak of Ebola hemorrhagic fever in and around Kikwit, Zaire (2, 3), have raised

  5. 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

  6. Ebola virus disease in mice with transplanted human hematopoietic stem cells.

    PubMed

    Lüdtke, Anja; Oestereich, Lisa; Ruibal, Paula; Wurr, Stephanie; Pallasch, Elisa; Bockholt, Sabrina; Ip, Wing Hang; Rieger, Toni; Gómez-Medina, Sergio; Stocking, Carol; Rodríguez, Estefanía; Günther, Stephan; Muñoz-Fontela, César

    2015-04-15

    The development of treatments for Ebola virus disease (EVD) has been hampered by the lack of small-animal models that mimick human disease. Here we show that mice with transplanted human hematopoetic stem cells reproduce features typical of EVD. Infection with Ebola virus was associated with viremia, cell damage, liver steatosis, signs of hemorrhage, and high lethality. Our study provides a small-animal model with human components for the development of EVD therapies. PMID:25673711

  7. LEPTOSPIROSIS AND EBOLA VIRUS INFECTION IN FIVE GOLD-PANNING VILLAGES IN NORTHEASTERN GABON

    Microsoft Academic Search

    ERIC BERTHERAT; ANDRE RENAUT; RENE NABIAS; GUY DUBREUIL; MARIE-CLAUDE GEORGES-COURBOT

    1999-01-01

    An exhaustive epidemiologic and serologic survey was carried out in five gold-panning villages situated in northeastern Gabon to estimate the degree of exposure of to leptospirosis and Ebola virus. The seroprevalence was 15.7% for leptospirosis and 10.2% for Ebola virus. Sixty years after the last seroepidemiologic survey of leptospirosis in Gabon, this study demonstrates the persistence of this infection among

  8. Ebola Virus Does Not Block Apoptotic Signaling Pathways

    PubMed Central

    Olejnik, Judith; Alonso, Jesus; Schmidt, Kristina M.; Yan, Zhen; Wang, Wei; Marzi, Andrea; Ebihara, Hideki; Yang, Jinghua; Patterson, Jean L.; Ryabchikova, Elena

    2013-01-01

    Since viruses rely on functional cellular machinery for efficient propagation, apoptosis is an important mechanism to fight viral infections. In this study, we sought to determine the mechanism of cell death caused by Ebola virus (EBOV) infection by assaying for multiple stages of apoptosis and hallmarks of necrosis. Our data indicate that EBOV does not induce apoptosis in infected cells but rather leads to a nonapoptotic form of cell death. Ultrastructural analysis confirmed necrotic cell death of EBOV-infected cells. To investigate if EBOV blocks the induction of apoptosis, infected cells were treated with different apoptosis-inducing agents. Surprisingly, EBOV-infected cells remained sensitive to apoptosis induced by external stimuli. Neither receptor- nor mitochondrion-mediated apoptosis signaling was inhibited in EBOV infection. Although double-stranded RNA (dsRNA)-induced activation of protein kinase R (PKR) was blocked in EBOV-infected cells, induction of apoptosis mediated by dsRNA was not suppressed. When EBOV-infected cells were treated with dsRNA-dependent caspase recruiter (dsCARE), an antiviral protein that selectively induces apoptosis in cells containing dsRNA, virus titers were strongly reduced. These data show that the inability of EBOV to block apoptotic pathways may open up new strategies toward the development of antiviral therapeutics. PMID:23468487

  9. 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

  10. 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.

  11. Release of cellular proteases into the acidic extracellular milieu exacerbates Ebola virus-induced cell damage.

    PubMed

    Barrientos, Laura G; Rollin, Pierre E

    2007-02-01

    Ebola virus is highly cytopathic through mechanisms that are largely unknown. We present evidence that progressive acidification of the extracellular milieu by Ebola virus-infected cells combined with reduced levels of natural cysteine protease inhibitor makes the cells vulnerable to uncontrolled proteolysis of extracellular matrix components by released active endosomal cathepsins, thereby exacerbating Ebola virus-induced cell destruction. The cell surface microenvironment was shown to be crucial in aiding this activity. Blocking the proteolytic activity with the cathepsin inhibitor E64 resulted in remarkable improvements with respect to viral cytopathicity and cell survival despite an overwhelmingly high viral load. We propose that the observed enzymatic matrix degradation, enhanced by an associated protease/inhibitor imbalance and metabolic acidosis, represents an effective viral strategy to boost infection and underlies, in part, the remarkable pathogenesis caused by Ebola virus. Further in vitro and in vivo research will establish whether a cellular protease with hemorrhagic activity is the leading cause of vascular leakage-the hallmark of Ebola virus hemorrhagic fever-and help understand the Ebola virus caused cell death. PMID:16982079

  12. Being Ready to Treat Ebola Virus Disease Patients

    PubMed Central

    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.

    2015-01-01

    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

  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. 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

  15. Ebola Virus Matrix Protein VP40 Interaction with Human Cellular Factors Tsg101 and Nedd4

    Microsoft Academic Search

    Joanna Timmins; Guy Schoehn; Sylvie Ricard-Blum; Sandra Scianimanico; Thierry Vernet; Rob W. H Ruigrok; Winfried Weissenhorn

    2003-01-01

    The Ebola virus matrix protein VP40 is a major viral structural protein and plays a central role in virus assembly and budding at the plasma membrane of infected cells. For efficient budding, a full amino terminus of VP40 is required, which includes a PPXY and a PT\\/SAP motif, both of which have been proposed to interact with cellular proteins. Here,

  16. Printed in Great Britain 333 Ebola Virus: Identification of Virion Structural Proteins

    E-print Network

    Michael P. K Iley; Russell L. Regnery; Karl; M. Johnson

    Polyacrylamide g l electrophoresis of purified Ebola virus revealed the presence of four major virion structural proteins which we have designated VPI, VP2, VP3 and VP4. Vesicular stomatitis virus (VSV) proteins were used as mol. wt. markers, and the virion proteins were found to have tool. wt. of

  17. Dispatches Isolation and Phylogenetic Characterization of Ebola Viruses Causing Different Outbreaks in Gabon

    E-print Network

    unknown authors

    Three outbreaks of Ebola hemorrhagic fever have recently occurred in Gabon. Virus has been isolated from clinical materials from all three outbreaks, and nucleotide sequence analysis of the glycoprotein gene of the isolates and virus present in clinical samples has been carried out. These data

  18. Isolation and Phylogenetic Characterization of Ebola Viruses Causing Different Outbreaks in Gabon

    Microsoft Academic Search

    1997-01-01

    Three outbreaks of Ebola hemorrhagic fever have recently occurred in Gabon. Virus has been isolated from clinical materials from all three outbreaks, and nucleotide sequence analysis of the glycoprotein gene of the isolates and virus present in clinical samples has been carried out. These data indicate that each of the three outbreaks should be considered an independent emergence of a

  19. 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

  20. Ebola Zaire Virus Blocks Type I Interferon Production by Exploiting the Host SUMO Modification Machinery

    Microsoft Academic Search

    Tsung-Hsien Chang; Toru Kubota; Mayumi Matsuoka; Steven Jones; Steven B. Bradfute; Mike Bray; Keiko Ozato

    2009-01-01

    Ebola Zaire virus is highly pathogenic for humans, with case fatality rates approaching 90% in large outbreaks in Africa. The virus replicates in macrophages and dendritic cells (DCs), suppressing production of type I interferons (IFNs) while inducing the release of large quantities of proinflammatory cytokines. Although the viral VP35 protein has been shown to inhibit IFN responses, the mechanism by

  1. 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

  2. Ebola Virus Disease: Essential Public Health Principles for Clinicians

    PubMed Central

    Koenig, Kristi L.; Majestic, Cassondra; Burns, Michael J.

    2014-01-01

    Ebola Virus Disease (EVD) has become a public health emergency of international concern. The World Health Organization and Centers for Disease Control and Prevention have developed guidance to educate and inform healthcare workers and travelers worldwide. Symptoms of EVD include abrupt onset of fever, myalgias, and headache in the early phase, followed by vomiting, diarrhea and possible progression to hemorrhagic rash, life-threatening bleeding, and multi-organ failure in the later phase. The disease is not transmitted via airborne spread like influenza, but rather from person-to-person, or animal to person, via direct contact with bodily fluids or blood. It is crucial that emergency physicians be educated on disease presentation and how to generate a timely and accurate differential diagnosis that includes exotic diseases in the appropriate patient population. A patient should be evaluated for EVD when both suggestive symptoms, including unexplained hemorrhage, AND risk factors within 3 weeks prior, such as travel to an endemic area, direct handling of animals from outbreak areas, or ingestion of fruit or other uncooked foods contaminated with bat feces containing the virus are present. There are experimental therapies for treatment of EVD virus; however the mainstay of therapy is supportive care. Emergency department personnel on the frontlines must be prepared to rapidly identify and isolate febrile travelers if indicated. All healthcare workers involved in care of EVD patients should wear personal protective equipment. Despite the intense media focus on EVD rather than other threats, emergency physicians must master and follow essential public health principles for management of all infectious diseases. This includes not only identification and treatment of individuals, but also protection of healthcare workers and prevention of spread, keeping in mind the possibility of other more common disease processes. PMID:25493109

  3. 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

  4. Evasion of interferon responses by Ebola and Marburg viruses.

    PubMed

    Basler, Christopher F; Amarasinghe, Gaya K

    2009-09-01

    The filoviruses, Ebola virus (EBOV) and Marburg virus (MARV), cause frequently lethal viral hemorrhagic fever. These infections induce potent cytokine production, yet these host responses fail to prevent systemic virus replication. Consistent with this, filoviruses have been found to encode proteins VP35 and VP24 that block host interferon (IFN)-alpha/beta production and inhibit signaling downstream of the IFN-alpha/beta and the IFN-gamma receptors, respectively. VP35, which is a component of the viral nucleocapsid complex and plays an essential role in viral RNA synthesis, acts as a pseudosubstrate for the cellular kinases IKK-epsilon and TBK-1, which phosphorylate and activate interferon regulatory factor 3 (IRF-3) and interferon regulatory factor 7 (IRF-7). VP35 also promotes SUMOylation of IRF-7, repressing IFN gene transcription. In addition, VP35 is a dsRNA-binding protein, and mutations that disrupt dsRNA binding impair VP35 IFN-antagonist activity while leaving its RNA replication functions intact. The phenotypes of recombinant EBOV bearing mutant VP35s unable to inhibit IFN-alpha/beta demonstrate that VP35 IFN-antagonist activity is critical for full virulence of these lethal pathogens. The structure of the VP35 dsRNA-binding domain, which has recently become available, is expected to provide insight into how VP35 IFN-antagonist and dsRNA-binding functions are related. The EBOV VP24 protein inhibits IFN signaling through an interaction with select host cell karyopherin-alpha proteins, preventing the nuclear import of otherwise activated STAT1. It remains to be determined to what extent VP24 may also modulate the nuclear import of other host cell factors and to what extent this may influence the outcome of infection. Notably, the Marburg virus VP24 protein does not detectably block STAT1 nuclear import, and, unlike EBOV, MARV infection inhibits STAT1 and STAT2 phosphorylation. Thus, despite their similarities, there are fundamental differences by which these deadly viruses counteract the IFN system. It will be of interest to determine how these differences influence pathogenesis. PMID:19694547

  5. Evasion of Interferon Responses by Ebola and Marburg Viruses

    PubMed Central

    Amarasinghe, Gaya K.

    2009-01-01

    The filoviruses, Ebola virus (EBOV) and Marburg virus (MARV), cause frequently lethal viral hemorrhagic fever. These infections induce potent cytokine production, yet these host responses fail to prevent systemic virus replication. Consistent with this, filoviruses have been found to encode proteins VP35 and VP24 that block host interferon (IFN)-?/? production and inhibit signaling downstream of the IFN-?/? and the IFN-? receptors, respectively. VP35, which is a component of the viral nucleocapsid complex and plays an essential role in viral RNA synthesis, acts as a pseudosubstrate for the cellular kinases IKK-? and TBK-1, which phosphorylate and activate interferon regulatory factor 3 (IRF-3) and interferon regulatory factor 7 (IRF-7). VP35 also promotes SUMOylation of IRF-7, repressing IFN gene transcription. In addition, VP35 is a dsRNA-binding protein, and mutations that disrupt dsRNA binding impair VP35 IFN-antagonist activity while leaving its RNA replication functions intact. The phenotypes of recombinant EBOV bearing mutant VP35s unable to inhibit IFN-?/? demonstrate that VP35 IFN-antagonist activity is critical for full virulence of these lethal pathogens. The structure of the VP35 dsRNA-binding domain, which has recently become available, is expected to provide insight into how VP35 IFN-antagonist and dsRNA-binding functions are related. The EBOV VP24 protein inhibits IFN signaling through an interaction with select host cell karyopherin-? proteins, preventing the nuclear import of otherwise activated STAT1. It remains to be determined to what extent VP24 may also modulate the nuclear import of other host cell factors and to what extent this may influence the outcome of infection. Notably, the Marburg virus VP24 protein does not detectably block STAT1 nuclear import, and, unlike EBOV, MARV infection inhibits STAT1 and STAT2 phosphorylation. Thus, despite their similarities, there are fundamental differences by which these deadly viruses counteract the IFN system. It will be of interest to determine how these differences influence pathogenesis. PMID:19694547

  6. The spatio-temporal distribution dynamics of Ebola virus proteins and RNA in infected cells

    PubMed Central

    Nanbo, Asuka; Watanabe, Shinji; Halfmann, Peter; Kawaoka, Yoshihiro

    2013-01-01

    Here, we used a biologically contained Ebola virus system to characterize the spatio-temporal distribution of Ebola virus proteins and RNA during virus replication. We found that viral nucleoprotein (NP), the polymerase cofactor VP35, the major matrix protein VP40, the transcription activator VP30, and the minor matrix protein VP24 were distributed in cytoplasmic inclusions. These inclusions enlarged near the nucleus, became smaller pieces, and subsequently localized near the plasma membrane. GP was distributed in the cytoplasm and transported to the plasma membrane independent of the other viral proteins. We also found that viral RNA synthesis occurred within the inclusions. Newly synthesized negative-sense RNA was distributed inside the inclusions, whereas positive-sense RNA was distributed both inside and outside. These findings provide useful insights into Ebola virus replication. PMID:23383374

  7. Lipid raft microdomains: a gateway for compartmentalized trafficking of Ebola and Marburg viruses.

    PubMed

    Bavari, Sina; Bosio, Catharine M; Wiegand, Elizabeth; Ruthel, Gordon; Will, Amy B; Geisbert, Thomas W; Hevey, Michael; Schmaljohn, Connie; Schmaljohn, Alan; Aman, M Javad

    2002-03-01

    Spatiotemporal aspects of filovirus entry and release are poorly understood. Lipid rafts act as functional platforms for multiple cellular signaling and trafficking processes. Here, we report the compartmentalization of Ebola and Marburg viral proteins within lipid rafts during viral assembly and budding. Filoviruses released from infected cells incorporated raft-associated molecules, suggesting that viral exit occurs at the rafts. Ectopic expression of Ebola matrix protein and glycoprotein supported raft-dependent release of filamentous, virus-like particles (VLPs), strikingly similar to live virus as revealed by electron microscopy. Our findings also revealed that the entry of filoviruses requires functional rafts, identifying rafts as the site of virus attack. The identification of rafts as the gateway for the entry and exit of filoviruses and raft-dependent generation of VLPs have important implications for development of therapeutics and vaccination strategies against infections with Ebola and Marburg viruses. PMID:11877482

  8. Ebola virus infection of human PBMCs causes massive death of macrophages, CD4 and CD8 T cell sub-populations in vitro

    Microsoft Academic Search

    Manisha Gupta; Christina Spiropoulou; Pierre E. Rollin

    2007-01-01

    Ebola virus causes an often fatal disease characterized by poor immune response and high inflammatory reaction in the patients. One of the causes for poor immunity is virus-mediated apoptosis of lymphocytes in the host. In this study, we infected human PBMCs with Ebola Zaire virus and study apoptosis of different cell types using flow cytometry. We have shown that Ebola

  9. 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

  10. Development of a cAdVax-Based Bivalent Ebola Virus Vaccine That Induces Immune Responses against both the Sudan and Zaire Species of Ebola Virus

    Microsoft Academic Search

    Danher Wang; Nicholas U. Raja; Charles M. Trubey; Laure Y. Juompan; Min Luo; Jan Woraratanadharm; Stephen B. Deitz; Hong Yu; Benjamin M. Swain; Kevin M. Moore; William D. Pratt; Mary Kate Hart; John Y. Dong

    2006-01-01

    Ebola virus (EBOV) causes a severe hemorrhagic fever for which there are currently no vaccines or effective treatments. While lethal human outbreaks have so far been restricted to sub-Saharan Africa, the potential exploitation of EBOV as a biological weapon cannot be ignored. Two species of EBOV, Sudan ebolavirus (SEBOV) and Zaire ebolavirus (ZEBOV), have been responsible for all of the

  11. 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

  12. The Ebola virus VP35 protein inhibits activation of interferon regulatory factor 3.

    PubMed

    Basler, Christopher F; Mikulasova, Andrea; Martinez-Sobrido, Luis; Paragas, Jason; Mühlberger, Elke; Bray, Mike; Klenk, Hans-Dieter; Palese, Peter; García-Sastre, Adolfo

    2003-07-01

    The Ebola virus VP35 protein was previously found to act as an interferon (IFN) antagonist which could complement growth of influenza delNS1 virus, a mutant influenza virus lacking the influenza virus IFN antagonist protein, NS1. The Ebola virus VP35 could also prevent the virus- or double-stranded RNA-mediated transcriptional activation of both the beta IFN (IFN-beta) promoter and the IFN-stimulated ISG54 promoter (C. Basler et al., Proc. Natl. Acad. Sci. USA 97:12289-12294, 2000). We now show that VP35 inhibits virus infection-induced transcriptional activation of IFN regulatory factor 3 (IRF-3)-responsive mammalian promoters and that VP35 does not block signaling from the IFN-alpha/beta receptor. The ability of VP35 to inhibit this virus-induced transcription correlates with its ability to block activation of IRF-3, a cellular transcription factor of central importance in initiating the host cell IFN response. We demonstrate that VP35 blocks the Sendai virus-induced activation of two promoters which can be directly activated by IRF-3, namely, the ISG54 promoter and the ISG56 promoter. Further, expression of VP35 prevents the IRF-3-dependent activation of the IFN-alpha4 promoter in response to viral infection. The inhibition of IRF-3 appears to occur through an inhibition of IRF-3 phosphorylation. VP35 blocks virus-induced IRF-3 phosphorylation and subsequent IRF-3 dimerization and nuclear translocation. Consistent with these observations, Ebola virus infection of Vero cells activated neither transcription from the ISG54 promoter nor nuclear accumulation of IRF-3. These data suggest that in Ebola virus-infected cells, VP35 inhibits the induction of antiviral genes, including the IFN-beta gene, by blocking IRF-3 activation. PMID:12829834

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

    PubMed Central

    Papaneri, Amy B.; Wirblich, Christoph; Cann, Jennifer A.; Cooper, Kurt; Jahrling, Peter B.; Schnell, Matthias J.; Blaney, Joseph E.

    2012-01-01

    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?G-GP) are both avirulent after intracerebral inoculation of adult mice. Furthermore, RV?G-GP is completely avirulent upon intracerebral inoculation of suckling mice unlike parental RABV vaccine or RV-GP. Analysis of RV?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?G-GP would appear to be an even safer alternative for use in wildlife or consideration for human use. PMID:22889613

  14. 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.

  15. A replication defective recombinant Ad5 vaccine expressing Ebola virus GP is safe and immunogenic in healthy adults

    Microsoft Academic Search

    J. E. Ledgerwood; P. Costner; N. Desai; L. Holman; M. E. Enama; G. Yamshchikov; S. Mulangu; Z. Hu; C. A. Andrews; R. A. Sheets; R. A. Koup; M. Roederer; R. Bailer; J. R. Mascola; M. G. Pau; N. J. Sullivan; J. Goudsmit; G. J. Nabel; B. S. Graham

    2010-01-01

    Ebola virus causes irregular outbreaks of severe hemorrhagic fever in equatorial Africa. Case mortality remains high; there is no effective treatment and outbreaks are sporadic and unpredictable. Studies of Ebola virus vaccine platforms in non-human primates have established that the induction of protective immunity is possible and safety and human immunogenicity has been demonstrated in a previous Phase I clinical

  16. 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:

  17. Studies of Ebola Virus Glycoprotein-Mediated Entry and Fusion by Using Pseudotyped Human Immunodeficiency Virus Type 1 Virions: Involvement of Cytoskeletal Proteins and Enhancement by Tumor Necrosis Factor Alpha

    Microsoft Academic Search

    Akihito Yonezawa; Marielle Cavrois; Warner C. Greene

    2005-01-01

    The Ebola filoviruses are aggressive pathogens that cause severe and often lethal hemorrhagic fever syndromes in humans and nonhuman primates. To date, no effective therapies have been identified. To analyze the entry and fusion properties of Ebola virus, we adapted a human immunodeficiency virus type 1 (HIV-1) virion-based fusion assay by substituting Ebola virus glycoprotein (GP) for the HIV-1 envelope.

  18. Caring for critically ill patients with ebola virus disease. Perspectives from West Africa.

    PubMed

    Fowler, Robert A; Fletcher, Thomas; Fischer, William A; Lamontagne, Francois; Jacob, Shevin; Brett-Major, David; Lawler, James V; Jacquerioz, Frederique A; Houlihan, Catherine; O'Dempsey, Tim; Ferri, Mauricio; Adachi, Takuya; Lamah, Marie-Claire; Bah, Elhadj Ibrahima; Mayet, Thierry; Schieffelin, John; McLellan, Susan L; Senga, Mikiko; Kato, Yasuyuki; Clement, Christophe; Mardel, Simon; Vallenas Bejar De Villar, Rosa Constanza; Shindo, Nahoko; Bausch, Daniel

    2014-10-01

    The largest ever Ebola virus disease outbreak is ravaging West Africa. The constellation of little public health infrastructure, low levels of health literacy, limited acute care and infection prevention and control resources, densely populated areas, and a highly transmissible and lethal viral infection have led to thousands of confirmed, probable, or suspected cases thus far. Ebola virus disease is characterized by a febrile severe illness with profound gastrointestinal manifestations and is complicated by intravascular volume depletion, shock, profound electrolyte abnormalities, and organ dysfunction. Despite no proven Ebola virus-specific medical therapies, the potential effect of supportive care is great for a condition with high baseline mortality and one usually occurring in resource-constrained settings. With more personnel, basic monitoring, and supportive treatment, many of the sickest patients with Ebola virus disease do not need to die. Ebola virus disease represents an illness ready for a paradigm shift in care delivery and outcomes, and the profession of critical care medicine can and should be instrumental in helping this happen. PMID:25166884

  19. Next-Generation Sequencing Reveals a Controlled Immune Response to Zaire Ebola Virus Challenge in Cynomolgus Macaques Immunized with Vesicular Stomatitis Virus Expressing Zaire Ebola Virus Glycoprotein (VSV?G/EBOVgp).

    PubMed

    Barrenas, Fredrik; Green, Richard R; Thomas, Matthew J; Law, G Lynn; Proll, Sean C; Engelmann, Flora; Messaoudi, Ilhem; Marzi, Andrea; Feldmann, Heinz; Katze, Michael G

    2015-03-01

    Vesicular stomatitis virus expressing Zaire Ebola virus (EBOV) glycoprotein (VSV?G/EBOVgp) could be used as a vaccine to meet the 2014 Ebola virus outbreak. To characterize the host response to this vaccine, we used mRNA sequencing to analyze peripheral blood mononuclear cells (PBMCs) from cynomolgus macaques after VSV?G/EBOVgp immunization and subsequent EBOV challenge. We found a controlled transcriptional response that transitioned to immune regulation as the EBOV was cleared. This observation supports the safety of the vaccine. PMID:25589554

  20. Characterizing the transmission dynamics and control of ebola virus disease.

    PubMed

    Chowell, Gerardo; Nishiura, Hiroshi

    2015-01-01

    Carefully calibrated transmission models have the potential to guide public health officials on the nature and scale of the interventions required to control epidemics. In the context of the ongoing Ebola virus disease (EVD) epidemic in Liberia, Drake and colleagues, in this issue of PLOS Biology, employed an elegant modeling approach to capture the distributions of the number of secondary cases that arise in the community and health care settings in the context of changing population behaviors and increasing hospital capacity. Their findings underscore the role of increasing the rate of safe burials and the fractions of infectious individuals who seek hospitalization together with hospital capacity to achieve epidemic control. However, further modeling efforts of EVD transmission and control in West Africa should utilize the spatial-temporal patterns of spread in the region by incorporating spatial heterogeneity in the transmission process. Detailed datasets are urgently needed to characterize temporal changes in population behaviors, contact networks at different spatial scales, population mobility patterns, adherence to infection control measures in hospital settings, and hospitalization and reporting rates. PMID:25607595

  1. Characterizing the Transmission Dynamics and Control of Ebola Virus Disease

    PubMed Central

    Chowell, Gerardo; Nishiura, Hiroshi

    2015-01-01

    Carefully calibrated transmission models have the potential to guide public health officials on the nature and scale of the interventions required to control epidemics. In the context of the ongoing Ebola virus disease (EVD) epidemic in Liberia, Drake and colleagues, in this issue of PLOS Biology, employed an elegant modeling approach to capture the distributions of the number of secondary cases that arise in the community and health care settings in the context of changing population behaviors and increasing hospital capacity. Their findings underscore the role of increasing the rate of safe burials and the fractions of infectious individuals who seek hospitalization together with hospital capacity to achieve epidemic control. However, further modeling efforts of EVD transmission and control in West Africa should utilize the spatial-temporal patterns of spread in the region by incorporating spatial heterogeneity in the transmission process. Detailed datasets are urgently needed to characterize temporal changes in population behaviors, contact networks at different spatial scales, population mobility patterns, adherence to infection control measures in hospital settings, and hospitalization and reporting rates. PMID:25607595

  2. 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

  3. A Replicating Cytomegalovirus-Based Vaccine Encoding a Single Ebola Virus Nucleoprotein CTL Epitope Confers Protection against Ebola Virus

    PubMed Central

    Tsuda, Yoshimi; Caposio, Patrizia; Parkins, Christopher J.; Botto, Sara; Messaoudi, Ilhem; Cicin-Sain, Luka; Feldmann, Heinz; Jarvis, Michael A.

    2011-01-01

    Background Human outbreaks of Ebola virus (EBOV) are a serious human health concern in Central Africa. Great apes (gorillas/chimpanzees) are an important source of EBOV transmission to humans due to increased hunting of wildlife including the ‘bush-meat’ trade. Cytomegalovirus (CMV) is an highly immunogenic virus that has shown recent utility as a vaccine platform. CMV-based vaccines also have the unique potential to re-infect and disseminate through target populations regardless of prior CMV immunity, which may be ideal for achieving high vaccine coverage in inaccessible populations such as great apes. Methodology/Principal Findings We hypothesize that a vaccine strategy using CMV-based vectors expressing EBOV antigens may be ideally suited for use in inaccessible wildlife populations. To establish a ‘proof-of-concept’ for CMV-based vaccines against EBOV, we constructed a mouse CMV (MCMV) vector expressing a CD8+ T cell epitope from the nucleoprotein (NP) of Zaire ebolavirus (ZEBOV) (MCMV/ZEBOV-NPCTL). MCMV/ZEBOV-NPCTL induced high levels of long-lasting (>8 months) CD8+ T cells against ZEBOV NP in mice. Importantly, all vaccinated animals were protected against lethal ZEBOV challenge. Low levels of anti-ZEBOV antibodies were only sporadically detected in vaccinated animals prior to ZEBOV challenge suggesting a role, at least in part, for T cells in protection. Conclusions/Significance This study demonstrates the ability of a CMV-based vaccine approach to protect against an highly virulent human pathogen, and supports the potential for ‘disseminating’ CMV-based EBOV vaccines to prevent EBOV transmission in wildlife populations. PMID:21858240

  4. Functional Importance of the Coiled-Coil of the Ebola Virus Glycoprotein

    PubMed Central

    Watanabe, Shinji; Takada, Ayato; Watanabe, Tokiko; Ito, Hiroshi; Kida, Hiroshi; Kawaoka, Yoshihiro

    2000-01-01

    Ebola virus contains a single glycoprotein (GP) that is responsible for receptor binding and membrane fusion and is proteolytically cleaved into disulfide-linked GP1 and GP2 subunits. The GP2 subunit possesses a coiled-coil motif, which plays an important role in the oligomerization and fusion activity of other viral GPs. To determine the functional significance of the coiled-coil motif of GP2, we examined the effects of peptides corresponding to the coiled-coil motif of GP2 on the infectivity of a mutant vesicular stomatitis virus (lacking the receptor-binding/fusion protein) pseudotyped with the Ebola virus GP. A peptide corresponding to the C-terminal helix reduced the infectivity of the pseudotyped virus. We next introduced alanine substitutions into hydrophobic residues in the coiled-coil motif to identify residues important for GP function. None of the substitutions affected GP oligomerization, but some mutations, two in the N-terminal helix and all in the C-terminal helix, reduced the ability of GP to confer infectivity to the mutant vesicular stomatitis virus without affecting the transport of GP to the cell surface, its incorporation into virions, and the production of virus particles. These results indicate that the coiled-coil motif of GP2 plays an important role in facilitating the entry of Ebola virus into host cells and that peptides corresponding to this region could act as efficient antiviral agents. PMID:11024148

  5. Functional importance of the coiled-coil of the Ebola virus glycoprotein.

    PubMed

    Watanabe, S; Takada, A; Watanabe, T; Ito, H; Kida, H; Kawaoka, Y

    2000-11-01

    Ebola virus contains a single glycoprotein (GP) that is responsible for receptor binding and membrane fusion and is proteolytically cleaved into disulfide-linked GP1 and GP2 subunits. The GP2 subunit possesses a coiled-coil motif, which plays an important role in the oligomerization and fusion activity of other viral GPs. To determine the functional significance of the coiled-coil motif of GP2, we examined the effects of peptides corresponding to the coiled-coil motif of GP2 on the infectivity of a mutant vesicular stomatitis virus (lacking the receptor-binding/fusion protein) pseudotyped with the Ebola virus GP. A peptide corresponding to the C-terminal helix reduced the infectivity of the pseudotyped virus. We next introduced alanine substitutions into hydrophobic residues in the coiled-coil motif to identify residues important for GP function. None of the substitutions affected GP oligomerization, but some mutations, two in the N-terminal helix and all in the C-terminal helix, reduced the ability of GP to confer infectivity to the mutant vesicular stomatitis virus without affecting the transport of GP to the cell surface, its incorporation into virions, and the production of virus particles. These results indicate that the coiled-coil motif of GP2 plays an important role in facilitating the entry of Ebola virus into host cells and that peptides corresponding to this region could act as efficient antiviral agents. PMID:11024148

  6. Development and Evaluation of a Fluorogenic 5? Nuclease Assay To Detect and Differentiate between Ebola Virus Subtypes Zaire and Sudan

    PubMed Central

    Gibb, Tammy R.; Norwood, David A.; Woollen, Neal; Henchal, Erik A.

    2001-01-01

    The ability to rapidly recognize Ebola virus infections is critical to quickly limit further spread of the disease. A rapid, sensitive, and specific laboratory diagnostic test is needed to confirm outbreaks of Ebola virus infection and to distinguish it from other diseases that can cause similar clinical symptoms. A one-tube reverse transcription-PCR assay for the identification of Ebola virus subtype Zaire (Ebola Zaire) and Ebola virus subtype Sudan (Ebola Sudan) was developed and evaluated by using the ABI PRISM 7700 sequence detection system. This assay uses one common primer set and two differentially labeled fluorescent probes to simultaneously detect and differentiate these two subtypes of Ebola virus. The sensitivity of the primer set was comparable to that of previously designed primer sets, as determined by limit-of-detection experiments. This assay is unique in its ability to simultaneously detect and differentiate Ebola Zaire and Ebola Sudan. In addition, this assay is compatible with emerging rapid nucleic acid analysis platforms and therefore may prove to be a very useful diagnostic tool for the control and management of future outbreaks. PMID:11682540

  7. 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

  8. 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

  9. Rapid and simple detection of Ebola virus by reverse transcription-loop-mediated isothermal amplification

    Microsoft Academic Search

    Yohei Kurosaki; Ayato Takada; Hideki Ebihara; Allen Grolla; Naoki Kamo; Heinz Feldmann; Yoshihiro Kawaoka; Jiro Yasuda

    2007-01-01

    Ebola virus (EBOV) causes severe hemorrhagic fever in humans and nonhuman primates with high mortality rates. Rapid identification of the virus is required to prevent spread of the infection. In this study, we developed and evaluated a one-step simple reverse transcription-loop mediated isothermal amplification (RT-LAMP) assay for the rapid detection of Zaire ebolavirus (ZEBOV), the most virulent species of EBOV,

  10. Computational prediction and identification of HLA-A2.1-specific Ebola virus CTL epitopes

    Microsoft Academic Search

    Krishnan Sundar; Agnieszka Boesen; Richard Coico

    2007-01-01

    Ebola virus (EBOV) is known to cause a severe hemorrhagic fever resulting in high mortality. Although the precise host defense mechanism(s) that afford protection against EBOV is not completely understood, T cell-mediated immune responses is believed to play a pivotal role in controlling virus replication and EBOV infection. There have been no reports on mapping of MHC Class I-binding CTL

  11. 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

  12. 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

  13. 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

  14. Induction of Immune Responses in Mice and Monkeys to Ebola Virus after Immunization with Liposome-Encapsulated Irradiated Ebola Virus: Protection in Mice Requires CD4+ T Cells

    Microsoft Academic Search

    Mangala Rao; Mike Bray; Carl R. Alving; Peter Jahrling; Gary R. Matyas

    2002-01-01

    Ebola Zaire virus (EBO-Z) causes severe hemorrhagic fever in humans, with a high mortality rate. It is thought that a vaccine against EBO-Z may have to induce both humoral and cell-mediated immune responses to successfully confer protection. Because it is known that liposome-encapsulated antigens induce both anti- body and cellular responses, we evaluated the protective efficacy of liposome-encapsulated irradiated EBO-Z

  15. 373. Simian Adenoviral Vector Based-Vaccine Fully Protect Against Ebola Virus Even in the Presence of Pre-Existing Immunity to Human Adenovirus

    Microsoft Academic Search

    Gary P. Kobinger; Heinz Feldmann; Yan Zhi; Gregory P. Schumer; Guangping Gao; Frederik Feldmann; Steven Jones; James M. Wilson

    2004-01-01

    Ebola virus is one of several pathogens that cause lethal hemorrhagic fever. Most strains of Ebola are highly lethal in humans and extremely infectious. The profile of Ebola virus infections that make it such a dangerous pathogen also contribute to its utility as a potential agent of biological warfare. Adenoviral vector was the only vaccine carrier recently shown to protect

  16. 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

  17. Spatial Localization of the Ebola Virus Glycoprotein Mucin-Like Domain Determined by Cryo-Electron Tomography

    PubMed Central

    Tran, Erin E. H.; Simmons, James A.; Bartesaghi, Alberto; Shoemaker, Charles J.; Nelson, Elizabeth; White, Judith M.

    2014-01-01

    The Ebola virus glycoprotein mucin-like domain (MLD) is implicated in Ebola virus cell entry and immune evasion. Using cryo-electron tomography of Ebola virus-like particles, we determined a three-dimensional structure for the full-length glycoprotein in a near-native state and compared it to that of a glycoprotein lacking the MLD. Our results, which show that the MLD is located at the apex and the sides of each glycoprotein monomer, provide a structural template for analysis of MLD function. PMID:25008940

  18. 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

  19. 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.

  20. A Current Review of Ebola Virus: Pathogenesis, Clinical Presentation, and Diagnostic Assessment

    Microsoft Academic Search

    Adrian M. Casillas; Adeline M. Nyamathi; Anthony Sosa; Cam L. Wilder; Heather Sands

    2003-01-01

    Ebola hemorrhagic fever (EHF) is an acute viral syndrome that presents with fever and an ensuing bleeding diathesis that is marked by high mortality in human and nonhuman primates. Fatality rates are between 50% and 100%. Due to its lethal nature, this filovirus is classified as a biological class 4 pathogen. The natural reservoir of the virus is unknown. As

  1. Kawaoka Y: Molecular determinants of Ebola virus virulence in mice. PLoS Pathog 2006

    E-print Network

    Hideki Ebihara; Ayato Takada; Darwyn Kobasa; Steven Jones; Gabriele Neumann; Steven Theriault; Mike Bray; Heinz Feldmann; Yoshihiro Kawaoka

    cause lethal infection in these animals. To understand the pathogenesis underlying the extreme virulence of Ebola virus (EBOV), here we identified the mutations responsible for the acquisition of the high virulence of the adapted Mayinga strain in mice, by using reverse genetics. We found that mutations

  2. Lipid raft microdomains: a gateway for compartmentalized trafficking of Ebola and Marburg viruses

    E-print Network

    Sina Bavari; Catharine M. Bosio; Elizabeth Wieg; Gordon Ruthel; Amy B. Will; Thomas W. Geisbert; Michael Hevey; Connie Schmaljohn; Alan Schmaljohn; M. Javad Aman

    2002-01-01

    budding. Filoviruses released from infected cells incorporated raft-associated molecules, suggesting that viral exit occurs at the rafts. Ectopic expression of Ebola matrix protein and glycoprotein supported raft-dependent release of filamentous, virus-like particles (VLPs), strikingly similar to live

  3. The Ebola Virus VP35 Protein Is a Suppressor of RNA Silencing

    E-print Network

    Joost Haasnoot; Walter De Vries; Ernst-jan Geutjes; Marcel Prins; Peter De Haan; Ben Berkhout

    encode RSSs, suggesting that RNAi also serves as an innate defence response in mammals. Here, we demonstrate that the Ebola virus VP35 protein is a suppressor of RNAi in mammalian cells and that its RSS activity is functionally equivalent to that of the HIV-1 Tat protein. We show that VP35 can replace

  4. Ebola virus glycoprotein-mediated anoikis of primary human cardiac microvascular endothelial cells

    Microsoft Academic Search

    Ratna B Ray; Arnab Basu; Robert Steele; Aster Beyene; Jane McHowat; Keith Meyer; Asish K Ghosh; Ranjit Ray

    2004-01-01

    Ebola virus glycoprotein (EGP) has been implicated for the induction of cytotoxicity and injury in vascular cells. On the other hand, EGP has also been suggested to induce massive cell rounding and detachment from the plastic surface by downregulating cell adhesion molecules without causing cytotoxicity. In this study, we have examined the cytotoxic role of EGP in primary endothelial cells

  5. The Ebola Virus Glycoprotein Contributes to but Is Not Sufficient for Virulence In Vivo

    Microsoft Academic Search

    Allison Groseth; Andrea Marzi; Thomas Hoenen; Astrid Herwig; Don Gardner; Stephan Becker; Hideki Ebihara; Heinz Feldmann

    2012-01-01

    Among the Ebola viruses most species cause severe hemorrhagic fever in humans; however, Reston ebolavirus (REBOV) has not been associated with human disease despite numerous documented infections. While the molecular basis for this difference remains unclear, in vitro evidence has suggested a role for the glycoprotein (GP) as a major filovirus pathogenicity factor, but direct evidence for such a role

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

    Microsoft Academic Search

    Devon J. Shedlock; Michael A. Bailey; Paul M. Popernack; James M. Cunningham; Dennis R. Burton; Nancy J. Sullivan

    2010-01-01

    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

  7. Ebola virus glycoprotein Fc fusion protein confers protection against lethal challenge in vaccinated mice

    Microsoft Academic Search

    Krishnamurthy Konduru; Steven B. Bradfute; Jerome Jacques; Mohanraj Manangeeswaran; Siham Nakamura; Sufi Morshed; Steven C. Wood; Sina Bavari; Gerardo G. Kaplan

    2011-01-01

    Ebola virus is a Filoviridae that causes hemorrhagic fever in humans and induces high morbidity and mortality rates. Filoviruses are classified as “Category A bioterrorism agents”, and currently there are no licensed therapeutics or vaccines to treat and prevent infection. The Filovirus glycoprotein (GP) is sufficient to protect individuals against infection, and several vaccines based on GP are under development

  8. Development, characterization and use of monoclonal VP40-antibodies for the detection of Ebola virus

    Microsoft Academic Search

    Andreas Lucht; Roland Grunow; Peggy Möller; Heinz Feldmann; Stephan Becker

    2003-01-01

    Ebola virus (EBOV) causes uncommon but dramatic outbreaks in remote regions of Africa, where diagnostic facilities are limited. In order to develop diagnostic tests, which can be handled and distributed easily, monoclonal antibodies (mAbs) to EBOV, species Zaire, were produced from mice immunized with inactivated viral particles. Nine stable hybridoma cell lines were obtained producing specific mAbs directed against the

  9. 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

  10. Modelling the effect of information feedback on the spread of the Ebola virus : A computer simulation

    Microsoft Academic Search

    Bernadette O’Regan; Richard Moles

    2001-01-01

    Describes the application of the tools and techniques of the system dynamics method to the complex problem of understanding the spread of the Ebola virus. The main deliverable of this research is a computer simulation model in the system dynamics tradition. The essence of system dynamics is to act as a framework for formalising mental models of a problem. In

  11. Postexposure Protection of Guinea Pigs against a Lethal Ebola Virus Challenge Is Conferred by RNA Interference

    Microsoft Academic Search

    Elliott Kagan; Kevin McClintock; Adam Judge; Ian MacLachlan

    2006-01-01

    Background. Ebola virus (EBOV) infection causes a frequently fatal hemorrhagic fever (HF) that is refractory to treatment with currently available antiviral therapeutics. RNA interference represents a powerful, naturally occurring biological strategy for the inhibition of gene expression and has demonstrated utility in the inhibition of viral replication. Here, we describe the development of a potential therapy for EBOV infection that

  12. The Ebola Virus Genomic Replication Promoter Is Bipartite and Follows the Rule of Six

    Microsoft Academic Search

    Michael Weik; Sven Enterlein; Kathrin Schlenz; Elke Muhlberger

    2005-01-01

    In this work we investigated the cis-acting signals involved in replication of Ebola virus (EBOV) genomic RNA. A set of mingenomes with mutant 3 ends were generated and used in a reconstituted replication and transcription system. Our results suggest that the EBOV genomic replication promoter is bipartite, consisting of a first element located within the leader region of the genome

  13. The ERK Mitogen-Activated Protein Kinase Pathway Contributes to Ebola Virus Glycoprotein-Induced Cytotoxicity

    Microsoft Academic Search

    Carisa A. Zampieri; Jean-Francois Fortin; Garry P. Nolan; Gary J. Nabel

    2007-01-01

    Ebola virus is a highly lethal pathogen that causes hemorrhagic fever in humans and nonhuman primates. Among the seven known viral gene products, the envelope glycoprotein (GP) alone induces cell rounding and detachment that ultimately leads to cell death. Cellular cytoxicity is not seen with comparable levels of expression of a mutant form of GP lacking a mucin-like domain (GPmuc).

  14. Modelling the effect of information feedback on the spread of the Ebola virus

    Microsoft Academic Search

    Bernadette O'Regan; Richard Moles

    This paper describes the application of the tools and techniques of the system dynamics method to the complex problem of understanding the spread of the Ebola virus. The main deliverable of this research is a computer simulation model in the system dynamics tradition. The essence of system dynamics is to act as a framework for formalising mental models of a

  15. Historical analysis of the Ebola virus: prospective implications for primary care nursing today.

    PubMed

    Amundsen, S B

    1998-11-01

    Ebola continues to attract worldwide attention as a highly lethal virus of unknown origin that leaves victims bleeding to death and has no known vaccine or cure. The purpose of this historical research was to review and analyze the primary and secondary sources available on Ebola for use by primary care nurses in the event of future outbreaks. A rich resource of history has been well documented by some of the original physicians, virologists, and members of international teams, but nothing was found to be documented by nurses during these outbreaks. Multiple themes emerged including the origins of the viral strains of Ebola, transmission factors, epidemiology, virology, nonhuman and genetic research, treatment, and clinical implications. This research will provide primary care nurses with historical information about Ebola to help in future treatment options and algorithm development. PMID:12596837

  16. Improving burial practices and cemetery management during an Ebola virus disease epidemic - Sierra Leone, 2014.

    PubMed

    Nielsen, Carrie F; Kidd, Sarah; Sillah, Ansumana R M; Davis, Edward; Mermin, Jonathan; Kilmarx, Peter H

    2015-01-16

    As of January 3, 2015, Ebola virus disease (Ebola) has killed more than 2,500 persons in Sierra Leone since the epidemic began there in May 2014. Ebola virus is transmitted principally by direct physical contact with an infected person or their body fluids during the later stages of illness or after death. Contact with the bodies and fluids of persons who have died of Ebola is especially common in West Africa, where family and community members often touch and wash the body of the deceased in preparation for funerals. These cultural practices have been a route of Ebola transmission. In September 2014, CDC, in collaboration with the Sierra Leone Ministry of Health and Sanitation (MOH), assessed burial practices, cemetery management, and adherence to practices recommended to reduce the risk for Ebola virus transmission. The assessment was conducted by directly observing burials and cemetery operations in three high-incidence districts. In addition, a community assessment was conducted to assess the acceptability to the population of safe, nontraditional burial practices and cemetery management intended to reduce the risk for Ebola virus transmission. This report summarizes the results of these assessments, which found that 1) there were not enough burial teams to manage the number of reported deaths, 2) Ebola surveillance, swab collection, and burial team responses to a dead body alert were not coordinated, 3) systematic procedures for testing and reporting of Ebola laboratory results for dead bodies were lacking, 4) cemetery space and management were inadequate, and 5) safe burial practices, as initially implemented, were not well accepted by communities. These findings were used to inform the development of a national standard operating procedure (SOP) for safe, dignified medical burials, released on October 1. A second, national-level, assessment was conducted during October 10-15 to assess burial team practices and training and resource needs for SOP implementation across all 14 districts in Sierra Leone. The national-level assessment confirmed that burial practices, challenges, and needs at the national level were similar to those found during the assessment conducted in the three districts. Recommendations based on the assessments included 1) district-level trainings on the components of the SOP and 2) rapid deployment across the 14 districts of additional trained burial teams supplied with adequate personal protective equipment (PPE), other equipment (e.g., chlorine, chlorine sprayers, body bags, and shovels), and vehicles. Although these assessments were conducted very early on in the response, during October-December national implementation of the SOP and recommendations might have made dignified burial safer and increased community support for these practices; an evaluation of this observation is planned. PMID:25590682

  17. 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. J. Med. Virol. 87:893-898, 2015. © 2015 Wiley Periodicals, Inc. PMID:25783989

  18. Ebola virus glycoprotein Fc fusion protein confers protection against lethal challenge in vaccinated mice

    PubMed Central

    Konduru, Krishnamurthy; Bradfute, Steven B.; Jacques, Jerome; Manangeeswaran, Mohanraj; Nakamura, Siham; Morshed, Sufi; Wood, Steven C.; Bavari, Sina

    2011-01-01

    Ebola virus is a Filoviridae that causes hemorrhagic fever in humans and induces high morbidity and mortality rates. Filoviruses are classified as "Category A bioterrorism agents", and currently there are no licensed therapeutics or vaccines to treat and prevent infection. The Filovirus glycoprotein (GP) is sufficient to protect individuals against infection, and several vaccines based on GP are under development including recombinant adenovirus, parainfluenza virus, Venezuelan equine encephalitis virus, vesicular stomatitis virus (VSV) and virus-like particles. Here we describe the development of a GP Fc fusion protein as a vaccine candidate. We expressed the extracellular domain of the Zaire Ebola virus (ZEBOV) GP fused to the Fc fragment of human IgG1 (ZEBOVGP-Fc) in mammalian cells and showed that GP undergoes the complex furin cleavage and processing observed in the native membrane-bound GP. Mice immunized with ZEBOVGP-Fc developed T-cell immunity against ZEBOV GP and neutralizing antibodies against replication-competent VSV-G deleted recombinant VSV containing ZEBOV GP. The ZEBOVGP-Fc vaccinated mice were protected against challenge with a lethal dose of ZEBOV. These results show that vaccination with the ZEBOVGP-Fc fusion protein alone without the need of a viral vector or assembly into virus-like particles is sufficient to induce protective immunity against ZEBOV in mice. Our data suggested that Filovirus GP Fc fusion proteins could be developed as a simple, safe, efficacious, and cost effective vaccine against Filovirus infection for human use. PMID:21329775

  19. Community quarantine to interrupt ebola virus transmission - mawah village, bong county, liberia, august-october, 2014.

    PubMed

    Nyenswah, Tolbert; Blackley, David J; Freeman, Tabeh; Lindblade, Kim A; Arzoaquoi, Samson K; Mott, Joshua A; Williams, Justin N; Halldin, Cara N; Kollie, Francis; Laney, A Scott

    2015-02-27

    On September 30, 2014, the Bong County health officer notified the county Ebola task force of a growing outbreak of Ebola virus disease (Ebola) in Mawah, a village of approximately 800 residents. During September 9-16, household quarantine had been used by the community in response to a new Ebola infection. Because the infection led to a local outbreak that grew during September 17-20, county authorities suggested community quarantine be considered, and beginning on approximately September 20, the Fuamah District Ebola Task Force (Task Force) engaged Mawah leaders to provide education about Ebola and to secure cooperation for the proposed measures. On September 30, Bong County requested technical assistance to develop strategies to limit transmission in the village and to prevent spread to other areas. The county health team, with support from the Task Force and CDC, traveled to Mawah on October 1 and identified approximately two dozen residents reporting symptoms consistent with Ebola. Because of an ambulance shortage, 2 days were required, beginning October 1, to transport the patients to an Ebola treatment unit in Monrovia. Community quarantine measures, consisting of restrictions on entering or leaving Mawah, regulated river crossings, and market closures, were implemented on October 1. Local leaders raised concerns about availability of medical care and food. The local clinic was reopened on October 11, and food was distributed on October 12. The Task Force reported a total of 22 cases of Ebola in Mawah during September 9-October 2, of which 19 were fatal. During October 3-November 21, no new cases were reported in the village. Involving community members during planning and implementation helped support a safe and effective community quarantine in Mawah. PMID:25719679

  20. 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 ...

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

    Microsoft Academic Search

    Katsuaki Usami; Keita Matsuno; Manabu Igarashi; Kaori Denda-Nagai; Ayato Takada; Tatsuro Irimura

    2011-01-01

    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

  2. Production of monoclonal antibodies and development of an antigen capture ELISA directed against the envelope glycoprotein GP of Ebola virus

    Microsoft Academic Search

    Andreas Lucht; Roland Grunow; Christian Otterbein; Peggy Möller; Heinz Feldmann; Stephan Becker

    2004-01-01

    Ebola virus (EBOV) causes severe outbreaks of Ebola hemorrhagic fever in endemic regions of Africa and is considered to be of impact for other parts of the world as an imported viral disease. To develop a new diagnostic test, monoclonal antibodies to EBOV were produced from mice immunized with inactivated EBOV species Zaire. Antibodies directed against the viral glycoprotein GP

  3. Emerging Targets and Novel Approaches to Ebola Virus Prophylaxis and Treatment

    PubMed Central

    Choi, Jin Huk; Croyle, Maria A.

    2013-01-01

    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-virus 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 United States (U.S.) Food and Drug Administration (FDA) and Phase I clinical trials initiated for two small molecule therapeutics, 1) anti-sense phosphorodiamidate morphino oligomers (PMOs: AVI-6002, AVI-6003), and 2) 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 will also be discussed. PMID:23813435

  4. Ebola virus disease in southern Sudan: hospital dissemination and intrafamilial spread

    PubMed Central

    Baron, Roy C.; McCormick, Joseph B.; Zubeir, Osman A.

    1983-01-01

    Between 31 July and 6 October 1979, 34 cases of Ebola virus disease (22 of which were fatal) occurred among five families in a rural district of southern Sudan; the disease was introduced into four of the families from a local hospital. Chains of secondary spread within the family units, accounting for 29 cases resulted from direct physical contact with an infected person. Among all persons with such contact in the family setting, those who provided nursing care had a 5.1-fold increased risk of infection, emphasizing the importance of intimate contact in the spread of this disease. The absence of illness among persons who were exposed to cases in confined spaces, but without physical contact, confirmed previous impressions that there is no risk of airborne transmission. While the ecology of Ebola virus is unknown, the presence of anti-Ebola antibodies in the sera of 18% of persons who were unassociated with the outbreak suggests that the region is an endemic focus of Ebola virus activity. PMID:6370486

  5. A cytomegalovirus-based vaccine provides long-lasting protection against lethal Ebola virus challenge after a single dose.

    PubMed

    Tsuda, Yoshimi; Parkins, Christopher J; Caposio, Patrizia; Feldmann, Friederike; Botto, Sara; Ball, Susan; Messaoudi, Ilhem; Cicin-Sain, Luka; Feldmann, Heinz; Jarvis, Michael A

    2015-05-01

    Ebola virus (Zaire ebolavirus; EBOV) is a highly lethal hemorrhagic disease virus that most recently was responsible for two independent 2014 outbreaks in multiple countries in Western Africa, and the Democratic Republic of the Congo, respectively. Herein, we show that a cytomegalovirus (CMV)-based vaccine provides durable protective immunity from Ebola virus following a single vaccine dose. This study has implications for human vaccination against ebolaviruses, as well as for development of a 'disseminating' vaccine to target these viruses in wild African great apes. PMID:25820063

  6. A Filovirus-Unique Region of Ebola Virus Nucleoprotein Confers Aberrant Migration and Mediates Its Incorporation into Virions

    Microsoft Academic Search

    Wei Shi; Yue Huang; Mark Sutton-Smith; Berangere Tissot; Maria Panico; Howard R. Morris; Anne Dell; Stuart M. Haslam; Jeffrey Boyington; Barney S. Graham; Zhi-Yong Yang; Gary J. Nabel

    2008-01-01

    Received 22 December 2007\\/Accepted 1 April 2008 The Ebola virus nucleoprotein (NP) is an essential component of the nucleocapsid, required for filovirus particle formation and replication. Together with virion protein 35 (VP35) and VP24, this gene product gives rise to the filamentous nucleocapsid within transfected cells. Ebola virus NP migrates aberrantly, with an apparent molecular mass of 115 kDa, although

  7. Marburg Virus Evades Interferon Responses by a Mechanism Distinct from Ebola Virus

    PubMed Central

    Schümann, Michael; Olejnik, Judith; Martinez, Osvaldo; Best, Sonja M.; Krähling, Verena; Basler, Christopher F.; Mühlberger, Elke

    2010-01-01

    Previous studies have demonstrated that Marburg viruses (MARV) and Ebola viruses (EBOV) inhibit interferon (IFN)-?/? signaling but utilize different mechanisms. EBOV inhibits IFN signaling via its VP24 protein which blocks the nuclear accumulation of tyrosine phosphorylated STAT1. In contrast, MARV infection inhibits IFN?/? induced tyrosine phosphorylation of STAT1 and STAT2. MARV infection is now demonstrated to inhibit not only IFN?/? but also IFN?-induced STAT phosphorylation and to inhibit the IFN?/? and IFN?-induced tyrosine phosphorylation of upstream Janus (Jak) family kinases. Surprisingly, the MARV matrix protein VP40, not the MARV VP24 protein, has been identified to antagonize Jak and STAT tyrosine phosphorylation, to inhibit IFN?/? or IFN?-induced gene expression and to inhibit the induction of an antiviral state by IFN?/?. Global loss of STAT and Jak tyrosine phosphorylation in response to both IFN?/? and IFN? is reminiscent of the phenotype seen in Jak1-null cells. Consistent with this model, MARV infection and MARV VP40 expression also inhibit the Jak1-dependent, IL-6-induced tyrosine phosphorylation of STAT1 and STAT3. Finally, expression of MARV VP40 is able to prevent the tyrosine phosphorylation of Jak1, STAT1, STAT2 or STAT3 which occurs following over-expression of the Jak1 kinase. In contrast, MARV VP40 does not detectably inhibit the tyrosine phosphorylation of STAT2 or Tyk2 when Tyk2 is over-expressed. Mutation of the VP40 late domain, essential for efficient VP40 budding, has no detectable impact on inhibition of IFN signaling. This study shows that MARV inhibits IFN signaling by a mechanism different from that employed by the related EBOV. It identifies a novel function for the MARV VP40 protein and suggests that MARV may globally inhibit Jak1-dependent cytokine signaling. PMID:20084112

  8. Responding to the Potential of Ebola Virus Disease (EVD) Importation into Malaysia

    PubMed Central

    WAN MOHAMED NOOR, Wan Noraini; SANDHU, Sukhvinder Singh; AHMAD MAHIR, Husna Maizura; KURUP, Devan; RUSLI, Norhayati; SAAT, Zainah; CHONG, Chee Kheong; SULAIMAN, Lokman Hakim; ABDULLAH, Noor Hisham

    2014-01-01

    The current Ebola outbreak, which is the first to affect West African countries, has been declared to have met the conditions for a Public Health Emergency of International Concern (PHEIC) by the World Health Organization (WHO). Thus, the Ministry of Health (MOH) of Malaysia has taken steps to strengthen and enhanced the five core components of preparedness and response to mitigate the outbreak. The National Crisis Preparedness and Response Centre (CPRC) commands, controls and coordinates the preparedness and response plans for disasters, outbreaks, crises and emergencies (DOCE) related to health in a centralised way. Through standardised case definition and mandatory notification of Ebola by public and private practitioners, surveillance of Ebola is made possible. Government hospitals and laboratories have been identified to manage and diagnose Ebola virus infections, and medical staff members have been trained to handle an Ebola outbreak, with emphasis on strict infection prevention and control practices. Monitoring of the points of entry, focusing on travellers and students visiting or coming from West African countries is made possible by interagency collaborations. To alleviate the public’s anxiety, effective risk communications are being delivered through various channels. With experience in past outbreak control, the MOH’s preparedness and response plans are in place to abate an Ebola outbreak.

  9. Clinical inquiries regarding Ebola virus disease received by CDC--United States, July 9-November 15, 2014.

    PubMed

    Karwowski, Mateusz P; Meites, Elissa; Fullerton, Kathleen E; Ströher, Ute; Lowe, Luis; Rayfield, Mark; Blau, Dianna M; Knust, Barbara; Gindler, Jacqueline; Van Beneden, Chris; Bialek, Stephanie R; Mead, Paul; Oster, Alexandra M

    2014-12-12

    Since early 2014, there have been more than 6,000 reported deaths from Ebola virus disease (Ebola), mostly in Guinea, Liberia, and Sierra Leone. On July 9, 2014, CDC activated its Emergency Operations Center for the Ebola outbreak response and formalized the consultation service it had been providing to assist state and local public health officials and health care providers evaluate persons in the United States thought to be at risk for Ebola. During July 9-November 15, CDC responded to clinical inquiries from public health officials and health care providers from 49 states and the District of Columbia regarding 650 persons thought to be at risk. Among these, 118 (18%) had initial signs or symptoms consistent with Ebola and epidemiologic risk factors placing them at risk for infection, thereby meeting the definition of persons under investigation (PUIs). Testing was not always performed for PUIs because alternative diagnoses were made or symptoms resolved. In total, 61 (9%) persons were tested for Ebola virus, and four, all of whom met PUI criteria, had laboratory-confirmed Ebola. Overall, 490 (75%) inquiries concerned persons who had neither traveled to an Ebola-affected country nor had contact with an Ebola patient. Appropriate medical evaluation and treatment for other conditions were noted in some instances to have been delayed while a person was undergoing evaluation for Ebola. Evaluating and managing persons who might have Ebola is one component of the overall approach to domestic surveillance, the goal of which is to rapidly identify and isolate Ebola patients so that they receive appropriate medical care and secondary transmission is prevented. Health care providers should remain vigilant and consult their local and state health departments and CDC when assessing ill travelers from Ebola-affected countries. Most of these persons do not have Ebola; prompt diagnostic assessments, laboratory testing, and provision of appropriate care for other conditions are essential for appropriate patient care and reflect hospital preparedness. PMID:25503923

  10. 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

  11. Assessment of the potential for international dissemination of Ebola virus via commercial air travel during the 2014 west African outbreak

    PubMed Central

    Bogoch, Isaac I; Creatore, Maria I; Cetron, Martin S; Brownstein, John S; Pesik, Nicki; Miniota, Jennifer; Tam, Theresa; Hu, Wei; Nicolucci, Adriano; Ahmed, Saad; Yoon, James W; Berry, Isha; Hay, Simon I; Anema, Aranka; Tatem, Andrew J; MacFadden, Derek; German, Matthew; Khan, Kamran

    2015-01-01

    Summary Background The WHO declared the 2014 west African Ebola epidemic a public health emergency of international concern in view of its potential for further international spread. Decision makers worldwide are in need of empirical data to inform and implement emergency response measures. Our aim was to assess the potential for Ebola virus to spread across international borders via commercial air travel and assess the relative efficiency of exit versus entry screening of travellers at commercial airports. Methods We analysed International Air Transport Association data for worldwide flight schedules between Sept 1, 2014, and Dec 31, 2014, and historic traveller flight itinerary data from 2013 to describe expected global population movements via commercial air travel out of Guinea, Liberia, and Sierra Leone. Coupled with Ebola virus surveillance data, we modelled the expected number of internationally exported Ebola virus infections, the potential effect of air travel restrictions, and the efficiency of airport-based traveller screening at international ports of entry and exit. We deemed individuals initiating travel from any domestic or international airport within these three countries to have possible exposure to Ebola virus. We deemed all other travellers to have no significant risk of exposure to Ebola virus. Findings Based on epidemic conditions and international flight restrictions to and from Guinea, Liberia, and Sierra Leone as of Sept 1, 2014 (reductions in passenger seats by 51% for Liberia, 66% for Guinea, and 85% for Sierra Leone), our model projects 2·8 travellers infected with Ebola virus departing the above three countries via commercial flights, on average, every month. 91?547 (64%) of all air travellers departing Guinea, Liberia, and Sierra Leone had expected destinations in low-income and lower-middle-income countries. Screening international travellers departing three airports would enable health assessments of all travellers at highest risk of exposure to Ebola virus infection. Interpretation Decision makers must carefully balance the potential harms from travel restrictions imposed on countries that have Ebola virus activity against any potential reductions in risk from Ebola virus importations. Exit screening of travellers at airports in Guinea, Liberia, and Sierra Leone would be the most efficient frontier at which to assess the health status of travellers at risk of Ebola virus exposure, however, this intervention might require international support to implement effectively. Funding Canadian Institutes of Health Research. PMID:25458732

  12. 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

  13. 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

  14. The Ebola Virus Matrix Protein Deeply Penetrates the Plasma Membrane: An Important Step in Viral Egress

    PubMed Central

    Soni, Smita P.; Adu-Gyamfi, Emmanuel; Yong, Sylvia S.; Jee, Clara S.; Stahelin, Robert V.

    2013-01-01

    Ebola virus, from the Filoviridae family has a high fatality rate in humans and nonhuman primates and to date, to the best of our knowledge, has no FDA approved vaccines or therapeutics. Viral protein 40 (VP40) is the major Ebola virus matrix protein that regulates assembly and egress of infectious Ebola virus particles. It is well established that VP40 assembles on the inner leaflet of the plasma membrane; however, the mechanistic details of VP40 membrane binding that are important for viral release remain to be elucidated. In this study, we used fluorescence quenching of a tryptophan on the membrane-binding interface with brominated lipids along with mutagenesis of VP40 to understand the depth of membrane penetration into lipid bilayers. Experimental results indicate that VP40 penetrates 8.1 Å into the hydrocarbon core of the plasma membrane bilayer. VP40 also induces substantial changes to membrane curvature as it tubulates liposomes and induces vesiculation into giant unilamellar vesicles, effects that are abrogated by hydrophobic mutations. This is a critical step in viral egress as cellular assays demonstrate that hydrophobic residues that penetrate deeply into the plasma membrane are essential for plasma membrane localization and virus-like particle formation and release from cells. PMID:23663837

  15. Transmission of ebola viruses: what we know and what we do not know.

    PubMed

    Osterholm, Michael T; Moore, Kristine A; Kelley, Nicholas S; Brosseau, Lisa M; Wong, Gary; Murphy, Frederick A; Peters, Clarence J; LeDuc, James W; Russell, Phillip K; Van Herp, Michel; Kapetshi, Jimmy; Muyembe, Jean-Jacques T; Ilunga, Benoit Kebela; Strong, James E; Grolla, Allen; Wolz, Anja; Kargbo, Brima; Kargbo, David K; Formenty, Pierre; Sanders, David Avram; Kobinger, Gary P

    2015-01-01

    Available evidence demonstrates that direct patient contact and contact with infectious body fluids are the primary modes for Ebola virus transmission, but this is based on a limited number of studies. Key areas requiring further study include (i) the role of aerosol transmission (either via large droplets or small particles in the vicinity of source patients), (ii) the role of environmental contamination and fomite transmission, (iii) the degree to which minimally or mildly ill persons transmit infection, (iv) how long clinically relevant infectiousness persists, (v) the role that "superspreading events" may play in driving transmission dynamics, (vi) whether strain differences or repeated serial passage in outbreak settings can impact virus transmission, and (vii) what role sylvatic or domestic animals could play in outbreak propagation, particularly during major epidemics such as the 2013-2015 West Africa situation. In this review, we address what we know and what we do not know about Ebola virus transmission. We also hypothesize that Ebola viruses have the potential to be respiratory pathogens with primary respiratory spread. PMID:25698835

  16. FDA-approved selective estrogen receptor modulators inhibit Ebola virus infection.

    PubMed

    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

    2013-06-19

    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

  17. Transmission of Ebola Viruses: What We Know and What We Do Not Know

    PubMed Central

    Moore, Kristine A.; Kelley, Nicholas S.; Brosseau, Lisa M.; Wong, Gary; Murphy, Frederick A.; Peters, Clarence J.; LeDuc, James W.; Russell, Phillip K.; Van Herp, Michel; Kapetshi, Jimmy; Muyembe, Jean-Jacques T.; Ilunga, Benoit Kebela; Strong, James E.; Grolla, Allen; Wolz, Anja; Kargbo, Brima; Kargbo, David K.; Formenty, Pierre; Sanders, David Avram; Kobinger, Gary P.

    2015-01-01

    ABSTRACT Available evidence demonstrates that direct patient contact and contact with infectious body fluids are the primary modes for Ebola virus transmission, but this is based on a limited number of studies. Key areas requiring further study include (i) the role of aerosol transmission (either via large droplets or small particles in the vicinity of source patients), (ii) the role of environmental contamination and fomite transmission, (iii) the degree to which minimally or mildly ill persons transmit infection, (iv) how long clinically relevant infectiousness persists, (v) the role that “superspreading events” may play in driving transmission dynamics, (vi) whether strain differences or repeated serial passage in outbreak settings can impact virus transmission, and (vii) what role sylvatic or domestic animals could play in outbreak propagation, particularly during major epidemics such as the 2013–2015 West Africa situation. In this review, we address what we know and what we do not know about Ebola virus transmission. We also hypothesize that Ebola viruses have the potential to be respiratory pathogens with primary respiratory spread. PMID:25698835

  18. C-type lectins DC-SIGN and L-SIGN mediate cellular entry by Ebola virus in cis and in trans.

    PubMed

    Alvarez, Carmen P; Lasala, Fátima; Carrillo, Jaime; Muñiz, Oscar; Corbí, Angel L; Delgado, Rafael

    2002-07-01

    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 to susceptible cells. Our data underscore a role for DC-SIGN and L-SIGN in the infective process and pathogenicity of Ebola virus infection. PMID:12050398

  19. Ebola Hemorrhagic Fever: Transmission

    MedlinePLUS

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  20. Ebola Hemorrhagic Fever: Prevention

    MedlinePLUS

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  1. Ebola Hemorrhagic Fever: Diagnosis

    MedlinePLUS

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  2. Ebola Hemorrhagic Fever: Treatment

    MedlinePLUS

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  3. 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 ...

  4. Ebola Zaire virus blocks type I interferon production by exploiting the host SUMO modification machinery.

    PubMed

    Chang, Tsung-Hsien; Kubota, Toru; Matsuoka, Mayumi; Jones, Steven; Bradfute, Steven B; Bray, Mike; Ozato, Keiko

    2009-06-01

    Ebola Zaire virus is highly pathogenic for humans, with case fatality rates approaching 90% in large outbreaks in Africa. The virus replicates in macrophages and dendritic cells (DCs), suppressing production of type I interferons (IFNs) while inducing the release of large quantities of proinflammatory cytokines. Although the viral VP35 protein has been shown to inhibit IFN responses, the mechanism by which it blocks IFN production has not been fully elucidated. We expressed VP35 from a mouse-adapted variant of Ebola Zaire virus in murine DCs by retroviral gene transfer, and tested for IFN transcription upon Newcastle Disease virus (NDV) infection and toll-like receptor signaling. We found that VP35 inhibited IFN transcription in DCs following these stimuli by disabling the activity of IRF7, a transcription factor required for IFN transcription. By yeast two-hybrid screens and coimmunoprecipitation assays, we found that VP35 interacted with IRF7, Ubc9 and PIAS1. The latter two are the host SUMO E2 enzyme and E3 ligase, respectively. VP35, while not itself a SUMO ligase, increased PIAS1-mediated SUMOylation of IRF7, and repressed Ifn transcription. In contrast, VP35 did not interfere with the activation of NF-kappaB, which is required for induction of many proinflammatory cytokines. Our findings indicate that Ebola Zaire virus exploits the cellular SUMOylation machinery for its advantage and help to explain how the virus overcomes host innate defenses, causing rapidly overwhelming infection to produce a syndrome resembling fulminant septic shock. PMID:19557165

  5. Considerations for Safe EMS Transport of Patients Infected with Ebola Virus.

    PubMed

    Lowe, John J; Jelden, Katelyn C; Schenarts, Paul J; Rupp, Lloyd E; Hawes, Kingdon J; Tysor, Benjamin M; Swansiger, Raymond G; Schwedhelm, Shelly S; Smith, Philip W; Gibbs, Shawn G

    2015-01-01

    The Nebraska Biocontainment Unit through the Nebraska Medical Center in Omaha, Nebraska, recently received patients with confirmed Ebola virus from West Africa. The Nebraska Biocontainment Unit and Omaha Fire Department's emergency medical services (EMS) coordinated patient transportation from airport to the high-level isolation unit. Transportation of these highly infectious patients capitalized on over 8 years of meticulous planning and rigorous infection control training to ensure the safety of transport personnel as well as the community during transport. Although these transports occurred with advanced notice and after confirmed Ebola virus disease (EVD) diagnosis, approaches and key lessons acquired through this effort will advance the ability of any EMS provider to safely transport a confirmed or suspected patient with EVD. Three critical areas have been identified from our experience: ambulance preparation, appropriate selection and use of personal protective equipment, and environmental decontamination. PMID:25380073

  6. Genomic surveillance elucidates Ebola virus origin and transmission during the 2014 outbreak.

    PubMed

    Gire, Stephen K; Goba, Augustine; Andersen, Kristian G; Sealfon, Rachel S G; Park, Daniel J; Kanneh, Lansana; Jalloh, Simbirie; Momoh, Mambu; Fullah, Mohamed; Dudas, Gytis; Wohl, Shirlee; Moses, Lina M; Yozwiak, Nathan L; Winnicki, Sarah; Matranga, Christian B; Malboeuf, Christine M; Qu, James; Gladden, Adrianne D; Schaffner, Stephen F; Yang, Xiao; Jiang, Pan-Pan; Nekoui, Mahan; Colubri, Andres; Coomber, Moinya Ruth; Fonnie, Mbalu; Moigboi, Alex; Gbakie, Michael; Kamara, Fatima K; Tucker, Veronica; Konuwa, Edwin; Saffa, Sidiki; Sellu, Josephine; Jalloh, Abdul Azziz; Kovoma, Alice; Koninga, James; Mustapha, Ibrahim; Kargbo, Kandeh; Foday, Momoh; Yillah, Mohamed; Kanneh, Franklyn; Robert, Willie; Massally, James L B; Chapman, Sinéad B; Bochicchio, James; Murphy, Cheryl; Nusbaum, Chad; Young, Sarah; Birren, Bruce W; Grant, Donald S; Scheiffelin, John S; Lander, Eric S; Happi, Christian; Gevao, Sahr M; Gnirke, Andreas; Rambaut, Andrew; Garry, Robert F; Khan, S Humarr; Sabeti, Pardis C

    2014-09-12

    In its largest outbreak, Ebola virus disease is spreading through Guinea, Liberia, Sierra Leone, and Nigeria. We sequenced 99 Ebola virus genomes from 78 patients in Sierra Leone to ~2000× coverage. We observed a rapid accumulation of interhost and intrahost genetic variation, allowing us to characterize patterns of viral transmission over the initial weeks of the epidemic. This West African variant likely diverged from central African lineages around 2004, crossed from Guinea to Sierra Leone in May 2014, and has exhibited sustained human-to-human transmission subsequently, with no evidence of additional zoonotic sources. Because many of the mutations alter protein sequences and other biologically meaningful targets, they should be monitored for impact on diagnostics, vaccines, and therapies critical to outbreak response. PMID:25214632

  7. A common feature pharmacophore for FDA-approved drugs inhibiting the Ebola virus

    PubMed Central

    Ekins, Sean; Freundlich, Joel S.; Coffee, Megan

    2014-01-01

    We are currently faced with a global infectious disease crisis which has been anticipated for decades. While many promising biotherapeutics are being tested, the search for a small molecule has yet to deliver an approved drug or therapeutic for the Ebola or similar filoviruses that cause haemorrhagic fever. Two recent high throughput screens published in 2013 did however identify several hits that progressed to animal studies that are FDA approved drugs used for other indications. The current computational analysis uses these molecules from two different structural classes to construct a common features pharmacophore. This ligand-based pharmacophore implicates a possible common target or mechanism that could be further explored. A recent structure based design project yielded nine co-crystal structures of pyrrolidinone inhibitors bound to the viral protein 35 (VP35). When receptor-ligand pharmacophores based on the analogs of these molecules and the protein structures were constructed, the molecular features partially overlapped with the common features of solely ligand-based pharmacophore models based on FDA approved drugs. These previously identified FDA approved drugs with activity against Ebola were therefore docked into this protein. The antimalarials chloroquine and amodiaquine docked favorably in VP35. We propose that these drugs identified to date as inhibitors of the Ebola virus may be targeting VP35. These computational models may provide preliminary insights into the molecular features that are responsible for their activity against Ebola virus in vitro and in vivo and we propose that this hypothesis could be readily tested. PMID:25653841

  8. 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.

  9. Clinical care of two patients with Ebola virus disease in the United States.

    PubMed

    Lyon, G Marshall; Mehta, Aneesh K; Varkey, Jay B; Brantly, Kent; Plyler, Lance; McElroy, Anita K; Kraft, Colleen S; Towner, Jonathan S; Spiropoulou, Christina; Ströher, Ute; Uyeki, Timothy M; Ribner, Bruce S

    2014-12-18

    West Africa is currently experiencing the largest outbreak of Ebola virus disease (EVD) in history. Two patients with EVD were transferred from Liberia to our hospital in the United States for ongoing care. Malaria had also been diagnosed in one patient, who was treated for it early in the course of EVD. The two patients had substantial intravascular volume depletion and marked electrolyte abnormalities. We undertook aggressive supportive measures of hydration (typically, 3 to 5 liters of intravenous fluids per day early in the course of care) and electrolyte correction. As the patients' condition improved clinically, there was a concomitant decline in the amount of virus detected in plasma. PMID:25390460

  10. Processing of the Ebola virus glycoprotein by the proprotein convertase furin

    PubMed Central

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

    1998-01-01

    In the present study, we have investigated processing and maturation of the envelope glycoprotein (GP) of Ebola virus. When GP expressed from vaccinia virus vectors was analyzed by pulse–chase experiments, the mature form and two different precursors were identified. First, the endoplasmic reticulum form preGPer, full-length GP with oligomannosidic N-glycans, was detected. preGPer (110 kDa) was replaced by the Golgi-specific form preGP (160 kDa), full-length GP containing mature carbohydrates. preGP was finally converted by proteolysis into mature GP1,2, which consisted of two disulfide-linked cleavage products, the amino-terminal 140-kDa fragment GP1, and the carboxyl-terminal 26-kDa fragment GP2. GP1,2 was also identified in Ebola virions. Studies employing site-directed mutagenesis revealed that GP was cleaved at a multibasic amino acid motif located at positions 497 to 501 of the ORF. Cleavage was blocked by a peptidyl chloromethylketone containing such a motif. GP is cleaved by the proprotein convertase furin. This was indicated by the observation that cleavage did not occur when GP was expressed in furin-defective LoVo cells but that it was restored in these cells by vector-expressed furin. The Reston subtype, which differs from all other Ebola viruses by its low human pathogenicity, has a reduced cleavability due to a mutation at the cleavage site. As a result of these observations, it should now be considered that proteolytic processing of GP may be an important determinant for the pathogenicity of Ebola virus. PMID:9576958

  11. 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

  12. Both matrix proteins of Ebola virus contribute to the regulation of viral genome replication and transcription

    Microsoft Academic Search

    T. Hoenen; S. Jung; A. Herwig; A. Groseth; S. Becker

    2010-01-01

    Ebola virus (EBOV) causes severe hemorrhagic fevers in humans and non-human primates. While the role of the EBOV major matrix protein VP40 in morphogenesis is well understood, nothing is known about its contributions to the regulation of viral genome replication and\\/or transcription. Similarly, while it was reported that the minor matrix protein VP24 impairs viral genome replication, it remains unclear

  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. 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

  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. 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

  17. 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

  18. Functional Importance of the Coiled-Coil of the Ebola Virus Glycoprotein

    Microsoft Academic Search

    SHINJI WATANABE; AYATO TAKADA; TOKIKO WATANABE; HIROSHI ITO; HIROSHI KIDA; YOSHIHIRO KAWAOKA

    2000-01-01

    Ebola virus contains a single glycoprotein (GP) that is responsible for receptor binding and membrane fusion and is proteolytically cleaved into disulfide-linked GP1 and GP2 subunits. The GP2 subunit possesses a coiled-coil motif, which plays an important role in the oligomerization and fusion activity of other viral GPs. To determine the functional significance of the coiled-coil motif of GP2, we

  19. Ebola Virus VP30-Mediated Transcription Is Regulated by RNA Secondary Structure Formation

    Microsoft Academic Search

    Michael Weik; Jens Modrof; Hans-Dieter Klenk; Stephan Becker; Elke Muhlberger

    2002-01-01

    The nucleocapsid protein VP30 of Ebola virus (EBOV), a member of the Filovirus family, is known to act as a transcription activator. By using a reconstituted minigenome system, the role of VP30 during transcription was investigated. We could show that VP30-mediated transcription activation is dependent on formation of a stem-loop structure at the first gene start site. Destruction of this

  20. Phosphatidylinositol-Dependent Membrane Fusion Induced by a Putative Fusogenic Sequence of Ebola Virus

    Microsoft Academic Search

    M. BEGONA RUIZ-ARGUELLO; FELIX M. GONI; FRANCISCA B. PEREIRA; JOSEL. NIEVA

    1998-01-01

    The membrane-interacting abilities of three sequences representing the putative fusogenic subdomain of the Ebola virus transmembrane protein have been investigated. In the presence of calcium, the sequence EBOGE (GAAIGLAWIPYFGPAAE) efficiently fused unilamellar vesicles composed of phosphatidylcholine, phosphati- dylethanolamine, cholesterol, and phosphatidylinositol (molar ratio, 2:1:1:0.5), a mixture that roughly resem- bles the lipid composition of the hepatocyte plasma membrane. Analysis of

  1. Ebola virus infection inversely correlates with the overall expression levels of promyelocytic leukaemia (PML) protein in cultured cells

    Microsoft Academic Search

    Asa Szekely Björndal; Laszlo Szekely; Fredrik Elgh

    2003-01-01

    BACKGROUND: Ebola virus causes severe, often fatal hemorrhagic fever in humans. The mechanism of escape from cellular anti-viral mechanisms is not yet fully understood. The promyelocytic leukaemia (PML) associated nuclear body is part of the interferon inducible cellular defense system. Several RNA viruses have been found to interfere with the anti-viral function of the PML body. The possible interaction between

  2. 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

  3. Inactivated or Live-Attenuated Bivalent Vaccines That Confer Protection against Rabies and Ebola Viruses ?

    PubMed Central

    Blaney, Joseph E.; Wirblich, Christoph; Papaneri, Amy B.; Johnson, Reed F.; Myers, Carey J.; Juelich, Terry L.; Holbrook, Michael R.; Freiberg, Alexander N.; Bernbaum, John G.; Jahrling, Peter B.; Paragas, Jason; Schnell, Matthias J.

    2011-01-01

    The search for a safe and efficacious vaccine for Ebola virus continues, as no current vaccine candidate is nearing licensure. We have developed (i) replication-competent, (ii) replication-deficient, and (iii) chemically inactivated rabies virus (RABV) vaccines expressing Zaire Ebola virus (ZEBOV) glycoprotein (GP) by a reverse genetics system based on the SAD B19 RABV wildlife vaccine. ZEBOV GP is efficiently expressed by these vaccine candidates and is incorporated into virions. The vaccine candidates were avirulent after inoculation of adult mice, and viruses with a deletion in the RABV glycoprotein had greatly reduced neurovirulence after intracerebral inoculation in suckling mice. Immunization with live or inactivated RABV vaccines expressing ZEBOV GP induced humoral immunity against each virus and conferred protection from both lethal RABV and EBOV challenge in mice. The bivalent RABV/ZEBOV vaccines described here have several distinct advantages that may speed the development of inactivated vaccines for use in humans and potentially live or inactivated vaccines for use in nonhuman primates at risk of EBOV infection in endemic areas. PMID:21849459

  4. Modeling of the Ebola virus delta peptide reveals a potential lytic sequence motif.

    PubMed

    Gallaher, William R; Garry, Robert F

    2015-01-01

    Filoviruses, such as Ebola and Marburg viruses, cause severe outbreaks of human infection, including the extensive epidemic of Ebola virus disease (EVD) in West Africa in 2014. In the course of examining mutations in the glycoprotein gene associated with 2014 Ebola virus (EBOV) sequences, a differential level of conservation was noted between the soluble form of glycoprotein (sGP) and the full length glycoprotein (GP), which are both encoded by the GP gene via RNA editing. In the region of the proteins encoded after the RNA editing site sGP was more conserved than the overlapping region of GP when compared to a distant outlier species, Tai Forest ebolavirus. Half of the amino acids comprising the "delta peptide", a 40 amino acid carboxy-terminal fragment of sGP, were identical between otherwise widely divergent species. A lysine-rich amphipathic peptide motif was noted at the carboxyl terminus of delta peptide with high structural relatedness to the cytolytic peptide of the non-structural protein 4 (NSP4) of rotavirus. EBOV delta peptide is a candidate viroporin, a cationic pore-forming peptide, and may contribute to EBOV pathogenesis. PMID:25609303

  5. Modeling of the Ebola Virus Delta Peptide Reveals a Potential Lytic Sequence Motif

    PubMed Central

    Gallaher, William R.; Garry, Robert F.

    2015-01-01

    Filoviruses, such as Ebola and Marburg viruses, cause severe outbreaks of human infection, including the extensive epidemic of Ebola virus disease (EVD) in West Africa in 2014. In the course of examining mutations in the glycoprotein gene associated with 2014 Ebola virus (EBOV) sequences, a differential level of conservation was noted between the soluble form of glycoprotein (sGP) and the full length glycoprotein (GP), which are both encoded by the GP gene via RNA editing. In the region of the proteins encoded after the RNA editing site sGP was more conserved than the overlapping region of GP when compared to a distant outlier species, Tai Forest ebolavirus. Half of the amino acids comprising the “delta peptide”, a 40 amino acid carboxy-terminal fragment of sGP, were identical between otherwise widely divergent species. A lysine-rich amphipathic peptide motif was noted at the carboxyl terminus of delta peptide with high structural relatedness to the cytolytic peptide of the non-structural protein 4 (NSP4) of rotavirus. EBOV delta peptide is a candidate viroporin, a cationic pore-forming peptide, and may contribute to EBOV pathogenesis. PMID:25609303

  6. 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 ...

  7. 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.

  8. Homologous and Heterologous Protection of Nonhuman Primates by Ebola and Sudan Virus-Like Particles

    PubMed Central

    Warfield, Kelly L.; Dye, John M.; Wells, Jay B.; Unfer, Robert C.; Holtsberg, Frederick W.; Shulenin, Sergey; Vu, Hong; Swenson, Dana L.; Bavari, Sina; Aman, M. Javad

    2015-01-01

    Filoviruses cause hemorrhagic fever resulting in significant morbidity and mortality in humans. Several vaccine platforms that include multiple virus-vectored approaches and virus-like particles (VLPs) have shown efficacy in nonhuman primates. Previous studies have shown protection of cynomolgus macaques against homologous infection for Ebola virus (EBOV) and Marburg virus (MARV) following a three-dose vaccine regimen of EBOV or MARV VLPs, as well as heterologous protection against Ravn Virus (RAVV) following vaccination with MARV VLPs. The objectives of the current studies were to determine the minimum number of vaccine doses required for protection (using EBOV as the test system) and then demonstrate protection against Sudan virus (SUDV) and Taï Forest virus (TAFV). Using the EBOV nonhuman primate model, we show that one or two doses of VLP vaccine can confer protection from lethal infection. VLPs containing the SUDV glycoprotein, nucleoprotein and VP40 matrix protein provide complete protection against lethal SUDV infection in macaques. Finally, we demonstrate protective efficacy mediated by EBOV, but not SUDV, VLPs against TAFV; this is the first demonstration of complete cross-filovirus protection using a single component heterologous vaccine within the Ebolavirus genus. Along with our previous results, this observation provides strong evidence that it will be possible to develop and administer a broad-spectrum VLP-based vaccine that will protect against multiple filoviruses by combining only three EBOV, SUDV and MARV components. PMID:25793502

  9. A Novel Life Cycle Modeling System for Ebola Virus Shows a Genome Length-Dependent Role of VP24 in Virus Infectivity

    PubMed Central

    Watt, Ari; Moukambi, Felicien; Banadyga, Logan; Groseth, Allison; Callison, Julie; Herwig, Astrid; Ebihara, Hideki

    2014-01-01

    ABSTRACT Work with infectious Ebola viruses is restricted to biosafety level 4 (BSL4) laboratories, presenting a significant barrier for studying these viruses. Life cycle modeling systems, including minigenome systems and transcription- and replication-competent virus-like particle (trVLP) systems, allow modeling of the virus life cycle under BSL2 conditions; however, all current systems model only certain aspects of the virus life cycle, rely on plasmid-based viral protein expression, and have been used to model only single infectious cycles. We have developed a novel life cycle modeling system allowing continuous passaging of infectious trVLPs containing a tetracistronic minigenome that encodes a reporter and the viral proteins VP40, VP24, and GP1,2. This system is ideally suited for studying morphogenesis, budding, and entry, in addition to genome replication and transcription. Importantly, the specific infectivity of trVLPs in this system was ?500-fold higher than that in previous systems. Using this system for functional studies of VP24, we showed that, contrary to previous reports, VP24 only very modestly inhibits genome replication and transcription when expressed in a regulated fashion, which we confirmed using infectious Ebola viruses. Interestingly, we also discovered a genome length-dependent effect of VP24 on particle infectivity, which was previously undetected due to the short length of monocistronic minigenomes and which is due at least partially to a previously unknown function of VP24 in RNA packaging. Based on our findings, we propose a model for the function of VP24 that reconciles all currently available data regarding the role of VP24 in nucleocapsid assembly as well as genome replication and transcription. IMPORTANCE Ebola viruses cause severe hemorrhagic fevers in humans, with no countermeasures currently being available, and must be studied in maximum-containment laboratories. Only a few of these laboratories exist worldwide, limiting our ability to study Ebola viruses and develop countermeasures. Here we report the development of a novel reverse genetics-based system that allows the study of Ebola viruses without maximum-containment laboratories. We used this system to investigate the Ebola virus protein VP24, showing that, contrary to previous reports, it only modestly inhibits virus genome replication and transcription but is important for packaging of genomes into virus particles, which constitutes a previously unknown function of VP24 and a potential antiviral target. We further propose a comprehensive model for the function of VP24 in nucleocapsid assembly. Importantly, on the basis of this approach, it should easily be possible to develop similar experimental systems for other viruses that are currently restricted to maximum-containment laboratories. PMID:24965473

  10. Ebola virus outbreak 2014: clinical review for emergency physicians.

    PubMed

    Meyers, Linda; Frawley, Thomas; Goss, Sarah; Kang, Christopher

    2015-01-01

    The 2014 Ebola outbreak in West Africa is the largest in history. Ebola viral disease is a severe and fatal illness characterized by a nonspecific viral syndrome followed by fulminant septic shock and coagulopathy. Despite ongoing efforts directed at experimental treatments and vaccine development, current medical management of Ebola viral disease is largely limited to supportive therapy, thus making early case identification and immediate implementation of appropriate control measures critical. Because a case of Ebola viral disease was confirmed in the United States on September 30, 2014, emergency medicine providers should be knowledgeable about it for a number of reasons: we are being called on to answer questions about Ebola and allay public fears, we are likely to be first to encounter an infected patient, and there are increasing numbers of US emergency physicians working in Africa who risk coming in direct contact with the disease. This article seeks to provide emergency physicians with the essential and up-to-date information required to identify, evaluate, and manage Ebola viral disease and to join global efforts to contain the current outbreak. PMID:25455908

  11. Treatment of lethal Ebola virus infection in mice with a single dose of an S-adenosyl- l-homocysteine hydrolase inhibitor

    Microsoft Academic Search

    Mike Bray; John Driscoll; John W. Huggins

    2000-01-01

    Ebola Zaire virus causes lethal hemorrhagic fever in humans, for which there is no effective treatment. A variety of adenosine analogues inhibit the replication of Ebola virus in vitro, probably by blocking the cellular enzyme, S-adenosyl-l-homocysteine hydrolase, thereby indirectly limiting methylation of the 5? cap of viral messenger RNA. We previously observed that adult, immunocompetent mice treated thrice daily for

  12. Single-Injection Vaccine Protects Nonhuman Primates against Infection with Marburg Virus and Three Species of Ebola Virus?

    PubMed Central

    Geisbert, Thomas W.; Geisbert, Joan B.; Leung, Anders; Daddario-DiCaprio, Kathleen M.; Hensley, Lisa E.; Grolla, Allen; Feldmann, Heinz

    2009-01-01

    The filoviruses Marburg virus and Ebola virus cause severe hemorrhagic fever with high mortality in humans and nonhuman primates. Among the most promising filovirus vaccines under development is a system based on recombinant vesicular stomatitis virus (VSV) that expresses a single filovirus glycoprotein (GP) in place of the VSV glycoprotein (G). Here, we performed a proof-of-concept study in order to determine the potential of having one single-injection vaccine capable of protecting nonhuman primates against Sudan ebolavirus (SEBOV), Zaire ebolavirus (ZEBOV), Cote d'Ivoire ebolavirus (CIEBOV), and Marburgvirus (MARV). In this study, 11 cynomolgus monkeys were vaccinated with a blended vaccine consisting of equal parts of the vaccine vectors VSV?G/SEBOVGP, VSV?G/ZEBOVGP, and VSV?G/MARVGP. Four weeks later, three of these animals were challenged with MARV, three with CIEBOV, three with ZEBOV, and two with SEBOV. Three control animals were vaccinated with VSV vectors encoding a nonfilovirus GP and challenged with SEBOV, ZEBOV, and MARV, respectively, and five unvaccinated control animals were challenged with CIEBOV. Importantly, none of the macaques vaccinated with the blended vaccine succumbed to a filovirus challenge. As expected, an experimental control animal vaccinated with VSV?G/ZEBOVGP and challenged with SEBOV succumbed, as did the positive controls challenged with SEBOV, ZEBOV, and MARV, respectively. All five control animals challenged with CIEBOV became severely ill, and three of the animals succumbed on days 12, 12, and 14, respectively. The two animals that survived CIEBOV infection were protected from subsequent challenge with either SEBOV or ZEBOV, suggesting that immunity to CIEBOV may be protective against other species of Ebola virus. In conclusion, we developed an immunization scheme based on a single-injection vaccine that protects nonhuman primates against lethal challenge with representative strains of all human pathogenic filovirus species. PMID:19386702

  13. Post-exposure efficacy of oral T-705 (Favipiravir) against inhalational Ebola virus infection in a mouse model.

    PubMed

    Smither, Sophie J; Eastaugh, Lin S; Steward, Jackie A; Nelson, Michelle; Lenk, Robert P; Lever, Mark S

    2014-04-01

    Filoviruses cause disease with high case fatality rates and are considered biological threat agents. Licensed post-exposure therapies that can be administered by the oral route are desired for safe and rapid distribution and uptake in the event of exposure or outbreaks. Favipiravir or T-705 has broad antiviral activity and has already undergone phase II and is undergoing phase III clinical trials for influenza. Here we report the first use of T-705 against Ebola virus. T-705 gave 100% protection against aerosol Ebola virus E718 infection; protection was shown in immune-deficient mice after 14 days of twice-daily dosing. T-705 was also shown to inhibit Ebola virus infection in cell culture. T-705 is likely to be licensed for use against influenza in the near future and could also be used with a new indication for filovirus infection. PMID:24462697

  14. 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.

  15. Regional spread of ebola virus, west Africa, 2014.

    PubMed

    Rainisch, Gabriel; Shankar, Manjunath; Wellman, Michael; Merlin, Toby; Meltzer, Martin I

    2015-03-01

    To explain the spread of the 2014 Ebola epidemic in West Africa, and thus help with response planning, we analyzed publicly available data. We found that the risk for infection in an area can be predicted by case counts, population data, and distances between affected and nonaffected areas. PMID:25693782

  16. Regional Spread of Ebola Virus, West Africa, 2014

    PubMed Central

    Shankar, Manjunath; Wellman, Michael; Merlin, Toby; Meltzer, Martin I.

    2015-01-01

    To explain the spread of the 2014 Ebola epidemic in West Africa, and thus help with response planning, we analyzed publicly available data. We found that the risk for infection in an area can be predicted by case counts, population data, and distances between affected and nonaffected areas. PMID:25693782

  17. Ebola Hemorrhagic Fever Associated with Novel Virus Strain, Uganda, 2007–2008

    PubMed Central

    Lukwago, Luswa; Malimbo, Mugagga; Nguku, Patrick; Yoti, Zabulon; Musenero, Monica; Amone, Jackson; Mbabazi, William; Nanyunja, Miriam; Zaramba, Sam; Opio, Alex; Lutwama, Julius J.; Talisuna, Ambrose O.; Okware, Sam I.

    2010-01-01

    During August 2007–February 2008, the novel Bundibugyo ebolavirus species was identified during an outbreak of Ebola viral hemorrhagic fever in Bundibugyo district, western Uganda. To characterize the outbreak as a requisite for determining response, we instituted a case-series investigation. We identified 192 suspected cases, of which 42 (22%) were laboratory positive for the novel species; 74 (38%) were probable, and 77 (40%) were negative. Laboratory confirmation lagged behind outbreak verification by 3 months. Bundibugyo ebolavirus was less fatal (case-fatality rate 34%) than Ebola viruses that had caused previous outbreaks in the region, and most transmission was associated with handling of dead persons without appropriate protection (adjusted odds ratio 3.83, 95% confidence interval 1.78–8.23). Our study highlights the need for maintaining a high index of suspicion for viral hemorrhagic fevers among healthcare workers, building local capacity for laboratory confirmation of viral hemorrhagic fevers, and institutionalizing standard precautions. PMID:20587179

  18. Evolution of Ebola Virus Disease from Exotic Infection to Global Health Priority, Liberia, Mid-2014

    PubMed Central

    Bawo, Luke; Hunter, Jennifer C.; Massaquoi, Moses; Matanock, Almea; Dahn, Bernice; Ayscue, Patrick; Nyenswah, Tolbert; Forrester, Joseph D.; Hensley, Lisa E.; Monroe, Benjamin; Schoepp, Randal J.; Chen, Tai-Ho; Schaecher, Kurt E.; George, Thomas; Rouse, Edward; Schafer, Ilana J.; Pillai, Satish K.; De Cock, Kevin M.

    2015-01-01

    Over the span of a few weeks during July and August 2014, events in West Africa changed perceptions of Ebola virus disease (EVD) from an exotic tropical disease to a priority for global health security. We describe observations during that time of a field team from the Centers for Disease Control and Prevention and personnel of the Liberian Ministry of Health and Social Welfare. We outline the early epidemiology of EVD within Liberia, including the practical limitations on surveillance and the effect on the country’s health care system, such as infections among health care workers. During this time, priorities included strengthening EVD surveillance; establishing safe settings for EVD patient care (and considering alternative isolation and care models when Ebola Treatment Units were overwhelmed); improving infection control practices; establishing an incident management system; and working with Liberian airport authorities to implement EVD screening of departing passengers. PMID:25811176

  19. Evolution of ebola virus disease from exotic infection to global health priority, liberia, mid-2014.

    PubMed

    Arwady, M Allison; Bawo, Luke; Hunter, Jennifer C; Massaquoi, Moses; Matanock, Almea; Dahn, Bernice; Ayscue, Patrick; Nyenswah, Tolbert; Forrester, Joseph D; Hensley, Lisa E; Monroe, Benjamin; Schoepp, Randal J; Chen, Tai-Ho; Schaecher, Kurt E; George, Thomas; Rouse, Edward; Schafer, Ilana J; Pillai, Satish K; De Cock, Kevin M

    2015-04-01

    Over the span of a few weeks during July and August 2014, events in West Africa changed perceptions of Ebola virus disease (EVD) from an exotic tropical disease to a priority for global health security. We describe observations during that time of a field team from the Centers for Disease Control and Prevention and personnel of the Liberian Ministry of Health and Social Welfare. We outline the early epidemiology of EVD within Liberia, including the practical limitations on surveillance and the effect on the country's health care system, such as infections among health care workers. During this time, priorities included strengthening EVD surveillance; establishing safe settings for EVD patient care (and considering alternative isolation and care models when Ebola Treatment Units were overwhelmed); improving infection control practices; establishing an incident management system; and working with Liberian airport authorities to implement EVD screening of departing passengers. PMID:25811176

  20. Emergency medical services public health implications and interim guidance for the Ebola virus in the United States.

    PubMed

    McCoy, Christopher E; Lotfipour, Shahram; Chakravarthy, Bharath; Schultz, Carl; Barton, Erik

    2014-11-01

    The 25th known outbreak of the Ebola Virus Disease (EVD) is now a global public health emergency and the World Health Organization (WHO) has declared the epidemic to be a Public Health Emergency of International Concern (PHEIC). Since the first cases of the West African epidemic were reported in March 2014, there has been an increase in infection rates of over 13,000% over a 6-month period. The Ebola virus has now arrived in the United States and public health professionals, doctors, hospitals, Emergency Medial Services Administrators, Medical Directors, and policy makers have been working with haste to develop strategies to prevent the disease from reaching epidemic proportions. Prehospital care providers (emergency medical technicians and paramedics) and medical first responders (including but not limited to firefighters and law enforcement) are the healthcare systems front lines when it comes to first medical contact with patients outside of the hospital setting. Risk of contracting Ebola can be particularly high in this population of first responders if the appropriate precautions are not implemented. This article provides a brief clinical overview of the Ebola Virus Disease and provides a comprehensive summary of the Center for Disease Control and Prevention's Interim Guidance for Emergency Medical Services (EMS) Systems and 9-1-1 Public Safety Answering Points (PSAPS) for Management of Patients with Known of Suspected Ebola Virus Disease in the United States. PMID:25493108

  1. Emergency Medical Services Public Health Implications and Interim Guidance for the Ebola Virus in the United States

    PubMed Central

    McCoy, Christopher E.; Lotfipour, Shahram; Chakravarthy, Bharath; Schultz, Carl; Barton, Erik

    2014-01-01

    The 25th known outbreak of the Ebola Virus Disease (EVD) is now a global public health emergency and the World Health Organization (WHO) has declared the epidemic to be a Public Health Emergency of International Concern (PHEIC). Since the first cases of the West African epidemic were reported in March 2014, there has been an increase in infection rates of over 13,000% over a 6-month period. The Ebola virus has now arrived in the United States and public health professionals, doctors, hospitals, Emergency Medial Services Administrators, Medical Directors, and policy makers have been working with haste to develop strategies to prevent the disease from reaching epidemic proportions. Prehospital care providers (emergency medical technicians and paramedics) and medical first responders (including but not limited to firefighters and law enforcement) are the healthcare systems front lines when it comes to first medical contact with patients outside of the hospital setting. Risk of contracting Ebola can be particularly high in this population of first responders if the appropriate precautions are not implemented. This article provides a brief clinical overview of the Ebola Virus Disease and provides a comprehensive summary of the Center for Disease Control and Prevention’s Interim Guidance for Emergency Medical Services (EMS) Systems and 9-1-1 Public Safety Answering Points (PSAPS) for Management of Patients with Known of Suspected Ebola Virus Disease in the United States. PMID:25493108

  2. 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

  3. Phosphorylation of Ebola Virus VP30 Influences the Composition of the Viral Nucleocapsid Complex

    PubMed Central

    Biedenkopf, Nadine; Hartlieb, Bettina; Hoenen, Thomas; Becker, Stephan

    2013-01-01

    Ebola virus is a non-segmented negative-sense RNA virus causing severe hemorrhagic fever with high fatality rates in humans and nonhuman primates. For transcription of the viral genome four viral proteins are essential: the nucleoprotein NP, the polymerase L, the polymerase cofactor VP35, and VP30. VP30 represents an essential Ebola virus-specific transcription factor whose activity is regulated via its phosphorylation state. In contrast to viral transcription, VP30 is not required for viral replication. Using a minigenome assay, we show that phosphorylation of VP30 inhibits viral transcription while viral replication is increased. Concurrently, phosphorylation of VP30 reciprocally regulates a newly described interaction of VP30 with VP35, and strengthens the interaction with NP. Our results indicate a critical role of VP30 phosphorylation for viral transcription and replication, suggesting a mechanism by which VP30 phosphorylation modulates the composition of the viral polymerase complex presumably forming a transcriptase in the presence of non-phosphorylated VP30 or a replicase in the presence of phosphorylated VP30. PMID:23493393

  4. 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

  5. Functional Genomics Reveals the Induction of Inflammatory Response and Metalloproteinase Gene Expression during Lethal Ebola Virus Infection?†

    PubMed Central

    Cilloniz, Cristian; Ebihara, Hideki; Ni, Chester; Neumann, Gabriele; Korth, Marcus J.; Kelly, Sara M.; Kawaoka, Yoshihiro; Feldmann, Heinz; Katze, Michael G.

    2011-01-01

    Ebola virus is the etiologic agent of a lethal hemorrhagic fever in humans and nonhuman primates with mortality rates of up to 90%. Previous studies with Zaire Ebola virus (ZEBOV), mouse-adapted virus (MA-ZEBOV), and mutant viruses (ZEBOV-NPma, ZEBOV-VP24ma, and ZEBOV-NP/VP24ma) allowed us to identify the mutations in viral protein 24 (VP24) and nucleoprotein (NP) responsible for acquisition of high virulence in mice. To elucidate specific molecular signatures associated with lethality, we compared global gene expression profiles in spleen samples from mice infected with these viruses and performed an extensive functional analysis. Our analysis showed that the lethal viruses (MA-ZEBOV and ZEBOV-NP/VP24ma) elicited a strong expression of genes 72 h after infection. In addition, we found that although the host transcriptional response to ZEBOV-VP24ma was nearly the same as that to ZEBOV-NP/VP24ma, the contribution of a mutation in the NP gene was required for a lethal phenotype. Further analysis indicated that one of the most relevant biological functions differentially regulated by the lethal viruses was the inflammatory response, as was the induction of specific metalloproteinases, which were present in our newly identify functional network that was associated with Ebola virus lethality. Our results suggest that this dysregulated proinflammatory response increased the severity of disease. Consequently, the newly discovered molecular signature could be used as the starting point for the development of new drugs and therapeutics. To our knowledge, this is the first study that clearly defines unique molecular signatures associated with Ebola virus lethality. PMID:21734050

  6. A novel Ebola virus expressing luciferase allows for rapid and quantitative testing of antivirals

    PubMed Central

    Hoenen, Thomas; Groseth, Allison; Callison, Julie; Takada, Ayato; Feldmann, Heinz

    2013-01-01

    Ebola virus (EBOV) causes a severe hemorrhagic fever with case fatality rates of up to 90%, for which no antiviral therapies are available. Antiviral screening is hampered by the fact that development of cytopathic effect, the easiest means to detect infection with wild-type EBOV, is relatively slow. To overcome this problem we generated a recombinant EBOV carrying a luciferase reporter. Using this virus we show that EBOV entry is rapid, with viral protein expression detectable within 2 hours after infection. Further, luminescence-based assays were developed to allow highly sensitive titer determination within 48 hours. As a proof-of-concept for its utility in antiviral screening we used this virus to assess neutralizing antibodies and siRNAs, with significantly faster screening times than currently available wild-type or recombinant viruses. The availability of this recombinant virus will allow for more rapid and quantitative evaluation of antivirals against EBOV, as well as the study of details of the EBOV life cycle. PMID:23751367

  7. Ebola Virus VP35 Interaction with Dynein LC8 Regulates Viral RNA Synthesis.

    PubMed

    Luthra, Priya; Jordan, David S; Leung, Daisy W; Amarasinghe, Gaya K; Basler, Christopher F

    2015-05-01

    Ebola virus VP35 inhibits alpha/beta interferon production and functions as a viral polymerase cofactor. Previously, the 8-kDa cytoplasmic dynein light chain (LC8) was demonstrated to interact with VP35, but the functional consequences were unclear. Here we demonstrate that the interaction is direct and of high affinity and that binding stabilizes the VP35 N-terminal oligomerization domain and enhances viral RNA synthesis. Mutational analysis demonstrates that VP35 interaction is required for the functional effects of LC8. PMID:25741013

  8. Evaluation of Ebola Virus Inactivation Procedures for Plasmodium falciparum Malaria Diagnostics.

    PubMed

    Lau, Rachel; Wang, Amanda; Chong-Kit, Ann; Ralevski, Filip; Boggild, Andrea K

    2015-04-01

    Plasmodium falciparum malaria is highly endemic in the three most affected countries in the current epidemic of Ebola virus disease (EVD) in West Africa. As EVD and malaria are clinically indistinguishable, both remain part of the differential diagnosis of ill travelers from returning from areas of EVD transmission. We compared the performances of a rapid diagnostic test (BinaxNOW) and real-time PCR with P. falciparum-positive specimens before and after heat and Triton X-100 inactivation, and we documented no loss of sensitivity. PMID:25631810

  9. Intranasal immunization with an adenovirus vaccine protects guinea pigs from Ebola virus transmission by infected animals.

    PubMed

    Wong, Gary; Richardson, Jason S; Cutts, Todd; Qiu, Xiangguo; Kobinger, Gary P

    2015-04-01

    Experimental Ebola virus (EBOV) vaccines have previously been shown to protect animals against a high dose intramuscular (IM) challenge, which is seen as a stringent challenge model. However, the protective efficacy against other modes of infection, such as contact with infectious hosts, is unknown. Using a previously established EBOV transmission animal model, we evaluated the efficacy of an adenovirus-based EBOV vaccine given to guinea pigs (gps) 4weeks before direct contact with untreated, infectious animals. Prior vaccination resulted in robust levels of EBOV-specific antibodies and conferred complete protection in gps. These results support the use of vaccines to prevent EBOV transmission between hosts. PMID:25596432

  10. Coverage of the Ebola Virus Disease Epidemic in Three Widely Circulated United States Newspapers: Implications for Preparedness and Prevention

    PubMed Central

    Basch, Corey H; Basch, Charles E; Redlener, Irwin

    2014-01-01

    Background:Widespread media attention about Ebola influences public awareness and interest, yet there is limited research on what aspects of Ebola have and have not been communicated through the media. Methods:We examined the nature and extent of coverage about Ebola in the three most widely circulated United States (U.S.) daily newspapers. Between September 17, 2014 and October 17, 2014, 301 articles about Ebola in The New York Times, USA Today, and The Wall Street Journal were identified and coded. Results:The most common topic was coverage of cases in the United States (39%), followed by the outbreak in Africa (33.6%). Conclusion:This is the first study to describe coverage of the Ebola epidemic in widely circulated U.S. newspapers. A substantial portion of the American public is concerned about being infected with Ebola virus disease (EVD). In this study, a large emphasis was placed on death tolls and the cases in the United States. Much more can be done to educate readers about relevant aspects of the Ebola epidemic, including how Ebola is and is not transmitted. PMID:25649411

  11. Ebola virus: The role of macrophages and dendritic cells in the pathogenesis of Ebola hemorrhagic fever

    Microsoft Academic Search

    Mike Bray; Thomas W. Geisbert

    2005-01-01

    Ebola hemorrhagic fever is a severe viral infection characterized by fever, shock and coagulation defects. Recent studies in macaques show that major features of illness are caused by effects of viral replication on macrophages and dendritic cells. Infected macrophages produce proinflammatory cytokines, chemokines and tissue factor, attracting additional target cells and inducing vasodilatation, increased vascular permeability and disseminated intravascular coagulation.

  12. Large serological survey showing cocirculation of Ebola and Marburg viruses in Gabonese bat populations, and a high seroprevalence of both viruses in Rousettus aegyptiacus

    Microsoft Academic Search

    Xavier Pourrut; Marc Souris; Jonathan S Towner; Pierre E Rollin; Stuart T Nichol; Jean-Paul Gonzalez; Eric Leroy

    2009-01-01

    BACKGROUND: Ebola and Marburg viruses cause highly lethal hemorrhagic fevers in humans. Recently, bats of multiple species have been identified as possible natural hosts of Zaire ebolavirus (ZEBOV) in Gabon and Republic of Congo, and also of marburgvirus (MARV) in Gabon and Democratic Republic of Congo. METHODS: We tested 2147 bats belonging to at least nine species sampled between 2003

  13. Vesicular stomatitis virus-based vaccines protect nonhuman primates against aerosol challenge with Ebola and Marburg viruses

    PubMed Central

    Geisbert, Thomas W.; Daddario-DiCaprio, Kathleen M.; Geisbert, Joan B.; Reed, Douglas S.; Feldmann, Friederike; Grolla, Allen; Ströher, Ute; Fritz, Elizabeth A.; Hensley, Lisa E.; Jones, Steven M.; Feldmann, Heinz

    2012-01-01

    Considerable progress has been made over the last decade in developing candidate preventive vaccines that can protect nonhuman primates against Ebola and Marburg viruses. A vaccine based on recombinant vesicular stomatitis virus (VSV) seems to be particularly robust as it can also confer protection when administered as a postexposure treatment. While filoviruses are not thought to be transmitted by aerosol in nature the inhalation route is among the most likely portals of entry in the setting of a bioterrorist event. At present, all candidate filoviral vaccines have been evaluated against parenteral challenges but none have been tested against an aerosol exposure. Here, we evaluated our recombinant VSV-based Zaire ebolavirus (ZEBOV) and Marburg virus (MARV) vaccines against aerosol challenge in cynomolgus macaques. All monkeys vaccinated with a VSV vector expressing the glycoprotein of ZEBOV were completely protected against an aerosol exposure of ZEBOV. Likewise, all monkeys vaccinated with a VSV vector expressing the glycoprotein of MARV were completely protected against an aerosol exposure of MARV. All control animals challenged by the aerosol route with either ZEBOV or MARV succumbed. Interestingly, disease in control animals appeared to progress slower than previously seen in macaques exposed to comparable doses by intramuscular injection. PMID:18930776

  14. Biomarker Correlates of Survival in Pediatric Patients with Ebola Virus Disease

    PubMed Central

    Erickson, Bobbie R.; Flietstra, Timothy D.; Rollin, Pierre E.; Nichol, Stuart T.; Towner, Jonathan S.; Spiropoulou, Christina F.

    2014-01-01

    Outbreaks of Ebola virus disease (EVD) occur sporadically in Africa and are associated with high case-fatality rates. Historically, children have been less affected than adults. The 2000–2001 Sudan virus–associated EVD outbreak in the Gulu district of Uganda resulted in 55 pediatric and 161 adult laboratory-confirmed cases. We used a series of multiplex assays to measure the concentrations of 55 serum analytes in specimens from patients from that outbreak to identify biomarkers specific to pediatric disease. Pediatric patients who survived had higher levels of the chemokine regulated on activation, normal T-cell expressed and secreted marker and lower levels of plasminogen activator inhibitor 1, soluble intracellular adhesion molecule, and soluble vascular cell adhesion molecule than did pediatric patients who died. Adult patients had similar levels of these analytes regardless of outcome. Our findings suggest that children with EVD may benefit from different treatment regimens than those for adults. PMID:25279581

  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. Cyanovirin-N binds to the viral surface glycoprotein, GP 1,2 and inhibits infectivity of Ebola virus

    Microsoft Academic Search

    Laura G. Barrientos; Barry R. O’Keefe; Mike Bray; Anthony Sanchez; Angela M. Gronenborn; Michael R. Boyd

    2003-01-01

    Ebola virus (Ebo) causes severe hemorrhagic fever and high mortality in humans. There are currently no effective therapies. Here, we have explored potential anti-Ebo activity of the human immunodeficiency virus (HIV)-inactivating protein cyanovirin-N (CV-N). CV-N is known to potently inhibit the infectivity of a broad spectrum of HIV strains at the level of viral entry. This involves CV-N binding to

  17. Enzyme-Linked Immunosorbent Assays for Detection of Antibodies to Ebola and Marburg Viruses Using Recombinant Nucleoproteins

    Microsoft Academic Search

    MASAYUKI SAIJO; MASAHIRO NIIKURA; SHIGERU MORIKAWA; THOMAS G. KSIAZEK; RICHARD F. MEYER; CLARENCE J. PETERS; ICHIRO KURANE

    2001-01-01

    The full-length nucleoprotein (NP) of Ebola virus (EBO) was expressed as a His-tagged recombinant protein (His-EBO-NP) by a baculovirus system. Carboxy-terminal halves of NPs of EBO and Marburg virus (MBG) were expressed as glutathione S-transferase-tagged recombinant proteins in an Escherichia coli system. The antigenic regions on the NPs of EBO and MBG were determined by both Western blotting and enzyme-linked

  18. Catheterized guinea pigs infected with Ebola Zaire virus allows safer sequential sampling to determine the pharmacokinetic profile of a phosphatidylserine-targeting monoclonal antibody.

    PubMed

    Dowall, Stuart; Taylor, Irene; Yeates, Paul; Smith, Leonie; Rule, Antony; Easterbrook, Linda; Bruce, Christine; Cook, Nicola; Corbin-Lickfett, Kara; Empig, Cyril; Schlunegger, Kyle; Graham, Victoria; Dennis, Mike; Hewson, Roger

    2013-02-01

    Sequential sampling from animals challenged with highly pathogenic organisms, such as haemorrhagic fever viruses, is required for many pharmaceutical studies. Using the guinea pig model of Ebola virus infection, a catheterized system was used which had the benefits of allowing repeated sampling of the same cohort of animals, and also a reduction in the use of sharps at high biological containment. Levels of a PS-targeting antibody (Bavituximab) were measured in Ebola-infected animals and uninfected controls. Data showed that the pharmacokinetics were similar in both groups, therefore Ebola virus infection did not have an observable effect on the half-life of the antibody. PMID:23165089

  19. In silico analysis suggests interaction between Ebola virus and the extracellular matrix

    PubMed Central

    Veljkovic, Veljko; Glisic, Sanja; Muller, Claude P.; Scotch, Matthew; Branch, Donald R.; Perovic, Vladimir R.; Sencanski, Milan; Veljkovic, Nevena; Colombatti, Alfonso

    2015-01-01

    The worst Ebola virus (EV) outbreak in history has hit Liberia, Sierra Leone and Guinea hardest and the trend lines in this crisis are grave, and now represents a global public health threat concern. Limited therapeutic and/or prophylactic options are available for people suffering from Ebola virus disease (EVD) and further complicate the situation. Previous studies suggested that the EV glycoprotein (GP) is the main determinant causing structural damage of endothelial cells that triggers the hemorrhagic diathesis, but molecular mechanisms underlying this phenomenon remains elusive. Using the informational spectrum method (ISM), a virtual spectroscopy method for analysis of the protein-protein interactions, the interaction of GP with endothelial extracellular matrix (ECM) was investigated. Presented results of this in silico study suggest that Elastin Microfibril Interface Located Proteins (EMILINs) are involved in interaction between GP and ECM. This finding could contribute to a better understanding of EV/endothelium interaction and its role in pathogenesis, prevention and therapy of EVD. PMID:25745423

  20. In silico analysis suggests interaction between Ebola virus and the extracellular matrix.

    PubMed

    Veljkovic, Veljko; Glisic, Sanja; Muller, Claude P; Scotch, Matthew; Branch, Donald R; Perovic, Vladimir R; Sencanski, Milan; Veljkovic, Nevena; Colombatti, Alfonso

    2015-01-01

    The worst Ebola virus (EV) outbreak in history has hit Liberia, Sierra Leone and Guinea hardest and the trend lines in this crisis are grave, and now represents a global public health threat concern. Limited therapeutic and/or prophylactic options are available for people suffering from Ebola virus disease (EVD) and further complicate the situation. Previous studies suggested that the EV glycoprotein (GP) is the main determinant causing structural damage of endothelial cells that triggers the hemorrhagic diathesis, but molecular mechanisms underlying this phenomenon remains elusive. Using the informational spectrum method (ISM), a virtual spectroscopy method for analysis of the protein-protein interactions, the interaction of GP with endothelial extracellular matrix (ECM) was investigated. Presented results of this in silico study suggest that Elastin Microfibril Interface Located Proteins (EMILINs) are involved in interaction between GP and ECM. This finding could contribute to a better understanding of EV/endothelium interaction and its role in pathogenesis, prevention and therapy of EVD. PMID:25745423

  1. 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

  2. Airway Delivery of an Adenovirus-Based Ebola Virus Vaccine Bypasses Existing Immunity to Homologous Adenovirus in Nonhuman Primates

    PubMed Central

    Richardson, Jason S.; Pillet, Stéphane; Bello, Alexander J.

    2013-01-01

    Anti-adenovirus serotype 5 antibodies are capable of neutralizing adenovirus serotype 5-based vaccines. In mice and guinea pigs, intranasal delivery of adenovirus serotype 5-based vaccine bypasses induced adenovirus serotype 5 preexisting immunity, resulting in protection against species-adapted Ebola virus challenge. In this study, nonhuman primates were vaccinated with adenovirus serotype 5-based vaccine either intramuscularly or via the airway route (intranasally/intratracheally) in the presence or absence of adenovirus serotype 5 preexisting immunity. Immune responses were evaluated to determine the effect of both the vaccine delivery route and preexisting immunity before and after a lethal Ebola virus (Zaïre strain Kikwit 95) challenge. Intramuscular vaccination fully protected nonhuman primates in the absence of preexisting immunity, whereas the presence of preexisting immunity abrogated vaccine efficacy and resulted in complete mortality. In contrast, the presence of preexisting immunity to adenovirus serotype 5 did not alter the survival rate of nonhuman primates receiving the adenovirus serotype 5-based Ebola virus vaccine in the airway. This study shows that airway vaccination with adenovirus serotype 5-based Ebola virus vaccine can efficiently bypass preexisting immunity to adenovirus serotype 5 and induce protective immune responses, albeit at lower efficacy than that using an intramuscular vaccine delivery route. PMID:23302894

  3. Development of an Immunofiltration?Based Antigen?Detection Assay for Rapid Diagnosis of Ebola Virus Infection

    Microsoft Academic Search

    Andreas Lucht; Pierre Formenty; Heinz Feldmann; Marion Götz; Eric Leroy; Pierre Bataboukila; Allen Grolla; Friederike Feldmann; Tatiana Wittmann; Patricia Campbell; Catherine Atsangandoko; Paul Boumandoki; Peter Miethe; Stephan Becker; Roland Grunow

    2007-01-01

    Ebola virus (EBOV) has caused outbreaks of severe viral hemorrhagic fever in regions of Central Africa where medical facilities are ill equipped and diagnostic capabilities are limited. To obtain a reliable test that can be implemented easily under these conditions, monoclonal antibodies to the EBOV matrix protein (VP40), which previously had been found to work in a conventional enzyme-linked immunosorbent

  4. Theoretical Evidence that the Ebola Virus Zaire Strain May Be Selenium-Dependent: A Factor in Pathogenesis and Viral Outbreaks?

    Microsoft Academic Search

    Ethan Will Taylor; Chandra Sekar Ramanathan

    A theoretical analysis of the genomic struc- ture of the Ebola virus Zaire strain reveals the existence of several open reading frames (ORFs) containing large numbers of in-frame UGA codons. This clustering of UGA codons is very unlikely to have arisen by chance, and raises the possibility that these ORFs may encode selenoproteins, since, in addi- tion to its usual

  5. 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

  6. Viruses

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Lytic bacteriophages, viruses which infect and lyse bacterial cells, can provide a natural method to reduce bacterial pathogens on produce commodities. The use of multi-phage cocktails is most likely to be effective against bacterial pathogens on produce commodities, and minimize the development of...

  7. 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

  8. Virus-Like Particles Activate Type I Interferon Pathways to Facilitate Post-Exposure Protection against Ebola Virus Infection.

    PubMed

    Ayithan, Natarajan; Bradfute, Steven B; Anthony, Scott M; Stuthman, Kelly S; Bavari, Sina; Bray, Mike; Ozato, Keiko

    2015-01-01

    Ebola virus (EBOV) causes a severe hemorrhagic disease with high fatality. Virus-like particles (VLPs) are a promising vaccine candidate against EBOV. We recently showed that VLPs protect mice from lethal EBOV infection when given before or after viral infection. To elucidate pathways through which VLPs confer post-exposure protection, we investigated the role of type I interferon (IFN) signaling. We found that VLPs lead to accelerated induction of IFN stimulated genes (ISGs) in liver and spleen of wild type mice, but not in Ifnar-/- mice. Accordingly, EBOV infected Ifnar-/- mice, unlike wild type mice succumbed to death even after VLP treatment. The ISGs induced in wild type mice included anti-viral proteins and negative feedback factors known to restrict viral replication and excessive inflammatory responses. Importantly, proinflammatory cytokine/chemokine expression was much higher in WT mice without VLPs than mice treated with VLPs. In EBOV infected Ifnar-/- mice, however, uninhibited viral replication and elevated proinflammatory factor expression ensued, irrespective of VLP treatment, supporting the view that type I IFN signaling helps to limit viral replication and attenuate inflammatory responses. Further analyses showed that VLP protection requires the transcription factor, IRF8 known to amplify type I IFN signaling in dendritic cells and macrophages, the probable sites of initial EBOV infection. Together, this study indicates that VLPs afford post-exposure protection by promoting expeditious initiation of type I IFN signaling in the host. PMID:25719445

  9. Virus-Like Particles Activate Type I Interferon Pathways to Facilitate Post-Exposure Protection against Ebola Virus Infection

    PubMed Central

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

    2015-01-01

    Ebola virus (EBOV) causes a severe hemorrhagic disease with high fatality. Virus-like particles (VLPs) are a promising vaccine candidate against EBOV. We recently showed that VLPs protect mice from lethal EBOV infection when given before or after viral infection. To elucidate pathways through which VLPs confer post-exposure protection, we investigated the role of type I interferon (IFN) signaling. We found that VLPs lead to accelerated induction of IFN stimulated genes (ISGs) in liver and spleen of wild type mice, but not in Ifnar-/- mice. Accordingly, EBOV infected Ifnar-/- mice, unlike wild type mice succumbed to death even after VLP treatment. The ISGs induced in wild type mice included anti-viral proteins and negative feedback factors known to restrict viral replication and excessive inflammatory responses. Importantly, proinflammatory cytokine/chemokine expression was much higher in WT mice without VLPs than mice treated with VLPs. In EBOV infected Ifnar-/- mice, however, uninhibited viral replication and elevated proinflammatory factor expression ensued, irrespective of VLP treatment, supporting the view that type I IFN signaling helps to limit viral replication and attenuate inflammatory responses. Further analyses showed that VLP protection requires the transcription factor, IRF8 known to amplify type I IFN signaling in dendritic cells and macrophages, the probable sites of initial EBOV infection. Together, this study indicates that VLPs afford post-exposure protection by promoting expeditious initiation of type I IFN signaling in the host. PMID:25719445

  10. Hanta virus (image)

    MedlinePLUS

    Hanta virus is a distant cousin of Ebola virus, but is found worldwide. The virus is spread by human contact with rodent waste. Dangerous respiratory illness develops. Effective treatment is not yet ...

  11. Assessment of ebola virus disease, health care infrastructure, and preparedness - four counties,Southeastern Liberia, august 2014.

    PubMed

    Forrester, Joseph D; Pillai, Satish K; Beer, Karlyn D; Neatherlin, John; Massaquoi, Moses; Nyenswah, Tolbert G; Montgomery, Joel M; De Cock, Kevin

    2014-10-10

    Ebola virus disease (Ebola) is a multisystem disease caused by a virus of the genus Ebolavirus. In late March 2014, Ebola cases were described in Liberia, with epicenters in Lofa County and later in Montserrado County. While information about case burden and health care infrastructure was available for the two epicenters, little information was available about remote counties in southeastern Liberia. Over 9 days, August 6-14, 2014, Ebola case burden, health care infrastructure, and emergency preparedness were assessed in collaboration with the Liberian Ministry of Health and Social Welfare in four counties in southeastern Liberia: Grand Gedeh, Grand Kru, River Gee, and Maryland. Data were collected by health care facility visits to three of the four county referral hospitals and by unstructured interviews with county and district health officials, hospital administrators, physicians, nurses, physician assistants, and health educators in all four counties. Local burial practices were discussed with county officials, but no direct observation of burial practices was conducted. Basic information about Ebola surveillance and epidemiology, case investigation, contact tracing, case management, and infection control was provided to local officials. PMID:25299605

  12. Tissue and cellular tropism, pathology and pathogenesis of Ebola and Marburg viruses.

    PubMed

    Martines, Roosecelis Brasil; Ng, Dianna L; Greer, Patricia W; Rollin, Pierre E; Zaki, Sherif R

    2015-01-01

    Ebola viruses and Marburg viruses include some of the most virulent and fatal pathogens known to humans. These viruses cause severe haemorrhagic fevers, with case fatality rates in the range 25-90%. The diagnosis of filovirus using formalin-fixed tissues from fatal cases poses a significant challenge. The most characteristic histopathological findings are seen in the liver; however, the findings overlap with many other viral and non-viral haemorrhagic diseases. The need to distinguish filovirus infections from other haemorrhagic fevers, particularly in areas with multiple endemic viral haemorrhagic agents, is of paramount importance. In this review we discuss the current state of knowledge of filovirus infections and their pathogenesis, including histopathological findings, epidemiology, modes of transmission and filovirus entry and spread within host organisms. The pathogenesis of filovirus infections is complex and involves activation of the mononuclear phagocytic system, with release of pro-inflammatory cytokines, chemokines and growth factors, endothelial dysfunction, alterations of the innate and adaptive immune systems, direct organ and endothelial damage from unrestricted viral replication late in infection, and coagulopathy. Although our understanding of the pathogenesis of filovirus infections has rapidly increased in the past few years, many questions remain unanswered. PMID:25297522

  13. Virology. Mutation rate and genotype variation of Ebola virus from Mali case sequences.

    PubMed

    Hoenen, T; Safronetz, D; Groseth, A; Wollenberg, K R; Koita, O A; Diarra, B; Fall, I S; Haidara, F C; Diallo, F; Sanogo, M; Sarro, Y S; Kone, A; Togo, A C G; Traore, A; Kodio, M; Dosseh, A; Rosenke, K; de Wit, E; Feldmann, F; Ebihara, H; Munster, V J; Zoon, K C; Feldmann, H; Sow, S

    2015-04-01

    The occurrence of Ebola virus (EBOV) in West Africa during 2013-2015 is unprecedented. Early reports suggested that in this outbreak EBOV is mutating twice as fast as previously observed, which indicates the potential for changes in transmissibility and virulence and could render current molecular diagnostics and countermeasures ineffective. We have determined additional full-length sequences from two clusters of imported EBOV infections into Mali, and we show that the nucleotide substitution rate (9.6 × 10(-4) substitutions per site per year) is consistent with rates observed in Central African outbreaks. In addition, overall variation among all genotypes observed remains low. Thus, our data indicate that EBOV is not undergoing rapid evolution in humans during the current outbreak. This finding has important implications for outbreak response and public health decisions and should alleviate several previously raised concerns. PMID:25814067

  14. 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

  15. Characterization of clinical and immunological parameters during Ebola virus infection of rhesus macaques.

    PubMed

    Martins, Karen; Cooper, Christopher; Warren, Travis; Wells, Jay; Bell, Todd; Raymond, Jolynne; Stuthman, Kelly; Benko, Jacqueline; Garza, Nicole; van Tongeren, Sean; Donnelly, Ginger; Retterer, Cary; Dong, Lian; Bavari, Sina

    2015-02-01

    The rhesus macaque serves as an animal model for Ebola virus (EBOV) infection. A thorough understanding of EBOV infection in this species would aid in further development of filovirus therapeutics and vaccines. In this study, pathological and immunological data from EBOV-infected rhesus macaques are presented. Changes in blood chemistries, hematology, coagulation, and immune parameters during infection, which were consistently observed in the animals, are presented. In an animal that survived challenge, a delay was observed in the detection of viral RNA and inflammatory cytokines and chemokines which may have contributed to survival. Collectively, these data add to the body of knowledge regarding EBOV pathogenesis in rhesus macaques and emphasize the reproducibility of the rhesus macaque challenge model. PMID:25514385

  16. A case of severe Ebola virus infection complicated by gram-negative septicemia.

    PubMed

    Kreuels, Benno; Wichmann, Dominic; Emmerich, Petra; Schmidt-Chanasit, Jonas; de Heer, Geraldine; Kluge, Stefan; Sow, Abdourahmane; Renné, Thomas; Günther, Stephan; Lohse, Ansgar W; Addo, Marylyn M; Schmiedel, Stefan

    2014-12-18

    Ebola virus disease (EVD) developed in a patient who contracted the disease in Sierra Leone and was airlifted to an isolation facility in Hamburg, Germany, for treatment. During the course of the illness, he had numerous complications, including septicemia, respiratory failure, and encephalopathy. Intensive supportive treatment consisting of high-volume fluid resuscitation (approximately 10 liters per day in the first 72 hours), broad-spectrum antibiotic therapy, and ventilatory support resulted in full recovery without the use of experimental therapies. Discharge was delayed owing to the detection of viral RNA in urine (day 30) and sweat (at the last assessment on day 40) by means of polymerase-chain-reaction (PCR) assay, but the last positive culture was identified in plasma on day 14 and in urine on day 26. This case shows the challenges in the management of EVD and suggests that even severe EVD can be treated effectively with routine intensive care. PMID:25337633

  17. 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

  18. 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

  19. Vesicular Stomatitis Virus–Based Ebola Vaccines With Improved Cross-Protective Efficacy

    PubMed Central

    Marzi, Andrea; Ebihara, Hideki; Callison, Julie; Groseth, Allison; Williams, Kinola J.; Geisbert, Thomas W.

    2011-01-01

    For Ebola virus (EBOV), 4 different species are known: Zaire, Sudan, Côte d’Ivoire, and Reston ebolavirus. The newly discovered Bundibugyo ebolavirus has been proposed as a 5th species. So far, no cross-neutralization among EBOV species has been described, aggravating progress toward cross-species protective vaccines. With the use of recombinant vesicular stomatitis virus (rVSV)–based vaccines, guinea pigs could be protected against Zaire ebolavirus (ZEBOV) infection only when immunized with a vector expressing the homologous, but not a heterologous, EBOV glycoprotein (GP). However, infection of guinea pigs with nonadapted wild-type strains of the different species resulted in full protection of all animals against subsequent challenge with guinea pig–adapted ZEBOV, showing that cross-species protection is possible. New vectors were generated that contain EBOV viral protein 40 (VP40) or EBOV nucleoprotein (NP) as a second antigen expressed by the same rVSV vector that encodes the heterologous GP. After applying a 2-dose immunization approach, we observed an improved cross-protection rate, with 5 of 6 guinea pigs surviving the lethal ZEBOV challenge if vaccinated with rVSV-expressing SEBOV-GP and -VP40. Our data demonstrate that cross-protection between the EBOV species can be achieved, although EBOV-GP alone cannot induce the required immune response. PMID:21987743

  20. 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

  1. 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

  2. Contribution of Sec61? to the Life Cycle of Ebola Virus

    PubMed Central

    Iwasa, Ayaka; Halfmann, Peter; Noda, Takeshi; Oyama, Masaaki; Kozuka-Hata, Hiroko; Watanabe, Shinji; Shimojima, Masayuki; Watanabe, Tokiko

    2011-01-01

    Background.?Similar to other viruses, the viral proteins of Ebola virus (EBOV) interact with a variety of host proteins for its replication. Of the 7 structural proteins encoded in the EBOV genome, VP24 is the smallest and is multifunctional. ?Methods.?To identify host factors that interact with VP24 and are required for EBOV replication, we transfected 293 cells with plasmid expressing FLAG- and HA-tagged VP24, immunoprecipitated the host proteins that bound to VP24, and analyzed the immunoprecipitants with use of mass spectrometry. Results.?Of the 68 candidate host proteins identified, we selected Sec61? because of its similar intracellular localization to that of VP24 (ie, perinuclear region), its involvement in various biological functions, and its roles in pathogenesis, such as type 2 diabetes and hepatosteatosis, and investigated its possible role in the EBOV life cycle. Our results suggest that Sec61? is not involved in EBOV entry, interferon antagonism by VP24, nucleocapsid formation, or budding. However, Sec61? colocalized with VP24 contributed to the ability of VP24 to inhibit EBOV genome transcription and reduced the polymerase activity of EBOV. Conclusions.?The present study indicates that Sec61? is a host protein involved in EBOV replication, specifically in EBOV genome transcription and replication. PMID:21987770

  3. 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

  4. The virion glycoproteins of Ebola viruses are encoded in two reading frames and are expressed through transcriptional editing.

    PubMed Central

    Sanchez, A; Trappier, S G; Mahy, B W; Peters, C J; Nichol, S T

    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 results in the addition of an extra nontemplated adenosine within a run of seven adenosines near the middle of the coding region. The primary gene product is a smaller (50-70 kDa), nonstructural, secreted glycoprotein, which is produced in large amounts and has an unknown function. Phylogenetic analysis indicates that EBO virus subtypes are genetically diverse and that the recent Ivory Coast isolate represents a new (fourth) subtype of EBO virus. In contrast, the EBO virus isolate from the 1995 outbreak in Kikwit, Zaire, is virtually identical to the virus that caused a similar epidemic in Yambuku, Zaire, almost 20 years earlier. This genetic stability may indicate that EBO viruses have coevolved with their natural reservoirs and do not change appreciably in the wild. Images Fig. 2 Fig. 3 PMID:8622982

  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. Cathepsin cleavage potentiates the Ebola virus glycoprotein to undergo a subsequent fusion-relevant conformational change.

    PubMed

    Brecher, Matthew; Schornberg, Kathryn L; Delos, Sue E; Fusco, Marnie L; Saphire, Erica Ollmann; White, Judith M

    2012-01-01

    Cellular entry of Ebola virus (EBOV), a deadly hemorrhagic fever virus, is mediated by the viral glycoprotein (GP). The receptor-binding subunit of GP must be cleaved (by endosomal cathepsins) in order for entry and infection to proceed. Cleavage appears to proceed through 50-kDa and 20-kDa intermediates, ultimately generating a key 19-kDa core. How 19-kDa GP is subsequently triggered to bind membranes and induce fusion remains a mystery. Here we show that 50-kDa GP cannot be triggered to bind to liposomes in response to elevated temperature but that 20-kDa and 19-kDa GP can. Importantly, 19-kDa GP can be triggered at temperatures ?10°C lower than 20-kDa GP, suggesting that it is the most fusion ready form. Triggering by heat (or urea) occurs only at pH 5, not pH 7.5, and involves the fusion loop, as a fusion loop mutant is defective in liposome binding. We further show that mild reduction (preferentially at low pH) triggers 19-kDa GP to bind to liposomes, with the wild-type protein being triggered to a greater extent than the fusion loop mutant. Moreover, mild reduction inactivates pseudovirion infection, suggesting that reduction can also trigger 19-kDa GP on virus particles. Our results support the hypothesis that priming of EBOV GP, specifically to the 19-kDa core, potentiates GP to undergo subsequent fusion-relevant conformational changes. Our findings also indicate that low pH and an additional endosomal factor (possibly reduction or possibly a process mimicked by reduction) act as fusion triggers. PMID:22031933

  7. Teaching themes Entry of viruses into cells: receptor binding, structural basis of the entry process and uncoating.

    E-print Network

    Brierley, Andrew

    important human and animal diseases are caused by RNA viruses - Influenza, Measles, SARS, Ebola, Polio Nadurelia capensis virus MS25CCMV Influenza virus Ebola virusMeasles virus SARS virus calicviruses dengue

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

    PubMed

    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

  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. 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

  11. 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

  12. Sustained protection against Ebola virus infection following treatment of infected nonhuman primates with ZMAb

    PubMed Central

    Qiu, Xiangguo; Audet, Jonathan; Wong, Gary; Fernando, Lisa; Bello, Alexander; Pillet, Stéphane; Alimonti, Judie B.; Kobinger, Gary P.

    2013-01-01

    Ebola virus (EBOV) is one of the most lethal filoviruses, with mortality rates of up to 90% in humans. Previously, we demonstrated 100% and 50% survival of EBOV-infected cynomologus macaques with a combination of 3 EBOV-GP-specific monoclonal antibodies (ZMAb) administered at 24 or 48 hours post-exposure, respectively. The survivors demonstrated EBOV-GP–specific humoral and cell-mediated immune responses. In order to evaluate whether the immune response induced in NHPs during the ZMAb treatment and EBOV challenge is sufficient to protect survivors against a subsequent exposure, animals that survived the initial challenge were rechallenged at 10 or 13 weeks after the initial challenge. The animals rechallenged at 10 weeks all survived whereas 4 of 6 animals survived a rechallenge at 13 weeks. The data indicate that a robust immune response was generated during the successful treatment of EBOV-infected NHPs with EBOV, which resulted in sustained protection against a second lethal exposure. PMID:24284388

  13. 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

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

    PubMed Central

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

    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 protein functions as an inhibitor of IFN-?/? and IFN-? signaling. Expression of VP24 results in an inhibition of IFN-induced gene expression and an inability of IFNs to induce an antiviral state. The VP24-mediated inhibition of cellular responses to IFNs correlates with the impaired nuclear accumulation of tyrosine-phosphorylated STAT1 (PY-STAT1), a key step in both IFN-?/? and IFN-? signaling. Consistent with this proposed function for VP24, infection of cells with EBOV also confers a block to the IFN-induced nuclear accumulation of PY-STAT1. Further, VP24 is found to specifically interact with karyopherin ?1, the nuclear localization signal receptor for PY-STAT1, but not with karyopherin ?2, ?3, or ?4. Overexpression of VP24 results in a loss of karyopherin ?1-PY-STAT1 interaction, indicating that the VP24-karyopherin ?1 interaction contributes to the block to IFN signaling. These data suggest that VP24 is likely to be an important virulence determinant that allows EBOV to evade the antiviral effects of IFNs. PMID:16698996

  15. 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.

  16. 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.

  17. Ebola virus VP30-mediated transcription is regulated by RNA secondary structure formation.

    PubMed

    Weik, Michael; Modrof, Jens; Klenk, Hans-Dieter; Becker, Stephan; Mühlberger, Elke

    2002-09-01

    The nucleocapsid protein VP30 of Ebola virus (EBOV), a member of the Filovirus family, is known to act as a transcription activator. By using a reconstituted minigenome system, the role of VP30 during transcription was investigated. We could show that VP30-mediated transcription activation is dependent on formation of a stem-loop structure at the first gene start site. Destruction of this secondary structure led to VP30-independent transcription. Analysis of the transcription products of bicistronic minigenomes with and without the ability to form the secondary structure at the first transcription start signal revealed that transcription initiation at the first gene start site is a prerequisite for transcription of the second gene, independent of the presence of VP30. When the transcription start signal of the second gene was exchanged with the transcription start signal of the first gene, transcription of the second gene also was regulated by VP30, indicating that the stem-loop structure of the first transcription start site acts autonomously and independently of its localization on the RNA genome. Our results suggest that VP30 regulates a very early step of EBOV transcription, most likely by inhibiting pausing of the transcription complex at the RNA structure of the first transcription start site. PMID:12163572

  18. Antibodies are necessary for rVSV/ZEBOV-GP-mediated protection against lethal Ebola virus challenge in nonhuman primates.

    PubMed

    Marzi, Andrea; Engelmann, Flora; Feldmann, Friederike; Haberthur, Kristen; Shupert, W Lesley; Brining, Douglas; Scott, Dana P; Geisbert, Thomas W; Kawaoka, Yoshihiro; Katze, Michael G; Feldmann, Heinz; Messaoudi, Ilhem

    2013-01-29

    Ebola viruses cause hemorrhagic disease in humans and nonhuman primates with high fatality rates. These viruses pose a significant health concern worldwide due to the lack of approved therapeutics and vaccines as well as their potential misuse as bioterrorism agents. Although not licensed for human use, recombinant vesicular stomatitis virus (rVSV) expressing the filovirus glycoprotein (GP) has been shown to protect macaques from Ebola virus and Marburg virus infections, both prophylactically and postexposure in a homologous challenge setting. However, the immune mechanisms of protection conferred by this vaccine platform remain poorly understood. In this study, we set out to investigate the role of humoral versus cellular immunity in rVSV vaccine-mediated protection against lethal Zaire ebolavirus (ZEBOV) challenge. Groups of cynomolgus macaques were depleted of CD4+ T, CD8+ T, or CD20+ B cells before and during vaccination with rVSV/ZEBOV-GP. Unfortunately, CD20-depleted animals generated a robust IgG response. Therefore, an additional group of vaccinated animals were depleted of CD4+ T cells during challenge. All animals were subsequently challenged with a lethal dose of ZEBOV. Animals depleted of CD8+ T cells survived, suggesting a minimal role for CD8+ T cells in vaccine-mediated protection. Depletion of CD4+ T cells during vaccination caused a complete loss of glycoprotein-specific antibodies and abrogated vaccine protection. In contrast, depletion of CD4+ T cells during challenge resulted in survival of the animals, indicating a minimal role for CD4+ T-cell immunity in rVSV-mediated protection. Our results suggest that antibodies play a critical role in rVSV-mediated protection against ZEBOV. PMID:23319647

  19. Ebola Virus VP24 Proteins Inhibit the Interaction of NPI-1 Subfamily Karyopherin ? Proteins with Activated STAT1?

    PubMed Central

    Reid, St. Patrick; Valmas, Charalampos; Martinez, Osvaldo; Sanchez, Freddy Mauricio; Basler, Christopher F.

    2007-01-01

    The Zaire ebolavirus protein VP24 was previously demonstrated to inhibit alpha/beta interferon (IFN-?/?)- and IFN-?-induced nuclear accumulation of tyrosine-phosphorylated STAT1 (PY-STAT1) and to inhibit IFN-?/?- and IFN-?-induced gene expression. These properties correlated with the ability of VP24 to interact with the nuclear localization signal receptor for PY-STAT1, karyopherin ?1. Here, VP24 is demonstrated to interact not only with overexpressed but also with endogenous karyopherin ?1. Mutational analysis demonstrated that VP24 binds within the PY-STAT1 binding region located in the C terminus of karyopherin ?1. In addition, VP24 was found to inhibit PY-STAT1 binding to both overexpressed and endogenous karyopherin ?1. We assessed the binding of both PY-STAT1 and the VP24 proteins from Zaire, mouse-adapted Zaire, and Reston Ebola viruses for interaction with all six members of the human karyopherin ? family. We found, in contrast to previous studies, that PY-STAT1 can interact not only with karyopherin ?1 but also with karyopherins ?5 and ?6, which together comprise the NPI-1 subfamily of karyopherin ?s. Similarly, all three VP24s bound and inhibited PY-STAT1 interaction with karyopherins ?1, ?5, and ?6. Consistent with their ability to inhibit the karyopherin-PY-STAT1 interaction, Zaire, mouse-adapted Zaire, and Reston Ebola virus VP24s displayed similar capacities to inhibit IFN-?-induced gene expression in human and mouse cells. These findings suggest that VP24 inhibits interaction of PY-STAT1 with karyopherins ?1, ?5, or ?6 by binding within the PY-STAT1 binding region of the karyopherins and that this function is conserved among the VP24 proteins of different Ebola virus species. PMID:17928350

  20. A Loop Region in the N-Terminal Domain of Ebola Virus VP40 Is Important in Viral Assembly, Budding, and Egress

    PubMed Central

    Adu-Gyamfi, Emmanuel; Soni, Smita P.; Jee, Clara S.; Digman, Michelle A.; Gratton, Enrico; Stahelin, Robert V.

    2014-01-01

    Ebola virus (EBOV) causes viral hemorrhagic fever in humans and can have clinical fatality rates of ~60%. The EBOV genome consists of negative sense RNA that encodes seven proteins including viral protein 40 (VP40). VP40 is the major Ebola virus matrix protein and regulates assembly and egress of infectious Ebola virus particles. It is well established that VP40 assembles on the inner leaflet of the plasma membrane of human cells to regulate viral budding where VP40 can produce virus like particles (VLPs) without other Ebola virus proteins present. The mechanistic details, however, of VP40 lipid-interactions and protein-protein interactions that are important for viral release remain to be elucidated. Here, we mutated a loop region in the N-terminal domain of VP40 (Lys127, Thr129, and Asn130) and find that mutations (K127A, T129A, and N130A) in this loop region reduce plasma membrane localization of VP40. Additionally, using total internal reflection fluorescence microscopy and number and brightness analysis we demonstrate these mutations greatly reduce VP40 oligomerization. Lastly, VLP assays demonstrate these mutations significantly reduce VLP release from cells. Taken together, these studies identify an important loop region in VP40 that may be essential to viral egress. PMID:25330123

  1. 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.

  2. Ebola Virus Modulates Transforming Growth Factor ? Signaling and Cellular Markers of Mesenchyme-Like Transition in Hepatocytes

    PubMed Central

    Wahl-Jensen, Victoria; Safronetz, David; Trost, Brett; Hoenen, Thomas; Arsenault, Ryan; Feldmann, Friederike; Traynor, Dawn; Postnikova, Elena; Kusalik, Anthony; Napper, Scott; Blaney, Joseph E.; Feldmann, Heinz; Jahrling, Peter B.

    2014-01-01

    ABSTRACT Ebola virus (EBOV) causes a severe hemorrhagic disease in humans and nonhuman primates, with a median case fatality rate of 78.4%. Although EBOV is considered a public health concern, there is a relative paucity of information regarding the modulation of the functional host response during infection. We employed temporal kinome analysis to investigate the relative early, intermediate, and late host kinome responses to EBOV infection in human hepatocytes. Pathway overrepresentation analysis and functional network analysis of kinome data revealed that transforming growth factor (TGF-?)-mediated signaling responses were temporally modulated in response to EBOV infection. Upregulation of TGF-? signaling in the kinome data sets correlated with the upregulation of TGF-? secretion from EBOV-infected cells. Kinase inhibitors targeting TGF-? signaling, or additional cell receptors and downstream signaling pathway intermediates identified from our kinome analysis, also inhibited EBOV replication. Further, the inhibition of select cell signaling intermediates identified from our kinome analysis provided partial protection in a lethal model of EBOV infection. To gain perspective on the cellular consequence of TGF-? signaling modulation during EBOV infection, we assessed cellular markers associated with upregulation of TGF-? signaling. We observed upregulation of matrix metalloproteinase 9, N-cadherin, and fibronectin expression with concomitant reductions in the expression of E-cadherin and claudin-1, responses that are standard characteristics of an epithelium-to-mesenchyme-like transition. Additionally, we identified phosphorylation events downstream of TGF-? that may contribute to this process. From these observations, we propose a model for a broader role of TGF-?-mediated signaling responses in the pathogenesis of Ebola virus disease. IMPORTANCE Ebola virus (EBOV), formerly Zaire ebolavirus, causes a severe hemorrhagic disease in humans and nonhuman primates and is the most lethal Ebola virus species, with case fatality rates of up to 90%. Although EBOV is considered a worldwide concern, many questions remain regarding EBOV molecular pathogenesis. As it is appreciated that many cellular processes are regulated through kinase-mediated phosphorylation events, we employed temporal kinome analysis to investigate the functional responses of human hepatocytes to EBOV infection. Administration of kinase inhibitors targeting signaling pathway intermediates identified in our kinome analysis inhibited viral replication in vitro and reduced EBOV pathogenesis in vivo. Further analysis of our data also demonstrated that EBOV infection modulated TGF-?-mediated signaling responses and promoted “mesenchyme-like” phenotypic changes. Taken together, these results demonstrated that EBOV infection specifically modulates TGF-?-mediated signaling responses in epithelial cells and may have broader implications in EBOV pathogenesis. PMID:24942569

  3. Monoclonal Antibodies Combined with Adenovirus-Vectored Interferon Significantly Extend the Treatment Window in Ebola Virus-Infected Guinea Pigs

    PubMed Central

    Wong, Gary; Fernando, Lisa; Ennis, Jane; Turner, Jeffrey D.; Alimonti, Judie B.; Yao, Xiaojian

    2013-01-01

    Monoclonal antibodies (MAbs) are currently a promising treatment strategy against Ebola virus infection. This study combined MAbs with an adenovirus-vectored interferon (DEF201) to evaluate the efficacy in guinea pigs and extend the treatment window obtained with MAbs alone. Initiating the combination therapy at 3 days postinfection (d.p.i.) provided 100% survival, a significant improvement over survival with either treatment alone. The administration of DEF201 within 2 d.p.i. permits later MAb use, with protective efficacy observed up to 8 d.p.i. PMID:23616649

  4. 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

  5. Public Knowledge, Perception and Source of Information on Ebola Virus Disease – Lagos, Nigeria; September, 2014

    PubMed Central

    Gidado, Saheed; Oladimeji, Abisola M.; Roberts, Alero Ann; Nguku, Patrick; Nwangwu, Iruoma Genevieve; Waziri, Ndadilnasiya Endie; Shuaib, Faisal; Oguntimehin, Olukayode; Musa, Emmanuel; Nzuki, Charles; Nasidi, Abdulsalami; Adewuyi, Peter; Daniel, Tom-Aba; Olayinka, Adebola; Odubanjo, Oladoyin; Poggensee, Gabriele

    2015-01-01

    Background: The first ever outbreak of Ebola virus disease (EVD) in Nigeria was declared in July, 2014. Level of public knowledge, perception and adequacy of information on EVD were unknown. We assessed the public preparedness level to adopt disease preventive behavior which is premised on appropriate knowledge, perception and adequate information. Methods: We enrolled 5,322 respondents in a community-based cross-sectional study. We used interviewer-administered questionnaire to collect data on socio-demographic characteristics, EVD–related knowledge, perception and source of information. We performed univariate and bivariate data analysis using Epi-Info software setting p-value of 0.05 as cut-off for statistical significance. Results: Mean age of respondents was 34 years (± 11.4 years), 52.3% were males. Forty one percent possessed satisfactory general knowledge; 44% and 43.1% possessed satisfactory knowledge on mode of spread and preventive measures, respectively. Residing in EVD cases districts, male respondents and possessing at least secondary education were positively associated with satisfactory general knowledge (p-value: 0.01, 0.001 and 0.000004, respectively). Seventy one percent perceived EVD as a public health problem while 61% believed they cannot contract the disease. Sixty two percent and 64% of respondents will not shake hands and hug a successfully treated EVD patient respectively. Only 2.2% of respondents practice good hand-washing practice. Television (68.8%) and radio (55.0%) are the most common sources of information on EVD. Conclusions: Gaps in EVD-related knowledge and perception exist. Targeted public health messages to raise knowledge level, correct misconception and discourage stigmatization should be widely disseminated, with television and radio as media of choice.

  6. 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

  7. Haematological, Biochemical and Coagulation Changes in Mice, Guinea-pigs and Monkeys Infected with a Mouse-adapted Variant of Ebola Zaire Virus

    Microsoft Academic Search

    M. Bray; S. Hatfill; L. Hensley; J. W. Huggins

    2001-01-01

    Ebola Zaire virus from the 1976 outbreak (EBO-Z) was recently adapted to the stage of lethal virulence in BALB\\/c mice through serial passage. In the present study, various parameters were examined in groups of mice and guinea-pigs and in three rhesus monkeys after infection with mouse-adapted EBO-Z. The virus caused fatal disease not only in mice but also in guinea-pigs,

  8. The VP35 Protein of Ebola Virus Inhibits the Antiviral Effect Mediated by Double-Stranded RNA-Dependent Protein Kinase PKR

    Microsoft Academic Search

    Zongdi Feng; Melissa Cerveny; Zhipeng Yan; Bin He

    2007-01-01

    The VP35 protein of Ebola virus is a viral antagonist of interferon. It acts to block virus or double-stranded RNA-mediated activation of interferon regulatory factor 3, a transcription factor that facilitates the expression of interferon and interferon-stimulated genes. In this report, we show that the VP35 protein is also able to inhibit the antiviral response induced by alpha interferon. This

  9. With strengthened guidelines for health care workers, the CDC ups its game against the deadly Ebola virus.

    PubMed

    2014-12-01

    Informed by the cases of two nurses who contracted Ebola virus disease (EVD) while caring for a patient with the disease in Dallas, TX, the Centers for Disease Control and Prevention (CDC) in Atlanta, GA, has unveiled strengthened guidance for health care workers. Further, nursing organizations are pledging to work together to identify gaps and make system-level improvements to protect both patients and caregivers. The CDC's new recommendations emphasize rigorous training for health care workers in how to put on and take off personal protective equipment (PPE), and they state that this activity should always be carefully supervised by a monitor. The guidance also states that health care workers should use either an N-95' respirator mask or a powered air purifying respirator (PAPR) when they are providing care to a patient with Ebola. Experts stress that the new guidance does not change the fundamental issue that Ebola is transmitted through contact with infectious substances from patients. Nursing organizations are pledging to work together to identify problems and improve safety for both caregivers and patients. PMID:25522493

  10. Analysis of Human Peripheral Blood Samples from Fatal and Nonfatal Cases of Ebola (Sudan) Hemorrhagic Fever: Cellular Responses, Virus Load, and Nitric Oxide Levels

    Microsoft Academic Search

    Anthony Sanchez; Matthew Lukwiya; Daniel Bausch; Siddhartha Mahanty; Angela J. Sanchez; Kent D. Wagoner; Pierre E. Rollin

    2004-01-01

    Peripheral blood samples obtained from patients during an outbreak of Ebola virus (Sudan species) disease in Uganda in 2000 were used to phenotype peripheral blood mononuclear cells (PBMC), quantitate gene expression, measure antigenemia, and determine nitric oxide levels. It was determined that as the severity of disease increased in infected patients, there was a corresponding increase in antigenemia and leukopenia.

  11. Designed protein mimics of the Ebola virus glycoprotein GP2 ?-helical bundle: stability and pH effects.

    PubMed

    Harrison, Joseph S; Higgins, Chelsea D; Chandran, Kartik; Lai, Jonathan R

    2011-09-01

    Ebola virus (EboV) belongs to the Filoviridae family of viruses that causes severe and fatal hemhorragic fever. Infection by EboV involves fusion between the virus and host cell membranes mediated by the envelope glycoprotein GP2 of the virus. Similar to the envelope glycoproteins of other viruses, the central feature of the GP2 ectodomain postfusion structure is a six-helix bundle formed by the protein's N- and C-heptad repeat regions (NHR and CHR, respectively). Folding of this six-helix bundle provides the energetic driving force for membrane fusion; in other viruses, designed agents that disrupt formation of the six-helix bundle act as potent fusion inhibitors. To interrogate determinants of EboV GP2-mediated membrane fusion, we designed model proteins that consist of the NHR and CHR segments linked by short protein linkers. Circular dichroism and gel filtration studies indicate that these proteins adopt stable ?-helical folds consistent with design. Thermal denaturation indicated that the GP2 six-helix bundle is highly stable at pH 5.3 (melting temperature, T(m) , of 86.8 ± 2.0°C and van't Hoff enthalpy, ?H(vH) , of -28.2 ± 1.0 kcal/mol) and comparable in stability to other viral membrane fusion six-helix bundles. We found that the stability of our designed ?-helical bundle proteins was dependent on buffering conditions with increasing stability at lower pH. Small pH differences (5.3-6.1) had dramatic effects (?T(m) = 37°C) suggesting a mechanism for conformational control that is dependent on environmental pH. These results suggest a role for low pH in stabilizing six-helix bundle formation during the process of GP2-mediated viral membrane fusion. PMID:21739501

  12. Conserved Motifs within Ebola and Marburg Virus VP40 Proteins Are Important for Stability, Localization, and Subsequent Budding of Virus-Like Particles ?

    PubMed Central

    Liu, Yuliang; Cocka, Luis; Okumura, Atsushi; Zhang, Yong-An; Sunyer, J. Oriol; Harty, Ronald N.

    2010-01-01

    The filovirus VP40 protein is capable of budding from mammalian cells in the form of virus-like particles (VLPs) that are morphologically indistinguishable from infectious virions. Ebola virus VP40 (eVP40) contains well-characterized overlapping L domains, which play a key role in mediating efficient virus egress. L domains represent only one component required for efficient budding and, therefore, there is a need to identify and characterize additional domains important for VP40 function. We demonstrate here that the 96LPLGVA101 sequence of eVP40 and the corresponding 84LPLGIM89 sequence of Marburg virus VP40 (mVP40) are critical for efficient release of VP40 VLPs. Indeed, deletion of these motifs essentially abolished the ability of eVP40 and mVP40 to bud as VLPs. To address the mechanism by which the 96LPLGVA101 motif of eVP40 contributes to egress, a series of point mutations were introduced into this motif. These mutants were then compared to the eVP40 wild type in a VLP budding assay to assess budding competency. Confocal microscopy and gel filtration analyses were performed to assess their pattern of intracellular localization and ability to oligomerize, respectively. Our results show that mutations disrupting the 96LPLGVA101 motif resulted in both altered patterns of intracellular localization and self-assembly compared to wild-type controls. Interestingly, coexpression of either Ebola virus GP-WT or mVP40-WT with eVP40-?LPLGVA failed to rescue the budding defective eVP40-?LPLGVA mutant into VLPs; however, coexpression of eVP40-WT with mVP40-?LPLGIM successfully rescued budding of mVP40-?LPLGIM into VLPs at mVP40-WT levels. In sum, our findings implicate the LPLGVA and LPLGIM motifs of eVP40 and mVP40, respectively, as being important for VP40 structure/stability and budding. PMID:20032189

  13. Reverse Genetic Generation of Recombinant Zaire Ebola Viruses Containing Disrupted IRF-3 Inhibitory Domains Results in Attenuated Virus Growth In Vitro and Higher Levels of IRF-3 Activation without Inhibiting Viral Transcription or Replication

    Microsoft Academic Search

    Amy L. Hartman; Jason E. Dover; Jonathan S. Towner; Stuart T. Nichol

    2006-01-01

    The VP35 protein of Zaire Ebola virus is an essential component of the viral RNA polymerase complex and also functions to antagonize the cellular type I interferon (IFN) response by blocking activation of the transcription factor IRF-3. We previously mapped the IRF-3 inhibitory domain within the C terminus of VP35. In the present study, we show that mutations that disrupt

  14. Recombinant Vesicular Stomatitis Virus Vector Mediates Postexposure Protection against Sudan Ebola Hemorrhagic Fever in Nonhuman Primates

    Microsoft Academic Search

    Thomas W. Geisbert; Kathleen M. Daddario-DiCaprio; Kinola J. N. Williams; Joan B. Geisbert; Anders Leung; Friederike Feldmann; Lisa E. Hensley; Heinz Feldmann; Steven M. Jones

    2008-01-01

    Recombinant vesicular stomatitis virus (VSV) vectors expressing homologous filoviral glycoproteins can completely protect rhesus monkeys against Marburg virus when administered after exposure and can partially protect macaques after challenge with Zaire ebolavirus. Here, we administered a VSV vector expressing the Sudan ebolavirus (SEBOV) glycoprotein to four rhesus macaques shortly after exposure to SEBOV. All four animals survived SEBOV challenge, while

  15. 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

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

    PubMed

    Usami, Katsuaki; Matsuno, Keita; Igarashi, Manabu; Denda-Nagai, Kaori; Takada, Ayato; Irimura, Tatsuro

    2011-04-01

    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. PMID:21362405

  17. Chains of transmission and control of Ebola Virus Disease in Conakry, Guinea in 2014

    PubMed Central

    Faye, Ousmane; Boëlle, Pierre-Yves; Heleze, Emmanuel; Faye, Oumar; Loucoubar, Cheikh; Magassouba, N’Faly; Soropogui, Barré; Keita, Sakoba; Gakou, Tata; Bah, El Hadji Ibrahima; Koivogui, Lamine; Sall, Amadou Alpha; Cauchemez, Simon

    2015-01-01

    Background An Ebola Virus Disease (EVD) epidemic of unprecedented magnitude is ongoing in West Africa, affecting for the first time large urban centers like Conakry, the capital of Guinea. Methods Interviews of EVD patients, relatives and neighbors and laboratory databases were used to reconstruct EVD chains of transmission in Conakry, from March to August 2014. Findings Out of 193 confirmed and probable EVD cases reported in Conakry, Boffa and Télimélé, 152 (79%) were positioned in the chains of transmission. In March, non-Health Care Workers cases infected on average 2.3 (95% CI: 1.6, 3.2) persons, breaking down into 1.4 (95% CI: 0.9, 2.2) persons in the community, 0.4 (95% CI: 0.1, 0.9) in the hospital and 0.5 (95% CI: 0.2, 1.0) at funerals. Following implementation of infection control in April, the reproduction number in the hospital and at funerals reduced below 0.1. In the community, the reproduction number, which was positively correlated with patients viremia, dropped by 50% for hospitalized cases but remained unchanged for those not hospitalized. Hospital and funeral transmission represented 35% (7/20) and 15% (3/20) of all transmissions in March; but only 9% (11/128) and 4% (5/128) from April onward. Overall, 82% (119/145) of transmission occurred in the community and 72% (105/145) between family members. Simulations showed that a 10% increase in hospitalizations could have reduced the length of chains by 26% (95% CI: 4%, 45%). Interpretation Monitoring chains of transmission is critical to evaluate and optimize local control strategies for EVD. In Conakry, interventions had the potential to stop the epidemic but reintroductions of the disease and lack of cooperation of a small number of families led to prolonged low-level spread, highlighting challenges of EVD control in large urban centers. Funding Labex IBEID, Reacting, PREDEMICS, NIGMS MIDAS initiative, Institut Pasteur de Dakar. PMID:25619149

  18. 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

  19. C-peptide inhibitors of Ebola virus glycoprotein-mediated cell entry: Effects of conjugation to cholesterol and side chain–side chain crosslinking

    PubMed Central

    Higgins, Chelsea D.; Koellhoffer, Jayne F.; Chandran, Kartik; Lai, Jonathan R.

    2013-01-01

    We previously described potent inhibition of Ebola virus entry by a ‘C-peptide’ based on the GP2 C-heptad repeat region (CHR) targeted to endosomes (‘Tat-Ebo’). Here, we report the synthesis and evaluation of C-peptides conjugated to cholesterol, and Tat-Ebo analogs containing covalent side chain–side chain crosslinks to promote ?-helical conformation. We found that the cholesterol-conjugated C-peptides were potent inhibitors of Ebola virus glycoprotein (GP)-mediated cell entry (~103-fold reduction in infection at 40 µM). However, this mechanism of inhibition is somewhat non-specific because the cholesterol-conjugated peptides also inhibited cell entry mediated by vesicular stomatitis virus glycoprotein G. One side chain–side chain crosslinked peptide had moderately higher activity than the parent compound Tat-Ebo. Circular dichroism revealed that the cholesterol-conjugated peptides unexpectedly formed a strong ?-helical conformation that was independent of concentration. Side chain–side chain crosslinking enhanced ?-helical stability of the Tat-Ebo variants, but only at neutral pH. These result provide insight into mechanisms of C-peptide inhibiton of Ebola virus GP-mediated cell entry. PMID:23962564

  20. 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.

  1. 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

  2. Preparedness for admission of patients with suspected Ebola virus disease in European hospitals: a survey, August-September 2014.

    PubMed

    de Jong, M D; Reusken, C; Horby, P; Koopmans, M; Bonten, M; Chiche, Jd; Giaquinto, C; Welte, T; Leus, F; Schotsman, J; Goossens, H

    2014-01-01

    In response to the Ebola virus disease (EVD) outbreak in West Africa, the World Health Organization has advised all nations to prepare for the detection, investigation and management of confirmed and suspected EVD cases in order to prevent further spread through international travel. To gain insights into the state of preparedness of European hospitals, an electronic survey was circulated in August–September 2014 to 984 medical professionals representing 736 hospitals in 40 countries. The survey addressed the willingness and capacity to admit patients with suspected EVD as well as specific preparedness activities in response to the current Ebola crisis. Evaluable responses were received from representatives of 254 (32%) hospitals in 38 countries, mostly tertiary care centres, of which 46% indicated that they would admit patients with suspected EVD. Patient transfer agreements were in place for the majority of hospitals that would not admit patients. Compared with non-admitting hospitals, admitting hospitals were more frequently engaged in various preparedness activities and more often contained basic infrastructural characteristics such as admission rooms and laboratories considered important for infection control, but some gaps and concerns were also identified. The results of this survey help to provide direction towards further preparedness activities and prioritisation thereof. PMID:25496571

  3. 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...

  4. Safety and pharmacokinetic profiles of phosphorodiamidate morpholino oligomers with activity against ebola virus and marburg virus: results of two single-ascending-dose studies.

    PubMed

    Heald, Alison E; Iversen, Patrick L; Saoud, Jay B; Sazani, Peter; Charleston, Jay S; Axtelle, Tim; Wong, Michael; Smith, William B; Vutikullird, Apinya; Kaye, Edward

    2014-11-01

    Two identical single-ascending-dose studies evaluated the safety and pharmacokinetics (PK) of AVI-6002 and AVI-6003, two experimental combinations of phosphorodiamidate morpholino oligomers with positive charges (PMOplus) that target viral mRNA encoding Ebola virus and Marburg virus proteins, respectively. Both AVI-6002 and AVI-6003 were found to suppress disease in virus-infected nonhuman primates in previous studies. AVI-6002 (a combination of AVI-7537 and AVI-7539) or AVI-6003 (a combination of AVI-7287 and AVI-7288) were administered as sequential intravenous (i.v.) infusions of a 1:1 fixed dose ratio of the two subcomponents. In each study, 30 healthy male and female subjects between 18 and 50 years of age were enrolled in six-dose escalation cohorts of five subjects each and received a single i.v. infusion of active study drug (0.005, 0.05, 0.5, 1.5, 3, and 4.5 mg/kg per component) or placebo in a 4:1 ratio. Both AVI-6002 and AVI-6003 were safe and well tolerated at the doses studied. A maximum tolerated dose was not observed in either study. The four chemically similar PMOplus components exhibited generally similar PK profiles. The mean peak plasma concentration and area under the concentration-time curve values of the four components exhibited dose-proportional PK. The estimated plasma half-life of all four components was 2 to 5 h. The safety of the two combinations and the PK of the four components were similar, regardless of the target RNA sequence. PMID:25155593

  5. Nomenclature- and database-compatible names for the two Ebola virus variants that emerged in Guinea and the Democratic Republic of the Congo in 2014.

    PubMed

    Kuhn, Jens H; Andersen, Kristian G; Baize, Sylvain; Bào, Y?míng; Bavari, Sina; Berthet, Nicolas; Blinkova, Olga; Brister, J Rodney; Clawson, Anna N; Fair, Joseph; Gabriel, Martin; Garry, Robert F; Gire, Stephen K; Goba, Augustine; Gonzalez, Jean-Paul; Günther, Stephan; Happi, Christian T; Jahrling, Peter B; Kapetshi, Jimmy; Kobinger, Gary; Kugelman, Jeffrey R; Leroy, Eric M; Maganga, Gael Darren; Mbala, Placide K; Moses, Lina M; Muyembe-Tamfum, Jean-Jacques; N'Faly, Magassouba; Nichol, Stuart T; Omilabu, Sunday A; Palacios, Gustavo; Park, Daniel J; Paweska, Janusz T; Radoshitzky, Sheli R; Rossi, Cynthia A; Sabeti, Pardis C; Schieffelin, John S; Schoepp, Randal J; Sealfon, Rachel; Swanepoel, Robert; Towner, Jonathan S; Wada, Jiro; Wauquier, Nadia; Yozwiak, Nathan L; Formenty, Pierre

    2014-11-01

    In 2014, Ebola virus (EBOV) was identified as the etiological agent of a large and still expanding outbreak of Ebola virus disease (EVD) in West Africa and a much more confined EVD outbreak in Middle Africa. Epidemiological and evolutionary analyses confirmed that all cases of both outbreaks are connected to a single introduction each of EBOV into human populations and that both outbreaks are not directly connected. Coding-complete genomic sequence analyses of isolates revealed that the two outbreaks were caused by two novel EBOV variants, and initial clinical observations suggest that neither of them should be considered strains. Here we present consensus decisions on naming for both variants (West Africa: "Makona", Middle Africa: "Lomela") and provide database-compatible full, shortened, and abbreviated names that are in line with recently established filovirus sub-species nomenclatures. PMID:25421896

  6. Nomenclature- and Database-Compatible Names for the Two Ebola Virus Variants that Emerged in Guinea and the Democratic Republic of the Congo in 2014

    PubMed Central

    Kuhn, Jens H.; Andersen, Kristian G.; Baize, Sylvain; Bào, Y?míng; Bavari, Sina; Berthet, Nicolas; Blinkova, Olga; Brister, J. Rodney; Clawson, Anna N.; Fair, Joseph; Gabriel, Martin; Garry, Robert F.; Gire, Stephen K.; Goba, Augustine; Gonzalez, Jean-Paul; Günther, Stephan; Happi, Christian T.; Jahrling, Peter B.; Kapetshi, Jimmy; Kobinger, Gary; Kugelman, Jeffrey R.; Leroy, Eric M.; Maganga, Gael Darren; Mbala, Placide K.; Moses, Lina M.; Muyembe-Tamfum, Jean-Jacques; N’Faly, Magassouba; Nichol, Stuart T.; Omilabu, Sunday A.; Palacios, Gustavo; Park, Daniel J.; Paweska, Janusz T.; Radoshitzky, Sheli R.; Rossi, Cynthia A.; Sabeti, Pardis C.; Schieffelin, John S.; Schoepp, Randal J.; Sealfon, Rachel; Swanepoel, Robert; Towner, Jonathan S.; Wada, Jiro; Wauquier, Nadia; Yozwiak, Nathan L.; Formenty, Pierre

    2014-01-01

    In 2014, Ebola virus (EBOV) was identified as the etiological agent of a large and still expanding outbreak of Ebola virus disease (EVD) in West Africa and a much more confined EVD outbreak in Middle Africa. Epidemiological and evolutionary analyses confirmed that all cases of both outbreaks are connected to a single introduction each of EBOV into human populations and that both outbreaks are not directly connected. Coding-complete genomic sequence analyses of isolates revealed that the two outbreaks were caused by two novel EBOV variants, and initial clinical observations suggest that neither of them should be considered strains. Here we present consensus decisions on naming for both variants (West Africa: “Makona”, Middle Africa: “Lomela”) and provide database-compatible full, shortened, and abbreviated names that are in line with recently established filovirus sub-species nomenclatures. PMID:25421896

  7. 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

  8. 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

  9. Enzyme-Linked Immunosorbent Assays for Detection of Antibodies to Ebola and Marburg Viruses Using Recombinant Nucleoproteins

    PubMed Central

    Saijo, Masayuki; Niikura, Masahiro; Morikawa, Shigeru; Ksiazek, Thomas G.; Meyer, Richard F.; Peters, Clarence J.; Kurane, Ichiro

    2001-01-01

    The full-length nucleoprotein (NP) of Ebola virus (EBO) was expressed as a His-tagged recombinant protein (His-EBO-NP) by a baculovirus system. Carboxy-terminal halves of NPs of EBO and Marburg virus (MBG) were expressed as glutathione S-transferase-tagged recombinant proteins in an Escherichia coli system. The antigenic regions on the NPs of EBO and MBG were determined by both Western blotting and enzyme-linked immunosorbent assay (ELISA) to be located on the C-terminal halves. The C-terminal 110 and 102 amino acids of the NPs of EBO and MBG, respectively, possess strong antigenicity. The full-length NP of EBO was strongly expressed in insect cells upon infection with the recombinant baculovirus, while expression of the full-length NP of MBG was weak. We developed an immunoglobulin G (IgG) ELISA using His-EBO-NP and the C-terminal halves of the NPs of EBO and MBG as antigens. We evaluated the IgG ELISA for the ability to detect IgG antibodies to EBO and MBG, using human sera collected from EBO and MBG patients. The IgG ELISA with the recombinant NPs showed high sensitivity and specificity in detecting EBO and MBG antibodies. The results indicate that ELISA systems prepared with the recombinant NPs of EBO and MBG are valuable tools for the diagnosis of EBO and MBG infections and for seroepidemiological field studies. PMID:11136739

  10. Ebola Virus Disease 2013-2014 Outbreak in West Africa: An Analysis of the Epidemic Spread and Response

    PubMed Central

    Cenciarelli, Orlando; Pietropaoli, Stefano; 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

  11. Mutual Antagonism between the Ebola Virus VP35 Protein and the RIG-I Activator PACT Determines Infection Outcome

    PubMed Central

    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.

    2013-01-01

    SUMMARY 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

  12. 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

  13. 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

  14. Anti-tetherin activities of HIV-1 Vpu and Ebola virus glycoprotein do not involve removal of tetherin from lipid rafts.

    PubMed

    Lopez, Lisa A; Yang, Su Jung; Exline, Colin M; Rengarajan, Srinivas; Haworth, Kevin G; Cannon, Paula M

    2012-05-01

    BST-2/tetherin is an interferon-inducible host restriction factor that blocks the release of newly formed enveloped viruses. It is enriched in lipid raft membrane microdomains, which are also the sites of assembly of several enveloped viruses. Viral anti-tetherin factors, such as the HIV-1 Vpu protein, typically act by removing tetherin from the cell surface. In contrast, the Ebola virus glycoprotein (GP) is unusual in that it blocks tetherin restriction without apparently altering its cell surface localization. We explored the possibility that GP acts to exclude tetherin from the specific sites of virus assembly without overtly removing it from the cell surface and that lipid raft exclusion is the mechanism involved. However, we found that neither GP nor Vpu had any effect on tetherin's distribution within lipid raft domains. Furthermore, GP did not prevent the colocalization of tetherin and budding viral particles. Contrary to previous reports, we also found no evidence that GP is itself a raft protein. Together, our data indicate that the exclusion of tetherin from lipid rafts is not the mechanism used by either HIV-1 Vpu or Ebola virus GP to counteract tetherin restriction. PMID:22398279

  15. Multiple Ebola Virus Transmission Events and Rapid Decline of Central African Wildlife

    Microsoft Academic Search

    Eric M. Leroy; Pierre Rouquet; Pierre Formenty; Sandrine Souquière; Annelisa Kilbourne; Jean-Marc Froment; Magdalena Bermejo; Sheilag Smit; William Karesh; Robert Swanepoel; Sherif R. Zaki; Pierre E. Rollin

    2004-01-01

    Several human and animal Ebola outbreaks have occurred over the past 4 years in Gabon and the Republic of Congo. The human outbreaks consisted of multiple simultaneous epidemics caused by different viral strains, and each epidemic resulted from the handling of a distinct gorilla, chimpanzee, or duiker carcass. These animal populations declined markedly during human Ebola outbreaks, apparently as a

  16. Human Ebola virus infection in West Africa: a review of available therapeutic agents that target different steps of the life cycle of Ebola virus.

    PubMed

    Lai, Kang Yiu; Ng, Wing Yiu George; Cheng, Fan Fanny

    2014-01-01

    The recent outbreak of the human Zaire ebolavirus (EBOV) epidemic is spiraling out of control in West Africa. Human EBOV hemorrhagic fever has a case fatality rate of up to 90%. The EBOV is classified as a biosafety level 4 pathogen and is considered a category A agent of bioterrorism by Centers for Disease Control and Prevention, with no approved therapies and vaccines available for its treatment apart from supportive care. Although several promising therapeutic agents and vaccines against EBOV are undergoing the Phase I human trial, the current epidemic might be outpacing the speed at which drugs and vaccines can be produced. Like all viruses, the EBOV largely relies on host cell factors and physiological processes for its entry, replication, and egress. We have reviewed currently available therapeutic agents that have been shown to be effective in suppressing the proliferation of the EBOV in cell cultures or animal studies. Most of the therapeutic agents in this review are directed against non-mutable targets of the host, which is independent of viral mutation. These medications are approved by the Food and Drug Administration (FDA) for the treatment of other diseases. They are available and stockpileable for immediate use. They may also have a complementary role to those therapeutic agents under development that are directed against the mutable targets of the EBOV. PMID:25699183

  17. Protective Efficacy of a Bivalent Recombinant Vesicular Stomatitis Virus Vaccine in the Syrian Hamster Model of Lethal Ebola Virus Infection

    PubMed Central

    Tsuda, Yoshimi; Safronetz, David; Brown, Kyle; LaCasse, Rachel; Marzi, Andrea; Ebihara, Hideki

    2011-01-01

    Background.?Outbreaks of filoviral hemorrhagic fever occur sporadically and unpredictably across wide regions in central Africa and overlap with the occurrence of other infectious diseases of public health importance. Methods.?As a proof of concept we developed a bivalent recombinant vaccine based on vesicular stomatitis virus (VSV) expressing the Zaire ebolavirus (ZEBOV) and Andes virus (ANDV) glycoproteins (VSV?G/Dual) and evaluated its protective efficacy in the common lethal Syrian hamster model. Hamsters were vaccinated with VSV?G/Dual and were lethally challenged with ZEBOV or ANDV. Time to immunity and postexposure treatment were evaluated by immunizing hamsters at different times prior to and post ZEBOV challenge. Results.?A single immunization with VSV?G/Dual conferred complete and sterile protection against lethal ZEBOV and ANDV challenge. Complete protection was achieved with an immunization as close as 3 days prior to ZEBOV challenge, and 40% of the animals were even protected when treated with VSV?G/Dual one day postchallenge. In comparison to the monovalent VSV vaccine, the bivalent vaccine has slightly reduced postexposure efficacy most likely due to its restricted lymphoid organ replication. Conclusions.?Bivalent VSV vectors are a feasible approach to vaccination against multiple pathogens. PMID:21987746

  18. Identification of Continuous Human B-Cell Epitopes in the VP35, VP40, Nucleoprotein and Glycoprotein of Ebola Virus

    PubMed Central

    Becquart, Pierre; Mahlakõiv, Tanel; Nkoghe, Dieudonné; Leroy, Eric M.

    2014-01-01

    Ebola virus (EBOV) is a highly virulent human pathogen. Recovery of infected patients is associated with efficient EBOV-specific immunoglobulin G (IgG) responses, whereas fatal outcome is associated with defective humoral immunity. As B-cell epitopes on EBOV are poorly defined, we sought to identify specific epitopes in four EBOV proteins (Glycoprotein (GP), Nucleoprotein (NP), and matrix Viral Protein (VP)40 and VP35). For the first time, we tested EBOV IgG+ sera from asymptomatic individuals and symptomatic Gabonese survivors, collected during the early humoral response (seven days after the end of symptoms) and the late memory phase (7–12 years post-infection). We also tested sera from EBOV-seropositive patients who had never had clinical signs of hemorrhagic fever or who lived in non-epidemic areas (asymptomatic subjects). We found that serum from asymptomatic individuals was more strongly reactive to VP40 peptides than to GP, NP or VP35. Interestingly, anti-EBOV IgG from asymptomatic patients targeted three immunodominant regions of VP40 reported to play a crucial role in virus assembly and budding. In contrast, serum from most survivors of the three outbreaks, collected a few days after the end of symptoms, reacted mainly with GP peptides. However, in asymptomatic subjects the longest immunodominant domains were identified in GP, and analysis of the GP crystal structure revealed that these domains covered a larger surface area of the chalice bowl formed by three GP1 subunits. The B-cell epitopes we identified in the EBOV VP35, VP40, NP and GP proteins may represent important tools for understanding the humoral response to this virus and for developing new antibody-based therapeutics or detection methods. PMID:24914933

  19. Ebola Virus Outbreak among Wild Chimpanzees Living in a Rain Forest of Cote d'Ivoire

    Microsoft Academic Search

    Pierre Formenty; Christophe Boesch; Monique Wyers; Claudia Steiner; Franca Donati; Frédéric Dind; Francine Walker; Bernard Le Guenno

    1999-01-01

    An outbreak of Ebola in nature is described for the first time. During a few weeks in November 1994, Ç25% of 43 members of a wild chimpanzee community disappeared or were found dead in the TaiF National Park, Cote d'Ivoire. A retrospective cohort study was done on the chimpanzee community. Laboratory procedures included histology, immunohistochemistry, bacteriology, and serology. Ebola-specific immunohistochemical

  20. The Ebola Virus VP35 Protein Is a Suppressor of RNA Silencing

    Microsoft Academic Search

    Joost Haasnoot; Walter de Vries; Ernst-Jan Geutjes; Marcel Prins; Peter de Haan; Ben Berkhout

    2007-01-01

    RNA silencing or interference (RNAi) is a gene regulation mechanism in eukaryotes that controls cell differentiation and developmental processes via expression of microRNAs. RNAi also serves as an innate antiviral defence response in plants, nematodes, and insects. This antiviral response is triggered by virus-specific double-stranded RNA molecules (dsRNAs) that are produced during infection. To overcome antiviral RNAi responses, many plant

  1. Long-term survival of an urban fruit bat seropositive for Ebola and Lagos bat viruses.

    PubMed

    Hayman, David T S; Emmerich, Petra; Yu, Meng; Wang, Lin-Fa; Suu-Ire, Richard; Fooks, Anthony R; Cunningham, Andrew A; Wood, James L N

    2010-01-01

    Ebolaviruses (EBOV) (family Filoviridae) cause viral hemorrhagic fevers in humans and non-human primates when they spill over from their wildlife reservoir hosts with case fatality rates of up to 90%. Fruit bats may act as reservoirs of the Filoviridae. The migratory fruit bat, Eidolon helvum, is common across sub-Saharan Africa and lives in large colonies, often situated in cities. We screened sera from 262 E. helvum using indirect fluorescent tests for antibodies against EBOV subtype Zaire. We detected a seropositive bat from Accra, Ghana, and confirmed this using western blot analysis. The bat was also seropositive for Lagos bat virus, a Lyssavirus, by virus neutralization test. The bat was fitted with a radio transmitter and was last detected in Accra 13 months after release post-sampling, demonstrating long-term survival. Antibodies to filoviruses have not been previously demonstrated in E. helvum. Radio-telemetry data demonstrates long-term survival of an individual bat following exposure to viruses of families that can be highly pathogenic to other mammal species. Because E. helvum typically lives in large urban colonies and is a source of bushmeat in some regions, further studies should determine if this species forms a reservoir for EBOV from which spillover infections into the human population may occur. PMID:20694141

  2. 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.

  3. 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

  4. Reversion of advanced Ebola virus disease in nonhuman primates with ZMapp™

    PubMed Central

    Qiu, Xiangguo; Wong, Gary; Audet, Jonathan; Bello, Alexander; Fernando, Lisa; Alimonti, Judie B.; Fausther-Bovendo, Hugues; Wei, Haiyan; Aviles, Jenna; Hiatt, Ernie; Johnson, Ashley; Morton, Josh; Swope, Kelsi; Bohorov, Ognian; Bohorova, Natasha; Goodman, Charles; Kim, Do; Pauly, Michael H.; Velasco, Jesus; Pettitt, James; Olinger, Gene G.; Whaley, Kevin; Xu, Bianli; Strong, James E.; Zeitlin, Larry; Kobinger, Gary P.

    2014-01-01

    Without an approved vaccine or treatment, Ebola outbreak management has been limited to palliative care and barrier methods to prevent transmission. These approaches, however, have yet to end the 2014 outbreak of Ebola after its prolonged presence in West Africa. Here we show that a combination of monoclonal antibodies (ZMapp™), optimized from two previous antibody cocktails, is able to rescue 100% of rhesus macaques when treatment is initiated up to 5 days post-challenge. High fever, viremia, and abnormalities in blood count and chemistry were evident in many animals before ZMapp™ intervention. Advanced disease, as indicated by elevated liver enzymes, mucosal hemorrhages and generalized petechia could be reversed, leading to full recovery. ELISA and neutralizing antibody assays indicate that ZMapp™ is cross-reactive with the Guinean variant of Ebola. ZMapp™ currently exceeds all previous descriptions of efficacy with other therapeutics, and results warrant further development of this cocktail for clinical use. PMID:25171469

  5. 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

  6. Evaluation of the potential impact of Ebola virus genomic drift on the efficacy of sequence-based candidate therapeutics.

    PubMed

    Kugelman, Jeffrey R; Sanchez-Lockhart, Mariano; Andersen, Kristian G; Gire, Stephen; Park, Daniel J; Sealfon, Rachel; Lin, Aaron E; Wohl, Shirlee; Sabeti, Pardis C; Kuhn, Jens H; Palacios, Gustavo F

    2015-01-01

    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 in West Africa that is still ongoing and has already caused thousands of deaths. Recent studies revealed the genomic changes this particular EBOV variant undergoes over time during human-to-human transmission. Here we highlight the genomic changes that might negatively impact the efficacy of currently available EBOV sequence-based candidate therapeutics, such as small interfering RNAs (siRNAs), phosphorodiamidate morpholino oligomers (PMOs), and antibodies. Ten of the observed mutations modify the sequence of the binding sites of monoclonal antibody (MAb) 13F6, MAb 1H3, MAb 6D8, MAb 13C6, and siRNA EK-1, VP24, and VP35 targets and might influence the binding efficacy of the sequence-based therapeutics, suggesting that their efficacy should be reevaluated against the currently circulating strain. PMID:25604787

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

    PubMed Central

    Sanchez-Lockhart, Mariano; Andersen, Kristian G.; Gire, Stephen; Park, Daniel J.; Sealfon, Rachel; Lin, Aaron E.; Wohl, Shirlee; Sabeti, Pardis C.

    2015-01-01

    ABSTRACT? 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 in West Africa that is still ongoing and has already caused thousands of deaths. Recent studies revealed the genomic changes this particular EBOV variant undergoes over time during human-to-human transmission. Here we highlight the genomic changes that might negatively impact the efficacy of currently available EBOV sequence-based candidate therapeutics, such as small interfering RNAs (siRNAs), phosphorodiamidate morpholino oligomers (PMOs), and antibodies. Ten of the observed mutations modify the sequence of the binding sites of monoclonal antibody (MAb) 13F6, MAb 1H3, MAb 6D8, MAb 13C6, and siRNA EK-1, VP24, and VP35 targets and might influence the binding efficacy of the sequence-based therapeutics, suggesting that their efficacy should be reevaluated against the currently circulating strain. PMID:25604787

  8. Toll-Like Receptor Agonist Augments Virus-Like Particle-Mediated Protection from Ebola Virus with Transient Immune Activation

    PubMed Central

    Martins, Karen A. O.; Steffens, Jesse T.; van Tongeren, Sean A.; Wells, Jay B.; Bergeron, Alison A.; Dickson, Samuel P.; Dye, John M.; Salazar, Andres M.; Bavari, Sina

    2014-01-01

    Identifying safe and effective adjuvants is critical for the advanced development of protein-based vaccines. Pattern recognition receptor (PRR) agonists are increasingly being explored as potential adjuvants, but there is concern that the efficacy of these molecules may be dependent on potentially dangerous levels of non-specific immune activation. The filovirus virus-like particle (VLP) vaccine protects mice, guinea pigs, and nonhuman primates from viral challenge. In this study, we explored the impact of a stabilized dsRNA mimic, polyICLC, on VLP vaccination of C57BL/6 mice and Hartley guinea pigs. We show that at dose levels as low as 100 ng, the adjuvant increased the efficacy of the vaccine in mice. Antigen-specific, polyfunctional CD4 and CD8 T cell responses and antibody responses increased significantly upon inclusion of adjuvant. To determine whether the efficacy of polyICLC correlated with systemic immune activation, we examined serum cytokine levels and cellular activation in the draining lymph node. PolyICLC administration was associated with increases in TNF?, IL6, MCP1, MIP1?, KC, and MIP1? levels in the periphery and with the activation of dendritic cells (DCs), NK cells, and B cells. However, this activation resolved within 24 to 72 hours at efficacious adjuvant dose levels. These studies are the first to examine the polyICLC-induced enhancement of antigen-specific immune responses in the context of non-specific immune activation, and they provide a framework from which to consider adjuvant dose levels. PMID:24586996

  9. Ebola virus entry requires the cholesterol transporter Niemann-Pick C1

    Microsoft Academic Search

    Jan E. Carette; Matthijs Raaben; Anthony C. Wong; Andrew S. Herbert; Gregor Obernosterer; Nirupama Mulherkar; Ana I. Kuehne; Philip J. Kranzusch; April M. Griffin; Gordon Ruthel; Paola Dal Cin; John M. Dye; Sean P. Whelan; Kartik Chandran; Thijn R. Brummelkamp

    2011-01-01

    Infections by the Ebola and Marburg filoviruses cause a rapidly fatal haemorrhagic fever in humans for which no approved antivirals are available. Filovirus entry is mediated by the viral spike glycoprotein (GP), which attaches viral particles to the cell surface, delivers them to endosomes and catalyses fusion between viral and endosomal membranes. Additional host factors in the endosomal compartment are

  10. Viruses 2014, 6, 3837-3854; doi:10.3390/v6103837 ISSN 1999-4915

    E-print Network

    Rose, Michael R.

    .mdpi.com/journal/viruses Article A Loop Region in the N-Terminal Domain of Ebola Virus VP40 Is Important in Viral Assembly, Budding 2014 / Published: 17 October 2014 Abstract: Ebola virus (EBOV) causes viral hemorrhagic fever in humans seven proteins including viral protein 40 (VP40). VP40 is the major Ebola virus matrix protein

  11. Serologic Cross-Reactivity of Human IgM and IgG Antibodies to Five Species of Ebola Virus

    PubMed Central

    MacNeil, Adam; Reed, Zachary; Rollin, Pierre E.

    2011-01-01

    Five species of Ebola virus (EBOV) have been identified, with nucleotide differences of 30–45% between species. Four of these species have been shown to cause Ebola hemorrhagic fever (EHF) in humans and a fifth species (Reston ebolavirus) is capable of causing a similar disease in non-human primates. While examining potential serologic cross-reactivity between EBOV species is important for diagnostic assays as well as putative vaccines, the nature of cross-reactive antibodies following EBOV infection has not been thoroughly characterized. In order to examine cross-reactivity of human serologic responses to EBOV, we developed antigen preparations for all five EBOV species, and compared serologic responses by IgM capture and IgG enzyme-linked immunosorbent assay (ELISA) in groups of convalescent diagnostic sera from outbreaks in Kikwit, Democratic Republic of Congo (n?=?24), Gulu, Uganda (n?=?20), Bundibugyo, Uganda (n?=?33), and the Philippines (n?=?18), which represent outbreaks due to four different EBOV species. For groups of samples from Kikwit, Gulu, and Bundibugyo, some limited IgM cross-reactivity was noted between heterologous sera-antigen pairs, however, IgM responses were largely stronger against autologous antigen. In some instances IgG responses were higher to autologous antigen than heterologous antigen, however, in contrast to IgM responses, we observed strong cross-reactive IgG antibody responses to heterologous antigens among all sets of samples. Finally, we examined autologous IgM and IgG antibody levels, relative to time following EHF onset, and observed early peaking and declining IgM antibody levels (by 80 days) and early development and persistence of IgG antibodies among all samples, implying a consistent pattern of antibody kinetics, regardless of EBOV species. Our findings demonstrate limited cross-reactivity of IgM antibodies to EBOV, however, the stronger tendency for cross-reactive IgG antibody responses can largely circumvent limitations in the utility of heterologous antigen for diagnostic assays and may assist in the development of antibody-mediated vaccines to EBOV. PMID:21666792

  12. Ebola Hemorrhagic Fever: Signs and Symptoms

    MedlinePLUS

    ... Persons Under Investigation Cleaning and Disinfecting Hospital Guidance Waste Management Survivability of Ebola Virus in Medical Waste Handling Ebola-Associated Waste Emergency Services Emergency Department ...

  13. 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

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

    E-print Network

    Firth, Andrew E.

    2014-01-01

    viruses. Such viruses include influenza A virus, Ebola virus, rabies virus, SARS virus, MERS virus, Japanese encephalitis virus, yellow fever virus, dengue virus, eastern equine encephalitis virus, and Lassa virus. Many other human pathogenic viruses... functional elements embedded within the coding sequences [40]. For Enterovirus C these include the cre (cis-acting replication element) [41], the RNase L ciRNA (competitive inhibitor of RNase L) [42], and the ?/3D-7000 element [7,10]. The synplot2 analysis...

  15. Heartland Virus

    MedlinePLUS

    ... Vector-Borne Diseases (DVBD) NCEZID Share Compartir Heartland virus On this Page What is Heartland virus? How ... Do I Need to Know? What is Heartland virus? Heartland virus belongs to a family of viruses ...

  16. Core structure of the envelope glycoprotein GP2 from Ebola virus at 1.9-? resolution

    PubMed Central

    Malashkevich, Vladimir N.; Schneider, Brian J.; McNally, Margaret L.; Milhollen, Michael A.; Pang, James X.; Kim, Peter S.

    1999-01-01

    Ebola virions contain a surface transmembrane glycoprotein (GP) that is responsible for binding to target cells and subsequent fusion of the viral and host-cell membranes. GP is expressed as a single-chain precursor that is posttranslationally processed into the disulfide-linked fragments GP1 and GP2. The GP2 subunit is thought to mediate membrane fusion. A soluble fragment of the GP2 ectodomain, lacking the fusion-peptide region and the transmembrane helix, folds into a stable, highly helical structure in aqueous solution. Limited proteolysis studies identify a stable core of the GP2 ectodomain. This 74-residue core, denoted Ebo-74, was crystallized, and its x-ray structure was determined at 1.9-? resolution. Ebo-74 forms a trimer in which a long, central three-stranded coiled coil is surrounded by shorter C-terminal helices that are packed in an antiparallel orientation into hydrophobic grooves on the surface of the coiled coil. Our results confirm the previously anticipated structural similarity between the Ebola GP2 ectodomain and the core of the transmembrane subunit from oncogenic retroviruses. The Ebo-74 structure likely represents the fusion-active conformation of the protein, and its overall architecture resembles several other viral membrane-fusion proteins, including those from HIV and influenza. PMID:10077567

  17. 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

  18. Questions and Answers about Ebola and Pets

    MedlinePLUS

    ... for Ebola is not available for pets. Can pigs become sick with Ebola? Pigs are the only ... in pigs experimentally infected with Reston virus. Can pigs spread Ebola? Pigs are not known to become ...

  19. More Dangerous Ebola Strain Unlikely, Study Shows

    MedlinePLUS

    ... on this page, please enable JavaScript. More Dangerous Ebola Strain Unlikely, Study Shows Researchers compared virus samples ... 2015) Thursday, March 26, 2015 Related MedlinePlus Page Ebola THURSDAY, March 26, 2015 (HealthDay News) -- Ebola likely ...

  20. Genetic Clues to the 2014 Ebola Outbreak

    MedlinePLUS

    ... 100 samples of Ebola virus from patients in West Africa. The findings are helping researchers track the origin ... Health Organization. It’s the first Ebola outbreak in West Africa and the first to affect major cities. Ebola ...

  1. 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

  2. Ebola Virus-Like Particles Stimulate Type I Interferons and Proinflammatory Cytokine Expression Through the Toll-Like Receptor and Interferon Signaling Pathways

    PubMed Central

    Ayithan, Natarajan; Bradfute, Steven B.; Anthony, Scott M.; Stuthman, Kelly S.; Dye, John M.; Bavari, Sina; Bray, Mike

    2014-01-01

    Ebola viruses (EBOV) can cause severe hemorrhagic disease with high case fatality rates. Currently, no vaccines or therapeutics are approved for use in humans. Ebola virus-like particles (eVLP) comprising of virus protein (VP40), glycoprotein, and nucleoprotein protect rodents and nonhuman primates from lethal EBOV infection, representing as a candidate vaccine for EBOV infection. Previous reports have shown that eVLP stimulate the expression of proinflammatory cytokines in dendritic cells (DCs) and macrophages (M?s) in vitro. However, the molecular mechanisms and signaling pathways through which eVLP induce innate immune responses remain obscure. In this study, we show that eVLP stimulate not only the expression of proinflammatory cytokines but also the expression of type I interferons (IFNs) and IFN-stimulated genes (ISGs) in murine bone marrow-derived DCs (BMDCs) and M?s. Our data indicate that eVLP trigger host responses through toll-like receptor (TLR) pathway utilizing 2 distinct adaptors, MyD88 and TRIF. More interestingly, eVLP activated the IFN signaling pathway by inducing a set of potent antiviral ISGs. Last, eVLP and synthetic adjuvants, Poly I:C and CpG DNA, cooperatively increased the expression of cytokines and ISGs. Further supporting this synergy, eVLP when administered together with Poly I:C conferred mice enhanced protection against EBOV infection. These results indicate that eVLP stimulate early innate immune responses through TLR and type I IFN signaling pathways to protect the host from EBOV infection. PMID:24102579

  3. Emergence of Divergent Zaire Ebola Virus Strains in Democratic Republic of the Congo in 2007 and 2008

    PubMed Central

    Biek, Roman; Muyembe Tamfum, Jean-Jacques; Fair, Joseph; Wolfe, Nathan; Formenty, Pierre; Paweska, Janusz; Leroy, Eric

    2011-01-01

    ?Background.?Zaire ebolavirus was responsible for 2 outbreaks in Democratic Republic of the Congo (DRC), in 1976 and 1995. The virus reemerged in DRC 12 years later, causing 2 successive outbreaks in the Luebo region, Kasai Occidental province, in 2007 and 2008. Methods.?Viruses of each outbreak were isolated and the full-length genomes were characterized. Phylogenetic analysis was then undertaken to characterize the relationships with previously described viruses. Results.?The 2 Luebo viruses are nearly identical but are not related to lineage A viruses known in DRC or to descendants of the lineage B viruses encountered in the Gabon–Republic of the Congo area, with which they do, however, share a common ancestor. Conclusions.?Our findings strongly suggest that the Luebo 2007 outbreak did not result from viral spread from previously identified foci but from an independent viral emergence. The previously identified epidemiological link with migratory bat species known to carry Zaire ebolavirus RNA support the hypothesis of viral spillover from this widely dispersed reservoir. The high level of similarity between the Luebo2007 and Luebo2008 viruses suggests that local wildlife populations (most likely bats) became infected and allowed local viral persistence and reemergence from year to year. PMID:21987750

  4. Virus Resistance

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Identification, characterization and deployment of virus resistant maize are complex tasks requiring multidisciplinary approaches. Insect transmission of viruses in nature and the potential presence of biologically distinct virus strains complicate screening for virus resistance. At least ten maize...

  5. The Lack of Maturation of Ebola Virus-Infected Dendritic Cells Results from the Cooperative Effect of at Least Two Viral Domains

    PubMed Central

    Lubaki, Ndongala M.; Ilinykh, Philipp; Pietzsch, Colette; Tigabu, Bersabeh; Freiberg, Alexander N.; Koup, Richard A.

    2013-01-01

    Ebola virus (EBOV) infections are characterized by deficient T lymphocyte responses, T lymphocyte apoptosis, and lymphopenia in the absence of direct infection of T lymphocytes. In contrast, dendritic cells (DC) are infected but fail to mature appropriately, thereby impairing the T cell response. We investigated the contributions of EBOV proteins in modulating DC maturation by generating recombinant viruses expressing enhanced green fluorescent protein and carrying mutations affecting several potentially immunomodulating domains. They included envelope glycoprotein (GP) domains, as well as innate response antagonist domains (IRADs) previously identified in the VP24 and VP35 proteins. GP expressed by an unrelated vector, but not the wild-type EBOV, was found to strongly induce DC maturation, and infections with recombinant EBOV carrying mutations disabling GP functional domains did not restore DC maturation. In contrast, each of the viruses carrying mutations disabling any IRAD in VP35 induced a dramatic upregulation of DC maturation markers. This was dependent on infection, but not interaction with GP. Disabling of IRADs also resulted in up to a several hundredfold increase in secretion of cytokines and chemokines. Furthermore, these mutations induced formation of homotypic DC clusters, which represent close correlates of their maturation and presumably facilitate transfer of antigen from migratory DC to lymph node DC. Thus, an individual IRAD is insufficient to suppress DC maturation; rather, the suppression of DC maturation and the “immune paralysis” observed during EBOV infections results from a cooperative effect of two or more individual IRADs. PMID:23616668

  6. The L–VP35 and L–L interaction domains reside in the amino terminus of the Ebola virus L protein and are potential targets for antivirals

    PubMed Central

    Trunschke, Martina; Conrad, Dominik; Enterlein, Sven; Olejnik, Judith; Brauburger, Kristina; Mühlberger, Elke

    2013-01-01

    The Ebola virus (EBOV) RNA-dependent RNA polymerase (RdRp) complex consists of the catalytic subunit of the polymerase, L, and its cofactor VP35. Using immunofluorescence analysis and coimmunoprecipitation assays, we mapped the VP35 binding site on L. A core binding domain spanning amino acids 280– 370 of L was sufficient to mediate weak interaction with VP35, while the entire N-terminus up to amino acid 380 was required for strong VP35–L binding. Interestingly, the VP35 binding site overlaps with an N-terminal L homo-oligomerization domain in a non-competitive manner. N-terminal L deletion mutants containing the VP35 binding site were able to efficiently block EBOV replication and transcription in a minigenome system suggesting the VP35 binding site on L as a potential target for the development of antivirals. PMID:23582637

  7. IFITMs restrict the replication of multiple pathogenic viruses.

    PubMed

    Perreira, Jill M; Chin, Christopher R; Feeley, Eric M; Brass, Abraham L

    2013-12-13

    The interferon-inducible transmembrane protein (IFITM) family inhibits a growing number of pathogenic viruses, among them influenza A virus, dengue virus, hepatitis C virus, and Ebola virus. This review covers recent developments in our understanding of the IFITM's molecular determinants, potential mechanisms of action, and impact on pathogenesis. PMID:24076421

  8. IFITMs restrict the replication of multiple pathogenic viruses

    PubMed Central

    Perreira, Jill M.; Chin, Christopher R.; Feeley, Eric M.; Brass, Abraham L.

    2014-01-01

    The IFITM family of proteins inhibit a growing number of pathogenic viruses, among them influenza A virus, dengue virus, hepatitis C virus, and Ebola virus. This review covers recent developments in our understanding of the IFITM’s molecular determinants, potential mechanisms of action, and impact on pathogenesis. PMID:24076421

  9. Ebola fever: The African emergency

    Microsoft Academic Search

    J. Bruce; P. Brysiewicz

    2002-01-01

    The Ebola virus produces one of Africa's most lethal viral hemorrhagic fever (VHF) infections. Statistically, Ebola fever is at the bottom of Africa's list of infectious diseases, but the speed with which it induces agonizing death puts Ebola fever at the top of Africa's emergencies. Many aspects of the virus are unknown and have eluded medical scientists for 3 decades.

  10. Transcriptional control of the RNA-dependent RNA polymerase of vesicular stomatitis virus

    Microsoft Academic Search

    John N Barr; Sean P. J Whelan; Gail W Wertz

    2002-01-01

    The nonsegmented negative strand (NNS) RNA viruses include some of the most problematic human, animal and plant pathogens extant: for example, rabies virus, Ebola virus, respiratory syncytial virus, the parainfluenza viruses, measles and infectious hemapoietic necrosis virus. The key feature of transcriptional control in the NNS RNA viruses is polymerase entry at a single 3? proximal site followed by obligatory

  11. 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

  12. The creation of stable cell lines expressing Ebola virus glycoproteins and the matrix protein VP40 and generating Ebola virus-like particles utilizing an ecdysone inducible mammalian expression system

    Microsoft Academic Search

    P. L. Melito; X. Qiu; L. M. Fernando; S. L. deVarennes; D. R. Beniac; T. F. Booth; S. M. Jones

    2008-01-01

    Ebolavirus is a filovirus that causes hemorrhagic fever in humans and is associated with case fatality rates of up to 90%. The lack of therapeutic interventions in combination with the threat of weaponizing this organism has enhanced research investigations. The expression of key viral proteins and the production of virus-like particles in mammalian systems are often pursued for characterization and

  13. VIROLOGY DIVISION NEWS Virus nomenclature below the species level: a standardized

    E-print Network

    Chandran, Kartik

    for full-length virus names (such as ``Ebola virus H.sapiens-tc/COD/1995/Kikwit- 9510621'') is proposed. These names contain information on the identity of the virus (e.g., Ebola virus), isolation host (e of this publication does not necessarily reflect the views or policies of the US Department of the Army, the US

  14. Viruses 2012, 4, 447-470; doi:10.3390/v4040447 ISSN 1999-4915

    E-print Network

    Chandran, Kartik

    ebolaviruses that cause hemorrhagic fever in humans or non-human primates (Ebola virus, Sudan virus, Reston neutralizing antibodies, and their relevance for virus neutralization. Keywords: Filovirus; Ebola; ebolavirus are filamentous viruses with a negative-sense RNA genome that cause severe hemorrhagic fever with high lethality

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

    PubMed Central

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

    2013-01-01

    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

  16. Identification of a Broad-Spectrum Antiviral Small Molecule against Severe Acute Respiratory Syndrome Coronavirus and Ebola, Hendra, and Nipah Viruses by Using a Novel High-Throughput Screening Assay

    PubMed Central

    Elshabrawy, Hatem A.; Fan, Jilao; Haddad, Christine S.; Ratia, Kiira; Broder, Christopher C.; Caffrey, Michael

    2014-01-01

    ABSTRACT Severe acute respiratory syndrome coronavirus (SARS-CoV) and Ebola, Hendra, and Nipah viruses are members of different viral families and are known causative agents of fatal viral diseases. These viruses depend on cathepsin L for entry into their target cells. The viral glycoproteins need to be primed by protease cleavage, rendering them active for fusion with the host cell membrane. In this study, we developed a novel high-throughput screening assay based on peptides, derived from the glycoproteins of the aforementioned viruses, which contain the cathepsin L cleavage site. We screened a library of 5,000 small molecules and discovered a small molecule that can inhibit the cathepsin L cleavage of all viral peptides with minimal inhibition of cleavage of a host protein-derived peptide (pro-neuropeptide Y). The small molecule inhibited the entry of all pseudotyped viruses in vitro and the cleavage of SARS-CoV spike glycoprotein in an in vitro cleavage assay. In addition, the Hendra and Nipah virus fusion glycoproteins were not cleaved in the presence of the small molecule in a cell-based cleavage assay. Furthermore, we demonstrate that the small molecule is a mixed inhibitor of cathepsin L. Our broad-spectrum antiviral small molecule appears to be an ideal candidate for future optimization and development into a potent antiviral against SARS-CoV and Ebola, Hendra, and Nipah viruses. IMPORTANCE We developed a novel high-throughput screening assay to identify small molecules that can prevent cathepsin L cleavage of viral glycoproteins derived from SARS-CoV and Ebola, Hendra, and Nipah viruses that are required for their entry into the host cell. We identified a novel broad-spectrum small molecule that could block cathepsin L-mediated cleavage and thus inhibit the entry of pseudotypes bearing the glycoprotein derived from SARS-CoV or Ebola, Hendra, or Nipah virus. The small molecule can be further optimized and developed into a potent broad-spectrum antiviral drug. PMID:24501399

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

    E-print Network

    Peterson, A. Townsend; Holder, Mark T.

    2012-07-01

    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...

  18. Regulation of Marburg virus (MARV) budding by Nedd4.1: a different WW domain of Nedd4.1 is critical for binding to MARV and Ebola virus VP40.

    PubMed

    Urata, Shuzo; Yasuda, Jiro

    2010-01-01

    The VP40 matrix protein of Marburg virus (MARV) has been shown to be the driving force behind MARV budding, a process in which the PPPY L-domain motif of VP40 plays a critical role. Here, we report that Vps4B and Nedd4.1 play critical roles in MARV VP40-mediated budding. We showed that unidentified activities of the Nedd4.1 HECT domain, along with its E3 ubiquitin ligase activity, may be required for MARV budding. Moreover, we showed that the first WW domain of Nedd4.1, WW1, is critical for binding to MARV VP40, indicating that MARV VP40 and Ebola virus VP40 are recognized by a different WW domain of Nedd4.1. This is the first report showing that the viral L-domains containing PPxY have specificities for binding to WW domains. Our findings provide new insights into MARV budding, which may contribute to the development of novel anti-MARV therapeutic strategies. PMID:19812267

  19. 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

  20. Ebola Tracker app.

    PubMed

    Evans, Roger

    2015-01-27

    Developer Bryan Ratledge claims his Ebola Tracker app is the only up to date mapping application of the 2014 Ebola virus disease outbreak centred in West Africa. With this app, you track the Ebola outbreak just as you would track a hurricane, or the weather. PMID:25605105

  1. Powassan (POW) Virus Basics

    MedlinePLUS

    Powassan (POW) Virus Basics Powassan (POW) virus is related to some mosquito-borne viruses, including West Nile virus. The virus is ... concerns? How do people get infected with POW virus? POW virus is passed to people by ticks: ...

  2. Ebola: Virology and Epidemiology

    Microsoft Academic Search

    Raymond Charles Sanders

    Since the 1976 Zaire and Sudan epidemic, extensive studies of the Ebola virus have been made This virus was morphologically identical to Marburg Virus; the cause of deadly outbreaks of hemorrhagic fever in Germany and Yugoslavia in 1967, but serologically distinct. Because of their unique filamentous form, these viruses have been placed in a separate family, the Filoviridae with one

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

    E-print Network

    Tammy Doukas; I. Background

    Ebola hemorrhagic fever is a disease in humans, chimpanzees, and monkeys, caused by infection with Ebola virus, and associated with high mortality. This virus was first recognized in Zaire (now the Democratic Republic of Congo), Africa in1976. The exact origin and location of Ebola virus is still

  4. 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...

  5. 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

  6. 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

  7. 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

  8. The Ebola Virus VP24 Protein Prevents hnRNP C1/C2 Binding to Karyopherin ?1 and Partially Alters its Nuclear Import

    PubMed Central

    Shabman, Reed S.; Gulcicek, Erol E.; Stone, Kathryn L.

    2011-01-01

    The Ebola virus (EBOV) protein VP24 inhibits type I and II interferon (IFN) signaling by binding to NPI-1 subfamily karyopherin ? (KPNA) nuclear import proteins, preventing their interaction with tyrosine-phosphorylated STAT1 (phospho-STAT1). This inhibits phospho-STAT1 nuclear import. A biochemical screen now identifies heterogenous nuclear ribonuclear protein complex C1/C2 (hnRNP C1/C2) nuclear import as an additional target of VP24. Co-immunoprecipitation studies demonstrate that hnRNP C1/C2 interacts with multiple KPNA family members, including KPNA1. Interaction with hnRNP C1/C2 occurs through the same KPNA1 C-terminal region (amino acids 424–457) that binds VP24 and phospho-STAT1. The ability of hnRNP C1/C2 to bind KPNA1 is diminished in the presence of VP24, and cells transiently expressing VP24 redistribute hnRNP C1/C2 from the nucleus to the cytoplasm. These data further define the mechanism of hnRNP C1/C2 nuclear import and demonstrate that the impact of EBOV VP24 on nuclear import extends beyond STAT1. PMID:21987768

  9. 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.

  10. Bat Flight and Zoonotic Viruses

    PubMed Central

    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. PMID:24750692

  11. Chlorella Viruses

    Microsoft Academic Search

    Takashi Yamada; Hideki Onimatsu; James L. Van Etten

    2006-01-01

    Chlorella viruses or chloroviruses are large, icosahedral, plaque?forming, double?stranded?DNA–containing viruses that replicate in certain strains of the unicellular green alga Chlorella. DNA sequence analysis of the 330?kbp genome of Paramecium bursaria chlorella virus 1 (PBCV?1), the prototype of this virus family (Phycodnaviridae), predict ?366 protein?encoding genes and 11 tRNA genes. The predicted gene products of ?50% of these genes resemble

  12. ECHO virus

    MedlinePLUS

    Enteric cytopathic human orphan (ECHO) viruses are a group of viruses that lead to gastrointestinal infection and skin rashes. ... Echovirus is one of several families of viruses that affect the ... are common. In the US, they are most common in the summer and ...

  13. VSV?G/EBOV GP-induced innate protection enhances natural killer cell activity to increase survival in a lethal mouse adapted Ebola virus infection.

    PubMed

    Williams, Kinola J N; Qiu, Xiangguo; Fernando, Lisa; Jones, Steven M; Alimonti, Judie B

    2015-02-01

    Members of the species Zaire ebolavirus cause severe hemorrhagic fever with up to a 90% mortality rate in humans. The VSV?G/EBOV GP vaccine has provided 100% protection in the mouse, guinea pig, and nonhuman primate (NHP) models, and has also been utilized as a post-exposure therapeutic to protect mice, guinea pigs, and NHPs from a lethal challenge of Ebola virus (EBOV). EBOV infection causes rapid mortality in human and animal models, with death occurring as early as 6 days after infection, suggesting a vital role for the innate immune system to control the infection before cells of the adaptive immune system can assume control. Natural killer (NK) cells are the predominant cell of the innate immune response, which has been shown to expand with VSV?G/EBOV GP treatment. In the current study, an in vivo mouse model of the VSV?G/EBOV GP post-exposure treatment was used for a mouse adapted (MA)-EBOV infection, to determine the putative VSV?G/EBOV GP-induced protective mechanism of NK cells. NK depletion studies demonstrated that mice with NK cells survive longer in a MA-EBOV infection, which is further enhanced with VSV?G/EBOV GP treatment. NK cell mediated cytotoxicity and IFN-? secretion was significantly higher with VSV?G/EBOV GP treatment. Cell mediated cytotoxicity assays and perforin knockout mice experiments suggest that there are perforin-dependent and -independent mechanisms involved. Together, these data suggest that NK cells play an important role in VSV?G/EBOV GP-induced protection of EBOV by increasing NK cytotoxicity, and IFN-? secretion. PMID:25494457

  14. Using next generation sequencing to identify yellow fever virus in Uganda

    Microsoft Academic Search

    Laura K. McMullan; Mike Frace; Scott A. Sammons; Trevor Shoemaker; Stephen Balinandi; Joseph F. Wamala; Julius J. Lutwama; Robert G. Downing; Ute Stroeher; Adam MacNeil; Stuart T. Nichol

    In October and November 2010, hospitals in northern Uganda reported patients with suspected hemorrhagic fevers. Initial tests for Ebola viruses, Marburg virus, Rift Valley fever virus, and Crimean Congo hemorrhagic fever virus were negative. Unbiased PCR amplification of total RNA extracted directly from patient sera and next generation sequencing resulted in detection of yellow fever virus and generation of 98%

  15. Virus World

    NSDL National Science Digital Library

    2002-01-01

    Created by the Institute for Molecular Virology at the University of Wisconsin-Madison, this Web site offers high quality virus images that may be used for seminar presentations or any other noncommercial use. Users can choose from American Society for Virology conference poster images, enhanced EM pictures, and images of virology-related book and journal covers. Images may be searched by virus name; the results page will provide links to summary information from the Protein Data Bank and to the Scripps Research Institute's Virus Particle Explorer. Movie animations and relevant links are provided for some of the virus images. Users can also access tutorials on virus structure and other topics.

  16. Ebola in the United States.

    PubMed

    Lindblad, Robert; El Fiky, Ashraf; Zajdowicz, Thad

    2015-04-01

    The ongoing epidemic of Ebola virus in West Africa and attendant cases described in other parts of the world has focused attention on this heretofore rare disease. In this brief opinion article, we provide a short primer on the epidemiology, pathogenesis, clinical manifestations, US-based hospital preparedness, vaccine and therapy development, and control of Ebola virus disease for noninfectious disease physicians. PMID:25533525

  17. Implication of the proprotein convertases furin, PC5 and PC7 in the cleavage of surface glycoproteins of Hong Kong, Ebola and respiratory syncytial viruses: a comparative analysis with fluorogenic peptides.

    PubMed

    Basak, A; Zhong, M; Munzer, J S; Chrétien, M; Seidah, N G

    2001-02-01

    Fluorogenic peptides encompassing the processing sites of envelope glycoproteins of the infectious influenza A Hong Kong virus (HKV), Ebola virus (EBOV) and respiratory syncytial virus (RSV) were tested for cleavage by soluble recombinants of the proprotein convertases furin, PC5 and PC7. Kinetic studies with these intramolecularly quenched fluorogenic peptides revealed selective cleavages at the physiological dibasic sites. The HKV peptide is cleaved by both furin and PC5 with similar efficacy; in comparison, PC7 cleaves this substrate poorly. In contrast with the basic tetrapeptide insertion within the haemagglutinin sequence of HKV, two other dipeptide insertions revealed a poorer cleavage with a similar rank order of potency. These results demonstrate that the N-terminal RERR insertion to the wild-type avian RKKR downward arrow sequence is functionally significant, and suggest that the approx. 5-fold increase in cleavage efficacy contributes to the high infectivity of the H5N1 virus subtype. With regard to RSV peptide processing, PC7 is twice as effective as PC5 and furin. The EBOV peptide was processed with similar efficiency by the three enzymes. Our observations that all of these cleavages can be effectively inhibited by a plant andrographolide derivative at 250 microM or less might aid in the design of potent convertase inhibitors as alternative antiviral therapies. PMID:11171050

  18. Marburg Virus Infection Detected in a Common African Bat

    Microsoft Academic Search

    Jonathan S. Towner; Xavier Pourrut; César G. Albariño; Chimène Nze Nkogue; Brian H. Bird; Gilda Grard; Thomas G. Ksiazek; Jean-Paul Gonzalez; Stuart T. Nichol; Eric M. Leroy; Philip Stevenson

    2007-01-01

    Marburg and Ebola viruses can cause large hemorrhagic fever (HF) outbreaks with high case fatality (80–90%) in human and great apes. Identification of the natural reservoir of these viruses is one of the most important topics in this field and a fundamental key to understanding their natural history. Despite the discovery of this virus family almost 40 years ago, the

  19. 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,

  20. CHLORELLA VIRUSES

    PubMed Central

    Yamada, Takashi; Onimatsu, Hideki; Van Etten, James L.

    2007-01-01

    Chlorella viruses or chloroviruses are large, icosahedral, plaque?forming, double?stranded?DNA—containing viruses that replicate in certain strains of the unicellular green alga Chlorella. DNA sequence analysis of the 330?kbp genome of Paramecium bursaria chlorella virus 1 (PBCV?1), the prototype of this virus family (Phycodnaviridae), predict ?366 protein?encoding genes and 11 tRNA genes. The predicted gene products of ?50% of these genes resemble proteins of known function, including many that are completely unexpected for a virus. In addition, the chlorella viruses have several features and encode many gene products that distinguish them from most viruses. These products include: (1) multiple DNA methyltransferases and DNA site?specific endonucleases, (2) the enzymes required to glycosylate their proteins and synthesize polysaccharides such as hyaluronan and chitin, (3) a virus?encoded K+ channel (called Kcv) located in the internal membrane of the virions, (4) a SET domain containing protein (referred to as vSET) that dimethylates Lys27 in histone 3, and (5) PBCV?1 has three types of introns; a self?splicing intron, a spliceosomal processed intron, and a small tRNA intron. Accumulating evidence indicates that the chlorella viruses have a very long evolutionary history. This review mainly deals with research on the virion structure, genome rearrangements, gene expression, cell wall degradation, polysaccharide synthesis, and evolution of PBCV?1 as well as other related viruses. PMID:16877063

  1. Chlorella viruses.

    PubMed

    Yamada, Takashi; Onimatsu, Hideki; Van Etten, James L

    2006-01-01

    Chlorella viruses or chloroviruses are large, icosahedral, plaque-forming, double-stranded-DNA-containing viruses that replicate in certain strains of the unicellular green alga Chlorella. DNA sequence analysis of the 330-kbp genome of Paramecium bursaria chlorella virus 1 (PBCV-1), the prototype of this virus family (Phycodnaviridae), predict approximately 366 protein-encoding genes and 11 tRNA genes. The predicted gene products of approximately 50% of these genes resemble proteins of known function, including many that are completely unexpected for a virus. In addition, the chlorella viruses have several features and encode many gene products that distinguish them from most viruses. These products include: (1) multiple DNA methyltransferases and DNA site-specific endonucleases, (2) the enzymes required to glycosylate their proteins and synthesize polysaccharides such as hyaluronan and chitin, (3) a virus-encoded K(+) channel (called Kcv) located in the internal membrane of the virions, (4) a SET domain containing protein (referred to as vSET) that dimethylates Lys27 in histone 3, and (5) PBCV-1 has three types of introns; a self-splicing intron, a spliceosomal processed intron, and a small tRNA intron. Accumulating evidence indicates that the chlorella viruses have a very long evolutionary history. This review mainly deals with research on the virion structure, genome rearrangements, gene expression, cell wall degradation, polysaccharide synthesis, and evolution of PBCV-1 as well as other related viruses. PMID:16877063

  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 data available...

  3. Cellular Entry of Ebola Virus Involves Uptake by a Macropinocytosis-Like Mechanism and Subsequent Trafficking through Early and Late Endosomes

    Microsoft Academic Search

    Mohammad F. Saeed; Andrey A. Kolokoltsov; Thomas Albrecht; Robert A. Davey

    2010-01-01

    Zaire ebolavirus (ZEBOV), a highly pathogenic zoonotic virus, poses serious public health, ecological and potential bioterrorism threats. Currently no specific therapy or vaccine is available. Virus entry is an attractive target for therapeutic intervention. However, current knowledge of the ZEBOV entry mechanism is limited. While it is known that ZEBOV enters cells through endocytosis, which of the cellular endocytic mechanisms

  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. TUMOR VIRUSES

    E-print Network

    It has been known for many years that infection of an experimental animal with one of a relatively small group of viruses somehow resulted in the appearance of gross tumors. Because of this and the known intimate relationships between the infecting virus and the functions of the cell it invades, many scientists have hypothesized that cancer in man may well be of viral etiology. Yet even today when the amount and sophistication of tumor virus research has markedly increased in recent years, it is not known how a virus transforms a normal cell to one having the properties of a tumor cell nor is there direct evidence that viruses cause cancer in man. However, in the last five years there has been a remarkable change in the experimental approach to the study of tumor viruses. Whereas most early investigations were limited to observations of biological phenomena at the whole animal-gross tumor level, now modern, virological, biochemical, and immunological methods are used to examine the quantitative interaction of tumor viruses with the single cell in the transforming event and to look for determining characteristics of the tumor virus particles, as such. This has been a logical development as techniques in these basic areas have been discovered and applied to other biological problems. Thus, although the final answers are still far from being achieved, we find that a number of basic factors of importance in viral oncogenesis have been defined in certain experimental virus-induced tumor systems. IMPORTANCE OF IN VITRO SYSTEMS FOR VIRUS TRANSFORMATION The chief reason that we are able to start formulating some tentative answers to the question of how a virus transforms a normal cell to a tumor cell is the development of tissue culture systems in which virus transformation occurs in vitro. The degree of control that these isolated systems

  6. 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...

  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. Molecular Ecology and Natural History of Simian Foamy Virus Infection in Wild-Living Chimpanzees

    Microsoft Academic Search

    Weimin Liu; Michael Worobey; Yingying Li; Brandon F. Keele; Frederic Bibollet-Ruche; Yuanyuan Guo; Paul A. Goepfert; Mario L. Santiago; Jean-Bosco N. Ndjango; Cecile Neel; Stephen L. Clifford; Crickette Sanz; Shadrack Kamenya; Michael L. Wilson; Anne E. Pusey; Nicole Gross-Camp; Christophe Boesch; Vince Smith; Koichiro Zamma; Michael A. Huffman; John C. Mitani; David P. Watts; Martine Peeters; George M. Shaw; William M. Switzer; Paul M. Sharp; Beatrice H. Hahn

    2008-01-01

    Identifying microbial pathogens with zoonotic potential in wild-living primates can be important to human health, as evidenced by human immunodeficiency viruses types 1 and 2 (HIV-1 and HIV-2) and Ebola virus. Simian foamy viruses (SFVs) are ancient retroviruses that infect Old and New World monkeys and apes. Although not known to cause disease, these viruses are of public health interest

  9. Properties of Replication-Competent Vesicular Stomatitis Virus Vectors Expressing Glycoproteins of Filoviruses and Arenaviruses

    PubMed Central

    Garbutt, Michael; Liebscher, Ryan; Wahl-Jensen, Victoria; Jones, Steven; Möller, Peggy; Wagner, Ralf; Volchkov, Viktor; Klenk, Hans-Dieter; Feldmann, Heinz; Ströher, Ute

    2004-01-01

    Replication-competent recombinant vesicular stomatitis viruses (rVSVs) expressing the type I transmembrane glycoproteins and selected soluble glycoproteins of several viral hemorrhagic fever agents (Marburg virus, Ebola virus, and Lassa virus) were generated and characterized. All recombinant viruses exhibited rhabdovirus morphology and replicated cytolytically in tissue culture. Unlike the rVSVs with an additional transcription unit expressing the soluble glycoproteins, the viruses carrying the foreign transmembrane glycoproteins in replacement of the VSV glycoprotein were slightly attenuated in growth. Biosynthesis and processing of the foreign glycoproteins were authentic, and the cell tropism was defined by the transmembrane glycoprotein. None of the rVSVs displayed pathogenic potential in animals. The rVSV expressing the Zaire Ebola virus transmembrane glycoprotein mediated protection in mice against a lethal Zaire Ebola virus challenge. Our data suggest that the recombinant VSV can be used to study the role of the viral glycoproteins in virus replication, immune response, and pathogenesis. PMID:15113924

  10. Ebola

    MedlinePLUS

    ... antelope. Ebola gets its name from the Ebola River in the Democratic Republic of Congo (formerly Zaire). ... was first reported in a village on the river in 1976. Since then, there have been a ...

  11. 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

  12. Computer viruses

    NASA Technical Reports Server (NTRS)

    Denning, Peter J.

    1988-01-01

    The worm, Trojan horse, bacterium, and virus are destructive programs that attack information stored in a computer's memory. Virus programs, which propagate by incorporating copies of themselves into other programs, are a growing menace in the late-1980s world of unprotected, networked workstations and personal computers. Limited immunity is offered by memory protection hardware, digitally authenticated object programs,and antibody programs that kill specific viruses. Additional immunity can be gained from the practice of digital hygiene, primarily the refusal to use software from untrusted sources. Full immunity requires attention in a social dimension, the accountability of programmers.

  13. Properties of Replication-Competent Vesicular Stomatitis Virus Vectors Expressing Glycoproteins of Filoviruses and Arenaviruses

    Microsoft Academic Search

    Michael Garbutt; Ryan Liebscher; Victoria Wahl-Jensen; Steven Jones; Peggy Moller; Ralf Wagner; Viktor Volchkov; Hans-Dieter Klenk; Heinz Feldmann; Ute Stroher

    2004-01-01

    Replication-competent recombinant vesicular stomatitis viruses (rVSVs) expressing the type I transmem- brane glycoproteins and selected soluble glycoproteins of several viral hemorrhagic fever agents (Marburg virus, Ebola virus, and Lassa virus) were generated and characterized. All recombinant viruses exhibited rhabdovirus morphology and replicated cytolytically in tissue culture. Unlike the rVSVs with an additional transcription unit expressing the soluble glycoproteins, the viruses

  14. Cellular Entry of Ebola Virus Involves Uptake by a Macropinocytosis-Like Mechanism and Subsequent Trafficking through Early and Late Endosomes

    PubMed Central

    Saeed, Mohammad F.; Kolokoltsov, Andrey A.; Albrecht, Thomas; Davey, Robert A.

    2010-01-01

    Zaire ebolavirus (ZEBOV), a highly pathogenic zoonotic virus, poses serious public health, ecological and potential bioterrorism threats. Currently no specific therapy or vaccine is available. Virus entry is an attractive target for therapeutic intervention. However, current knowledge of the ZEBOV entry mechanism is limited. While it is known that ZEBOV enters cells through endocytosis, which of the cellular endocytic mechanisms used remains unclear. Previous studies have produced differing outcomes, indicating potential involvement of multiple routes but many of these studies were performed using noninfectious surrogate systems such as pseudotyped retroviral particles, which may not accurately recapitulate the entry characteristics of the morphologically distinct wild type virus. Here we used replication-competent infectious ZEBOV as well as morphologically similar virus-like particles in specific infection and entry assays to demonstrate that in HEK293T and Vero cells internalization of ZEBOV is independent of clathrin, caveolae, and dynamin. Instead the uptake mechanism has features of macropinocytosis. The binding of virus to cells appears to directly stimulate fluid phase uptake as well as localized actin polymerization. Inhibition of key regulators of macropinocytosis including Pak1 and CtBP/BARS as well as treatment with the drug EIPA, which affects macropinosome formation, resulted in significant reduction in ZEBOV entry and infection. It is also shown that following internalization, the virus enters the endolysosomal pathway and is trafficked through early and late endosomes, but the exact site of membrane fusion and nucleocapsid penetration in the cytoplasm remains unclear. This study identifies the route for ZEBOV entry and identifies the key cellular factors required for the uptake of this filamentous virus. The findings greatly expand our understanding of the ZEBOV entry mechanism that can be applied to development of new therapeutics as well as provide potential insight into the trafficking and entry mechanism of other filoviruses. PMID:20862315

  15. 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.

  16. The pathogenesis of Ebola hemorrhagic fever

    Microsoft Academic Search

    Ayato Takada; Yoshihiro Kawaoka

    2001-01-01

    Ebola virus causes lethal hemorrhagic disease in humans, yet there are still no satisfactory biological explanations to account for its extreme virulence. This review focuses on recent findings relevant to understanding the pathogenesis of Ebola virus infection and developing vaccines and effective therapy. The available data suggest that the envelope glycoprotein and the interaction of some viral proteins with the

  17. Membrane Fusion-Competent Virus-Like Proteoliposomes and Proteinaceous Supported Bilayers Made Directly from Cell Plasma

    E-print Network

    Daniel, Susan

    ) that coats the walls of microfluidic channels and acts as a host membrane mimic.2,3 This biomimetic material membrane- enveloped viruses, like pandemic strains of influenza, Ebola virus, or severe acute respirato

  18. West Nile Virus

    MedlinePLUS

    ... virus is a virus that can infect humans, birds, horses and mosquitoes. Infection from this virus is ... spread by mosquitoes. Mosquitoes become infected by biting birds that carry the virus. People can get West ...

  19. Proposal for a revised taxonomy of the family Filoviridae: classification, names of taxa and viruses, and virus abbreviations.

    PubMed

    Kuhn, Jens H; Becker, Stephan; Ebihara, Hideki; Geisbert, Thomas W; Johnson, Karl M; Kawaoka, Yoshihiro; Lipkin, W Ian; Negredo, Ana I; Netesov, Sergey V; Nichol, Stuart T; Palacios, Gustavo; Peters, Clarence J; Tenorio, Antonio; Volchkov, Viktor E; Jahrling, Peter B

    2010-12-01

    The taxonomy of the family Filoviridae (marburgviruses and ebolaviruses) has changed several times since the discovery of its members, resulting in a plethora of species and virus names and abbreviations. The current taxonomy has only been partially accepted by most laboratory virologists. Confusion likely arose for several reasons: species names that consist of several words or which (should) contain diacritical marks, the current orthographic identity of species and virus names, and the similar pronunciation of several virus abbreviations in the absence of guidance for the correct use of vernacular names. To rectify this problem, we suggest (1) to retain the current species names Reston ebolavirus, Sudan ebolavirus, and Zaire ebolavirus, but to replace the name Cote d'Ivoire ebolavirus [sic] with Taï Forest ebolavirus and Lake Victoria marburgvirus with Marburg marburgvirus; (2) to revert the virus names of the type marburgviruses and ebolaviruses to those used for decades in the field (Marburg virus instead of Lake Victoria marburgvirus and Ebola virus instead of Zaire ebolavirus); (3) to introduce names for the remaining viruses reminiscent of jargon used by laboratory virologists but nevertheless different from species names (Reston virus, Sudan virus, Taï Forest virus), and (4) to introduce distinct abbreviations for the individual viruses (RESTV for Reston virus, SUDV for Sudan virus, and TAFV for Taï Forest virus), while retaining that for Marburg virus (MARV) and reintroducing that used over decades for Ebola virus (EBOV). Paying tribute to developments in the field, we propose (a) to create a new ebolavirus species (Bundibugyo ebolavirus) for one member virus (Bundibugyo virus, BDBV); (b) to assign a second virus to the species Marburg marburgvirus (Ravn virus, RAVV) for better reflection of now available high-resolution phylogeny; and (c) to create a new tentative genus (Cuevavirus) with one tentative species (Lloviu cuevavirus) for the recently discovered Lloviu virus (LLOV). Furthermore, we explain the etymological derivation of individual names, their pronunciation, and their correct use, and we elaborate on demarcation criteria for each taxon and virus. PMID:21046175

  20. Computer Viruses. Technology Update.

    ERIC Educational Resources Information Center

    Ponder, Tim, Comp.; Ropog, Marty, Comp.; Keating, Joseph, Comp.

    This document provides general information on computer viruses, how to help protect a computer network from them, measures to take if a computer becomes infected. Highlights include the origins of computer viruses; virus contraction; a description of some common virus types (File Virus, Boot Sector/Partition Table Viruses, Trojan Horses, and…