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1

Ebola Virus University Preparedness for Ebola  

E-print Network

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

Shepard, Kenneth

2

Packaging of actin into Ebola virus VLPs  

Microsoft Academic Search

The actin cytoskeleton has been implicated in playing an important role assembly and budding of several RNA virus families including retroviruses and paramyxoviruses. In this report, we sought to determine whether actin is incorporated into Ebola VLPs, and thus may play a role in assembly and\\/or budding of Ebola virus. Our results indicated that actin and Ebola virus VP40 strongly

Ziying Han; Ronald N Harty

2005-01-01

3

Treatment of ebola virus disease.  

PubMed

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

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

2015-01-01

4

THE EBOLA VIRUS BY R. AARON ROBISON  

E-print Network

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

Faraon, Andrei

5

Fruit bats as reservoirs of Ebola virus  

Microsoft Academic Search

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

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

6

Characteristics of Filoviridae: Marburg and Ebola Viruses  

NASA Astrophysics Data System (ADS)

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.

Beer, Brigitte; Kurth, Reinhard; Bukreyev, Alexander

7

Ebola Virus Disease  

MedlinePLUS

... outbreaks. The first EVD outbreaks occurred in remote villages in Central Africa, near tropical rainforests, but the ... Republic of Congo. The latter occurred in a village near the Ebola River, from which the disease ...

8

Ebola virus: questions, answers, and more questions.  

PubMed

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

Brizendine, Kyle D

2014-12-01

9

Ebola virus disease: radiology preparedness.  

PubMed

At present, there is a major emphasis on Ebola virus disease (EVD) preparedness training at medical facilities throughout the United States. Failure to have proper EVD procedures in place was cited as a major reason for infection of medical personnel in the United States. Medical imaging does not provide diagnosis of EVD, but patient assessment in the emergency department and treatment isolation care unit is likely to require imaging services. The purpose of this article is to present an overview of relevant aspects of EVD disease and preparedness relevant to the radiologic community. © RSNA, 2014. PMID:25405643

Bluemke, David A; Meltzer, Carolyn C

2015-02-01

10

[Ebola virus disease].  

PubMed

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

Grünewald, Th

2014-12-01

11

Ebola Virus Antibody Prevalence in Dogs  

E-print Network

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 reaction amplification. Seven (8.9%) of 79 samples from the 2 main towns, 15 (15.2%) of 99 samples from Mekambo, and 40 (25.2%) of 159 samples from villages in the Ebola virus–epidemic area had detectable Ebola virus–IgG, compared to only 2 (2%) of 102 samples from France. Among dogs from villages with both infected animal carcasses and human cases, seroprevalence was 31.8%. A significant positive direct association existed between seroprevalence and the distances to the Ebola virus–epidemic area. This study suggests that dogs can be infected by Ebola virus and that the putative infection is asymptomatic. *Centre International de Recherches Médicales de Franceville,

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

12

The Ebola virus epidemic: Preparation, not panic.  

PubMed

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

Borchardt, Roy A

2015-02-01

13

Successful Delivery of RRT in Ebola Virus Disease.  

PubMed

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

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

14

Successful Delivery of RRT in Ebola Virus Disease  

PubMed Central

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

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

2015-01-01

15

Ebola virus (EboV) infection causes fatal  

E-print Network

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

Chandran, Kartik

16

Development of therapeutics for treatment of Ebola virus infection.  

PubMed

Ebola virus infection can cause Ebola virus disease (EVD). Patients usually show severe symptoms, and the fatality rate can reach up to 90%. No licensed medicine is available. In this review, development of therapeutics for treatment of Ebola virus infection and EVD will be discussed. PMID:25498866

Li, Haoyang; Ying, Tianlei; Yu, Fei; Lu, Lu; Jiang, Shibo

2015-02-01

17

Ebola Virus: Immune Mechanisms of Protection and Vaccine Development  

Microsoft Academic Search

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

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

2003-01-01

18

Ebola virus: a clear and present danger.  

PubMed

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

Burd, Eileen M

2015-01-01

19

Ebola Virus Infection: What Should Be Known?  

PubMed Central

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.

Wiwanitkit, Viroj

2014-01-01

20

Ebola Virus: Identification of Virion Structural Proteins  

Microsoft Academic Search

SUMMARY Polyacrylamide gel 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 125ooo (VPI), IO4OOO (VP2), 40000 (VP3) and 26ooo (VP4). VPI was labelled

MICHAEL P. KILEY; RUSSELL L. REGNERY; KARL M. JOHNSON

1980-01-01

21

Successful Topical Respiratory Tract Immunization of Primates against Ebola Virus  

Microsoft Academic Search

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

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

22

EbolaVirus Disease (Ebola) Algorithm for Evaluation of the ReturnedTraveler  

E-print Network

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

Thaxton, Christopher S.

23

Development of vaccines for prevention of Ebola virus infection.  

PubMed

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

Ye, Ling; Yang, Chinglai

2015-02-01

24

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

PubMed Central

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

2015-01-01

25

Release of Viral Glycoproteins during Ebola Virus Infection  

Microsoft Academic Search

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

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

1998-01-01

26

Persistent Infection with Ebola Virus under Conditions of Partial Immunity  

Microsoft Academic Search

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

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

2004-01-01

27

Endosomal Proteolysis of the Ebola Virus Glycoprotein Is  

E-print Network

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 rapidly fatal hemorrhagic fever in humans and there is currently no effective treatment. We found

Chandran, Kartik

28

Antibody-Dependent Enhancement of Ebola Virus Infection  

Microsoft Academic Search

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

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

2003-01-01

29

Protective efficacy of neutralizing antibodies against Ebola virus infection  

Microsoft Academic Search

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

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

2007-01-01

30

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

PubMed

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

2015-02-01

31

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

Microsoft Academic Search

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

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

2003-01-01

32

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

Microsoft Academic Search

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

JULIE A. WILSON; MARY KATE HART

2001-01-01

33

Ebola virus: the search for vaccines and treatments  

Microsoft Academic Search

:   Ebola viruses belong to the family Filoviridae, which are among the most virulent infectious agents known. These viruses\\u000a cause acute, and frequently fatal, hemorrhagic fever in humans and nonhuman primates. Currently, no vaccines or treatments\\u000a are available for human use. This review describes Ebola viruses, with a particular focus on the status of research efforts\\u000a to develop vaccines and

J. A. Wilson; C. M. Bosio; M. K. Hart

2001-01-01

34

Recombinant human monoclonal antibodies to Ebola virus.  

PubMed

Human Fab (IgG1kappa) phage display libraries were constructed from bone marrow RNA from 2 donors who recovered from infection with Ebola (EBO) virus during the 1995 outbreak in Kikwit, Democratic Republic of the Congo. The libraries were initially panned against a radiation-inactivated EBO virus-infected Vero cell lysate, but only weak binders were identified. In contrast, panning against secreted EBO glycoprotein (SGP) resulted in Fabs showing very strong reactivity with SGP in ELISA. These Fabs also reacted with a virion membrane preparation. The Fabs were strongly positive in IFAs with cells infected with EBO (subtype Zaire) virus but negative with uninfected cells, with a characteristic punctate staining pattern in the cytoplasm. The Fabs showed weak or no reactivity with the virus cell lysate although donor serum did react. The Fabs are now being characterized in structural and functional terms. Major interest will focus on the ability of antibodies to neutralize EBO virus and, later, to protect animals against infection. PMID:9988189

Maruyama, T; Parren, P W; Sanchez, A; Rensink, I; Rodriguez, L L; Khan, A S; Peters, C J; Burton, D R

1999-02-01

35

[Monoclonal antibodies to Ebola virus: isolation, characteristics, and study of cross reactivity with Marburg virus].  

PubMed

Thirteen hybridoma strains producing monoclonal antibodies (Mabs) to Ebola virus were prepared by fusion of NS-O mouse myeloma cells with splenocytes of BALB/c mice immunized with purified and inactivated Ebola virus (Mayinga strain). Mabs directed against viral proteins were selected and tested by ELISA. Protein specificity of 13 Mabs was determined by immunoblotting with SDS-PAGE proteins of Ebola virus. Of these, 11 hybridoma Mabs reacted with 116 kDa protein (NP) and 2 with Ebola virus VP35. Antigenic cross-reactivity between Ebola and Marburg viruses was examined in ELISA and immunoblotting with polyclonal and monoclonal antibodies. In ELISA, polyclonal antibodies of immune sera to Ebola or Marburg viruses reacted with heterologous filoviruses, and two anti-NP Ebola antibodies (Mabs 7E1 and 6G8) cross-reacted with both viruses. Target proteins for cross-reactivity, Ebola NP (116 kDa) and Marburg NP (96 kDa), and VP35 of both filoviruses were detected by immunoblotting with polyclonal and monoclonal antibodies (6G8) to Ebola virus. PMID:10867995

Kazachinskaia, E I; Pereboev, A V; Chepurnov, A A; Belanov, E F; Razumov, I A

2000-01-01

36

Immunopathology of highly virulent pathogens: insights from Ebola virus  

Microsoft Academic Search

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

Carisa A Zampieri; Nancy J Sullivan; Gary J Nabel

2007-01-01

37

Ebola virus (EBOV) infection: Therapeutic strategies.  

PubMed

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

De Clercq, Erik

2015-01-01

38

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

Microsoft Academic Search

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

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

2000-01-01

39

Ebola virus transmission in guinea pigs.  

PubMed

Ebola virus (EBOV) transmission is currently poorly characterized and thought to occur primarily by direct contact with infectious material; however transmission from swine to nonhuman primates via the respiratory tract has been documented. To establish an EBOV transmission model for performing studies with statistical significance, groups of six guinea pigs (gps) were challenged intranasally (IN) or intraperitoneally (IP) with 10,000 x LD50 of gp-adapted EBOV, and naïve gps were then introduced as cage-mates for contact exposure at 1 day post-infection (dpi). Animals were monitored for survival and clinical signs of disease, and quantitated for virus shedding post-exposure. Changes in contact duration of naïve gps with infected animals were evaluated for impact on transmission efficiency. Transmission was more efficient from IN compared to IP-challenged gps, with 17% versus 83% of naïve gps surviving exposure, respectively. Virus shedding was detected beginning at 3 dpi from both IN- and IP-challenged animals. Contact duration positively correlated with transmission efficiency, and the abrogation of direct contact between infected and naïve animals through the erection of a steel mesh is effective at stopping virus spread, provided that infectious animal bedding was absent in the cages. Histopathological and immunohistochemical findings show that IN-infected gps display enhanced lung pathology and EBOV antigen in the trachea, which support increased virus transmission from these animals. The results suggest that IN-challenged gps are more infectious to naïve animals than their systemically-infected counterparts, and that transmission occurs through direct contact with infectious materials, including those transported through air movement over short distances. PMID:25392221

Wong, Gary; Qiu, Xiangguo; Richardson, Jason S; Cutts, Todd; Collignon, Brad; Gren, Jason; Aviles, Jenna; Embury-Hyatt, Carissa; Kobinger, Gary P

2014-11-12

40

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

41

Reemerging Sudan Ebola Virus Disease in Uganda, 2011  

PubMed Central

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

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

42

An Introduction to Ebola: The Virus and the Disease  

Microsoft Academic Search

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

1999-01-01

43

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 aware of these ... Preidt Tuesday, January 20, 2015 Related MedlinePlus Pages Ebola Genes and Gene Therapy TUESDAY, Jan. 20, 2015 (HealthDay News) -- Genetic changes ...

44

Development of an immunofluorescence focus assay for Ebola virus.  

PubMed Central

A 48-h indirect immunofluorescence focus assay for the quantitation of Ebola virus was developed, utilizing HeLa-229 cell monolayers. The dose dependency and the sensitivity of this assay as compared with conventional assays are reported. This indirect immunofluorescence focus assay can be used as a rapid, quantitative test for the detection of Ebola virus, an agent from Africa known to cause hemorrhagic fever. Images PMID:6352735

Truant, A L; Regnery, R L; Kiley, M P

1983-01-01

45

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

46

Update: Ebola virus disease outbreak--West Africa, October 2014.  

PubMed

CDC is assisting ministries of health and working with other organizations to control and end the ongoing outbreak 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 as defined by each country. These data reflect reported cases, which make up an unknown proportion of all actual cases and reporting delays that vary from country to country. PMID:25356606

2014-10-31

47

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

Microsoft Academic Search

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

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

2012-01-01

48

Ebola virus: Melatonin as a readily available treatment option.  

PubMed

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

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

2015-04-01

49

How Ebola virus counters the interferon system.  

PubMed

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

Kühl, A; Pöhlmann, S

2012-09-01

50

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

E-print Network

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

Chandran, Kartik

51

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

PubMed Central

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). PMID:25633975

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

2015-01-01

52

Vesicular Stomatitis Virus-Based Vaccines against Lassa and Ebola Viruses.  

PubMed

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

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

2015-02-01

53

Vesicular Stomatitis Virus–Based Vaccines against Lassa and Ebola Viruses  

PubMed Central

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

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

2015-01-01

54

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

E-print Network

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

Rockwell, Robert F.

55

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

E-print Network

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

Chandran, Kartik

56

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

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

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

2002-01-01

57

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

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

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

58

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

Microsoft Academic Search

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

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

1995-01-01

59

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

PubMed

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

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

2014-10-24

60

Phosphoinositide3 Kinase-Akt Pathway Controls Cellular Entry of Ebola Virus  

Microsoft Academic Search

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.

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

2008-01-01

61

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

Microsoft Academic Search

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

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

62

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

E-print Network

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

Gerdes, J. Christian

63

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

64

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

E-print Network

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

Gleeson, Joseph G.

65

Professional Development Implications of Ebola Virus Disease Education: Part II.  

PubMed

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. J Contin Educ Nurs. 2015;46(2):56-58. PMID:25633300

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

2015-02-01

66

Inactivation of Ebola virus with a surfactant nanoemulsion  

Microsoft Academic Search

Hemorrhagic fever caused by Ebola virus (EBO) is a highly contagious infection. This necessitates that the contaminated instruments, clothes, and hospital premises must be completely disinfected. Nanoemulsions are a new form of disinfectant composed of detergents and vegetable oil suspended in water. The antiviral activity of nanoemulsion ATB has been investigated against EBO. The nanoemulsion was tested against two preparations

A. A Chepurnov; L. F Bakulina; A. A Dadaeva; E. N Ustinova; T. S Chepurnova; J. R Baker

2003-01-01

67

How Ebola and Marburg viruses battle the immune system  

Microsoft Academic Search

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

Lieping Chen; Mansour Mohamadzadeh; Alan L. Schmaljohn

2007-01-01

68

Evaluation in Nonhuman Primates of Vaccines against Ebola Virus  

Microsoft Academic Search

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

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

2002-01-01

69

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

70

A case of Ebola virus infection  

Microsoft Academic Search

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

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

1977-01-01

71

GB Virus C Coinfections in West African Ebola Patients.  

PubMed

In 49 patients with known Ebola virus disease outcomes during the ongoing outbreak in Sierra Leone, 13 were coinfected with the immunomodulatory pegivirus GB virus C (GBV-C). Fifty-three percent of these GBV-C(+) patients survived; in contrast, only 22% of GBV-C(-) patients survived. Both survival and GBV-C status were associated with age, with older patients having lower survival rates and intermediate-age patients (21 to 45 years) having the highest rate of GBV-C infection. Understanding the separate and combined effects of GBV-C and age on Ebola virus survival may lead to new treatment and prevention strategies, perhaps through age-related pathways of immune activation. PMID:25473056

Lauck, Michael; Bailey, Adam L; Andersen, Kristian G; Goldberg, Tony L; Sabeti, Pardis C; O'Connor, David H

2015-02-15

72

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 ...

73

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

E-print Network

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. Since the first recognized outbreaks of human Ebola virus hemorrhagic fever in Africa in the 1970s, biological and genetic differences have been described among the four distinct Ebola viruses isolated: Zaire, Sudan, and Côte d’Ivoire, all isolated from humans, and Reston virus isolated from macaque monkeys from the Philippines (1-5). Serologic evidence has suggested the presence

unknown authors

74

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

Microsoft Academic Search

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.

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

2004-01-01

75

Ebola virus disease outbreak - Nigeria, July-September 2014.  

PubMed

On July 20, 2014, an acutely ill traveler from Liberia arrived at the international airport in Lagos, Nigeria, and was confirmed to have Ebola virus disease (Ebola) after being admitted to a private hospital. This index patient potentially exposed 72 persons at the airport and the hospital. The Federal Ministry of Health, with guidance from the Nigeria Centre for Disease Control (NCDC), declared an Ebola emergency. Lagos, (pop. 21 million) is a regional hub for economic, industrial, and travel activities and a setting where communicable diseases can be easily spread and transmission sustained. Therefore, implementing a rapid response using all available public health assets was the highest priority. On July 23, the Federal Ministry of Health, with the Lagos State government and international partners, activated an Ebola Incident Management Center as a precursor to the current Emergency Operations Center (EOC) to rapidly respond to this outbreak. The index patient died on July 25; as of September 24, there were 19 laboratory-confirmed Ebola cases and one probable case in two states, with 894 contacts identified and followed during the response. Eleven patients with laboratory-confirmed Ebola had been discharged, an additional patient was diagnosed at convalescent stage, and eight patients had died (seven with confirmed Ebola; one probable). The isolation wards were empty, and 891 (all but three) contacts had exited follow-up, with the remainder due to exit on October 2. No new cases had occurred since August 31, suggesting that the Ebola outbreak in Nigeria might be contained. The EOC, established quickly and using an Incident Management System (IMS) to coordinate the response and consolidate decision making, is largely credited with helping contain the Nigeria outbreak early. National public health emergency preparedness agencies in the region, including those involved in Ebola responses, should consider including the development of an EOC to improve the ability to rapidly respond to urgent public health threats. PMID:25275332

Shuaib, Faisal; Gunnala, Rajni; Musa, Emmanuel O; Mahoney, Frank J; Oguntimehin, Olukayode; Nguku, Patrick M; Nyanti, Sara Beysolow; Knight, Nancy; Gwarzo, Nasir Sani; Idigbe, Oni; Nasidi, Abdulsalam; Vertefeuille, John F

2014-10-01

76

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

Microsoft Academic Search

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

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

77

Clinical presentation and management of severe ebola virus disease.  

PubMed

Clinicians caring for patients infected with Ebola virus must be familiar not only with screening and infection control measures but also with management of severe disease. By integrating experience from several Ebola epidemics with best practices for managing critical illness, this report focuses on the clinical presentation and management of severely ill infants, children, and adults with Ebola virus disease. Fever, fatigue, vomiting, diarrhea, and anorexia are the most common symptoms of the 2014 West African outbreak. Profound fluid losses from the gastrointestinal tract result in volume depletion, metabolic abnormalities (including hyponatremia, hypokalemia, and hypocalcemia), shock, and organ failure. Overt hemorrhage occurs infrequently. The case fatality rate in West Africa is at least 70%, and individuals with respiratory, neurological, or hemorrhagic symptoms have a higher risk of death. There is no proven antiviral agent to treat Ebola virus disease, although several experimental treatments may be considered. Even in the absence of antiviral therapies, intensive supportive care has the potential to markedly blunt the high case fatality rate reported to date. Optimal treatment requires conscientious correction of fluid and electrolyte losses. Additional management considerations include searching for coinfection or superinfection; treatment of shock (with intravenous fluids and vasoactive agents), acute kidney injury (with renal replacement therapy), and respiratory failure (with invasive mechanical ventilation); provision of nutrition support, pain and anxiety control, and psychosocial support; and the use of strategies to reduce complications of critical illness. Cardiopulmonary resuscitation may be appropriate in certain circumstances, but extracorporeal life support is not advised. Among other ethical issues, patients' medical needs must be carefully weighed against healthcare worker safety and infection control concerns. However, meticulous attention to the use of personal protective equipment and strict adherence to infection control protocols should permit the safe provision of intensive treatment to severely ill patients with Ebola virus disease. PMID:25369317

West, T Eoin; von Saint André-von Arnim, Amélie

2014-11-01

78

Ebola virus disease outbreak - West Africa, September 2014.  

PubMed

CDC is assisting ministries of health and working with other organizations to control and end the ongoing outbreak of Ebola virus disease (Ebola) in West Africa. The updated data in this report were compiled from ministry of health situation reports and World Health Organization (WHO) sources. Total case counts include all suspected, probable, and confirmed cases as defined by each country. These data reflect reported cases, which make up an unknown proportion of all actual cases. The data also reflect reporting delays that might vary from country to country. PMID:25275331

2014-10-01

79

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

Microsoft Academic Search

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

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

2000-01-01

80

Antigen Capture Enzyme-Linked Immunosorbent Assay for Specific Detection of Reston Ebola Virus Nucleoprotein  

Microsoft Academic Search

Antigen capture enzyme-linked immunosorbent assay (ELISA) is one of the most useful methods to detect Ebola virus rapidly. We previously developed an antigen capture ELISA using a monoclonal antibody (MAb), 3-3D, which reacted not only to the nucleoprotein (NP) of Zaire Ebola virus (EBO-Z) but also to the NPs of Sudan (EBO-S) and Reston Ebola (EBO-R) viruses. In this study,

Tetsuro Ikegami; Masahiro Niikura; Masayuki Saijo; Mary E. Miranda; Alan B. Calaor; Marvin Hernandez; Luz P. Acosta; Daria L. Manalo; Ichiro Kurane; Yasuhiro Yoshikawa; Shigeru Morikawa

2003-01-01

81

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

SciTech Connect

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.

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

1982-10-01

82

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

SciTech Connect

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.

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

1982-10-01

83

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

Microsoft Academic Search

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

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

1999-01-01

84

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

Microsoft Academic Search

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

Laura J Hughes

2010-01-01

85

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

Microsoft Academic Search

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

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

2003-01-01

86

Vesicular Release of Ebola Virus Matrix Protein VP40  

Microsoft Academic Search

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

Joanna Timmins; Sandra Scianimanico; Guy Schoehn; Winfried Weissenhorn

2001-01-01

87

Frequently Asked Questions on Ebola Virus Disease  

MedlinePLUS

... authority. While there is no specific drug against Ebola, the best treatment is intensive supportive treatment provided in the hospital ... and communities to prepare for and respond to Ebola outbreaks. WHO ... and treatment options; deployments of experts and the distribution of ...

88

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

E-print Network

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 virus-like particles (VLPs), containing the glycoprotein (GP) and matrix protein virus protein (VP)40, administered 1–3 d before Ebola virus infection rapidly induced protective immunity. VLP injection enhanced the numbers of natural killer (NK) cells in lymphoid tissues. In contrast to live Ebola virus, VLP treatment of NK cells enhanced cytokine secretion and cytolytic activity against NK-sensitive targets. Unlike wild-type mice, treatment of NK-deficient or-depleted mice with VLPs had no protective effect against Ebola virus infection and NK cells treated with VLPs protected against Ebola virus infection when adoptively transferred to naive mice. The mechanism of NK cell–mediated protection clearly depended on perforin, but not interferon-? secretion. Particles containing only VP40 were sufficient to induce NK cell responses and provide protection from infection in the absence of the viral GP. These findings revealed a decisive role for NK cells during lethal Ebola virus infection. This work should open new doors for better understanding

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

89

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

Microsoft Academic Search

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.

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

2005-01-01

90

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

Microsoft Academic Search

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

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

2002-01-01

91

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

Microsoft Academic Search

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

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

2001-01-01

92

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

Microsoft Academic Search

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

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

93

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

Microsoft Academic Search

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

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

2007-01-01

94

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

Microsoft Academic Search

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

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

95

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

Microsoft Academic Search

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

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

96

Complete genome sequences of three ebola virus isolates from the 2014 outbreak in west Africa.  

PubMed

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

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

2014-01-01

97

Analysis of Ebola virus and VLP release using an immunocapture assay  

Microsoft Academic Search

Ebola virus (EBOV), an emerging pathogen, is the causative agent of a rapidly progressive hemorrhagic fever with high mortality rates. There are currently no approved vaccines or treatments available for Ebola hemorrhagic fever. Standard plaque assays are currently the only reliable techniques for enumerating the virus. Effective drug-discovery screening as well as target identification and validation require simple and more

George Kallstrom; Kelly L. Warfield; Dana L. Swenson; Shannon Mort; Rekha G. Panchal; Gordon Ruthel; Sina Bavari; M. Javad Aman

2005-01-01

98

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

PubMed Central

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

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

2014-01-01

99

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

Microsoft Academic Search

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

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

100

Pathogenesis of experimental Ebola virus infection in guinea pigs.  

PubMed

The subtype Zaire of Ebola (EBO) virus (Mayinga strain) was adapted to produce lethal infections in guinea pigs. In many ways, the disease was similar to EBO infections in nonhuman primates and humans. The guinea pig model was used to investigate the pathologic events in EBO infection that lead to death. Analytical methods included immunohistochemistry, in situ hybridization, and electron microscopy. Cells of the mononuclear phagocyte system, primarily macrophages, were identified as the early and sustained targets of EBO virus. During later stages of infection, interstitial fibroblasts in various tissues were infected, and there was evidence of endothelial cell infection and fibrin deposition. The distribution of lesions, hematologic profiles, and increases in serum biochemical enzymes associated with EBO virus infection in guinea pigs was similar to reported findings in experimentally infected nonhuman primates and naturally infected humans. PMID:9988186

Connolly, B M; Steele, K E; Davis, K J; Geisbert, T W; Kell, W M; Jaax, N K; Jahrling, P B

1999-02-01

101

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

.g., antiviral drug) is available for Ebola. Experimental vaccines and treatments for Ebola are under development information: http://www.cdc.gov/vhf/ebola/treatment/index.html What is the incubation period for Ebola information, please see www.cdc.gov/ebola Ebola Virus Disease FAQ for the Purdue Community What is Ebola

Ginzel, Matthew

102

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

Microsoft Academic Search

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

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

2004-01-01

103

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

104

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

105

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

Microsoft Academic Search

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

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

2003-01-01

106

3-Deazaneplanocin A induces massively increased interferon-? production in Ebola virus-infected mice  

Microsoft Academic Search

3-Deazaneplanocin A, an analog of adenosine, is a potent inhibitor of Ebola virus replication. A single dose early in infection prevents illness and death in Ebola virus-infected mice. The ability of this and similar compounds to block both RNA and DNA viruses has been attributed to the inhibition of a cellular enzyme, S-adenosylhomocysteine hydrolase (SAH), indirectly resulting in reduced methylation

Mike Bray; Jo Lynne Raymond; Tom Geisbert; Robert O Baker

2002-01-01

107

Ebola virus disease: roles and considerations for pharmacists.  

PubMed

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

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

2015-02-01

108

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

PubMed

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

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

2004-12-01

109

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

Microsoft Academic Search

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

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

2000-01-01

110

Serological evidence of Ebola virus infection in Indonesian orangutans.  

PubMed

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

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

2012-01-01

111

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

Microsoft Academic Search

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-?

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

2001-01-01

112

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

Microsoft Academic Search

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

HIROSHI ITO; SHINJI WATANABE; AYATO TAKADA; YOSHIHIRO KAWAOKA

2001-01-01

113

Vesicular Stomatitis Virus-Based Ebola Vaccine Is Well-Tolerated and Protects Immunocompromised Nonhuman Primates  

Microsoft Academic Search

Ebola virus (EBOV) is a significant human pathogen that presents a public health concern as an emerging\\/re-emerging virus and as a potential biological weapon. Substantial progress has been made over the last decade in developing candidate preventive vaccines that can protect nonhuman primates against EBOV. Among these prospects, a vaccine based on recombinant vesicular stomatitis virus (VSV) is particularly robust,

Thomas W. Geisbert; Kathleen M. Daddario-DiCaprio; Mark G. Lewis; Joan B. Geisbert; Allen Grolla; Anders Leung; Jason Paragas; Lennox Matthias; Mark A. Smith; Steven M. Jones; Lisa E. Hensley; Heinz Feldmann; Peter B. Jahrling

2008-01-01

114

Elucidating variations in the nucleotide sequence of Ebola virus associated with increasing pathogenicity.  

PubMed

BackgroundEbolaviruses causes a severe and often fatal hemorrhagic fever in humans, with some species such as Ebola virus having case fatality rates approaching 90%. Currently the worst Ebola virus outbreak since the disease was discovered is occurring in West Africa. Although thought to be a zoonotic infection, a concern is that with increasing numbers of humans being infected, Ebola virus variants could be selected which are better adapted for human-to-human transmission.ResultsTo investigate whether genetic changes in Ebola virus become established in response to adaptation in a different host, a guinea pig model of infection was used. In this experimental system, guinea pigs were infected with Ebola virus (EBOV), which initially did not cause disease. To simulate transmission to uninfected individuals, the virus was serially passaged five times in naive animals. As the virus was passaged, virulence increased and clinical effects were observed in the guinea pig. An RNAseq and consensus mapping approach was then used to evaluate potential nucleotide changes in the Ebola virus genome at each passage.ConclusionsUpon passage in the guinea pig model, EBOV become more virulent, RNA editing and also coding changes in key proteins become established. The data suggest that the initial evolutionary trajectory of EBOV in a new host can lead to a gain in virulence. Given the circumstances of the sustained transmission of EBOV in the current outbreak in West Africa, increases in virulence may be associated with prolonged and uncontrolled epidemics of EBOV. PMID:25416632

Dowall, Stuart D; Matthews, David A; García-Dorival, Isabel; Taylor, Irene; Kenny, John; Hertz-Fowler, Christiane; Hall, Neil; Corbin-Lickfett, Kara; Empig, Cyril; Schlunegger, Kyle; Barr, John N; Carroll, Miles W; Hewson, Roger; Hiscox, Julian A

2014-11-22

115

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

E-print Network

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

Harrison, Stephen C.

116

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

E-print Network

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

Wong, Pak Kin

117

Euthanasia Assessment in Ebola Virus Infected Nonhuman Primates  

PubMed Central

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

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

118

Mapping the zoonotic niche of Ebola virus disease in Africa  

PubMed Central

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

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

119

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

PubMed

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

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

120

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

Microsoft Academic Search

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

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

2008-01-01

121

Ebola virus disease cases among health care workers not working in Ebola treatment units--Liberia, June-August, 2014.  

PubMed

West Africa is experiencing the largest Ebola virus disease (Ebola) epidemic in recorded history. Health care workers (HCWs) are at increased risk for Ebola. In Liberia, as of August 14, 2014, a total of 810 cases of Ebola had been reported, including 10 clusters of Ebola cases among HCWs working in facilities that were not Ebola treatment units (non-ETUs). The Liberian Ministry of Health and Social Welfare and CDC investigated these clusters by reviewing surveillance data, interviewing county health officials, HCWs, and contact tracers, and visiting health care facilities. Ninety-seven cases of Ebola (12% of the estimated total) were identified among HCWs; 62 HCW cases (64%) were part of 10 distinct clusters in non-ETU health care facilities, primarily hospitals. Early recognition and diagnosis of Ebola in patients who were the likely source of introduction to the HCWs (i.e., source patients) was missed in four clusters. Inconsistent recognition and triage of cases of Ebola, overcrowding, limitations in layout of physical spaces, lack of training in the use of and adequate supply of personal protective equipment (PPE), and limited supervision to ensure consistent adherence to infection control practices all were observed. Improving infection control infrastructure in non-ETUs is essential for protecting HCWs. Since August, the Liberian Ministry of Health and Social Welfare with a consortium of partners have undertaken collaborative efforts to strengthen infection control infrastructure in non-ETU health facilities. PMID:25412067

Matanock, Almea; Arwady, M Allison; Ayscue, Patrick; Forrester, Joseph D; Gaddis, Bethany; Hunter, Jennifer C; Monroe, Benjamin; Pillai, Satish K; Reed, Christie; Schafer, Ilana J; Massaquoi, Moses; Dahn, Bernice; De Cock, Kevin M

2014-11-21

122

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

E-print Network

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

Chandran, Kartik

123

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

Microsoft Academic Search

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

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

1999-01-01

124

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

Microsoft Academic Search

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

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

2002-01-01

125

Ebola Virus Does Not Block Apoptotic Signaling Pathways  

PubMed Central

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

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

126

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

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.

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

127

Stimulation of Ebola virus production from persistent infection through activation of the Ras\\/MAPK pathway  

Microsoft Academic Search

Human infections with Ebola virus (EBOV) result in a deadly viral disease known as Ebola hemorrhagic fever. Up to 90% of infected patients die, and there is no available treatment or vaccine. The sporadic human outbreaks are believed to result when EBOV ``jumps'' from an infected animal to a person and is subsequently transmitted between persons by direct contact with

James E. Strong; Gary Wong; Shane E. Jones; Allen Grolla; Steven Theriault; Gary P. Kobinger; Heinz Feldmann

2008-01-01

128

Development of a broad-spectrum antiviral with activity against Ebola virus  

Microsoft Academic Search

We report herein the identification of a small molecule therapeutic, FGI-106, which displays potent and broad-spectrum inhibition of lethal viral hemorrhagic fevers pathogens, including Ebola, Rift Valley and Dengue Fever viruses, in cell-based assays. Using mouse models of Ebola virus, we further demonstrate that FGI-106 can protect animals from an otherwise lethal infection when used either in a prophylactic or

M. Javad Aman; Michael S. Kinch; Kelly Warfield; Travis Warren; Abdul Yunus; Sven Enterlein; Eric Stavale; Peifang Wang; Shaojing Chang; Qingsong Tang; Kevin Porter; Michael Goldblatt; Sina Bavari

2009-01-01

129

Role for Amino Acids 212KLR214 of Ebola Virus VP40 in Assembly and Budding  

Microsoft Academic Search

Received 20 April 2007\\/Accepted 30 July 2007 Ebola virus VP40 is able to produce virus-like particles (VLPs) in the absence of other viral proteins. At least three domains within VP40 are thought to be required for efficient VLP release: the late domain (L-domain), membrane association domain (M-domain), and self-interaction domain (I-domain). While the L-domain of Ebola VP40 has been well

Sarah E. McCarthy; Reed F. Johnson; Yong-An Zhang; J. Oriol Sunyer; Ronald N. Harty

2007-01-01

130

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

Microsoft Academic Search

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

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

2011-01-01

131

Being ready to treat ebola virus disease patients.  

PubMed

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

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

132

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

PubMed Central

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

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

133

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

PubMed

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 immunization with an adenoviral (ADV) vector encoding the Ebola glycoprotein (GP) was induced more rapidly than with DNA priming and ADV boosting, but it was of lower magnitude. To determine whether this earlier immune response could nonetheless protect against disease, cynomolgus macaques were challenged with Ebola virus after vaccination with ADV-GP and nucleoprotein (NP) vectors. Protection was highly effective and correlated with the generation of Ebola-specific CD8(+) T-cell and antibody responses. Even when animals were immunized once with ADV-GP/NP and challenged 28 days later, they remained resistant to challenge with either low or high doses of virus. This accelerated vaccine provides an intervention that may help to limit the epidemic spread of Ebola, and is applicable to other viruses. PMID:12904795

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

2003-08-01

134

ELISA for the detection of antibodies to Ebola viruses.  

PubMed

EIAs for IgG and IgM antibodies directed against Ebola (EBO) viral antigens have been developed and evaluated using sera of animals and humans surviving infection with EBO viruses. The IgM capture assay detected anti-EBO (subtype Reston) antibodies in the sera of 5 of 5 experimentally infected animals at the time they succumbed to lethal infections. IgM antibodies were also detected in the serum of a human who was infected with EBO (subtype Reston) during a postmortem examination of an infected monkey. The antibody was detectable as early as day 6 after infection in experimentally infected animals and persisted for <90 days. The IgG response was less rapid; however, it persisted for >400 days in 3 animals who survived infection, and it persisted for approximately 10 years after infection in the sera of 2 humans. Although these data are limited by the number of sera available for verification, the IgM assay seems to have great promise as a diagnostic tool. Furthermore the long-term persistence of the IgG antibodies measured by this test strongly suggests that the ELISA will be useful in field investigations of EBO virus. PMID:9988184

Ksiazek, T G; West, C P; Rollin, P E; Jahrling, P B; Peters, C J

1999-02-01

135

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

Microsoft Academic Search

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

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

136

Rapid identification of Ebola virus and related filoviruses in fluid specimens using indirect immunoelectron microscopy  

Microsoft Academic Search

Recent filoviral outbreaks in animal primates have raised public awareness of the potential for filoviruses to become a public health concern; methods that efficiently identify these viruses are therefore of high priority. An indirect immunoelectron microscopy method, which uses homologous guinea pig polyclonal antiserum, successfully identified Ebola-related (Reston) virus particles in serum and tissue culture fluid specimens with infectivity titres

T W Geisbert; J B Rhoderick; P B Jahrling

1991-01-01

137

Neutralizing Antibody Fails to Impact the Course of Ebola Virus Infection in Monkeys  

Microsoft Academic Search

Prophylaxis with high doses of neutralizing antibody typically offers protection against challenge with viruses producing acute infections. In this study, we have investigated the ability of the neutralizing human monoclonal antibody, KZ52, to protect against Ebola virus in rhesus macaques. This antibody was previously shown to fully protect guinea pigs from infection. Four rhesus macaques were given 50 mg\\/kg of

Wendelien B. Oswald; Thomas W. Geisbert; Kelly J. Davis; Joan B. Geisbert; Nancy J. Sullivan; Peter B. Jahrling; Paul W. H. I. Parren; Dennis R. Burton

2007-01-01

138

Animal models for Ebola and Marburg virus infections  

PubMed Central

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

Nakayama, Eri; Saijo, Masayuki

2013-01-01

139

Ebola Virus Disease: Essential Public Health Principles for Clinicians  

PubMed Central

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

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

2014-01-01

140

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

PubMed

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

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

2013-01-01

141

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

SciTech Connect

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.

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

142

Detection of Cell-Cell Fusion Mediated by Ebola Virus Glycoproteins  

Microsoft Academic Search

Ebola viruses (EboV) are enveloped RNA viruses infecting cells by a pH-dependent process mediated by viral glycoproteins (GP) involving endocytosis of virions and their routing into acidic endosomes. As with well- characterized pH-dependent viral entry proteins, in particular influenza virus hemagglutinin, it is thought that EboV GP require activation by low pH in order to mediate fusion of the viral

Severine Bar; Ayato Takada; Yoshihiro Kawaoka; Marc Alizon

2006-01-01

143

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

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

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

144

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

Microsoft Academic Search

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

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

2001-01-01

145

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

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.

Akihito Yonezawa; Marielle Cavrois; Warner C. Greene

2005-01-01

146

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

Microsoft Academic Search

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:

Herwig Leirs; Dudu Akaibe; Neal Woollen; George Ludwig

1999-01-01

147

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

Microsoft Academic Search

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

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

148

Ebola virus infection induces irregular dendritic cell gene expression.  

PubMed

Abstract Filoviruses subvert the human immune system in part by infecting and replicating in dendritic cells (DCs). Using gene arrays, a phenotypic profile of filovirus infection in human monocyte-derived DCs was assessed. Monocytes from human donors were cultured in GM-CSF and IL-4 and were infected with Ebola virus Kikwit variant for up to 48?h. Extracted DC RNA was analyzed on SuperArray's Dendritic and Antigen Presenting Cell Oligo GEArray and compared to uninfected controls. Infected DCs exhibited increased expression of cytokine, chemokine, antiviral, and anti-apoptotic genes not seen in uninfected controls. Significant increases of intracellular antiviral and MHC I and II genes were also noted in EBOV-infected DCs. However, infected DCs failed to show any significant difference in co-stimulatory T-cell gene expression from uninfected DCs. Moreover, several chemokine genes were activated, but there was sparse expression of chemokine receptors that enabled activated DCs to home to lymph nodes. Overall, statistically significant expression of several intracellular antiviral genes was noted, which may limit viral load but fails to stop replication. EBOV gene expression profiling is of vital importance in understanding pathogenesis and devising novel therapeutic treatments such as small-molecule inhibitors. PMID:25493356

Melanson, Vanessa R; Kalina, Warren V; Williams, Priscilla

2015-02-01

149

[Antigenic structure of Ebola virus VP35 protein].  

PubMed

Antigenic structure of Ebola virus (EV) (strain Mayinga) nucleocapsid protein VP35 was analyzed using monoclonal antibodies to EV VP35 and polyclonal antibodies to EV. EV protein VP35 was shown to have antigenic sites inducing the production of antibodies in animals. For better characterization of protein VP35 antigenic structure. EV gene encoding the full-length VP35 was cloned in vector pQE31 as a recombinant fusion protein (rec.VP35). The antigenic and immunogenic properties of rec.VP35 and EV VP35 were compared by ELISA and Western blot analysis with polyclonal and monoclonal antibodies. Antibodies of positive sera and VP35 MAbs cross reacted with the analyzed antigens. The topography of epitopes on EV VP35 and rec.VP35 was studied using MAbs and polyclonal antibodies to rec.VP35 in a competitive antibody binding assay. Two epitopes of one site were identified on these proteins. These epitopes are present on infectious virion protein VP35 and are stable during physicochemical exposures. PMID:11715705

Kazachinskaia, E I; Ternovo?, V A; Rudzevich, T N; Netesov, S V; Chepurnov, A A; Razumov, I A

2001-01-01

150

Characterizing the Transmission Dynamics and Control of Ebola Virus Disease  

PubMed Central

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

Chowell, Gerardo; Nishiura, Hiroshi

2015-01-01

151

Characterizing the transmission dynamics and control of ebola virus disease.  

PubMed

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

Chowell, Gerardo; Nishiura, Hiroshi

2015-01-01

152

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

PubMed

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

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

2010-01-01

153

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

E-print Network

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 concerns about the public health threat of these human pathogens. Filoviruses are classified as biosafety level 4 agents because of the extreme pathogenicity of certain strains and the lack of a protective vaccine or effective antiviral drug. Moreover, filoviruses are among the most mysterious groups of viruses known because their natural history and reservoirs remain undefined and their pathogenesis is poorly understood. Ebola virus infections were first recognized in

Consists Of Ebola; Marburg Viruses

154

Protection of Nonhuman Primates against Two Species of Ebola Virus Infection with a Single Complex Adenovirus Vector?  

PubMed Central

Ebola viruses are highly pathogenic viruses that cause outbreaks of hemorrhagic fever in humans and other primates. To meet the need for a vaccine against the several types of Ebola viruses that cause human diseases, we developed a multivalent vaccine candidate (EBO7) that expresses the glycoproteins of Zaire ebolavirus (ZEBOV) and Sudan ebolavirus (SEBOV) in a single complex adenovirus-based vector (CAdVax). We evaluated our vaccine in nonhuman primates against the parenteral and aerosol routes of lethal challenge. EBO7 vaccine provided protection against both Ebola viruses by either route of infection. Significantly, protection against SEBOV given as an aerosol challenge, which has not previously been shown, could be achieved with a boosting vaccination. These results demonstrate the feasibility of creating a robust, multivalent Ebola virus vaccine that would be effective in the event of a natural virus outbreak or biological threat. PMID:20181765

Pratt, William D.; Wang, Danher; Nichols, Donald K.; Luo, Min; Woraratanadharm, Jan; Dye, John M.; Holman, David H.; Dong, John Y.

2010-01-01

155

Ebola and Marburg virus antibody prevalence in selected populations of the Central African Republic.  

PubMed

With the natural history of the filovirus family seemingly unknown, filovirus ecology in its natural environment remains a rudimentary field of research. In order to investigate the maintenance cycle of filovirus in Central Africa, a study was conducted within the rain forest of the Central African Republic. The epidemiological study determines the frequency and distribution of filovirus seroprevalence in a selected human population. Using an ELISA, serum samples from Pygmy and non-Pygmy populations were tested for Ebola-Zaire virus and Marburg (MBG) virus antibody. Filovirus antibody reacting sera were found in all zones investigated, and in all populations studied (Ebola virus IgG 5.3%; Marburg virus IgG 2.4%). Pygmies appeared to have a significantly higher seroprevalence (P < 0.03) against Ebola-Zaire virus (7.02%) than non-Pygmies (4.2%). MBG virus or related unknown filovirus strains also seem to be present in the western part of Central Africa. MBG virus antibodies were present in different Pygmy groups (ranging from 0.7 to 5.6%, mean 2.05%) and in several non-Pygmy populations (ranging from 0.0 to 3.9%, mean 3.4%) without an overall significant difference between the two groups (P = 0.14). The potentialities of nonpathogenic filovirus strains circulating in the Central African Republic are discussed. PMID:10717539

Gonzalez, J P; Nakoune, E; Slenczka, W; Vidal, P; Morvan, J M

2000-01-01

156

Inflammatory responses in Ebola virus-infected patients  

PubMed Central

Ebola virus subtype Zaire (Ebo-Z) induces acute haemorrhagic fever and a 60–80% mortality rate in humans. Inflammatory responses were monitored in victims and survivors of Ebo-Z haemorrhagic fever during two recent outbreaks in Gabon. Survivors were characterized by a transient release in plasma of interleukin-1? (IL-1?), IL-6, tumour necrosis factor-? (TNF?), macrophage inflammatory protein-1? (MIP-1?) and MIP-1? early in the disease, followed by circulation of IL-1 receptor antagonist (IL-1RA) and soluble receptors for TNF? (sTNF-R) and IL-6 (sIL-6R) towards the end of the symptomatic phase and after recovery. Fatal infection was associated with moderate levels of TNF? and IL-6, and high levels of IL-10, IL-1RA and sTNF-R, in the days before death, while IL-1? was not detected and MIP-1? and MIP-1? concentrations were similar to those of endemic controls. Simultaneous massive activation of monocytes/macrophages, the main target of Ebo-Z, was suggested in fatal infection by elevated neopterin levels. Thus, presence of IL-1? and of elevated concentrations of IL-6 in plasma during the symptomatic phase can be used as markers of non-fatal infection, while release of IL-10 and of high levels of neopterin and IL-1RA in plasma as soon as a few days after the disease onset is indicative of a fatal outcome. In conclusion, recovery from Ebo-Z infection is associated with early and well-regulated inflammatory responses, which may be crucial in controlling viral replication and inducing specific immunity. In contrast, defective inflammatory responses and massive monocyte/macrophage activation were associated with fatal outcome. PMID:11982604

BAIZE, S; LEROY, E M; GEORGES, A J; GEORGES-COURBOT, M-C; CAPRON, M; BEDJABAGA, I; LANSOUD-SOUKATE, J; MAVOUNGOU, E

2002-01-01

157

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

Microsoft Academic Search

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

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

2000-01-01

158

Ebola Virus VP40Induced Particle Formation and Association with the Lipid Bilayer  

Microsoft Academic Search

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

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

2001-01-01

159

Serological reactivity of baculovirus-expressed Ebola virus VP35 and nucleoproteins  

Microsoft Academic Search

Ebola virus (EBOV) is a member of the family Filoviridae and is classified as a biosafety level 4 virus. This classification makes the preparation of antigen and performance of diagnostic assays time-consuming and complicated. The objective of this study was to evaluate the value of EBOV immunoassays based on recombinant nucleoprotein (r-NP) and recombinant VP35 (r-VP35) using large serum panels

Jan Groen; Bernadette G. van den Hoogen; Chantal P. Burghoorn-Maas; Anthony R. Fooks; Jane Burton; Chris J. S. C. Clegg; Herve Zeller; Albert D. M. E. Osterhaus

2003-01-01

160

Endosomal Proteolysis of the Ebola Virus Glycoprotein Is Necessary for Infection  

Microsoft Academic Search

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

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

2005-01-01

161

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

Microsoft Academic Search

BackgroundFiloviruses, 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 FindingsWe have investigated

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

2012-01-01

162

Inhibition of heat-shock protein 90 reduces Ebola virus replication  

Microsoft Academic Search

Ebola virus (EBOV), a negative-sense RNA virus in the family Filoviridae, is known to cause severe hemorrhagic fever in humans and other primates. Infection with EBOV causes a high mortality rate and currently there is no FDA-licensed vaccine or therapeutic treatment available. Recently, heat-shock protein 90 (Hsp90), a molecular chaperone, was shown to be an important host factor for the

Darci R. Smith; Sarah McCarthy; Andrew Chrovian; Gene Olinger; Andrea Stossel; Thomas W. Geisbert; Lisa E. Hensley; John H. Connor

2010-01-01

163

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

PubMed

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

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

2014-12-12

164

Support services for survivors of ebola virus disease - sierra leone, 2014.  

PubMed

As of December 6, 2014, Sierra Leone reported 6,317 laboratory-confirmed cases of Ebola virus disease (Ebola), the highest number of reported cases in the current West Africa epidemic. The Sierra Leone Ministry of Health and Sanitation reported that as of December 6, 2014, there were 1,181 persons who had survived and were discharged. Survivors from previous Ebola outbreaks have reported major barriers to resuming normal lives after release from treatment, such as emotional distress, health issues, loss of possessions, and difficulty regaining their livelihoods. In August 2014, a knowledge, attitude, and practice survey regarding the Ebola outbreak in Sierra Leone, administered by a consortium of partners that included the Ministry of Health and Sanitation, UNICEF, CDC, and a local nongovernmental organization, Focus 1000, found that 96% of the general population respondents reported some discriminatory attitude towards persons with suspected or known Ebola. Access to increased psychosocial support, provision of goods, and family and community reunification programs might reduce these barriers. Survivors also have unique potential to contribute to the Ebola response, particularly because survivors might have some immunity to the same virus strain. In previous outbreaks, survivors served as burial team members, contact tracers, and community educators promoting messages that seeking treatment improves the chances for survival and that persons who survived Ebola can help their communities. As caregivers in Ebola treatment units, survivors have encouraged patients to stay hydrated and eat and inspired them to believe that they, too, can survive. Survivors regaining livelihood through participation in the response might offset the stigma associated with Ebola. PMID:25522090

Lee-Kwan, Seung Hee; DeLuca, Nickolas; Adams, Monica; Dalling, Matthew; Drevlow, Elizabeth; Gassama, Gladys; Davies, Tina

2014-12-19

165

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

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

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

2002-01-01

166

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

PubMed

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

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

2003-09-01

167

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

Microsoft Academic Search

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

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

1996-01-01

168

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

E-print Network

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

Napp, Nils

169

Nucleoprotein-based indirect enzyme-linked immunosorbent assay (indirect ELISA) for detecting antibodies specific to Ebola virus and Marbug virus.  

PubMed

Full-length nucleoproteins from Ebola and Marburg viruses were expressed as His-tagged recombinant proteins in Escherichia coli and nucleoprotein-based enzyme-linked immunosorbent assays (ELISAs) were established for the detection of antibodies specific to Ebola and Marburg viruses. The ELISAs were evaluated by testing antisera collected from rabbit immunized with Ebola and Marburg virus nucleoproteins. Although little cross-reactivity of antibodies was observed in anti-Ebola virus nucleoprotein rabbit antisera, the highest reactions to immunoglobulin G (IgG) were uniformly detected against the nucleoprotein antigens of homologous viruses. We further evaluated the ELISA's ability to detect antibodies to Ebola and Marburg viruses using human sera samples collected from individuals passing through the Guangdong port of entry. With a threshold set at the mean plus three standard deviations of average optical densities of sera tested, the ELISA systems using these two recombinant nucleoproteins have good sensitivity and specificity. These results demonstrate the usefulness of ELISA for diagnostics as well as ecological and serosurvey studies of Ebola and Marburg virus infection. PMID:25547682

Huang, Yi; Zhu, Youjie; Yang, Mengshi; Zhang, Zhenqing; Song, Donglin; Yuan, Zhiming

2014-12-01

170

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

Microsoft Academic Search

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

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

2002-01-01

171

Analysis of Ebola virus and VLP release using an immunocapture assay.  

PubMed

Ebola virus (EBOV), an emerging pathogen, is the causative agent of a rapidly progressive hemorrhagic fever with high mortality rates. There are currently no approved vaccines or treatments available for Ebola hemorrhagic fever. Standard plaque assays are currently the only reliable techniques for enumerating the virus. Effective drug-discovery screening as well as target identification and validation require simple and more rapid detection methods. This report describes the development of a rapid ELISA that measures virus release with high sensitivity. This assay detects both Ebola virus and EBOV-like particles (VLPs) directly from cell-culture supernatants with the VP40 matrix protein serving as antigen. Using this assay, the contribution of the EBOV nucleocapsid (NC) proteins in VLP release was determined. These findings indicate that a combination of NC proteins together with the envelope components is optimal for VLP formation and release, a finding that is important for vaccination with Ebola VLPs. Furthermore, this assay can be used in surrogate models in non-biocontainment environment, facilitating both basic research on the mechanism of EBOV assembly and budding as well as drug-discovery research. PMID:15893559

Kallstrom, George; Warfield, Kelly L; Swenson, Dana L; Mort, Shannon; Panchal, Rekha G; Ruthel, Gordon; Bavari, Sina; Aman, M Javad

2005-07-01

172

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

Microsoft Academic Search

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

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

2010-01-01

173

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

Microsoft Academic Search

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

Elliott Kagan; Kevin McClintock; Adam Judge; Ian MacLachlan

2006-01-01

174

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

Microsoft Academic Search

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

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

2003-01-01

175

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

SciTech Connect

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.

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

176

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

PubMed Central

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 an Ebola virus vaccine in its first phase I human study. A three-plasmid DNA vaccine encoding the envelope glycoproteins (GP) from the Zaire and Sudan/Gulu species as well as the nucleoprotein was evaluated in a randomized, placebo-controlled, double-blinded, dose escalation study. Healthy adults, ages 18 to 44 years, were randomized to receive three injections of vaccine at 2 mg (n = 5), 4 mg (n = 8), or 8 mg (n = 8) or placebo (n = 6). Immunogenicity was assessed by enzyme-linked immunosorbent assay (ELISA), immunoprecipitation-Western blotting, intracellular cytokine staining (ICS), and enzyme-linked immunospot assay. The vaccine was well-tolerated, with no significant adverse events or coagulation abnormalities. Specific antibody responses to at least one of the three antigens encoded by the vaccine as assessed by ELISA and CD4+ T-cell GP-specific responses as assessed by ICS were detected in 20/20 vaccinees. CD8+ T-cell GP-specific responses were detected by ICS assay in 6/20 vaccinees. This Ebola virus DNA vaccine was safe and immunogenic in humans. Further assessment of the DNA platform alone and in combination with replication-defective adenoviral vector vaccines, in concert with challenge and immune data from nonhuman primates, will facilitate evaluation and potential licensure of an Ebola virus vaccine under the Animal Rule. PMID:16988008

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

2006-01-01

177

A DNA vaccine for Ebola virus is safe and immunogenic in a phase I clinical trial.  

PubMed

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 an Ebola virus vaccine in its first phase I human study. A three-plasmid DNA vaccine encoding the envelope glycoproteins (GP) from the Zaire and Sudan/Gulu species as well as the nucleoprotein was evaluated in a randomized, placebo-controlled, double-blinded, dose escalation study. Healthy adults, ages 18 to 44 years, were randomized to receive three injections of vaccine at 2 mg (n = 5), 4 mg (n = 8), or 8 mg (n = 8) or placebo (n = 6). Immunogenicity was assessed by enzyme-linked immunosorbent assay (ELISA), immunoprecipitation-Western blotting, intracellular cytokine staining (ICS), and enzyme-linked immunospot assay. The vaccine was well-tolerated, with no significant adverse events or coagulation abnormalities. Specific antibody responses to at least one of the three antigens encoded by the vaccine as assessed by ELISA and CD4(+) T-cell GP-specific responses as assessed by ICS were detected in 20/20 vaccinees. CD8(+) T-cell GP-specific responses were detected by ICS assay in 6/20 vaccinees. This Ebola virus DNA vaccine was safe and immunogenic in humans. Further assessment of the DNA platform alone and in combination with replication-defective adenoviral vector vaccines, in concert with challenge and immune data from nonhuman primates, will facilitate evaluation and potential licensure of an Ebola virus vaccine under the Animal Rule. PMID:16988008

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

2006-11-01

178

CD8+ cellular immunity mediates rAd5 vaccine protection against Ebola virus infection of nonhuman primates.  

PubMed

Vaccine-induced immunity to Ebola virus infection in nonhuman primates (NHPs) is marked by potent antigen-specific cellular and humoral immune responses; however, the immune mechanism of protection remains unknown. Here we define the immune basis of protection conferred by a highly protective recombinant adenovirus virus serotype 5 (rAd5) encoding Ebola virus glycoprotein (GP) in NHPs. Passive transfer of high-titer polyclonal antibodies from vaccinated Ebola virus-immune cynomolgus macaques to naive macaques failed to confer protection against disease, suggesting a limited role of humoral immunity. In contrast, depletion of CD3(+) T cells in vivo after vaccination and immediately before challenge eliminated immunity in two vaccinated macaques, indicating a crucial requirement for T cells in this setting. The protective effect was mediated largely by CD8(+) cells, as depletion of CD8(+) cells in vivo using the cM-T807 monoclonal antibody (mAb), which does not affect CD4(+) T cell or humoral immune responses, abrogated protection in four out of five subjects. These findings indicate that CD8(+) cells have a major role in rAd5-GP-induced immune protection against Ebola virus infection in NHPs. Understanding the immunologic mechanism of Ebola virus protection will facilitate the development of vaccines for Ebola and related hemorrhagic fever viruses in humans. PMID:21857654

Sullivan, Nancy J; Hensley, Lisa; Asiedu, Clement; Geisbert, Thomas W; Stanley, Daphne; Johnson, Joshua; Honko, Anna; Olinger, Gene; Bailey, Michael; Geisbert, Joan B; Reimann, Keith A; Bao, Saran; Rao, Srinivas; Roederer, Mario; Jahrling, Peter B; Koup, Richard A; Nabel, Gary J

2011-09-01

179

Improving burial practices and cemetery management during an ebola virus disease epidemic - sierra leone, 2014.  

PubMed

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

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

2015-01-16

180

Marburg virus evades interferon responses by a mechanism distinct from ebola virus.  

PubMed

Previous studies have demonstrated that Marburg viruses (MARV) and Ebola viruses (EBOV) inhibit interferon (IFN)-alpha/beta 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 IFNalpha/beta induced tyrosine phosphorylation of STAT1 and STAT2. MARV infection is now demonstrated to inhibit not only IFNalpha/beta but also IFNgamma-induced STAT phosphorylation and to inhibit the IFNalpha/beta and IFNgamma-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 IFNalpha/beta or IFNgamma-induced gene expression and to inhibit the induction of an antiviral state by IFNalpha/beta. Global loss of STAT and Jak tyrosine phosphorylation in response to both IFNalpha/beta and IFNgamma 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

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

2010-01-01

181

Structure of an Antibody in Complex with Its Mucin Domain Linear Epitope That Is Protective against Ebola Virus  

PubMed Central

Antibody 14G7 is protective against lethal Ebola virus challenge and recognizes a distinct linear epitope in the prominent mucin-like domain of the Ebola virus glycoprotein GP. The structure of 14G7 in complex with its linear peptide epitope has now been determined to 2.8 Å. The structure shows that this GP sequence forms a tandem ?-hairpin structure that binds deeply into a cleft in the antibody-combining site. A key threonine at the apex of one turn is critical for antibody interaction and is conserved among all Ebola viruses. This work provides further insight into the mechanism of protection by antibodies that target the protruding, highly accessible mucin-like domain of Ebola virus and the structural framework for understanding and characterizing candidate immunotherapeutics. PMID:22171276

Olal, Daniel; Kuehne, Ana I.; Bale, Shridhar; Halfmann, Peter; Hashiguchi, Takao; Fusco, Marnie L.; Lee, Jeffrey E.; King, Liam B.; Kawaoka, Yoshihiro; Dye, John M.

2012-01-01

182

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

E-print Network

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 ...

Kugelman, Jeffrey R.

183

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

Microsoft Academic Search

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

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

2004-01-01

184

Development of a highly sensitive, field operable biosensor for serological studies of Ebola virus in central Africa  

Microsoft Academic Search

We describe herein a newly developed optical immunosensor for detection of antibodies directed against antigens of the Ebola virus strains Zaire and Sudan. We employed a photo immobilization methodology based on a photoactivatable electrogenerated poly(pyrrole-benzophenone) film deposited upon an indium tin oxide (ITO) modified conductive surface fiber-optic. It was then linked to a biological receptor, Ebola virus antigen in this

A. Petrosova; T. Konry; S. Cosnier; I. Trakht; J. Lutwama; E. Rwaguma; A. Chepurnov; E. Mühlberger; L. Lobel; R. S. Marks

2007-01-01

185

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

Microsoft Academic Search

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

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

2002-01-01

186

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

PubMed Central

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

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

187

FDA-Approved Selective Estrogen Receptor Modulators Inhibit Ebola Virus Infection  

PubMed Central

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

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

188

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

PubMed

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

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

189

Respiratory tract immunization of non-human primates with a Newcastle disease virus-vectored vaccine candidate against Ebola virus elicits a neutralizing antibody response  

Microsoft Academic Search

We previously developed a respiratory tract vaccine candidate against Ebola virus (EBOV) based on human parainfluenza virus type 3 (HPIV3), a respiratory paramyxovirus, expressing the EBOV GP envelope protein (HPIV3\\/GP) from an added gene. Two doses of this vaccine candidate delivered by the intranasal and intratracheal route protected monkeys against intraperitoneal challenge with EBOV; however, concerns exist that the vaccine

Joshua M. DiNapoli; Lijuan Yang; Siba K. Samal; Brian R. Murphy; Peter L. Collins; Alexander Bukreyev

2010-01-01

190

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

PubMed Central

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-?B, 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

Jones, Steven; Bradfute, Steven B.; Bray, Mike; Ozato, Keiko

2009-01-01

191

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

SciTech Connect

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.

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

1984-09-01

192

Zaire Ebola virus entry into human dendritic cells is insensitive to cathepsin L inhibition  

PubMed Central

Cathepsins B and L contribute to Ebola virus (EBOV) entry into Vero cells and MEFs. However, the role of cathepsins in EBOV-infection of human dendritic cells (DCs), important targets of infection in vivo, remains undefined. Here, EBOV-like particles containing a beta-lactamase-VP40 fusion reporter and Ebola virus were used to demonstrate the cathepsin-dependence of EBOV entry into human monocyte-derived DCs. However, while DC-infection is blocked by cathepsin B inhibitor, it is insensitive to cathepsin L inhibitor. Furthermore, DCs pretreated for 48 hours with TNF? were generally less susceptible to entry and infection by EBOV. This decrease in infection was associated with a decrease in cathepsin B activity. Thus, cathepsin L plays a minimal, if any, role in EBOV infection in human DCs. The inflammatory cytokine TNF? modulates cathepsin B activity and affects EBOV entry into and infection of human DCs. PMID:19775255

Martinez, Osvaldo; Johnson, Joshua; Manicassamy, Balaji; Rong, Lijun; Olinger, Gene G.; Hensley, Lisa E.; Basler, Christopher F.

2010-01-01

193

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

PubMed

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

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

194

Comparison of the protective efficacy of DNA and baculovirus-derived protein vaccines for EBOLA virus in guinea pigs  

Microsoft Academic Search

The filoviruses Ebola virus (EBOV) and Marburg virus (MARV) cause severe hemorrhagic fever in humans for which no vaccines are available. Previously, a priming dose of a DNA vaccine expressing the glycoprotein (GP) gene of MARV followed by boosting with recombinant baculovirus-derived GP protein was found to confer protective immunity to guinea pigs (Hevey et al., 2001. Vaccine 20, 568–593).

Jenny L. Mellquist-Riemenschneider; Aura R. Garrison; Joan B. Geisbert; Kamal U. Saikh; Kelli D. Heidebrink; Peter B. Jahrling; Robert G. Ulrich; Connie S. Schmaljohn

2003-01-01

195

Recombinant Ebola virus nucleoprotein and glycoprotein (Gabon 94 strain) provide new tools for the detection of human infections  

Microsoft Academic Search

After cloning and sequencing the glycoprotein (GP) gene of one of the Gabonese strains of Ebola virus isolated during the 1994-1996 outbreak, it was shown that the circulating virus was of the Zaire subtype. This was confirmed in this study by cloning and sequencing the nucleoprotein (NP) gene of this strain. These two structural proteins were also expressed as recombinant

C. Prehaud; E. Hellebrand; D. Coudrier; V. E. Volchkov; V. A. Volchkova; H. Feldmann; B. Le Guenno; M. Bouloy

1998-01-01

196

Still the Heart of Darkness: The Ebola Virus and the Meta-Narrative of Disease in The Hot Zone  

Microsoft Academic Search

“Still the Heart of Darkness” analyzes Richard Preston's best-selling account of an Ebola virus outbreak in Reston, Virginia in 1989. Through a textual examination of The Hot Zone, this essay demonstrates how Preston grounds his narrative about the threat of rare emerging viruses from the third world in terms of the colonialist discourse about Africa as “the white man's grave,”

Douglas M. Haynes

2002-01-01

197

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

Microsoft Academic Search

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

Asa Szekely Björndal; Laszlo Szekely; Fredrik Elgh

2003-01-01

198

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

E-print Network

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 ...

Karp, Peter D.

199

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

PubMed Central

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

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

2014-01-01

200

Managing Potential Laboratory Exposure to Ebola Virus by Using a Patient Biocontainment Care Unit1  

PubMed Central

In 2004, a scientist from the US Army Medical Research Institute of Infectious Diseases (USAMRIID) was potentially exposed to a mouse-adapted variant of the Zaire species of Ebola virus. The circumstances surrounding the case are presented, in addition to an update on historical admissions to the medical containment suite at USAMRIID. Research facilities contemplating work with pathogens requiring Biosafety Level 4 laboratory precautions should be mindful of the occupational health issues highlighted in this article. PMID:18507897

Martin, James W.; Rusnak, Janice M.; Cieslak, Theodore J.; Warfield, Kelly L.; Anderson, Edwin L.; Ranadive, Manmohan V.

2008-01-01

201

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

Microsoft Academic Search

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

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

1998-01-01

202

Isolation and partial characterisation of a new strain of Ebola virus  

Microsoft Academic Search

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

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

1995-01-01

203

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

Microsoft Academic Search

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

ROUVEN J. WOOL-LEWIS; PAUL BATES

1999-01-01

204

Biochemical Analysis of the Secreted and Virion Glycoproteins of Ebola Virus  

Microsoft Academic Search

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

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

1998-01-01

205

Ebola virus circulation in Africa: a balance between clinical expression and epidemiological silence.  

PubMed

Nearly thirty years after the first epidemics, Ebola virus (EBOV) remains hardly described, its transmission unclear and its reservoir elusive. Soon after the Ebola fever outbreak and virus discovery in 1976 and in order to investigate the distribution of EBOV in Central Africa, several countries including a range of ecological zones were investigated in the early 1980s, using extensive survey: Central African Republic (CAR), Cameroon, Chad, Congo, Gabon and Equatorial Guinea. Since 1992, ELISA antibody test along with a RT-PCR have been used to detect specific virus antibodies and characterize viral RNA. The widely separated geographic locations of outbreaks have suggested that the reservoir and the transmission cycle of EBOV are probably closely associated with the rain forest ecosystem, what is supported by the distribution of antibodies. The fact that outbreaks seldom occur suggests the presence of a rare or ecologically isolated animal reservoir having few contacts with humans and non-human primates. However various serological investigations showed a high prevalence in humans without any pathology reported. This suggests a circulation of both pathogenic and non-pathogenic strains as well as more frequent contacts with man than expected, and could partially explain fifteen years of Ebola fever silence between the emergence and re-emergence of Ebola virus in the Congolese basin. Nowadays, largely enlightened by the study of recent epizootic and epidemic manifestations of EBOV in Gabon and neighboring countries, EBOV natural history starts to be understood as for the fundamentals of epizootic in non-human primates and chains of transmission. PMID:16267963

Gonzalez, J P; Herbreteau, V; Morvan, J; Leroy, E M

2005-09-01

206

Ebola Virus VP24 Binds Karyopherin  1 and Blocks STAT1 Nuclear Accumulation  

Microsoft Academic Search

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

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

207

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

Microsoft Academic Search

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

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

2005-01-01

208

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

PubMed Central

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

Gallaher, William R.; Garry, Robert F.

2015-01-01

209

Antigen capture enzyme-linked immunosorbent assay for specific detection of Reston Ebola virus nucleoprotein.  

PubMed

Antigen capture enzyme-linked immunosorbent assay (ELISA) is one of the most useful methods to detect Ebola virus rapidly. We previously developed an antigen capture ELISA using a monoclonal antibody (MAb), 3-3D, which reacted not only to the nucleoprotein (NP) of Zaire Ebola virus (EBO-Z) but also to the NPs of Sudan (EBO-S) and Reston Ebola (EBO-R) viruses. In this study, we developed antigen capture ELISAs using two novel MAbs, Res2-6C8 and Res2-1D8, specific to the NP of EBO-R. Res2-6C8 and Res2-1D8 recognized epitopes consisting of 4 and 8 amino acid residues, respectively, near the C-terminal region of the EBO-R NP. The antigen capture ELISAs using these two MAbs detected the EBO-R NP in the tissues from EBO-R-infected cynomolgus macaques. The antigen capture ELISAs using Res2-6C8 and Res2-1D8 are useful for the rapid detection of the NP in EBO-R-infected cynomolgus macaques. PMID:12853385

Ikegami, Tetsuro; Niikura, Masahiro; Saijo, Masayuki; Miranda, Mary E; Calaor, Alan B; Hernandez, Marvin; Acosta, Luz P; Manalo, Daria L; Kurane, Ichiro; Yoshikawa, Yasuhiro; Morikawa, Shigeru

2003-07-01

210

Modeling of the ebola virus delta Peptide reveals a potential lytic sequence motif.  

PubMed

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

Gallaher, William R; Garry, Robert F

2015-01-01

211

Ebola Hemorrhagic Fever: Treatment  

MedlinePLUS

... Search The CDC Cancel Submit Search The CDC Ebola (Ebola Virus Disease) Note: Javascript is disabled or is ... message, please visit this page: About CDC.gov . Ebola (Ebola Virus Disease) About Ebola Questions & Answers 2014 ...

212

Ebola Hemorrhagic Fever: Prevention  

MedlinePLUS

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213

Ebola Hemorrhagic Fever: Transmission  

MedlinePLUS

... Search The CDC Cancel Submit Search The CDC Ebola (Ebola Virus Disease) Note: Javascript is disabled or is ... message, please visit this page: About CDC.gov . Ebola (Ebola Virus Disease) About Ebola Questions & Answers 2014 ...

214

Importation and containment of Ebola virus disease - Senegal, August-September 2014.  

PubMed

On August 29, 2014, Senegal confirmed its first case of Ebola virus disease (Ebola) in a Guinean man, aged 21 years, who had traveled from Guinea to Dakar, Senegal, in mid-August to visit family. Senegalese medical and public health personnel were alerted about this patient after public health staff in Guinea contacted his family in Senegal on August 27. The patient had been admitted to a referral hospital in Senegal on August 26. He was promptly isolated, and a blood sample was sent for laboratory confirmation; Ebola was confirmed by reverse transcriptase-polymerase chain reaction at Institut Pasteur Dakar on August 29. The patient's mother and sister had been admitted to an Ebola treatment unit in Guinea on August 26, where they had named the patient as a contact and reported his recent travel to Senegal. Ebola was likely transmitted to the family from the brother of the patient, who had traveled by land from Sierra Leone to Guinea in early August seeking treatment from a traditional healer. The brother died in Guinea on August 10; family members, including the patient, participated in preparing the body for burial. PMID:25275333

Mirkovic, Kelsey; Thwing, Julie; Diack, Papa Amadou

2014-10-01

215

Transmission dynamics and control of Ebola virus disease (EVD): a review.  

PubMed

The complex and unprecedented Ebola epidemic ongoing in West Africa has highlighted the need to review the epidemiological characteristics of Ebola Virus Disease (EVD) as well as our current understanding of the transmission dynamics and the effect of control interventions against Ebola transmission. Here we review key epidemiological data from past Ebola outbreaks and carry out a comparative review of mathematical models of the spread and control of Ebola in the context of past outbreaks and the ongoing epidemic in West Africa. We show that mathematical modeling offers useful insights into the risk of a major epidemic of EVD and the assessment of the impact of basic public health measures on disease spread. We also discuss the critical need to collect detailed epidemiological data in real-time during the course of an ongoing epidemic, carry out further studies to estimate the effectiveness of interventions during past outbreaks and the ongoing epidemic, and develop large-scale modeling studies to study the spread and control of viral hemorrhagic fevers in the context of the highly heterogeneous economic reality of African countries. PMID:25300956

Chowell, Gerardo; Nishiura, Hiroshi

2014-10-10

216

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

PubMed Central

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.

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

217

Ebola virus outbreak 2014: clinical review for emergency physicians.  

PubMed

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

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

2015-01-01

218

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

E-print Network

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-linked im- munosorbent assay (ELISA) demonstrated that while the F88A mutation impairs GP binding to human

Chandran, Kartik

219

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

Microsoft Academic Search

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

Mike Bray; John Driscoll; John W. Huggins

2000-01-01

220

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

PubMed

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

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

2014-12-01

221

Mission critical: mobilization of essential animal models for ebola, nipah, and machupo virus infections.  

PubMed

The reports for Ebola virus Zaire (EBOV), Nipah virus, and Machupo virus (MACV) pathogenesis, in this issue of Veterinary Pathology, are timely considering recent events, both nationally and internationally. EBOV, Nipah virus, and MACV cause highly lethal infections for which no Food and Drug Administration (FDA) licensed vaccines or therapies exist. Not only are there concerns that these agents could be used by those with malicious intent, but shifts in ecological distribution of viral reservoirs due to climate change or globalization could lead to more frequent infections within remote regions than previously seen as well as outbreaks in more populous areas. The current EBOV epidemic shows no sign of abating across 3 West African nations (as of October 2014), including densely populated areas, far outpacing infection rates of previous outbreaks. A limited number of cases have also arisen in the United States and Europe. With few treatment options for these deadly viruses, development of animal models reflective of human disease is paramount to combat these diseases. As an example of this potential, a new treatment compound, ZMapp, that had demonstrated efficacy against EBOV infection in nonhuman primates (NHPs) received an emergency compassionate use exception from the FDA for the treatment of 2 American medical workers infected with EBOV, and they are currently virus free and recovering. PMID:25352204

Zumbrun, E E

2015-01-01

222

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

PubMed

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

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

2014-12-01

223

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

Microsoft Academic Search

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

Adam MacNeil; Zachary Reed; Pierre E. Rollin

2011-01-01

224

Measuring the Strength of Interaction between the Ebola Fusion Peptide and Lipid Rafts: Implications for Membrane Fusion and Virus Infection  

Microsoft Academic Search

The Ebola fusion peptide (EBO16) is a hydrophobic domain that belongs to the GP2 membrane fusion protein of the Ebola virus. It adopts a helical structure in the presence of mimetic membranes that is stabilized by the presence of an aromatic-aromatic interaction established by Trp8 and Phe12. In spite of its infectious cycle becoming better understood recently, several steps still

Mônica S. Freitas; Cristian Follmer; Lilian T. Costa; Cecília Vilani; M. Lucia Bianconi; Carlos Alberto Achete; Jerson L. Silva; Vladimir N. Uversky

2011-01-01

225

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

PubMed

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

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

2015-02-01

226

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

PubMed

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 trial of a 1st generation Ebola DNA vaccine. We now report the safety and immunogenicity of a recombinant adenovirus serotype 5 (rAd5) vaccine encoding the envelope glycoprotein (GP) from the Zaire and Sudan Ebola virus species, in a randomized, placebo-controlled, double-blinded, dose escalation, Phase I human study. Thirty-one healthy adults received vaccine at 2×10(9) (n=12), or 2×10(10) (n=11) viral particles or placebo (n=8) as an intramuscular injection. Antibody responses were assessed by ELISA and neutralizing assays; and T cell responses were assessed by ELISpot and intracellular cytokine staining assays. This recombinant Ebola virus vaccine was safe and subjects developed antigen specific humoral and cellular immune responses. PMID:21034824

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

2010-12-16

227

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

PubMed

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

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

2014-11-01

228

Mucosal parainfluenza virus-vectored vaccine against Ebola virus replicates in the respiratory tract of vector-immune monkeys and is immunogenic  

Microsoft Academic Search

We previously used human parainfluenza virus type 3 (HPIV3) as a vector to express the Ebola virus (EBOV) GP glycoprotein. The resulting HPIV3\\/EboGP vaccine was immunogenic and protective against EBOV challenge in a non-human primate model. However, it remained unclear whether the vaccine would be effective in adults due to preexisting immunity to HPIV3. Here, the immunogenicity of HPIV3\\/EboGP was

Alexander A. Bukreyev; Joshua M. DiNapoli; Lijuan Yang; Brian R. Murphy; Peter L. Collins

2010-01-01

229

A nonreplicating subunit vaccine protects mice against lethal Ebola virus challenge.  

PubMed

Ebola hemorrhagic fever is an acute and often deadly disease caused by Ebola virus (EBOV). The possible intentional use of this virus against human populations has led to design of vaccines that could be incorporated into a national stockpile for biological threat reduction. We have evaluated the immunogenicity and efficacy of an EBOV vaccine candidate in which the viral surface glycoprotein is biomanufactured as a fusion to a monoclonal antibody that recognizes an epitope in glycoprotein, resulting in the production of Ebola immune complexes (EICs). Although antigen-antibody immune complexes are known to be efficiently processed and presented to immune effector cells, we found that codelivery of the EIC with Toll-like receptor agonists elicited a more robust antibody response in mice than did EIC alone. Among the compounds tested, polyinosinic:polycytidylic acid (PIC, a Toll-like receptor 3 agonist) was highly effective as an adjuvant agent. After vaccinating mice with EIC plus PIC, 80% of the animals were protected against a lethal challenge with live EBOV (30,000 LD(50) of mouse adapted virus). Surviving animals showed a mixed Th1/Th2 response to the antigen, suggesting this may be important for protection. Survival after vaccination with EIC plus PIC was statistically equivalent to that achieved with an alternative viral vector vaccine candidate reported in the literature. Because nonreplicating subunit vaccines offer the possibility of formulation for cost-effective, long-term storage in biothreat reduction repositories, EIC is an attractive option for public health defense measures. PMID:22143779

Phoolcharoen, Waranyoo; Dye, John M; Kilbourne, Jacquelyn; Piensook, Khanrat; Pratt, William D; Arntzen, Charles J; Chen, Qiang; Mason, Hugh S; Herbst-Kralovetz, Melissa M

2011-12-20

230

[Development of a method for rapid detection of Ebola virus antibodies and antigen].  

PubMed

Despite the wide spectrum of reliable methods for identifying Ebola virus, their performance requires highly-skilled personnel, specialized laboratories, complicated equipment, and much time. Therefore, there is a need for a method that allows a physician or a medical attendant to identify the causative agent in field or bedside tests without special equipment as soon as possible. The immunoassay involving nitrocellulose membrane immuno-filtration, by using a fixed antigen (antibodies) or their immunosols, is a tried-and-true method. The time of the analysis is 7-15 min. PMID:17601052

Chepurnov, A A; Fedosova, N I; Egoricheva, I N; Poltavchenko, A G; Elgh, F

2007-01-01

231

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

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

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

2009-01-01

232

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

PubMed Central

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

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

2014-01-01

233

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

SciTech Connect

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.

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

234

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

Microsoft Academic Search

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

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

2001-01-01

235

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

Microsoft Academic Search

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.

Mike Bray; Thomas W. Geisbert

2005-01-01

236

Preparation and use of hyperimmune serum for prophylaxis and therapy of Ebola virus infections.  

PubMed

To obtain hyperimmune serum appropriate for the treatment of filovirus infection, methods were developed to immunize nonsusceptible animals with live Ebola (EBO) virus preparations. Immune plasma with high ELISA and neutralization-specific antibody titers was obtained by multiple immunization of sheep and goats with preparations of live EBO virus. Goat immunoglobulin was prepared by Cohn's method and tested on guinea pigs, using an EBO virus strain that is highly pathogenic for guinea pigs. Prophylaxis with these immunoglobulins within 48 h after infection was effective in challenge experiments, with a log10 prophylaxis index as high as 1.92+/-0.52. Other studies have shown that equine anti-EBO virus immunoglobulins worked well in baboons. The goat immunoglobulins were also tested in preclinical trials on laboratory animals; after being positively evaluated, they were administered to volunteers in clinical trials for biologic safety and reactivity, and they were administered to researchers suspected of becoming infected with EBO during their experimental work. These immunoglobulins may be useful for the emergency treatment of persons accidentally infected with EBO. PMID:9988187

Kudoyarova-Zubavichene, N M; Sergeyev, N N; Chepurnov, A A; Netesov, S V

1999-02-01

237

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

PubMed

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

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

238

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

PubMed Central

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.

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

2015-01-01

239

Immunoglobulin G enzyme-linked immunosorbent assay using truncated nucleoproteins of Reston Ebola virus.  

PubMed

We developed an immunoglobulin G (IgG) enzyme-linked immunosorbent assay (ELISA), using partial recombinant nucleoproteins (rNP) of Reston Ebola virus (EBO-R) and Zaire Ebola virus (EBO-Z). We examined the reaction of 10 sera from cynomolgus macaques naturally infected with EBO-R to each of the partial rNP in the IgG ELISA. All the sera reacted to the C-terminal halves of the rNP of both EBO-R and EBO-Z. Most of the sera reacted to the RdeltaC (amino acid (aa) 360-739), and Rdelta6 (aa 451-551) and/or Rdelta8 (aa 631-739) at a higher dilution than to the corresponding truncated rNPs of EBO-Z. The results indicate that this IgG ELISA is useful for detecting EBO-R specific antibody, and may have a potential to discriminate EBO-R infection from other subtypes. PMID:12825739

Ikegami, T; Saijo, M; Niikura, M; Miranda, M E; Calaor, A B; Hernandez, M; Manalo, D L; Kurane, I; Yoshikawa, Y; Morikawa, S

2003-06-01

240

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

PubMed

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 infection and its hemorrhagic symptoms. Hybridoma cell fusion technology was used for production of MAbs. The MAbs were characterized using ELISA and Western blot analysis. Furthermore, five recombinant sub-domains of GP(1) subfragment D were produced, which were used as antigen in Western blot analysis for epitope mapping. Seventeen MAbs of different epitope specificities against EBOV antigens [virion protein (VP40), secreted glycoprotein (sGP), and GP(1) subfragment D] were developed. Based on epitope mapping studies, the anti-GP MAbs were categorized into six groups. The binding of the three anti-sGP MAbs with different epitope specificities were mostly between aa 157 and 221. The two anti-VP40 MAbs with the same or overlapping epitopes are potentially good candidates for developing antigen detection assays for early diagnosis of EBOV infection. The anti-GP MAbs with different epitope specificities as an oligoclonal cocktail could be tested for therapy. PMID:17368819

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

2007-07-01

241

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

Microsoft Academic Search

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

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

2002-01-01

242

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

PubMed Central

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

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

2013-01-01

243

Airway delivery of an adenovirus-based Ebola virus vaccine bypasses existing immunity to homologous adenovirus in nonhuman primates.  

PubMed

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

Richardson, Jason S; Pillet, Stéphane; Bello, Alexander J; Kobinger, Gary P

2013-04-01

244

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

Microsoft Academic Search

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

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

245

Cyanovirin-N binds to the viral surface glycoprotein, GP1,2 and inhibits infectivity of Ebola virus.  

PubMed

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 N-linked high-mannose oligossacharides on the viral glycoprotein gp120. The Ebola envelope contains somewhat similar oligosaccharide constituents, suggesting possible susceptibility to inhibition by CV-N. Our initial results revealed that CV-N had both in vitro and in vivo antiviral activity against the Zaire strain of the Ebola virus (Ebo-Z). Addition of CV-N to the cell culture medium at the time of Ebo-Z infection inhibited the development of viral cytopathic effects (CPEs). CV-N also delayed the death of Ebo-Z-infected mice, both when given as a series of daily subcutaneous injections and when the virus was incubated ex vivo together with CV-N before inoculation into the mice. Furthermore, similar to earlier results with HIV gp120, CV-N bound with considerable affinity to the Ebola surface envelope glycoprotein, GP(1,2). Competition experiments with free oligosaccharides were consistent with the view that carbohydrate-mediated CV-N/GP(1,2) interactions involve oligosaccharides residing on the Ebola viral envelope. Overall, these studies broaden the range of viruses known to be inhibited by CV-N, and further implicate carbohydrate moieties on viral surface proteins as common viral molecular targets for this novel protein. PMID:12719006

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

2003-03-01

246

Public health response to commercial airline travel of a person with ebola virus infection - United States, 2014.  

PubMed

Before the current Ebola epidemic in West Africa, there were few documented cases of symptomatic Ebola patients traveling by commercial airline, and no evidence of transmission to passengers or crew members during airline travel. In July 2014 two persons with confirmed Ebola virus infection who were infected early in the Nigeria outbreak traveled by commercial airline while symptomatic, involving a total of four flights (two international flights and two Nigeria domestic flights). It is not clear what symptoms either of these two passengers experienced during flight; however, one collapsed in the airport shortly after landing, and the other was documented to have fever, vomiting, and diarrhea on the day the flight arrived. Neither infected passenger transmitted Ebola to other passengers or crew on these flights. In October 2014, another airline passenger, a U.S. health care worker who had traveled domestically on two commercial flights, was confirmed to have Ebola virus infection. Given that the time of onset of symptoms was uncertain, an Ebola airline contact investigation in the United States was conducted. In total, follow-up was conducted for 268 contacts in nine states, including all 247 passengers from both flights, 12 flight crew members, eight cleaning crew members, and one federal airport worker (81 of these contacts were documented in a report published previously). All contacts were accounted for by state and local jurisdictions and followed until completion of their 21-day incubation periods. No secondary cases of Ebola were identified in this investigation, confirming that transmission of Ebola during commercial air travel did not occur. PMID:25632954

Regan, Joanna J; Jungerman, Robynne; Montiel, Sonia H; Newsome, Kimberly; Objio, Tina; Washburn, Faith; Roland, Efrosini; Petersen, Emily; Twentyman, Evelyn; Olaiya, Oluwatosin; Naughton, Mary; Alvarado-Ramy, Francisco; Lippold, Susan A; Tabony, Laura; McCarty, Carolyn L; Kinsey, Cara Bicking; Barnes, Meghan; Black, Stephanie; Azzam, Ihsan; Stanek, Danielle; Sweitzer, John; Valiani, Anita; Kohl, Katrin S; Brown, Clive; Pesik, Nicki

2015-01-30

247

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

PubMed

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. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. PMID:25297522

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

2015-01-01

248

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

PubMed

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

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

249

Detection of antibodies against the four subtypes of ebola virus in sera from any species using a novel antibody-phage indicator assay.  

PubMed

The natural host for Ebola virus, presumed to be an animal, has not yet been identified despite an extensive search following several major outbreaks in Africa. A straightforward approach used to determine animal contact with Ebola virus is by assessing the presence of specific antibodies in serum. This approach however has been made very difficult by the absence of specific reagents required for the detection of antibodies from the majority of wild animal species. In this study, we isolated a human monoclonal antibody Fab fragment, KZ51, that reacts with an immunodominant epitope on Ebola virus nucleoprotein (NP) that is conserved on all four Ebola virus subtypes. The antibody KZ51 represents a major specificity as sera from all convalescent patients tested (10/10) and sera from guinea pigs infected with each of the four Ebola virus subtypes competed strongly with KZ51 for binding to radiation-inactivated Ebola virus. These features allowed us to develop a novel assay for the detection of seroconversion irrespective of Ebola virus subtype or animal species. In this assay, the binding of KZ51 Fab-phage particles is used as an indicator assay and the presence of specific antibodies against Ebola virus in sera is indicated by binding competition. A prominent feature of the assay is that the Fab-phage particles may be prestained with a dye so that detection of binding can be directly determined by visual inspection. The assay is designed to be both simple and economical to enable its use in the field. PMID:12350354

Meissner, Felix; Maruyama, Toshiaki; Frentsch, Marco; Hessell, Ann J; Rodriguez, Luis L; Geisbert, Tom W; Jahrling, Peter B; Burton, Dennis R; Parren, Paul W H I

2002-09-01

250

Immune parameters correlate with protection against ebola virus infection in rodents and nonhuman primates.  

PubMed

Ebola virus causes severe hemorrhagic fever in susceptible hosts. Currently, no licensed vaccines or treatments are available; however, several experimental vaccines have been successful in protecting rodents and nonhuman primates (NHPs) from the lethal Zaire ebolavirus (ZEBOV) infection. The objective of this study was to evaluate immune responses correlating with survival in these animals after lethal challenge with ZEBOV. Knockout mice with impaired ability to generate normal T and/or B cell responses were vaccinated and challenged with ZEBOV. Vaccine-induced protection in mice was mainly mediated by B cells and CD4(+) T cells. Vaccinated, outbred guinea pigs and NHPs demonstrated the highest correlation between survival and levels of total immunoglobulin G (IgG) specific to the ZEBOV glycoprotein (ZGP). These results highlight the relevance of total ZGP-specific IgG levels as a meaningful correlate of protection against ZEBOV exposure. PMID:23115355

Wong, Gary; Richardson, Jason S; Pillet, Stéphane; Patel, Ami; Qiu, Xiangguo; Alimonti, Judie; Hogan, Jeff; Zhang, Yi; Takada, Ayato; Feldmann, Heinz; Kobinger, Gary P

2012-10-31

251

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

PubMed

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 viral structural protein VP40. These mAbs were characterized by enzyme-linked immunosorbent, immunoblot and immunofluorescence assays. Subsequently, an antigen capture enzyme-linked immunosorbent assay was established, which detects VP40 of all known species of EBOV. This assay could detect viral material in spiked human serum that has been sodium dodecylsulfate-inactivated. The established enzyme-linked immunosorbent assay therefore has the ability to become a very useful tool for obtaining an accurate diagnosis in the field, limiting the risk of laboratory infections. PMID:12821193

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

2003-07-01

252

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

PubMed

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

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

253

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

PubMed

Abstract 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

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

254

Newly discovered ebola virus associated with hemorrhagic fever outbreak in Uganda.  

PubMed

Over the past 30 years, Zaire and Sudan ebolaviruses have been responsible for large hemorrhagic fever (HF) outbreaks with case fatalities ranging from 53% to 90%, while a third species, Côte d'Ivoire ebolavirus, caused a single non-fatal HF case. In November 2007, HF cases were reported in Bundibugyo District, Western Uganda. Laboratory investigation of the initial 29 suspect-case blood specimens by classic methods (antigen capture, IgM and IgG ELISA) and a recently developed random-primed pyrosequencing approach quickly identified this to be an Ebola HF outbreak associated with a newly discovered ebolavirus species (Bundibugyo ebolavirus) distantly related to the Côte d'Ivoire ebolavirus found in western Africa. Due to the sequence divergence of this new virus relative to all previously recognized ebolaviruses, these findings have important implications for design of future diagnostic assays to monitor Ebola HF disease in humans and animals, and ongoing efforts to develop effective antivirals and vaccines. PMID:19023410

Towner, Jonathan S; Sealy, Tara K; Khristova, Marina L; Albariño, César G; Conlan, Sean; Reeder, Serena A; Quan, Phenix-Lan; Lipkin, W Ian; Downing, Robert; Tappero, Jordan W; Okware, Samuel; Lutwama, Julius; Bakamutumaho, Barnabas; Kayiwa, John; Comer, James A; Rollin, Pierre E; Ksiazek, Thomas G; Nichol, Stuart T

2008-11-01

255

Pathogenesis of experimental Ebola Zaire virus infection in BALB/c mice.  

PubMed

Guinea-pigs and non-human primates have traditionally been used as animal models for studying Ebola Zaire virus (EBO-Z) infections. The virus was also recently adapted to the stage of lethal virulence in BALB/c mice. This murine model is now in use for testing antiviral medications and vaccines. However, the pathological features of EBO-Z infection in mice have not yet been fully described. To identify sites of viral replication and characterize sequential morphological changes in BALB/c mice, adult female mice were infected with mouse-adapted EBO-Z and killed in groups each day for 5 days post-infection. Tissues were examined by light microscopy, immunohistochemistry, electron microscopy and in-situ hybridization. As in guinea-pigs and non-human primates, cells of the mononuclear phagocytic system were the earliest targets of infection. Viral replication was observed by day 2 in macrophages in lymph nodes and spleen. By the time of onset of illness and weight loss (day 3), the infection had spread to hepatocytes and adrenal cortical cells, and to macrophages and fibroblast-like cells in many organs. Severe lymphocytolysis was observed in the spleen, lymph nodes and thymus. There was minimal infection of endothelial cells. All of these changes resembled those observed in EBO-Z-infected guinea-pigs and non-human primates. In contrast to the other animal models, however, there was little fibrin deposition in the late stage of disease. The availability of immunodeficient, "gene-knockout" and transgenic mice will make the mouse model particularly useful for studying the early steps of Ebola pathogenesis. PMID:11798240

Gibb, T R; Bray, M; Geisbert, T W; Steele, K E; Kell, W M; Davis, K J; Jaax, N K

2001-11-01

256

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

PubMed

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

Katz, Louis M; Tobian, Aaron A R

2014-12-01

257

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

PubMed

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

Omotuyi, I Olaposi

2015-03-01

258

Association of KIR2DS1 and KIR2DS3 with fatal outcome in Ebola virus infection  

PubMed Central

Zaïre ebolavirus (ZEBOV) infection rapidly outruns the host's immunity and leads to death within a week. Fatal cases have been associated with an aberrant innate, proinflammatory immune response followed by a suppressed adaptive response leading to the rapid depletion of peripheral NK cells and lymphocytes. A critical role for NK cells has been suggested but not elucidated. In this genetic study, we investigated the association of KIR genotype with disease outcome by comparing genotypes of a Gabonese control population, IgG+ contacts, survivors, and fatalities of ZEBOV infection. We showed that the activating KIR2DS1 and KIR2DS3 genes associate with fatal outcome in Ebola virus infection. In addition, this study brings supplemental evidence in favor of the specificity of the IgG+ contact population. The outcome of fulminating Ebola virus infection could depend in part on the host's inherited KIR gene repertoire. This supports a key role for KIRs in disease susceptibility to infections. PMID:20878400

Padilla, Cindy; Becquart, Pierre; Leroy, Eric; Vieillard, Vincent

2010-01-01

259

Suppressive effect of Ebola virus on T cell proliferation in vitro is provided by a 125-kDa GP viral protein  

Microsoft Academic Search

Ebola virus (EV), an extremely infectious pathogen, causes severe hemorrhagic fever in humans and nonhuman primates. The disease pattern includes damage of parenchymal cells of vital organs in association with hemostatic and immune disorders. Vaccination with the inactivated virions does not provide an effective immune protection against the disease. The inadequate immune response may be directly caused by the virus,

Alexander A Chepurnov; Marina N Tuzova; Vladimir A Ternovoy; Igor V Chernukhin

1999-01-01

260

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

Microsoft Academic Search

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

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

1998-01-01

261

Radiographic imaging for patients with contagious infectious diseases: how to acquire chest radiographs of patients infected with the ebola virus.  

PubMed

OBJECTIVE. Contagious infectious diseases add a new dimension to radiology and pose many unanswered questions. In particular, what is the safest way to image patients with contagious and potentially lethal infectious diseases? Here, we describe protocols used by Emory University to successfully acquire chest radiographs of patients with Ebola virus disease. CONCLUSION. Radiology departments need to develop new protocols for various modalities used in imaging patients with contagious and potentially lethal infectious diseases. PMID:25402496

Auffermann, William F; Kraft, Colleen S; Vanairsdale, Sharon; Lyon, G Marshall; Tridandapani, Srini

2015-01-01

262

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

PubMed Central

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

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

2014-01-01

263

Association of Ebola-related Reston virus particles and antigen with tissue lesions of monkeys imported to the United States.  

PubMed

During 1989-1990, an epizootic involving a filovirus closely related to Ebola virus occurred in a Reston, Virginia, primate-holding facility. Tissues were collected from cynomolgus monkeys and examined by electron microscopy and immunohistochemistry for Ebola-related viral antigen. Viral replication was extensive in fixed tissue macrophages, interstitial fibroblasts of many organs, circulating macrophages and monocytes, and was observed less frequently in vascular endothelial cells, hepatocytes, adrenal cortical cells and renal tubular epithelium. Viral replication was observed infrequently in epithelial cells lining ducts or mucous membranes, intestinal epithelial cells, eosinophils and plasma cells. Replication of Reston virus in lymphocytes was never observed, in contrast to reports of lymphocytes of monkeys experimentally infected with the Ebola-Zaire virus. Free filoviral particles were seen in pulmonary alveoli and renal tubular lumina, which correlates with epidemiological evidence of droplet and fomite transmission. Viral infection of interstitial fibroblasts and macrophages caused multisystemic disruptive lesions involving connective tissue. Focal necrosis in organs where viral replication was minimal may have been secondary to ischaemia caused by fibrin deposition and occasional platelet-fibrin thrombi. Immunoelectron microscopy on sections of liver, differentiated viral tubular inclusion masses and precursor material from non-viral tubuloreticular inclusions. Immunohistochemistry showed that the distribution of viral antigen in affected tissue correlated well with ultrastructural localization of virions. PMID:1597531

Geisbert, T W; Jahrling, P B; Hanes, M A; Zack, P M

1992-02-01

264

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

PubMed Central

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 and 2008 in three regions of Gabon and in the Ebola epidemic region of north Congo for IgG antibodies specific for ZEBOV and MARV. Results Overall, IgG antibodies to ZEBOV and MARV were found in 4% and 1% of bats, respectively. ZEBOV-specific antibodies were found in six bat species (Epomops franqueti, Hypsignathus monstrosus, Myonycteris torquata, Micropteropus pusillus, Mops condylurus and Rousettus aegyptiacus), while MARV-specific antibodies were only found in Rousettus aegyptiacus and Hypsignathus monstrosus. The prevalence of MARV-specific IgG was significantly higher in R. aegyptiacus members captured inside caves than elsewhere. No significant difference in prevalence was found according to age or gender. A higher prevalence of ZEBOV-specific IgG was found in pregnant females than in non pregnant females. Conclusion These findings confirm that ZEBOV and MARV co-circulate in Gabon, the only country where bats infected by each virus have been found. IgG antibodies to both viruses were detected only in Rousettus aegyptiacus, suggesting that this bat species may be involved in the natural cycle of both Marburg and Ebola viruses. The presence of MARV in Gabon indicates a potential risk for a first human outbreak. Disease surveillance should be enhanced in areas near caves. PMID:19785757

2009-01-01

265

Prevalence of IgG antibodies to Ebola virus in individuals during an Ebola outbreak, Democratic Republic of the Congo, 1995.  

PubMed

During the 1995 outbreak of Ebola (EBO) hemorrhagic fever in Kikwit, Democratic Republic of Congo, two surveys using a new ELISA for EBO (subtype Zaire) virus antigen were conducted to assess the prevalence of EBO IgG antibodies among residents of Kikwit and the surrounding area. The first study determined the proportion of antibody-positive individuals who were self-identified forest and city workers from the Kikwit area. Serum samples from 9 (2.2%) of 414 workers had IgG EBO antibodies. The second study determined the proportion of EBO antibody-positive individuals who lived in villages surrounding Kikwit. The prevalence of IgG EBO antibodies in this population was 9.3% (151161). The difference in the overall prevalence of EBO antibodies may indicate that villagers have a greater chance of exposure to EBO virus compared with those living in and in close proximity to cities. PMID:9988172

Busico, K M; Marshall, K L; Ksiazek, T G; Roels, T H; Fleerackers, Y; Feldmann, H; Khan, A S; Peters, C J

1999-02-01

266

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

SciTech Connect

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.

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

2009-05-20

267

Mouse LSECtin as a model for a human Ebola virus receptor  

PubMed Central

The biochemical properties of mouse LSECtin, a glycan-binding receptor that is a member of the C-type lectin family found on sinusoidal endothelial cells, have been investigated. The C-type carbohydrate-recognition domain of mouse LSECtin, expressed in bacteria, has been used in solid-phase binding assays, and a tetramerized form has been used to probe a glycan array. In spite of sequence differences near the glycan-binding sites, the mouse receptor closely mimics the properties of the human receptor, showing high affinity binding to glycans bearing terminal GlcNAc?1-2Man motifs. Site-directed mutagenesis has been used to confirm that residues near the binding site that differ between the human and the mouse proteins do not affect this binding specificity. Mouse and human LSECtin have been shown to bind Ebola virus glycoprotein with equivalent affinities, and the GlcNAc?1-2Man disaccharide has been demonstrated to be an effective inhibitor of this interaction. These studies provide a basis for using mouse LSECtin, and knockout mice lacking this receptor, to model the biological properties of the human receptor. PMID:21257728

Pipirou, Zoi; Powlesland, Alex S; Steffen, Imke; Pöhlmann, Stefan; Taylor, Maureen E; Drickamer, Kurt

2011-01-01

268

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

SciTech Connect

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.

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

269

Profiling the native specific human humoral immune response to Sudan Ebola virus strain Gulu by chemiluminescence enzyme-linked immunosorbent assay.  

PubMed

Ebolavirus, a member of the family Filoviridae, causes high lethality in humans and nonhuman primates. Research focused on protection and therapy for Ebola virus infection has investigated the potential role of antibodies. Recent evidence suggests that antibodies can be effective in protection from lethal challenge with Ebola virus in nonhuman primates. However, despite these encouraging results, studies have not yet determined the optimal antibodies and composition of an antibody cocktail, if required, which might serve as a highly effective and efficient prophylactic. To better understand optimal antibodies and their targets, which might be important for protection from Ebola virus infection, we sought to determine the profile of viral protein-specific antibodies generated during a natural cycle of infection in humans. To this end, we characterized the profile of antibodies against individual viral proteins of Sudan Ebola virus (Gulu) in human survivors and nonsurvivors of the outbreak in Gulu, Uganda, in 2000-2001. We developed a unique chemiluminescence enzyme-linked immunosorbent assay (ELISA) for this purpose based on the full-length recombinant viral proteins NP, VP30, and VP40 and two recombinant forms of the viral glycoprotein (GP(1-294) and GP(1-649)) of Sudan Ebola virus (Gulu). Screening results revealed that the greatest immunoreactivity was directed to the viral proteins NP and GP(1-649), followed by VP40. Comparison of positive immunoreactivity between the viral proteins NP, GP(1-649), and VP40 demonstrated a high correlation of immunoreactivity between these viral proteins, which is also linked with survival. Overall, our studies of the profile of immunorecognition of antibodies against four viral proteins of Sudan Ebola virus in human survivors may facilitate development of effective monoclonal antibody cocktails in the future. PMID:22993411

Sobarzo, Ariel; Perelman, Eddie; Groseth, Allison; Dolnik, Olga; Becker, Stephan; Lutwama, Julius Julian; Dye, John M; Yavelsky, Victoria; Lobel, Leslie; Marks, Robert S

2012-11-01

270

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

PubMed

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 were characterized by ELISA, Western blot and immunofluorescence analyses. An antigen capture ELISA was established, which is specific for EBOV-Zaire and shows a sensitivity of approximately 10(3) plaque-forming units/ml. Since the ELISA is able to detect even SDS-inactivated EBOV in spiked human sera, it could complement the existing diagnostic tools in the field and in routine laboratories where high containment facilities are not available. PMID:14593476

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

2004-11-01

271

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

PubMed Central

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

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

2013-01-01

272

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

PubMed

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

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

273

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

PubMed Central

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

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

2013-01-01

274

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

PubMed Central

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

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

2012-01-01

275

Serological reactivity of baculovirus-expressed Ebola virus VP35 and nucleoproteins.  

PubMed

Ebola virus (EBOV) is a member of the family Filoviridae and is classified as a biosafety level 4 virus. This classification makes the preparation of antigen and performance of diagnostic assays time-consuming and complicated. The objective of this study was to evaluate the value of EBOV immunoassays based on recombinant nucleoprotein (r-NP) and recombinant VP35 (r-VP35) using large serum panels of African origin and from primates. Furthermore, we investigated whether the results obtained with EBOV r-VP35 enzyme-linked immunosorbent assay (ELISA) could improve on the findings obtained with the EBOV r-NP ELISA. The full-length EBOV NP and VP35 of the EBOV subtype Zaire were expressed as histidine-tagged recombinant proteins in the baculovirus expression system. The antigenic reactivity and specificity of these recombinant proteins were determined by Western blotting and ELISA using EBOV specific monoclonal antibodies. The results obtained with the r-NP and r-VP35 ELISAs were compared with the results obtained in an indirect immunofluorescence assay based on native EBOV subtype Zaire. EBOV specific monoclonal antibodies reacted specifically with the respective proteins in both Western blot and ELISA. Five hundred and twenty six samples from humans and primates were tested with r-NP and r-VP35 ELISAs. Monkey serum samples positive for EBOV subtype Reston and Zaire were both positive in the EBOV r-NP ELISA, whereas only the EBOV Zaire infected monkeys were positive in the r-VP35 ELISA. The sensitivity and specificity values of the EBOV recombinants' ELISAs compared to those of the immunofluorescence assay were 92% and 99% for r-NP and 44% and 100% for r-VP35. r-NP ELISA proved to be a sensitive and specific assay for EBOV diagnosis and for epidemiological studies for both EBOV subtypes Reston and Zaire. The use of r-VP35 in an ELISA format has no additional value for EBOV serodiagnosis. PMID:12737993

Groen, Jan; van den Hoogen, Bernadette G; Burghoorn-Maas, Chantal P; Fooks, Anthony R; Burton, Jane; Clegg, Chris J S C; Zeller, Herve; Osterhaus, Albert D M E

2003-04-01

276

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

PubMed

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

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

2012-11-01

277

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

PubMed Central

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

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

2014-01-01

278

Clinical presentation of patients with ebola virus disease in conakry, Guinea.  

PubMed

Background In March 2014, the World Health Organization was notified of an outbreak of Zaire ebolavirus in a remote area of Guinea. The outbreak then spread to the capital, Conakry, and to neighboring countries and has subsequently become the largest epidemic of Ebola virus disease (EVD) to date. Methods From March 25 to April 26, 2014, we performed a study of all patients with laboratory-confirmed EVD in Conakry. Mortality was the primary outcome. Secondary outcomes included patient characteristics, complications, treatments, and comparisons between survivors and nonsurvivors. Results Of 80 patients who presented with symptoms, 37 had laboratory-confirmed EVD. Among confirmed cases, the median age was 38 years (interquartile range, 28 to 46), 24 patients (65%) were men, and 14 (38%) were health care workers; among the health care workers, nosocomial transmission was implicated in 12 patients (32%). Patients with confirmed EVD presented to the hospital a median of 5 days (interquartile range, 3 to 7) after the onset of symptoms, most commonly with fever (in 84% of the patients; mean temperature, 38.6°C), fatigue (in 65%), diarrhea (in 62%), and tachycardia (mean heart rate, >93 beats per minute). Of these patients, 28 (76%) were treated with intravenous fluids and 37 (100%) with antibiotics. Sixteen patients (43%) died, with a median time from symptom onset to death of 8 days (interquartile range, 7 to 11). Patients who were 40 years of age or older, as compared with those under the age of 40 years, had a relative risk of death of 3.49 (95% confidence interval, 1.42 to 8.59; P=0.007). Conclusions Patients with EVD presented with evidence of dehydration associated with vomiting and severe diarrhea. Despite attempts at volume repletion, antimicrobial therapy, and limited laboratory services, the rate of death was 43%. PMID:25372658

Bah, Elhadj Ibrahima; Lamah, Marie-Claire; Fletcher, Tom; Jacob, Shevin T; Brett-Major, David M; Sall, Amadou Alpha; Shindo, Nahoko; Fischer, William A; Lamontagne, Francois; Saliou, Sow Mamadou; Bausch, Daniel G; Moumié, Barry; Jagatic, Tim; Sprecher, Armand; Lawler, James V; Mayet, Thierry; Jacquerioz, Frederique A; Méndez Baggi, María F; Vallenas, Constanza; Clement, Christophe; Mardel, Simon; Faye, Ousmane; Faye, Oumar; Soropogui, Baré; Magassouba, Nfaly; Koivogui, Lamine; Pinto, Ruxandra; Fowler, Robert A

2015-01-01

279

Rapid High Yield Production of Different Glycoforms of Ebola Virus Monoclonal Antibody  

PubMed Central

Background Fc-glycosylation of monoclonal antibodies (mAbs) has profound implications on the Fc-mediated effector functions. Alteration of this glycosylation may affect the efficiency of an antibody. However, difficulties in the production of mAbs with homogeneous N-glycosylation profiles in sufficient amounts hamper investigations of the potential biological impact of different glycan residues. Methodology/Principal Findings Here we set out to evaluate a transient plant viral based production system for the rapid generation of different glycoforms of a monoclonal antibody. Ebola virus mAb h-13F6 was generated using magnICON expression system in Nicotiana benthamiana, a plant species developed for commercial scale production of therapeutic proteins. h-13F6 was co-expressed with a series of modified mammalian enzymes involved in the processing of complex N-glycans. Using wild type (WT) plants and the glycosylation mutant ?XTFT that synthesizes human like biantennary N-glycans with terminal N-acetylglucosamine on each branch (GnGn structures) as expression hosts we demonstrate the generation of h-13F6 complex N-glycans with (i) bisected structures, (ii) core ?1,6 fucosylation and (iii) ?1,4 galactosylated oligosaccharides. In addition we emphasize the significance of precise sub Golgi localization of enzymes for engineering of IgG Fc-glycosylation. Conclusion The method described here allows the efficient generation of a series of different human-like glycoforms at large homogeneity of virtually any antibody within one week after cDNA delivery to plants. This accelerates follow up functional studies and thus may contribute to study the biological role of N-glycan residues on Fcs and maximizing the clinical efficacy of therapeutic antibodies. PMID:22039433

Castilho, Alexandra; Bohorova, Natasha; Grass, Josephine; Bohorov, Ognian; Zeitlin, Larry; Whaley, Kevin; Altmann, Friedrich; Steinkellner, Herta

2011-01-01

280

Delta-Peptide Is the Carboxy-Terminal Cleavage Fragment of the Nonstructural Small Glycoprotein sGP of Ebola Virus  

Microsoft Academic Search

In the present study we have investigated processing and maturation of the nonstructural small glycoprotein (sGP) of Ebola virus. When sGP expressed from vaccinia virus vectors was analyzed by pulse-chase experiments using SDS–PAGE under reducing conditions, the mature form and two different precursors have been identified. First, the endoplasmic reticulum form sGPer, full-length sGP with oligomannosidic N-glycans, was detected, sGPer

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

1999-01-01

281

Assembly of Ebola Virus Matrix Protein VP40 Is Regulated by Latch-Like Properties of N and C Terminal Tails  

Microsoft Academic Search

The matrix protein VP40 coordinates numerous functions in the viral life cycle of the Ebola virus. These range from the regulation of viral transcription to morphogenesis, packaging and budding of mature virions. Similar to the matrix proteins of other nonsegmented, negative-strand RNA viruses, VP40 proceeds through intermediate states of assembly (e.g. octamers) but it remains unclear how these intermediates are

Leslie P. Silva; Michael Vanzile; Sina Bavari; J. M. Javad Aman; David C. Schriemer

2012-01-01

282

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

Microsoft Academic Search

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

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

2011-01-01

283

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

PubMed

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

2014-12-01

284

The Ebola Virus Glycoprotein and HIV-1 Vpu Employ Different Strategies to Counteract the Antiviral Factor Tetherin  

PubMed Central

The antiviral protein tetherin/BST2/CD317/HM1.24 restricts cellular egress of human immunodeficiency virus (HIV) and of particles mimicking the Ebola virus (EBOV), a hemorrhagic fever virus. The HIV-1 viral protein U (Vpu) and the EBOV-glycoprotein (EBOV-GP) both inhibit tetherin. Here, we compared tetherin counteraction by EBOV-GP and Vpu. We found that EBOV-GP but not Vpu counteracted tetherin from different primate species, indicating that EBOV-GP and Vpu target tetherin differentially. Tetherin interacted with the GP2 subunit of EBOV-GP, which might encode the determinants for tetherin counteraction. Vpu reduced cell surface expression of tetherin while EBOV-GP did not, suggesting that both proteins employ different mechanisms to counteract tetherin. Finally, Marburg virus (MARV)–GP also inhibited tetherin and downregulated tetherin in a cell type–dependent fashion, indicating that tetherin antagonism depends on the cellular source of tetherin. Collectively, our results indicate that EBOV-GP counteracts tetherin by a novel mechanism and that tetherin inhibition is conserved between EBOV-GP and MARV-GP. PMID:21987761

Kühl, Annika; Banning, Carina; Marzi, Andrea; Votteler, Jörg; Steffen, Imke; Bertram, Stephanie; Glowacka, Ilona; Konrad, Andreas; Stürzl, Michael; Guo, Ju-Tao; Schubert, Ulrich; Feldmann, Heinz; Behrens, Georg; Schindler, Michael

2011-01-01

285

Development of an immunofiltration-based antigen-detection assay for rapid diagnosis of Ebola virus infection.  

PubMed

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 assay, were used to develop an immunofiltration assay for the detection of EBOV antigen in chemically inactivated clinical specimens. The assay was evaluated by use of defined virus stocks and specimens from experimentally infected animals. Its field application was tested during an outbreak of Ebola hemorrhagic fever in 2003. Although the original goal was to develop an assay that would detect all EBOV species, only the Zaire and Sudan species were detected in practice. The assay represents a first-generation rapid field test for the detection of EBOV antigen that can be performed in 30 min without electrical power or expensive or sensitive equipment. PMID:17940948

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

2007-11-15

286

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

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.

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

2004-01-01

287

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

Microsoft Academic Search

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

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

288

Conserved proline-rich region of Ebola virus matrix protein VP40 is essential for plasma membrane targeting and virus-like particle release.  

PubMed

The matrix protein VP40 is essential for Ebola virus (EBOV) and Marburg virus assembly and budding at the plasma membrane. In this study we have investigated the effect of single amino acid substitutions in a conserved proline-rich region of the EBOV VP40 located in the carboxy-terminal part of the protein. We demonstrate that substitutions within this region result in an alteration of intracellular VP40 localization and also cause a reduction or a complete block of virus-like particle budding, a benchmark of VP40 function. Furthermore, some mutated VP40s revealed an enhanced binding with cellular Sec24C, a part of the coat protein complex II (COPII) vesicular transport system. Analysis of the 3-dimensional structure of VP40 revealed the spatial proximity of the proline-rich region and an earlier identified site of interaction with Sec24C, thus allowing us to hypothesize that the altered intracellular localization of the VP40 mutants is a consequence of defects in their interaction with COPII-mediated vesicular transport. PMID:21987765

Reynard, Olivier; Nemirov, Kirill; Page, Audrey; Mateo, Mathieu; Raoul, Hervé; Weissenhorn, Winfried; Volchkov, Viktor E

2011-11-01

289

Mucosal parainfluenza virus-vectored vaccine against Ebola virus replicates in the respiratory tract of vector-immune monkeys and is immunogenic.  

PubMed

We previously used human parainfluenza virus type 3 (HPIV3) as a vector to express the Ebola virus (EBOV) GP glycoprotein. The resulting HPIV3/EboGP vaccine was immunogenic and protective against EBOV challenge in a non-human primate model. However, it remained unclear whether the vaccine would be effective in adults due to preexisting immunity to HPIV3. Here, the immunogenicity of HPIV3/EboGP was compared in HPIV3-naive and HPIV3-immune Rhesus monkeys. After a single dose of HPIV3/EboGP, the titers of EBOV-specific serum ELISA or neutralization antibodies were substantially less in HPIV3-immune animals compared to HPIV3-naive animals. However, after two doses, which were previously determined to be required for complete protection against EBOV challenge, the antibody titers were indistinguishable between the two groups. The vaccine virus appeared to replicate, at a reduced level, in the respiratory tract despite the preexisting immunity. This may reflect the known ability of HPIV3 to re-infect and may also reflect the presence of EBOV GP in the vector virion, which confers resistance to neutralization in vitro by HPIV3-specific antibodies. These data suggest that HPIV3/EboGP will be immunogenic in adults as well as children. PMID:20129638

Bukreyev, Alexander A; Dinapoli, Joshua M; Yang, Lijuan; Murphy, Brian R; Collins, Peter L

2010-04-10

290

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

E-print Network

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 discovered: Ebola virus (EBOV; formerly known as Zaire ebolavirus), Sudan virus (SUDV), Reston virus (RESTV

Chandran, Kartik

291

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 available and over 50% of cases end in fatality.

292

Identification of Ebola virus sequences present as RNA or DNA in organs of terrestrial small mammals of the Central African Republic.  

PubMed

The life cycle of the Ebola (EBO) virus remains enigmatic. We tested for EBO virus in the organs of 242 small mammals captured during ecological studies in the Central African Republic. EBO virus glycoprotein or polymerase gene sequences were detected by reverse transcription PCR in RNA extracts of the organs of seven animals and by PCR in DNA extract of one animal. Neither live virus nor virus antigen was detected in any organ sample. Direct sequencing of amplicons identified the virus as being of the Zaire/Gabon subtype. Virus-like nucleocapsids were observed by electron microscopy in the cytoplasm of the spleen cells of one animal. The animals belonged to two genera of rodents (Muridae; Mus setulosus, Praomys sp1 and P. sp2) and one species of shrew (Soricidae; Sylvisorex ollula). These preliminary results provide evidence that common terrestrial small mammals living in peripheral forest areas have been in contact with the EBO virus and demonstrate the persistence of EBO virus RNA and DNA in the organs of the animals. Our findings should lead to better targeting of research into the life cycle of the EBO virus. PMID:10580275

Morvan, J M; Deubel, V; Gounon, P; Nakouné, E; Barrière, P; Murri, S; Perpète, O; Selekon, B; Coudrier, D; Gautier-Hion, A; Colyn, M; Volehkov, V

1999-12-01

293

Monocyte-derived human macrophages and peripheral blood mononuclear cells infected with ebola virus secrete MIP-1alpha and TNF-alpha and inhibit poly-IC-induced IFN-alpha in vitro.  

PubMed

Ebola virus infection of humans is associated with high levels of circulating inflammatory chemokines and cytokines. We demonstrate that direct infection of human PBMC results in the induction of MCP-1, MIP-1alpha, RANTES, and TNF-alpha as early as 24 h p.i. in response to live virus. Monocyte-derived macrophages infected with live Ebola-virus secreted MIP-1alpha and TNF-alpha specifically while RANTES and MCP-1 were secreted by with both live or inactivated virus stimulation and do not require viral replication. Type I interferons (IFN-alpha and -beta), IL-1beta and IL-10, were not induced by Ebola virus. Furthermore, live virus infection of both PBMCs and monocytes-derived macrophages inhibited IFN-alpha induced by double-stranded RNA in vitro. These data provide the first direct evidence of a role for macrophages in the pathogenesis to Ebola virus and suggest that Ebola virus can inhibit cellular antiviral mechanisms mediated by type I interferons. PMID:11352664

Gupta, M; Mahanty, S; Ahmed, R; Rollin, P E

2001-05-25

294

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

295

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

SciTech Connect

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.

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

296

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

PubMed

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

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

297

Respiratory tract immunization of non-human primates with a Newcastle disease virus-vectored vaccine candidate against Ebola virus elicits a neutralizing antibody response.  

PubMed

We previously developed a respiratory tract vaccine candidate against Ebola virus (EBOV) based on human parainfluenza virus type 3 (HPIV3), a respiratory paramyxovirus, expressing the EBOV GP envelope protein (HPIV3/GP) from an added gene. Two doses of this vaccine candidate delivered by the intranasal and intratracheal route protected monkeys against intraperitoneal challenge with EBOV; however, concerns exist that the vaccine candidate may have reduced immunogenicity in the adult human population due to pre-existing immunity against HPIV3. Here we developed a new vaccine candidate (NDV/GP) based on Newcastle disease virus (NDV), an avian paramyxovirus that is antigenically distinct from human viral pathogens and is highly attenuated in monkeys. Following one intranasal and intratracheal inoculation of Rhesus monkeys with NDV/GP, titers of EBOV-specific antibodies in respiratory tract secretions and serum samples determined by ELISA, as well as serum EBOV-neutralizing antibodies, were undetectable or low compared to those induced by HPIV3/GP. A second immunization resulted in a substantial boost in serum IgG ELISA titers, yet the titers remained lower than those induced by a second dose of HPIV3/GP. In contrast, the ELISA IgA titers in respiratory tract secretions and, more importantly, the serum EBOV-neutralizing antibody titers were equal to those induced after the second dose of HPIV3/GP. These data suggest that NDV/GP can be effective for immunization against EBOV alone, or in combination with either HPIV3/GP or another vaccine platform in a heterologous prime-boost regimen. PMID:21034822

DiNapoli, Joshua M; Yang, Lijuan; Samal, Siba K; Murphy, Brian R; Collins, Peter L; Bukreyev, Alexander

2010-12-10

298

Biochemical and structural characterization of cathepsin L-processed Ebola virus glycoprotein: implications for viral entry and immunogenicity.  

PubMed

Ebola virus (EBOV) cellular attachment and entry is initiated by the envelope glycoprotein (GP) on the virion surface. Entry of this virus is pH dependent and associated with the cleavage of GP by proteases, including cathepsin L (CatL) and/or CatB, in the endosome or cell membrane. Here, we characterize the product of CatL cleavage of Zaire EBOV GP (ZEBOV-GP) and evaluate its relevance to entry. A stabilized recombinant form of the EBOV GP trimer was generated using a trimerization domain linked to a cleavable histidine tag. This trimer was purified to homogeneity and cleaved with CatL. Characterization of the trimeric product by N-terminal sequencing and mass spectrometry revealed three cleavage fragments, with masses of 23, 19, and 4 kDa. Structure-assisted modeling of the cathepsin L-cleaved ZEBOV-GP revealed that cleavage removes a glycosylated glycan cap and mucin-like domain (MUC domain) and exposes the conserved core residues implicated in receptor binding. The CatL-cleaved ZEBOV-GP intermediate bound with high affinity to a neutralizing antibody, KZ52, and also elicited neutralizing antibodies, supporting the notion that the processed intermediate is required for viral entry. Together, these data suggest that CatL cleavage of EBOV GP exposes its receptor-binding domain, thereby facilitating access to a putative cellular receptor in steps that lead to membrane fusion. PMID:20053739

Hood, Chantelle L; Abraham, Jonathan; Boyington, Jeffrey C; Leung, Kwanyee; Kwong, Peter D; Nabel, Gary J

2010-03-01

299

Enzyme-linked immunosorbent assays for detection of antibodies to Ebola and Marburg viruses using recombinant nucleoproteins.  

PubMed

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

Saijo, M; Niikura, M; Morikawa, S; Ksiazek, T G; Meyer, R F; Peters, C J; Kurane, I

2001-01-01

300

Induction of ebolavirus cross-species immunity using retrovirus-like particles bearing the Ebola virus glycoprotein lacking the mucin-like domain  

PubMed Central

Background The genus Ebolavirus includes five distinct viruses. Four of these viruses cause hemorrhagic fever in humans. Currently there are no licensed vaccines for any of them; however, several vaccines are under development. Ebola virus envelope glycoprotein (GP1,2) is highly immunogenic, but antibodies frequently arise against its least conserved mucin-like domain (MLD). We hypothesized that immunization with MLD-deleted GP1,2 (GP?MLD) would induce cross-species immunity by making more conserved regions accessible to the immune system. Methods To test this hypothesis, mice were immunized with retrovirus-like particles (retroVLPs) bearing Ebola virus GP?MLD, DNA plasmids (plasmo-retroVLP) that can produce such retroVLPs in vivo, or plasmo-retroVLP followed by retroVLPs. Results Cross-species neutralizing antibody and GP1,2-specific cellular immune responses were successfully induced. Conclusion Our findings suggest that GP?MLD presented through retroVLPs may provide a strategy for development of a vaccine against multiple ebolaviruses. Similar vaccination strategies may be adopted for other viruses whose envelope proteins contain highly variable regions that may mask more conserved domains from the immune system. PMID:22273269

2012-01-01

301

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

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

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

1998-01-01

302

Detection of Ebola virus envelope using monoclonal and polyclonal antibodies in ELISA, surface plasmon resonance and a quartz crystal microbalance immunosensor  

Microsoft Academic Search

Ebola virus (EBOV) Zaire, Sudan, as well as Ivory Coast are virulent human EBOV species. Both polyclonal and monoclonal antibodies (MAbs) were developed against soluble EBOV envelope glycoprotein (GP) for the study of EBOV envelope diversity and development of diagnostic reagents. Three EBOV Sudan-Gulu GP peptides, from the N-terminus, mid-GP, and C-terminus regions were used to immunize rabbits for the

Jae-Sung Yu; Hua-Xin Liao; Aren E. Gerdon; Brian Huffman; Richard M. Scearce; Mille McAdams; S. Munir Alam; Paul M. Popernack; Nancy J. Sullivan; David Wright; David E. Cliffel; Gary J. Nabel; Barton F. Haynes

2006-01-01

303

Analysis of the expressed heavy chain variable-region genes of Macaca fascicularis and isolation of monoclonal antibodies specific for the Ebola virus' soluble glycoprotein  

Microsoft Academic Search

The cynomolgus macaque, Macaca fascicularis, is frequently used in immunological and other biomedical research as a model for man; understanding it's antibody repertoire is, therefore, of fundamental interest. The expressed variable-region gene repertoire of a single M. fascicularis, which was immune to the Ebola virus, was studied. Using 5' rapid amplification of cDNA ends with immunoglobulin (Ig)G-specific primers, we obtained

Chris Druar; Surinder S. Saini; Meredith A. Cossitt; Fei Yu; Xiangguo Qiu; Thomas W. Geisbert; Steven Jones; Peter B. Jahrling; Donald I. H. Stewart; Erik J. Wiersma

2005-01-01

304

Ebola/Marburg Research  

MedlinePLUS

... transmission of Ebola virus from animals to humans. Ebola Therapeutics Research NIAID is supporting a number of projects designed to develop Ebola treatments. For example, NIAID supported Mapp Biopharmaceutical, Inc., in ...

305

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

PubMed Central

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

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

2014-01-01

306

Identification of N-glycans from Ebola virus glycoproteins by matrix-assisted laser desorption/ionisation time-of-flight and negative ion electrospray tandem mass spectrometry  

PubMed Central

The larger fragment of the transmembrane glycoprotein (GP1) and the soluble glycoprotein (sGP) of Ebola virus were expressed in human embryonic kidney cells and the secreted products were purified from the supernatant for carbohydrate analysis. The N-glycans were released with PNGase F from within sodium dodecyl sulphate/polyacrylamide gel electrophoresis (SDS-PAGE) gels. Identification of the glycans was made with normal-phase high-performance liquid chromatography (HPLC), matrix-assisted laser desorption/ionisation mass spectrometry, negative ion electrospray ionisation fragmentation mass spectrometry and exoglycosidase digestion. Most glycans were complex bi-, tri-and tetra-antennary compounds with reduced amounts of galactose. No bisected compounds were detected. Triantennary glycans were branched on the 6-antenna; fucose was attached to the core GlcNAc residue. Sialylated glycans were present on sGP but were largely absent from GP1, the larger fragment of the transmembrane glycoprotein. Consistent with this was the generally higher level of processing of carbohydrates found on sGP as evidenced by a higher percentage of galactose and lower levels of high-mannose glycans than were found on GP1. These results confirm and expand previous findings on partial characterisation of the Ebola virus transmembrane glycoprotein. They represent the first detailed data on carbohydrate structures of the Ebola virus sGP. PMID:20131323

Ritchie, Gayle; Harvey, David J.; Stroeher, Ute; Feldmann, Friederike; Feldmann, Heinz; Wahl-Jensen, Victoria; Royle, Louise; Dwek, Raymond A.; Rudd, Pauline M.

2012-01-01

307

Clinical virology of Ebola hemorrhagic fever (EHF): virus, virus antigen, and IgG and IgM antibody findings among EHF patients in Kikwit, Democratic Republic of the Congo, 1995.  

PubMed

Ebola hemorrhagic fever (EHF) patients treated at Kikwit General Hospital during the 1995 outbreak were tested for viral antigen, IgG and IgM antibody, and infectious virus. Viral antigen could be detected in virtually all patients during the acute phase of illness, while antibody was not always detectable before death. Virus was also isolated from patients during the course of their febrile illness, but attempts to quantify virus in Vero E6 cells by standard plaque assay were often unsuccessful. IgG and IgM antibody appeared at approximately the same time after disease onset (8-10 days), but IgM persisted for a much shorter period among the surviving convalescent patients. IgG antibody was detectable in surviving patients through about 2 years after onset, the latest time that samples were obtained. Detection of Ebola virus antigens or virus isolation appears to be the most reliable means of diagnosis for patients with suspected acute EHF, since patients with this often-fatal disease (80% mortality) may not develop detectable antibodies before death. PMID:9988182

Ksiazek, T G; Rollin, P E; Williams, A J; Bressler, D S; Martin, M L; Swanepoel, R; Burt, F J; Leman, P A; Khan, A S; Rowe, A K; Mukunu, R; Sanchez, A; Peters, C J

1999-02-01

308

Ebola infection reported  

NSDL National Science Digital Library

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

Sean Henahan

1995-01-01

309

Toxicological Safety Evaluation of DNA Plasmid Vaccines against HIV1, Ebola, Severe Acute Respiratory Syndrome, or West Nile Virus Is Similar Despite Differing Plasmid Backbones or Gene-Inserts  

Microsoft Academic Search

The Vaccine Research Center has developed a number of vaccine candidates for different diseases\\/infectious agents (HIV- 1, Severe Acute Respiratory Syndrome virus, West Nile virus, and Ebola virus, plus a plasmid cytokine adjuvant—IL-2\\/Ig) based on a DNA plasmid vaccine platform. To support the clinical de- velopment of each of these vaccine candidates, preclinical studies were performed to screen for potential

Rebecca L. Sheets; Judith Stein; T. Scott Manetz; Charla Andrews; Robert Bailer; John Rathmann; Phillip L. Gomezjj

2006-01-01

310

Ebola Reston virus infection of pigs: clinical significance and transmission potential.  

PubMed

In 2008, Reston ebolavirus (REBOV) was isolated from pigs during a disease investigation in the Philippines. Porcine reproductive and respiratory syndrome virus (PRRSV) and porcine circovirus type 2 (PCV-2) infections were also confirmed in affected herds and the contribution of REBOV to the disease outbreak remains uncertain. We have conducted experimental challenge studies in 5-week-old pigs, with exposure of animals to 10(6) TCID(50) of a 2008 swine isolate of REBOV via either the oronasal or subcutaneous route. Replication of virus in internal organs and viral shedding from the nasopharynx were documented in the absence of clinical signs of disease in infected pigs. These observations confirm not only that asymptomatic infection of pigs with REBOV occurs, but that animals so affected pose a transmission risk to farm, veterinary, and abattoir workers. PMID:21987755

Marsh, Glenn A; Haining, Jessica; Robinson, Rachel; Foord, Adam; Yamada, Manabu; Barr, Jennifer A; Payne, Jean; White, John; Yu, Meng; Bingham, John; Rollin, Pierre E; Nichol, Stuart T; Wang, Lin-Fa; Middleton, Deborah

2011-11-01

311

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

Microsoft Academic Search

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

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

1999-01-01

312

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

PubMed Central

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

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

313

Comparison of the protective efficacy of DNA and baculovirus-derived protein vaccines for EBOLA virus in guinea pigs.  

PubMed

The filoviruses Ebola virus (EBOV) and Marburg virus (MARV) cause severe hemorrhagic fever in humans for which no vaccines are available. Previously, a priming dose of a DNA vaccine expressing the glycoprotein (GP) gene of MARV followed by boosting with recombinant baculovirus-derived GP protein was found to confer protective immunity to guinea pigs (Hevey et al., 2001. Vaccine 20, 568-593). To determine whether a similar prime-boost vaccine approach would be effective for EBOV, we generated and characterized recombinant baculoviruses expressing full-length EBOV GP (GP(1,2)) or a terminally-deleted GP (GPa-) and examined their immunogenicity in guinea pigs. As expected, cells infected with the GPa- recombinant secreted more GP(1) than those infected with the GP(1,2) recombinant. In lectin binding studies, the insect cell culture-derived GPs were found to differ from mammalian cell derived virion GP, in that they had no complex/hybrid N-linked glycans or glycans containing sialic acid. Despite these differences, the baculovirus-derived GPs were able to bind monoclonal antibodies to five distinct epitopes on EBOV GP, indicating that the antigenic structures of the proteins remain intact. As a measure of the ability of the baculovirus-derived proteins to elicit cell-mediated immune responses, we evaluated the T-cell stimulatory capacity of the GPa- protein in cultured human dendritic cells. Increases in cytotoxicity as compared to controls suggest that the baculovirus proteins have the capacity to evoke cell-mediated immune responses. Guinea pigs vaccinated with the baculovirus-derived GPs alone, or in a DNA prime-baculovirus protein boost regimen developed antibody responses as measured by ELISA and plaque reduction neutralization assays; however, incomplete protection was achieved when the proteins were given alone or in combination with DNA vaccines. These data indicate that a vaccine approach that was effective for MARV is not effective for EBOV in guinea pigs. PMID:12686428

Mellquist-Riemenschneider, Jenny L; Garrison, Aura R; Geisbert, Joan B; Saikh, Kamal U; Heidebrink, Kelli D; Jahrling, Peter B; Ulrich, Robert G; Schmaljohn, Connie S

2003-04-01

314

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

PubMed Central

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

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

315

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

PubMed

Without an approved vaccine or treatments, 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, viraemia and abnormalities in blood count and blood chemistry were evident in many animals before ZMapp intervention. Advanced disease, as indicated by elevated liver enzymes, mucosal haemorrhages 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 exceeds the efficacy of any other therapeutics described so far, and results warrant further development of this cocktail for clinical use. PMID:25171469

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

2014-10-01

316

HSPA5 is an essential host factor for Ebola virus infection.  

PubMed

Development of novel strategies targeting the highly virulent ebolaviruses is urgently required. A proteomic study identified the ER chaperone HSPA5 as an ebolavirus-associated host protein. Here, we show using the HSPA5 inhibitor (-)- epigallocatechin gallate (EGCG) that the chaperone is essential for virus infection, thereby demonstrating a functional significance for the association. Furthermore, in vitro and in vivo gene targeting impaired viral replication and protected animals in a lethal infection model. These findings demonstrate that HSPA5 is vital for replication and can serve as a viable target for the design of host-based countermeasures. PMID:25017472

Reid, St Patrick; Shurtleff, Amy C; Costantino, Julie A; Tritsch, Sarah R; Retterer, Cary; Spurgers, Kevin B; Bavari, Sina

2014-09-01

317

Camouflage and Misdirection: The Full-On Assault of Ebola Virus Disease.  

PubMed

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

Misasi, John; Sullivan, Nancy J

2014-10-23

318

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

PubMed

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

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

319

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

PubMed Central

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

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

2015-01-01

320

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

E-print Network

.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

Rose, Michael R.

321

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

Microsoft Academic Search

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

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

2004-01-01

322

Low seroprevalence of IgG antibodies to Ebola virus in an epidemic zone: Ogooué-Ivindo region, Northeastern Gabon, 1997.  

PubMed

A population-based serosurvey was performed to determine the seroprevalence of antibodies to Ebola virus (EBO) in a region that has experienced multiple epidemics of EBO hemorrhagic fever. Of 2533 residents in 8 villages, serum samples from 979 (38.6%) were tested by enzyme-linked immunosorbent assay for immunoglobulin (Ig) G and IgM antibodies to Ebola-Zaire (EBO-Z) virus. Fourteen samples (1.4%) were found positive for IgG antibodies, and 4 of these (.4%) were samples from survivors of an epidemic of EBO hemorrhagic fever. Seroprevalence based on the remaining 10 IgG-seropositive individuals with no history of exposure to EBO was 1.0% (exact binomial 95% confidence interval, 0.5%-1.9%). No serum samples were found positive for IgM antibodies to EBO-Z virus. The low seroprevalence suggests that, outside of recognized outbreaks, human exposure to EBO in this epidemic zone is rare. PMID:15717273

Heffernan, Richard T; Pambo, Bertin; Hatchett, Richard J; Leman, Patricia A; Swanepoel, Robert; Ryder, Robert W

2005-03-15

323

Serologic cross-reactivity of human IgM and IgG antibodies to five species of Ebola virus.  

PubMed

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

Macneil, Adam; Reed, Zachary; Rollin, Pierre E

2011-06-01

324

Whole-genome expression profiling reveals that inhibition of host innate immune response pathways by Ebola virus can be reversed by a single amino acid change in the VP35 protein.  

PubMed

Ebola hemorrhagic fever is a rapidly progressing acute febrile illness characterized by high virus replication, severe immunosuppression, and case fatalities of ca. 80%. Inhibition of phosphorylation of interferon regulatory factor 3 (IRF-3) by the Ebola VP35 protein may block the host innate immune response and play an important role in the severity of disease. We used two precisely defined reverse genetics-generated Ebola viruses to investigate global host cell responses resulting from the inhibition of IRF-3 phosphorylation. The two viruses encoded either wild-type (WT) VP35 protein (recEbo-VP35/WT) or VP35 with an arginine (R)-to-alanine (A) amino acid substitution at position 312 (recEbo-VP35/R312A) within a previously defined IRF-3 inhibitory domain. When sucrose-gradient purified virus was used for infection, host cell whole-genome expression profiling revealed striking differences in human liver cell responses to these viruses differing by a single amino acid. The inhibition of host innate immune responses by WT Ebola virus was so potent that little difference in interferon and antiviral gene expression could be discerned between cells infected with purified WT, inactivated virus, or mock-infected cells. However, infection with recEbo-VP35/R312A virus resulted in a strong innate immune response including increased expression of MDA-5, RIG-I, RANTES, MCP-1, ISG-15, ISG-54, ISG-56, ISG-60, STAT1, IRF-9, OAS, and Mx1. The clear gene expression differences were obscured if unpurified virus stocks were used to initiate infection, presumably due to soluble factors present in virus-infected cell supernatant preparations. Ebola virus VP35 protein clearly plays a pivotal role in the potent inhibition of the host innate immune responses, and the present study indicates that VP35 has a wider effect on host cell responses than previously shown. The ability to eliminate this inhibitory effect with a single amino acid change in VP35 demonstrates the critical role this protein must play in the severe aspects this highly fatal disease. PMID:18353943

Hartman, Amy L; Ling, Ling; Nichol, Stuart T; Hibberd, Martin L

2008-06-01

325

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

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

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

326

Cutaneous DNA vaccination against Ebola virus by particle bombardment: histopathology and alteration of CD3-positive dendritic epidermal cells.  

PubMed

We analyzed the localization of gold particles, expression of immunogenic protein, and histopathologic changes after vaccinating guinea pigs and mice with a DNA vaccine to the Ebola virus glycoprotein administered by cutaneous particle bombardment. Gold particles were deposited in all layers of the epidermis and in the dermis. Those in the epidermis were lost as the damaged layers sloughed, while those in the dermis were phagocytized by macrophages. Glycoprotein was demonstrated by immunohistochemistry primarily in keratinocytes in the epidermis and hair follicle epithelium and less frequently in dermal macrophages, fibroblasts, sebocytes, and cells that appeared to be Langerhans cells. The number of cells that expressed glycoprotein increased between 4 and 8 hours postvaccination, then decreased to near zero by 48 hours. The vaccine sites were histologically divisible into three zones. The central portion, zone 1, contained the most gold particles in the dermis and epidermis and had extensive tissue damage, including full-thickness epidermal necrosis. Zone 2 contained fewer gold particles in the epidermis and dermis and had less extensive necrosis. The majority of cells in which glycoprotein was expressed were in zone 2. Zone 3 contained gold particles only in the epidermis and had necrosis of only a few scattered cells. Regeneration of the epidermis in damaged areas was evident at 24 hours postvaccination and was essentially complete by day 5 in the mice and day 10 in the guinea pigs. Inflammatory changes were characterized by hemorrhage, edema, and infiltrates of neutrophils initially and by infiltrates of lymphocytes and macrophages at later times. In zone 1, inflammation affected both the epidermis and dermis. Peripherally, inflammation was relatively limited to the epidermis. CD3-positive dendritic epidermal cells were demonstrated in the epidermis and superficial hair follicles of unvaccinated immunocompetent mice and beige mice but not of SCID mice. These cells disappeared from all but the most peripheral portions of the vaccine sites of vaccinated mice within 24 hours. They reappeared slowly, failing to reach numbers comparable with unvaccinated mice by 35 days postvaccination. The epidermis of control guinea pigs also had CD3-positive cells, but they did not have dendrites. These findings should contribute to a better understanding of the mechanisms operating in response to DNA vaccination by particle bombardment. PMID:11280377

Steele, K E; Stabler, K; VanderZanden, L

2001-03-01

327

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

PubMed

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 bystander apoptosis. Increased levels of interferon (IFN)-alpha, IFN-beta, interleukin (IL)-6, IL-18, MIP-1alpha, and MIP-1beta were observed in all EBOV-infected monkeys, indicating the occurrence of a strong proinflammatory response. To investigate the mechanism(s) involved in lymphoid apoptosis, soluble Fas (sFas) and nitrate accumulation were measured. sFas was detected in 4/9 animals, while, elevations of nitrate accumulation occurred in 3/3 animals. To further evaluate the potential role of these factors in the observed bystander apoptosis and intact animals, in vitro cultures were prepared of adherent human monocytes/macrophages (PHM), and monocytes differentiated into immature dendritic cells (DC). These cultures were infected with EBOV and analyzed for cytokine/chemokine induction and expression of apoptosis-related genes. In addition, the in vitro EBOV infection of peripheral blood mononuclear cells (PBMC) resulted in strong cytokine/chemokine induction, a marked increase in lactate dehydrogenase (LDH) activity, and an increase in the number of apoptotic lymphocytes examined by electron microscopy. Increased levels of sFAS were detected in PHM cultures, although, <10% of the cells were positive by immunohistochemistry. In contrast, >90% of EBOV-infected PHM were positive for tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) by immunohistochemistry, RNA analysis, and flow cytometry. Inactivated EBOV also effected increased TRAIL expression in PHM, suggesting that the TNF receptor superfamily may be involved in apoptosis of the host lymphoid cells, and that induction may occur independent of viral replication. In further studies with infected PHM, expression of MHC II was remarkably suppressed after 6 days, an additional correlate of immunological dysregulation. In conclusion, our findings suggest that infection of mononuclear phagocytes is critical, triggering a cascade of events involving cytokines/chemokines and oxygen free radicals. It is the consequence of these events rather than direct viral infection that results in much of the observed pathology. Identification of cytokine/chemokine, nitric oxide, and reactive oxygen species involvement in the observed filoviral pathogenesis may lend insight into the rational design of therapeutic countermeasures of filoviral pathogenesis. PMID:11803049

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

2002-03-01

328

Middletown, Connecticut 06459 Ebola Travel Advisory  

E-print Network

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

Devoto, Stephen H.

329

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 ...

330

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

PubMed Central

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

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

2013-01-01

331

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

PubMed

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

Eisa-Beygi, Shahram; Wen, Xiao-Yan

2015-02-01

332

Ebola Drug Shows Promise in Monkey Trial  

MedlinePLUS

... that we can protect non-human primates from Ebola virus, using only a single . . . agent," study lead author ... of VP24 alone is enough to protect against Ebola virus infection, and that targeting VP24 may lead to ...

333

IFITMs restrict the replication of multiple pathogenic viruses.  

PubMed

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

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

2013-12-13

334

IFITMs restrict the replication of multiple pathogenic viruses  

PubMed Central

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

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

2014-01-01

335

Viruses 2012, 4, 2471-2484; doi:10.3390/v4112471 ISSN 1999-4915  

E-print Network

as a filovirus receptor. Keywords: Ebola virus; Marburg virus; filovirus; viral entry; Niemann-Pick C1; NPC1; Niemann-Pick C1-like1; NPC1L1; host factor; viral receptor 1. Introduction Ebola virus (EBOV) and Marburg no approved vaccines or treatments exist. These viruses are members of the family Filoviridae of enveloped

Chandran, Kartik

336

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

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

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

2008-01-01

337

Ebola fever: The African emergency  

Microsoft Academic Search

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.

J. Bruce; P. Brysiewicz

2002-01-01

338

Analysis of Ebola Glycoprotein Sequences from Strains of Varying Lethality  

E-print Network

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 unknown. Ebola virus is one of only two known members of a family of RNA viruses, the Filoviridae. (The other member is the Marburg virus.) The Filoviridae consists of enveloped viruses containing a non-segmented negative-stranded RNA genome. The Ebola genome shows a linear gene arrangement in the order 3 ' untranslated region--

Tammy Doukas; I. Background

339

Biodistribution of DNA Plasmid Vaccines against HIV-1, Ebola, Severe Acute Respiratory Syndrome, or West Nile Virus Is Similar, without Integration, despite Differing Plasmid Backbones or Gene Inserts  

PubMed Central

The Vaccine Research Center has developed a number of vaccine candidates for different diseases/infectious agents (HIV-1, Severe Acute Respiratory Syndrome virus, West Nile virus, and Ebola virus, plus a plasmid cytokine adjuvant—IL-2/Ig) based on a DNA plasmid vaccine platform. To support the clinical development of each of these vaccine candidates, preclinical studies have been performed in mice or rabbits to determine where in the body these plasmid vaccines would biodistribute and how rapidly they would clear. In the course of these studies, it has been observed that regardless of the gene insert (expressing the vaccine immunogen or cytokine adjuvant) and regardless of the promoter used to drive expression of the gene insert in the plasmid backbone, the plasmid vaccines do not biodistribute widely and remain essentially in the site of injection, in the muscle and overlying subcutis. Even though ? 1014 molecules are inoculated in the studies in rabbits, by day 8 or 9(? 1 week postinoculation), already all but on the order of 104?106 molecules per microgram of DNA extracted from tissue have been cleared at the injection site. Over the course of 2 months, the plasmid clears from the site of injection with only a small percentage of animals (generally 10?20%) retaining a small number of copies (generally around 100 copies) in the muscle at the injection site. This pattern of biodistribution (confined to the injection site) and clearance (within 2 months) is consistent regardless of differences in the promoter in the plasmid backbone or differences in the gene insert being expressed by the plasmid vaccine. In addition, integration has not been observed with plasmid vaccine candidates inoculated i.m. by Biojector 2000 or by needle and syringe. These data build on the repeated-dose toxicology studies performed (see companion article, Sheets et al., 2006) to demonstrate the safety and suitability for investigational human use of DNA plasmid vaccine candidates for a variety of infectious disease prevention indications. PMID:16569729

Sheets, Rebecca L.; Stein, Judith; Manetz, T. Scott; Duffy, Chris; Nason, Martha; Andrews, Charla; Kong, Wing-Pui; Nabel, Gary J.; Gomez, Phillip L.

2008-01-01

340

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...

341

Bat Flight and Zoonotic Viruses  

PubMed Central

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

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

342

Bat flight and zoonotic viruses  

USGS Publications Warehouse

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.

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

343

Ebola Tracker app.  

PubMed

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

Evans, Roger

2015-01-21

344

A mutation in the Ebola virus envelope glycoprotein restricts viral entry in a host species- and cell-type-specific manner.  

PubMed

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

Martinez, Osvaldo; Ndungo, Esther; Tantral, Lee; Miller, Emily Happy; Leung, Lawrence W; Chandran, Kartik; Basler, Christopher F

2013-03-01

345

Ebola: Virology and Epidemiology  

Microsoft Academic Search

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

Raymond Charles Sanders

346

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

PubMed

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

Walsh, Michael G; Haseeb, Ma

2015-01-01

347

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

PubMed Central

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

Haseeb, MA

2015-01-01

348

Detection of Ebola virus envelope using monoclonal and polyclonal antibodies in ELISA, surface plasmon resonance and a quartz crystal microbalance immunosensor.  

PubMed

Ebola virus (EBOV) Zaire, Sudan, as well as Ivory Coast are virulent human EBOV species. Both polyclonal and monoclonal antibodies (MAbs) were developed against soluble EBOV envelope glycoprotein (GP) for the study of EBOV envelope diversity and development of diagnostic reagents. Three EBOV Sudan-Gulu GP peptides, from the N-terminus, mid-GP, and C-terminus regions were used to immunize rabbits for the generation of anti-EBOV polyclonal antibodies. Polyclonal antisera raised against the C-terminus peptide could detect both Sudan-Gulu as well as Zaire GPs, while anti-N and mid-region peptide polyclonal sera recognized only EBOV Sudan-Gulu GP. Of the three anti-EBOV GP mouse MAbs produced, MAb 15H10 recognized all human EBOV GP species tested (Zaire, Sudan and Ivory Coast), and as well as reacted with the Reston non-human primate EBOV GPs. In addition, MAb 15H10 bound virion-associated GP of all known EBOV species. MAb 17A3 recognized GPs of both EBOV Sudan-Gulu and Zaire, while MAb 6D11 recognized only EBOV Sudan-Gulu GP. To detect EBOV GP, these antibody reagents were used in ELISA, surface plasmon resonance and in a quartz crystal microbalance immunosensor. Thus, polyclonal and monoclonal antibodies can be used in combination to identify and differentiate both human and non-human primate EBOV GPs. PMID:16857271

Yu, Jae-Sung; Liao, Hua-Xin; Gerdon, Aren E; Huffman, Brian; Scearce, Richard M; McAdams, Mille; Alam, S Munir; Popernack, Paul M; Sullivan, Nancy J; Wright, David; Cliffel, David E; Nabel, Gary J; Haynes, Barton F

2006-11-01

349

Hepadna viruses  

SciTech Connect

This book examines the molecular biology, disease pathogenesis, epidemiology, and clinical features of hepadna and other viruses with hepatic tropism and outlines future directions and approaches for their management. The volume's six sections provide a review of the various features, mechanisms, and functions of these viruses, ranging from hepadna virus replication and regulation of gene expression to the structure and function of hepadna-virus gene products.

Robinson, W.; Koike, K.; Will, H.

1987-01-01

350

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 ...

351

Biodistribution of DNA plasmid vaccines against HIV-1, Ebola, Severe Acute Respiratory Syndrome, or West Nile virus is similar, without integration, despite differing plasmid backbones or gene inserts.  

PubMed

The Vaccine Research Center has developed a number of vaccine candidates for different diseases/infectious agents (HIV-1, Severe Acute Respiratory Syndrome virus, West Nile virus, and Ebola virus, plus a plasmid cytokine adjuvant-IL-2/Ig) based on a DNA plasmid vaccine platform. To support the clinical development of each of these vaccine candidates, preclinical studies have been performed in mice or rabbits to determine where in the body these plasmid vaccines would biodistribute and how rapidly they would clear. In the course of these studies, it has been observed that regardless of the gene insert (expressing the vaccine immunogen or cytokine adjuvant) and regardless of the promoter used to drive expression of the gene insert in the plasmid backbone, the plasmid vaccines do not biodistribute widely and remain essentially in the site of injection, in the muscle and overlying subcutis. Even though approximately 10(14) molecules are inoculated in the studies in rabbits, by day 8 or 9 ( approximately 1 week postinoculation), already all but on the order of 10(4)-10(6) molecules per microgram of DNA extracted from tissue have been cleared at the injection site. Over the course of 2 months, the plasmid clears from the site of injection with only a small percentage of animals (generally 10-20%) retaining a small number of copies (generally around 100 copies) in the muscle at the injection site. This pattern of biodistribution (confined to the injection site) and clearance (within 2 months) is consistent regardless of differences in the promoter in the plasmid backbone or differences in the gene insert being expressed by the plasmid vaccine. In addition, integration has not been observed with plasmid vaccine candidates inoculated i.m. by Biojector 2000 or by needle and syringe. These data build on the repeated-dose toxicology studies performed (see companion article, Sheets et al., 2006) to demonstrate the safety and suitability for investigational human use of DNA plasmid vaccine candidates for a variety of infectious disease prevention indications. PMID:16569729

Sheets, Rebecca L; Stein, Judith; Manetz, T Scott; Duffy, Chris; Nason, Martha; Andrews, Charla; Kong, Wing-Pui; Nabel, Gary J; Gomez, Phillip L

2006-06-01

352

Virus World  

NSDL National Science Digital Library

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.

2005-12-14

353

CHLORELLA VIRUSES  

PubMed Central

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

Yamada, Takashi; Onimatsu, Hideki; Van Etten, James L.

2007-01-01

354

VSV?G/EBOV GP-Induced Innate Protection Enhances Natural Killer Cell Activity to Increase Survival in a Lethal Mouse Adapted Ebola Virus Infection.  

PubMed

Abstract 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

Williams, Kinola J N; Qiu, Xiangguo; Fernando, Lisa; Jones, Steven M; Alimonti, Judie B

2015-02-01

355

Obesity Virus  

NSDL National Science Digital Library

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.

Science Update (AAAS;)

2007-06-12

356

Virus Crystallography  

NASA Astrophysics Data System (ADS)

Crystallography provides a means of visualizing intact virus particles as well as their isolated constituent proteins and enzymes (1-3) at near-atomic resolution, and is thus an extraordinarily powerful tool in the pursuit of a fuller understanding of the functioning of these simple biological systems. We have already expanded our knowledge of virus evolution, assembly, antigenic variation, and host-cell interactions; further studies will no doubt reveal much more. Although the rewards are enormous, an intact virus structure determination is not a trivial undertaking and entails a significant scaling up in terms of time and resources through all stages of data collection and processing compared to a traditional protein crystallographic structure determination. It is the methodology required for such studies that will be the focus of this chapter. The computational requirements were satisfied in the late 1970s, and when combined with the introduction of phase improvement techniques utilizing the virus symmetry (4,5), the application of crystallography to these massive macromolecular assemblies became feasible. This led to the determination of the first virus structure (the small RNA plant virus, tomato bushy stunt virus), by Harrison and coworkers in 1978 (6). The structures of two other plant viruses followed rapidly (7,8). In the 1980s, a major focus of attention was a family of animal RNA viruses; the Picornaviridae.

Fry, Elizabeth; Logan, Derek; Stuart, David

357

Structure of the dengue virus envelope protein after membrane fusion  

E-print Network

, and filoviruses such as Ebola virus (reviewed in ref. 1). All of these `class I' viral fusion proteins are twoStructure of the dengue virus envelope protein after membrane fusion Yorgo Modis1 , Steven Ogata2 ........................................................................................................................................................................................................................... Dengue virus enters a host cell when the viral envelope glycoprotein, E, binds to a receptor and responds

Harrison, Stephen C.

358

RESEARCH Open Access Molecular evolution of Azagny virus, a newfound  

E-print Network

well established in humans [1,2]; Ebola virus, a filovirus harbored by fruit bats [3,4], which is amongRESEARCH Open Access Molecular evolution of Azagny virus, a newfound hantavirus harbored Dubey3 , François Jacquet4 and Richard Yanagihara1* Abstract Background: Tanganya virus (TGNV), the only

Alvarez, Nadir

359

Cellular Entry of Ebola Virus Involves Uptake by a Macropinocytosis-Like Mechanism and Subsequent Trafficking through Early and Late Endosomes  

Microsoft Academic Search

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

Mohammad F. Saeed; Andrey A. Kolokoltsov; Thomas Albrecht; Robert A. Davey

2010-01-01

360

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

E-print Network

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...

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 I.; 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

361

Hendra virus.  

PubMed

Hendra virus infection of horses occurred sporadically between 1994 and 2010 as a result of spill-over from the viral reservoir in Australian mainland flying-foxes, and occasional onward transmission to people also followed from exposure to affected horses. An unprecedented number of outbreaks were recorded in 2011 leading to heightened community concern. Release of an inactivated subunit vaccine for horses against Hendra virus represents the first commercially available product that is focused on mitigating the impact of a Biosafety Level 4 pathogen. Through preventing the development of acute Hendra virus disease in horses, vaccine use is also expected to reduce the risk of transmission of infection to people. PMID:25281398

Middleton, Deborah

2014-12-01

362

Computer viruses  

NASA Technical Reports Server (NTRS)

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.

Denning, Peter J.

1988-01-01

363

2005 Nature Publishing Group Step by step for Ebola entry  

E-print Network

© 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 haemorrhagic fever in humans and no effective treatment has been found so far. The EboV surface glycoprotein GP initi

Chandran, Kartik

364

Molecular Ecology and Natural History of Simian Foamy Virus Infection in Wild-Living Chimpanzees  

Microsoft Academic Search

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

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

365

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 ...

366

Computer Viruses. Technology Update.  

ERIC Educational Resources Information Center

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…

Ponder, Tim, Comp.; Ropog, Marty, Comp.; Keating, Joseph, Comp.

367

Ebola Transmission Through Cough Possible, but Not Likely  

MedlinePLUS

... the report concluded. "We should not assume that Ebola viruses are not capable of surprising us again at some point in the future." Still, they stressed that airborne transmission of Ebola -- similar to that which occurs with the flu ...

368

Ecological dynamics of emerging bat virus spillover.  

PubMed

Viruses that originate in bats may be the most notorious emerging zoonoses that spill over from wildlife into domestic animals and humans. Understanding how these infections filter through ecological systems to cause disease in humans is of profound importance to public health. Transmission of viruses from bats to humans requires a hierarchy of enabling conditions that connect the distribution of reservoir hosts, viral infection within these hosts, and exposure and susceptibility of recipient hosts. For many emerging bat viruses, spillover also requires viral shedding from bats, and survival of the virus in the environment. Focusing on Hendra virus, but also addressing Nipah virus, Ebola virus, Marburg virus and coronaviruses, we delineate this cross-species spillover dynamic from the within-host processes that drive virus excretion to land-use changes that increase interaction among species. We describe how land-use changes may affect co-occurrence and contact between bats and recipient hosts. Two hypotheses may explain temporal and spatial pulses of virus shedding in bat populations: episodic shedding from persistently infected bats or transient epidemics that occur as virus is transmitted among bat populations. Management of livestock also may affect the probability of exposure and disease. Interventions to decrease the probability of virus spillover can be implemented at multiple levels from targeting the reservoir host to managing recipient host exposure and susceptibility. PMID:25392474

Plowright, Raina K; Eby, Peggy; Hudson, Peter J; Smith, Ina L; Westcott, David; Bryden, Wayne L; Middleton, Deborah; Reid, Peter A; McFarlane, Rosemary A; Martin, Gerardo; Tabor, Gary M; Skerratt, Lee F; Anderson, Dale L; Crameri, Gary; Quammen, David; Jordan, David; Freeman, Paul; Wang, Lin-Fa; Epstein, Jonathan H; Marsh, Glenn A; Kung, Nina Y; McCallum, Hamish

2015-01-01

369

Ecological dynamics of emerging bat virus spillover  

PubMed Central

Viruses that originate in bats may be the most notorious emerging zoonoses that spill over from wildlife into domestic animals and humans. Understanding how these infections filter through ecological systems to cause disease in humans is of profound importance to public health. Transmission of viruses from bats to humans requires a hierarchy of enabling conditions that connect the distribution of reservoir hosts, viral infection within these hosts, and exposure and susceptibility of recipient hosts. For many emerging bat viruses, spillover also requires viral shedding from bats, and survival of the virus in the environment. Focusing on Hendra virus, but also addressing Nipah virus, Ebola virus, Marburg virus and coronaviruses, we delineate this cross-species spillover dynamic from the within-host processes that drive virus excretion to land-use changes that increase interaction among species. We describe how land-use changes may affect co-occurrence and contact between bats and recipient hosts. Two hypotheses may explain temporal and spatial pulses of virus shedding in bat populations: episodic shedding from persistently infected bats or transient epidemics that occur as virus is transmitted among bat populations. Management of livestock also may affect the probability of exposure and disease. Interventions to decrease the probability of virus spillover can be implemented at multiple levels from targeting the reservoir host to managing recipient host exposure and susceptibility. PMID:25392474

Plowright, Raina K.; Eby, Peggy; Hudson, Peter J.; Smith, Ina L.; Westcott, David; Bryden, Wayne L.; Middleton, Deborah; Reid, Peter A.; McFarlane, Rosemary A.; Martin, Gerardo; Tabor, Gary M.; Skerratt, Lee F.; Anderson, Dale L.; Crameri, Gary; Quammen, David; Jordan, David; Freeman, Paul; Wang, Lin-Fa; Epstein, Jonathan H.; Marsh, Glenn A.; Kung, Nina Y.; McCallum, Hamish

2015-01-01

370

Virus Information Database  

NSDL National Science Digital Library

Symantec Corporation's AntiVirus Research Center has recently released a virus information database that includes over 10,000 computer viruses. The searchable and browseable database can include information about aliases for each virus, infection length, area of infection, likelihood of infection, region reported, characteristics, target platform and target date, in addition to a brief description of how the virus works. The site also provides a basic tutorial on viruses. Symantec, under the Norton name, produces several anti-virus products.

371

Virus and Spam Protection Virus Protection  

E-print Network

Virus and Spam Protection Virus Protection On November 14, 2002, we installed software that detects and protects our I-Mail from viruses. This software works in the following way: If someone sends a piece, for some reason, actually wants the quarantined file we will make this (virus infected) file available

California at Santa Barbara, University of

372

The Geometry of Viruses.  

ERIC Educational Resources Information Center

Presented is an activity in which students make models of viruses, which allows them to visualize the shape of these microorganisms. Included are some background on viruses, the biology and geometry of viruses, directions for building viruses, a comparison of cells and viruses, and questions for students. (KR)

Case, Christine L.

1991-01-01

373

Vesicular Stomatitis Virus Disease  

NSDL National Science Digital Library

Images of Vesicular Stomatitis Virus Disease.  Vesicular stomatitis viruses (VSV) are in the family Rhabdoviridae and the genus Vesiculovirus and are enveloped viruses with bullet-shaped capsids.

American Society For Microbiology;

2007-01-09

374

Chikungunya Virus (CHIKV)  

MedlinePLUS

... Caribbean Countries with reported local transmission of chikungunya virus (as of July 2014) The mosquitoes • Aedes species mosquitoes transmit chikungunya virus • These same types of mosquitoes transmit dengue virus • ...

375

Computer Viruses: An Overview.  

ERIC Educational Resources Information Center

Discusses the early history and current proliferation of computer viruses that occur on Macintosh and DOS personal computers, mentions virus detection programs, and offers suggestions for how libraries can protect themselves and their users from damage by computer viruses. (LRW)

Marmion, Dan

1990-01-01

376

Measles virus.  

PubMed

Measles was an inevitable infection during the human development with substantial degree of morbidity and mortality. The severity of measles virus (MV) infection was largely contained by the development of a live attenuated vaccine that was introduced into the vaccination programs. However, all efforts to eradicate the disease failed and continued to annually result in significant deaths. The development of molecular biology techniques allowed the rescue of MV from cDNA that enabled important insights into a variety of aspects of the biology of the virus and its pathogenesis. Subsequently these technologies facilitated the development of novel vaccine candidates that induce immunity against measles and other pathogens. Based on the promising prospective, the use of MV as a recombinant vaccine and a therapeutic vector is addressed. PMID:25483511

Naim, Hussein Y

2015-01-01

377

evolved to promote and integrate virus pro-duction with VS formation.  

E-print Network

including HIV-1 and the Ebola virus, which efficiently infect cells by a cell- free route in vitro, may rely1671 evolved to promote and integrate virus pro- duction with VS formation. In addition activates the uninfected target cell. Activation would ensure expression of virus receptors

Dinsmore, Tony

378

Virus Movement Maintains Local Virus Population Diversity  

SciTech Connect

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

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

2007-11-01

379

Crystallization of viruses and virus proteins  

NASA Astrophysics Data System (ADS)

Methods for crystallizing six isometric plant and insect viruses are presented. Procedures developed for modifying, purifying and crystallizing coat protein subunits isolated from a virus forming asymmetric, spheroidal particles, stabilized almost exclusively by protein-RNA interactions, are also discussed. The tertiary and quaternary structures of small RNA viruses are compared.

Sehnke, Paul C.; Harrington, Melissa; Hosur, M. V.; Li, Yunge; Usha, R.; Craig Tucker, R.; Bomu, Wu; Stauffacher, Cynthia V.; Johnson, John E.

1988-07-01

380

The UCSC Ebola Genome Portal  

PubMed Central

Background: With the Ebola epidemic raging out of control in West Africa, there has been a flurry of research into the Ebola virus, resulting in the generation of much genomic data. Methods: In response to the clear need for tools that integrate multiple strands of research around molecular sequences, we have created the University of California Santa Cruz (UCSC) Ebola Genome Browser, an adaptation of our popular UCSC Genome Browser web tool, which can be used to view the Ebola virus genome sequence from GenBank and nearly 30 annotation tracks generated by mapping external data to the reference sequence. Significant annotations include a multiple alignment comprising 102 Ebola genomes from the current outbreak, 56 from previous outbreaks, and 2 Marburg genomes as an outgroup; a gene track curated by NCBI; protein annotations curated by UniProt and antibody-binding epitopes curated by IEDB. We have extended the Genome Browser’s multiple alignment color-coding scheme to distinguish mutations resulting from non-synonymous coding changes, synonymous changes, or changes in untranslated regions. Discussion: Our Ebola Genome portal at http://genome.ucsc.edu/ebolaPortal/ links to the Ebola virus Genome Browser and an aggregate of useful information, including a collection of Ebola antibodies we are curating.

Haeussler, Maximilian; Karolchik, Donna; Clawson, Hiram; Raney, Brian J; Rosenbloom, Kate R.; Fujita, Pauline A.; Hinrichs, Angie S.; Speir, Matthew L; Eisenhart, Chris; Zweig, Ann S.; Haussler, David; Kent, W. James

2014-01-01

381

Virus entry by macropinocytosis  

Microsoft Academic Search

As obligatory intracellular parasites, viruses rely on host-cell functions for most aspects of their replication cycle. This is born out during entry, when most viruses that infect vertebrate and insect cells exploit the endocytic activities of the host cell to move into the cytoplasm. Viruses belonging to vaccinia, adeno, picorna and other virus families have been reported to take advantage

Jason Mercer; Ari Helenius

2009-01-01

382

The Tobacco Mosaic Virus.  

ERIC Educational Resources Information Center

Explains how the tobacco mosaic virus can be used to study virology. Presents facts about the virus, procedures to handle the virus in the laboratory, and four laboratory exercises involving the viruses' survival under inactivating conditions, dilution end point, filterability, and microscopy. (MDH)

Sulzinski, Michael A.

1992-01-01

383

[Characterization of Marburg virus morphology].  

PubMed

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

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

2014-05-01

384

Detection of Ebola Viral Antigen by Enzyme-Linked Immunosorbent Assay Using a Novel Monoclonal Antibody to Nucleoprotein  

Microsoft Academic Search

With the increase in international traffic, the risk of introducing rare but severe infectious diseases like Ebola hemorrhagic fever is increasing all over the world. However, the system for the diagnosis of Ebola virus infection is available in a limited number of countries. In the present study, we developed an Ebola virus antigen-detection enzyme-linked immunosorbent assay (ELISA) system using a

MASAHIRO NIIKURA; TETSURO IKEGAMI; MASAYUKI SAIJO; ICHIRO KURANE; MARY E. MIRANDA; SHIGERU MORIKAWA

2001-01-01

385

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

PubMed

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

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

2014-10-01

386

West Nile Virus  

Microsoft Academic Search

The West Nile virus (WNV) belongs to the genus Flavivirus (family Flaviviridae) and was previously classified as a group B\\u000a arbovirus. These disease-causing pathogens are spread to humans by insects, usually mosquitoes. Other flaviviruses include\\u000a the Yellow fever virus, Japanese encephalitis virus, dengue virus, and the Saint Louis encephalitis virus (see sections on\\u000a flaviviruses in Chapters 19 and 23). The

Vassil St. Georgiev

387

What is Ebola?  

PubMed

On 23 March 2014, the World Health Organization first announced a new Ebola virus outbreak that started in December 2013 in the eastern part of the Republic of Guinea. Human infections shortly emerged in Liberia, Sierra Leone, and Nigeria. On 30 September 2014, the Centers for Disease Control and Prevention confirmed through laboratory testing the first Ebola virus infection diagnosed in the USA, in a patient who travelled from West Africa to Texas. On 6 October 2014, the first human infection occurring outside of Africa was reported, in a Spanish nurse who treated two priests, both of whom died, and on 23 October 2014, the first human infection was reported in New York City. To date, the 2014 Ebola virus outbreak is the longest, largest, and most persistent one since 1976, when the virus was first identified in humans, and the number of human cases exceeded, as of mid-September 2014, the cumulative number of infections from all the previous outbreaks. The early clinical presentation overlaps with other infectious diseases, opening differential diagnosis difficulties. Understanding the transmission routes and identifying the natural reservoir of the virus are additional challenges in studying Ebola hemorrhagic fever outbreaks. Ebola virus is as much a public health challenge for developing countries as it is for the developed world, and previous outbreaks underscored that the relative contribution of the risk factors may differ among outbreaks. The implementation of effective preparedness plans is contingent on integrating teachings from previous Ebola virus outbreaks with those from the current outbreak and with lessons provided by other infectious diseases, along with developing a multifaceted inter-disciplinary and cross-disciplinary framework that should be established and shaped by biomedical as well as sociopolitical sciences. PMID:25496121

Stein, R A

2015-01-01

388

Toxicological safety evaluation of DNA plasmid vaccines against HIV-1, Ebola, Severe Acute Respiratory Syndrome, or West Nile virus is similar despite differing plasmid backbones or gene-inserts.  

PubMed

The Vaccine Research Center has developed a number of vaccine candidates for different diseases/infectious agents (HIV-1, Severe Acute Respiratory Syndrome virus, West Nile virus, and Ebola virus, plus a plasmid cytokine adjuvant-IL-2/Ig) based on a DNA plasmid vaccine platform. To support the clinical development of each of these vaccine candidates, preclinical studies were performed to screen for potential toxicities (intrinsic and immunotoxicities). All treatment-related toxicities identified in these repeated-dose toxicology studies have been confined primarily to the sites of injection and seem to be the result of both the delivery method (as they are seen in both control and treated animals) and the intended immune response to the vaccine (as they occur with greater frequency and severity in treated animals). Reactogenicity at the site of injection is generally seen to be reversible as the frequency and severity diminished between doses and between the immediate and recovery termination time points. This observation also correlated with the biodistribution data reported in the companion article (Sheets et al., 2006), in which DNA plasmid vaccine was shown to remain at the site of injection, rather than biodistributing widely, and to clear over time. The results of these safety studies have been submitted to the Food and Drug Administration to support the safety of initiating clinical studies with these and related DNA plasmid vaccines. Thus far, standard repeated-dose toxicology studies have not identified any target organs for toxicity (other than the injection site) for our DNA plasmid vaccines at doses up to 8 mg per immunization, regardless of disease indication (i.e., expressed gene-insert) and despite differences (strengths) in the promoters used to drive this expression. As clinical data accumulate with these products, it will be possible to retrospectively compare the safety profiles of the products in the clinic to the results of the repeated-dose toxicology studies, in order to determine the utility of such toxicology studies for signaling potential immunotoxicities or intrinsic toxicities from DNA vaccines. These data build on the biodistribution studies performed (see companion article, Sheets et al., 2006) to demonstrate the safety and suitability for investigational human use of DNA plasmid vaccine candidates for a variety of infectious disease prevention indications. PMID:16569728

Sheets, Rebecca L; Stein, Judith; Manetz, T Scott; Andrews, Charla; Bailer, Robert; Rathmann, John; Gomez, Phillip L

2006-06-01

389

Toxicological Safety Evaluation of DNA Plasmid Vaccines against HIV-1, Ebola, Severe Acute Respiratory Syndrome, or West Nile Virus Is Similar Despite Differing Plasmid Backbones or Gene-Inserts  

PubMed Central

The Vaccine Research Center has developed a number of vaccine candidates for different diseases/infectious agents (HIV-1, Severe Acute Respiratory Syndrome virus, West Nile virus, and Ebola virus, plus a plasmid cytokine adjuvant—IL-2/Ig) based on a DNA plasmid vaccine platform. To support the clinical development of each of these vaccine candidates, preclinical studies were performed to screen for potential toxicities (intrinsic and immunotoxicities). All treatment-related toxicities identified in these repeated-dose toxicology studies have been confined primarily to the sites of injection and seem to be the result of both the delivery method (as they are seen in both control and treated animals) and the intended immune response to the vaccine (as they occur with greater frequency and severity in treated animals). Reactogenicity at the site of injection is generally seen to be reversible as the frequency and severity diminished between doses and between the immediate and recovery termination time points. This observation also correlated with the biodistribution data reported in the companion article (Sheets et al., 2006), in which DNA plasmid vaccine was shown to remain at the site of injection, rather than biodistributing widely, and to clear over time. The results of these safety studies have been submitted to the Food and Drug Administration to support the safety of initiating clinical studies with these and related DNA plasmid vaccines. Thus far, standard repeated-dose toxicology studies have not identified any target organs for toxicity (other than the injection site) for our DNA plasmid vaccines at doses up to 8 mg per immunization, regardless of disease indication (i.e., expressed gene-insert) and despite differences (strengths) in the promoters used to drive this expression. As clinical data accumulate with these products, it will be possible to retrospectively compare the safety profiles of the products in the clinic to the results of the repeated-dose toxicology studies, in order to determine the utility of such toxicology studies for signaling potential immunotoxicities or intrinsic toxicities from DNA vaccines. These data build on the biodistribution studies performed (see companion article, Sheets et al., 2006) to demonstrate the safety and suitability for investigational human use of DNA plasmid vaccine candidates for a variety of infectious disease prevention indications. PMID:16569728

Sheets, Rebecca L.; Stein, Judith; Manetz, T. Scott; Andrews, Charla; Bailer, Robert; Rathmann, John; Gomez, Phillip L.

2008-01-01

390

Analysis of Ebola Glycoprotein Sequences from Strains of Varying Lethality  

E-print Network

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

391

Meeting the Challenge of Developing Drugs for Ebola  

E-print Network

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

Gleeson, Joseph G.

392

Viruses of the family Filoviridae --which consists of the genera Marburgvirus and  

E-print Network

of Ebolavirus and one of Marburgvirus. Among these, Ebola virus (EBOV; formerly known as Zaire ebolavirus treatments for filovirus infections, whether they arise at endemic sites or are caused by accidental

Dever, Jennifer A.

393

10/16/14 1:29 PMThe Virus Next Time? -Civil Beat Page 1 of 4http://www.civilbeat.com/2014/10/the-virus-next-time/#comments  

E-print Network

10/16/14 1:29 PMThe Virus Next Time? - Civil Beat Page 1 of 4http://www.civilbeat.com/2014/10/the-virus-next-time/#comments The Virus Next Time? Take action against new viruses by making Hawaii less hospitable for mosquitoes on the African outbreak of Ebola virus and whether it could spread to the rest of the planet, another fortunately

Duffy, David Cameron

394

Ebola protein analyses for the determination of genetic organization  

Microsoft Academic Search

Summary Amino-acid sequencing of the purified major nucleoprotein (NP), VP 35 and VP 40 from purified Ebola virus proved that they are the protein products of the first three genes, and that the open reading frame (ORF) of the NP begins at nucleotide 470. Because of the many unusual features of the ORFs of Ebola virus, we thought that our

Luanne H. Elliott; A. Sanchez; B. P. Holloway; M. P. Kiley; J. B. McCormick

1993-01-01

395

Virus-Vectored Influenza Virus Vaccines  

PubMed Central

Despite the availability of an inactivated vaccine that has been licensed for >50 years, the influenza virus continues to cause morbidity and mortality worldwide. Constant evolution of circulating influenza virus strains and the emergence of new strains diminishes the effectiveness of annual vaccines that rely on a match with circulating influenza strains. Thus, there is a continued need for new, efficacious vaccines conferring cross-clade protection to avoid the need for biannual reformulation of seasonal influenza vaccines. Recombinant virus-vectored vaccines are an appealing alternative to classical inactivated vaccines because virus vectors enable native expression of influenza antigens, even from virulent influenza viruses, while expressed in the context of the vector that can improve immunogenicity. In addition, a vectored vaccine often enables delivery of the vaccine to sites of inductive immunity such as the respiratory tract enabling protection from influenza virus infection. Moreover, the ability to readily manipulate virus vectors to produce novel influenza vaccines may provide the quickest path toward a universal vaccine protecting against all influenza viruses. This review will discuss experimental virus-vectored vaccines for use in humans, comparing them to licensed vaccines and the hurdles faced for licensure of these next-generation influenza virus vaccines. PMID:25105278

Tripp, Ralph A.; Tompkins, S. Mark

2014-01-01

396

Viruses Infecting Reptiles  

PubMed Central

A large number of viruses have been described in many different reptiles. These viruses include arboviruses that primarily infect mammals or birds as well as viruses that are specific for reptiles. Interest in arboviruses infecting reptiles has mainly focused on the role reptiles may play in the epidemiology of these viruses, especially over winter. Interest in reptile specific viruses has concentrated on both their importance for reptile medicine as well as virus taxonomy and evolution. The impact of many viral infections on reptile health is not known. Koch’s postulates have only been fulfilled for a limited number of reptilian viruses. As diagnostic testing becomes more sensitive, multiple infections with various viruses and other infectious agents are also being detected. In most cases the interactions between these different agents are not known. This review provides an update on viruses described in reptiles, the animal species in which they have been detected, and what is known about their taxonomic positions. PMID:22163336

Marschang, Rachel E.

2011-01-01

397

Epstein-Barr Virus (Mononucleosis)  

MedlinePLUS Videos and Cool Tools

... person becomes infected with a virus, their immune system defends their body against the virus. The immune system stops the ... person becomes infected with a virus, their immune system defends their body against the virus. This is why most people ...

398

MFR PAPER 1338 Viruses and Virus Diseases of  

E-print Network

MFR PAPER 1338 Viruses and Virus Diseases of Salmonid Fishes Phillip E. McAllister is with the Na (IPN) virus, infectious hematopoietic necrosis (IHN) virus, viral hemorrhagic septicemia (YHS) virus, and Herpesvirus salmonis- cause disease among salmonid fishes. In addition, a virus may be the cause

399

Arthropods as a source of new RNA viruses.  

PubMed

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

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

2014-12-01

400

Received 13 Jun 2012 | Accepted 15 Nov 2012 | Published 18 Dec 2012 Virus-like glycodendrinanoparticles displaying  

E-print Network

dendritic cells by Ebola virus. The high associated polyvalency effects (b4106, b/N B102­103) dis- playedARTICLE Received 13 Jun 2012 | Accepted 15 Nov 2012 | Published 18 Dec 2012 Virus some viruses are capable of escaping from the processing and degradation events carried out

Davis, Ben G.

401

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

E-print Network

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

402

Tumorigenic DNA viruses  

SciTech Connect

The eighth volume of Advances in Viral Oncology focuses on the three major DNA virus groups with a postulated or proven tumorigenic potential: papillomaviruses, animal hepatitis viruses, and the Epstein-Bar virus. In the opening chapters, the contributors analyze the evidence that papillomaviruses and animal hepatitis viruses are involved in tumorigenesis and describe the mechanisms that trigger virus-host cell interactions. A detailed section on the Epstein-Barr virus (EBV) - comprising more than half the book - examines the transcription and mRNA processing patterns of the virus genome; the mechanisms by which EBV infects lymphoid and epithelial cells; the immunological aspects of the virus; the actions of EBV in hosts with Acquired Immune Deficiency Syndrome; and the involvement of EBV in the etiology of Burkitt's lymphoma.

Klein, G.

1989-01-01

403

SOLENOPSIS INVICTA VIRUSES  

Technology Transfer Automated Retrieval System (TEKTRAN)

Unique Solenopsis invicta viruses (SINV) have been identified and their genome sequenced. Oligonucleotide primers have been developed using the isolated nucleic acid sequences of the SINV. The viruses are used as a biocontrol agent for control of fire ants....

404

Human Parainfluenza Viruses  

MedlinePLUS

... Search The CDC Cancel Submit Search The CDC Human Parainfluenza Viruses (HPIVs) Note: Javascript is disabled or ... visit this page: About CDC.gov . Share Compartir Human parainfluenza viruses (HPIVs) commonly cause respiratory illnesses in ...

405

Virus Assembly and Maturation  

NASA Astrophysics Data System (ADS)

We use two techniques to look at three-dimensional virus structure: electron cryomicroscopy (cryoEM) and X-ray crystallography. Figure 1 is a gallery of virus particles whose structures Timothy Baker, one of my former colleagues at Purdue University, used cryoEM to determine. It illustrates the variety of sizes of icosahedral virus particles. The largest virus particle on this slide is the Herpes simplex virus, around 1200Å in diameter; the smallest we examined was around 250Å in diameter. Viruses bear their genomic information either as positive-sense DNA and RNA, double-strand DNA, double-strand RNA, or negative-strand RNA. Viruses utilize the various structure and function "tactics" seen throughout cell biology to replicate at high levels. Many of the biological principles that we consider general were in fact discovered in the context of viruses ...

Johnson, John E.

2004-03-01

406

Ebola  

MedlinePLUS

... breathing. It's very important that infected people get treatment right away. People who have Ebola need to be cared for in a special ... purposes only. For specific medical advice, diagnoses, and treatment, consult your ... Science Source Images, Shutterstock, and Clipart.com

407

Interaction of Tsg101 with Marburg Virus VP40 Depends on the PPPY Motif, but Not the PT\\/SAP Motif as in the Case of Ebola Virus, and Tsg101 Plays a Critical Role in the Budding of Marburg Virus-Like Particles Induced by VP40, NP, and GP  

Microsoft Academic Search

Marburg virus (MARV) VP40 is a matrix protein that can be released from mammalian cells in the form of virus-like particles (VLPs) and contains the PPPY sequence, which is an L-domain motif. Here, we demonstrate that the PPPY motif is important for VP40-induced VLP budding and that VLP production is significantly enhanced by coexpression of NP and GP. We show

S. Urata; T. Noda; Yoshihiro Kawaoka; Shigeru Morikawa; Hideyoshi Yokosawa; Jiro Yasuda

2007-01-01

408

Computer Virus Protection  

ERIC Educational Resources Information Center

A computer virus is a program--a piece of executable code--that has the unique ability to replicate. Like biological viruses, computer viruses can spread quickly and are often difficult to eradicate. They can attach themselves to just about any type of file, and are spread by replicating and being sent from one individual to another. Simply having…

Rajala, Judith B.

2004-01-01

409

Ecology of prokaryotic viruses  

Microsoft Academic Search

The finding that total viral abundance is higher than total prokaryotic abundance and that a significant fraction of the prokaryotic community is infected with phages in aquatic systems has stimulated research on the ecology of prokaryotic viruses and their role in ecosystems. This review treats the ecology of prokaryotic viruses (`phages') in marine, freshwater and soil systems from a `virus

Markus G Weinbauer

2004-01-01

410

MAIZE FINE STREAK VIRUS  

Technology Transfer Automated Retrieval System (TEKTRAN)

The report outlines the salient features of maize fine streak virus (MFSV) including a general description of the causal virus species, virion properties, genome description, the relationship of the virus to other taxa, biological properties of the disease and agronomic aspects of the disease. Maize...

411

Tobacco mosaic virus  

NSDL National Science Digital Library

This resource demonstrates how the Tobacco mosaic virus (TMV) provides an excellent model for teaching students about properties of a plant virus and the relationship between a virus and its host plant. Four activities geared toward grades 9-12 are described. Teaching tips, troubleshooting help and sources of materials information is also included.

Rosemary Ford (Washington College; )

2003-05-28

412

VIRUSES IN WASTEWATER  

EPA Science Inventory

Viruses of animals, plants, and bacteria abound in sewage and receiving waters. Their ecological impact has, for the most part, gone unheeded except as it relates to viruses from human sources. Viruses present at levels infective to man have been recovered from waters used for re...

413

Hunt announces more robust checks for Ebola.  

PubMed

Healthcare workers who have cared for Ebola patients in west Africa may now be referred to an infectious diseases specialist if they feel ill when returning to the UK, as part of strengthened screening for the virus. PMID:25585723

2015-01-14

414

Identification of a broad-spectrum inhibitor of virus RNA synthesis: validation of a prototype virus-based approach  

PubMed Central

There are no approved therapeutics for the most deadly nonsegmented negative-strand (NNS) RNA viruses, including Ebola (EBOV). To identify new chemical scaffolds for development of broad-spectrum antivirals, we undertook a prototype-based lead identification screen. Using the prototype NNS virus, vesicular stomatitis virus (VSV), multiple inhibitory compounds were identified. Three compounds were investigated for broad-spectrum activity, and inhibited EBOV infection. The most potent, CMLDBU3402, was selected for further study. CMLDBU3402 did not show significant activity against segmented negative-strand RNA viruses suggesting proscribed broad-spectrum activity. Mechanistic analysis indicated that CMLDBU3402 blocked VSV viral RNA synthesis and inhibited EBOV RNA transcription, demonstrating a consistent mechanism of action against genetically distinct viruses. The identification of this chemical backbone as a broad-spectrum inhibitor of viral RNA synthesis offers significant potential for the development of new therapies for highly pathogenic viruses. PMID:23521799

Filone, Claire Marie; Hodges, Erin N.; Honeyman, Brian; Bushkin, G. Guy; Boyd, Karla; Platt, Andrew; Ni, Feng; Strom, Kyle; Hensley, Lisa; Snyder, John K.; Connor, John H.

2013-01-01

415

METHODOLOGY Open Access Virus replicon particle based Chikungunya virus  

E-print Network

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

Boyer, Edmond

416

Review article PRRSV, the virus  

E-print Network

Review article PRRSV, the virus Janneke J.M. MEULENBERG Department of Virology, Institute Abstract ­ Porcine reproductive and respiratory syndrome virus (PRRSV) is a positive-strand RNA virusDNA clone Résumé ­ Syndrome dysgénésique et respiratoire porcin, le virus. Le virus du syndrome dys

Paris-Sud XI, Université de

417

RNA Viruses Infecting Pest Insects  

Technology Transfer Automated Retrieval System (TEKTRAN)

RNA viruses are viruses whose genetic material is ribonucleic acid (RNA). RNA viruses may be double or single-stranded based on the type of RNA they contain. Single-stranded RNA viruses can be further grouped into negative sense or positive-sense viruses according to the polarity of their RNA. Fur...

418

[The great virus comeback].  

PubMed

Viruses have been considered for a long time as by-products of biological evolution. This view is changing now as a result of several recent discoveries. Viral ecologists have shown that viral particles are the most abundant biological entities on our planet, whereas metagenomic analyses have revealed an unexpected abundance and diversity of viral genes in the biosphere. Comparative genomics have highlighted the uniqueness of viral sequences, in contradiction with the traditional view of viruses as pickpockets of cellular genes. On the contrary, cellular genomes, especially eukaryotic ones, turned out to be full of genes derived from viruses or related elements (plasmids, transposons, retroelements and so on). The discovery of unusual viruses infecting archaea has shown that the viral world is much more diverse than previously thought, ruining the traditional dichotomy between bacteriophages and viruses. Finally, the discovery of giant viruses has blurred the traditional image of viruses as small entities. Furthermore, essential clues on virus history have been obtained in the last ten years. In particular, structural analyses of capsid proteins have uncovered deeply rooted homologies between viruses infecting different cellular domains, suggesting that viruses originated before the last universal common ancestor (LUCA). These studies have shown that several lineages of viruses originated independently, i.e., viruses are polyphyletic. From the time of LUCA, viruses have coevolved with their hosts, and viral lineages can be viewed as lianas wrapping around the trunk, branches and leaves of the tree of life. Although viruses are very diverse, with genomes encoding from one to more than one thousand proteins, they can all be simply defined as organisms producing virions. Virions themselves can be defined as infectious particles made of at least one protein associated with the viral nucleic acid, endowed with the capability to protect the viral genome and ensure its delivery to the infected cell. These definitions, which clearly distinguish viruses from plasmids, suggest that infectious RNA molecules that only encode an RNA replicase presently classified among viruses by the ICTV (International Committee for the Taxonomy of Viruses) into families of Endornaviridae and Hypoviridae are in fact RNA plasmids. Since a viral genome should encode for at least one structural protein, these definitions also imply that viruses originated after the emergence of the ribosome in an RNA-protein cellular world. Although virions are the hallmarks of viruses, viruses and virions should not be confused. The infection transforms the ribocell (cell encoding ribosomes and dividing by binary fission) into a virocell (cell producing virions) or ribovirocell (cell that produces virions but can still divide by binary fission). In the ribovirocell, two different organisms, defined by their distinct evolutionary histories, coexist in symbiosis in the same cell. The virocells or ribovirocells are the living forms of the virus, which can be in fine considered to be a living organism. In the virocell, the metabolism is reorganized for the production of virions, while the ability to capture and store free energy is retained, as in other cellular organisms. In the virocell, viral genomes replicate, recombine and evolve, leading to the emergence of new viral proteins and potentially novel functions. Some of these new functions can be later on transferred to the cell, explaining how viruses can play a major (often underestimated) role in the evolution of cellular organisms. The virocell concept thus helps to understand recent hypotheses suggesting that viruses played a critical role in major evolutionary transitions, such as the origin of DNA genomes or else the origin of the eukaryotic nucleus. Finally, it is more and more recognized that viruses are the major source of variation and selection in living organisms (both viruses and cells), the two pillars of darwinism. One can thus conclude that the continuous interaction between viruses and cells, all along

Forterre, Patrick

2013-01-01

419

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

E-print Network

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

Portman, Douglas

420

Lifestyles of plant viruses.  

PubMed

The vast majority of well-characterized eukaryotic viruses are those that cause acute or chronic infections in humans and domestic plants and animals. However, asymptomatic persistent viruses have been described in animals, and are thought to be sources for emerging acute viruses. Although not previously described in these terms, there are also many viruses of plants that maintain a persistent lifestyle. They have been largely ignored because they do not generally cause disease. The persistent viruses in plants belong to the family Partitiviridae or the genus Endornavirus. These groups also have members that infect fungi. Phylogenetic analysis of the partitivirus RNA-dependent RNA polymerase genes suggests that these viruses have been transmitted between plants and fungi. Additional families of viruses traditionally thought to be fungal viruses are also found frequently in plants, and may represent a similar scenario of persistent lifestyles, and some acute or chronic viruses of crop plants may maintain a persistent lifestyle in wild plants. Persistent, chronic and acute lifestyles of plant viruses are contrasted from both a functional and evolutionary perspective, and the potential role of these lifestyles in host evolution is discussed. PMID:20478885

Roossinck, Marilyn J

2010-06-27

421

Lifestyles of plant viruses  

PubMed Central

The vast majority of well-characterized eukaryotic viruses are those that cause acute or chronic infections in humans and domestic plants and animals. However, asymptomatic persistent viruses have been described in animals, and are thought to be sources for emerging acute viruses. Although not previously described in these terms, there are also many viruses of plants that maintain a persistent lifestyle. They have been largely ignored because they do not generally cause disease. The persistent viruses in plants belong to the family Partitiviridae or the genus Endornavirus. These groups also have members that infect fungi. Phylogenetic analysis of the partitivirus RNA-dependent RNA polymerase genes suggests that these viruses have been transmitted between plants and fungi. Additional families of viruses traditionally thought to be fungal viruses are also found frequently in plants, and may represent a similar scenario of persistent lifestyles, and some acute or chronic viruses of crop plants may maintain a persistent lifestyle in wild plants. Persistent, chronic and acute lifestyles of plant viruses are contrasted from both a functional and evolutionary perspective, and the potential role of these lifestyles in host evolution is discussed. PMID:20478885

Roossinck, Marilyn J.

2010-01-01

422

Viruses of botrytis.  

PubMed

Botrytis cinerea (gray mold) is one of the most widespread and destructive fungal diseases of horticultural crops. Propagation and dispersal is usually by asexual conidia but the sexual stage (Botryotinia fuckeliana (de Bary) Whetzel) also occurs in nature. DsRNAs, indicative of virus infection, are common in B. cinerea, but only four viruses (Botrytis virus F (BVF), Botrytis virus X (BVX), Botrytis cinerea mitovirus 1 (BcMV1), and Botrytis porri RNA virus) have been sequenced. BVF and BVX are unusual mycoviruses being ssRNA flexous rods and have been designated the type species of the genera Mycoflexivirus and Botrexvirus (family Betaflexivirdae), respectively. The reported effects of viruses on Botrytis range from negligible to severe, with Botrytis cinerea mitovirus 1 causing hypovirulence. Little is currently known about the effects of viruses on Botrytis metabolism but recent complete sequencing of the B. cinerea genome now provides an opportunity to investigate the host-pathogen interactions at the molecular level. There is interest in the possible use of mycoviruses as biological controls for Botrytis because of the common problem of fungicide resistance. Unfortunately, hyphal anastomosis is the only known mechanism of horizontal virus transmission and the large number of vegetative incompatibility groups in Botrytis is a potential constraint on the spread of an introduced virus. Although some Botrytis viruses, such as BVF and BVX, are known to have international distribution, there is a distinct lack of epidemiological data and the means of spread are unknown. PMID:23498909

Pearson, Michael N; Bailey, Andrew M

2013-01-01

423

Manufacture of measles viruses.  

PubMed

Measles viruses have shown potent oncolytic activity as a therapeutic against a variety of human cancers in animal models and are currently being tested in clinical trials in patients. In contrast to using measles virus as a vaccine, oncolytic activity depends on high concentrations of infectious virus. For use in humans, the high-titer measles virus preparations must also be purified to remove significant levels of cellular proteins and nucleic acid resulting from the cytolytic products of measles virus replication and release. Pleomorphic measles virus must be treated as >1-?m particles that are extremely shear sensitive to maximize recoveries and retain infectivity. Therefore, to maximize the recovery of sterile, high titer infectious measles viruses, the entire production and purification process must be done using gentle conditions and aseptic processing. Here we describe a procedure applicable to the production of small (a few liters) to large (50-60 L) batches of measles virus amplified in Vero cells adapted to serum-free growth. Cell culture supernatant containing the measles virus is clarified by filtration to remove intact Vero cells and other debris, and then treated with Benzonase(®) in the presence of magnesium chloride to digest contaminating nucleic acid. The measles virus in the treated cell culture supernatant is then concentrated and purified using tangential flow filtration (TFF) and diafiltration. The concentrated and diafiltered measles virus is passed through a final clarifying filter prior to final vialing and storage at <-65°C. An infectivity assay to quantify infectious measles virus concentration based on the TCID(50) method is also described. This procedure can be readily adapted to the production and purification of measles viruses using good manufacturing practices (GMP). PMID:21590404

Langfield, Kirsten K; Walker, Henry J; Gregory, Linda C; Federspiel, Mark J

2011-01-01

424

#ISurvivedEbola app.  

PubMed

People who have recovered from Ebola virus disease in the three west African countries worst hit by the outbreak are sharing stories through a mobile app launched earlier this month, in a Unicef-backed campaign to inform and fight stigma. PMID:25585757

Evans, Roger

2015-01-14

425

Water system virus detection  

NASA Technical Reports Server (NTRS)

The performance of a waste water reclamation system is monitored by introducing a non-pathogenic marker virus, bacteriophage F2, into the waste-water prior to treatment and, thereafter, testing the reclaimed water for the presence of the marker virus. A test sample is first concentrated by absorbing any marker virus onto a cellulose acetate filter in the presence of a trivalent cation at low pH and then flushing the filter with a limited quantity of a glycine buffer solution to desorb any marker virus present on the filter. Photo-optical detection of indirect passive immune agglutination by polystyrene beads indicates the performance of the water reclamation system in removing the marker virus. A closed system provides for concentrating any marker virus, initiating and monitoring the passive immune agglutination reaction, and then flushing the system to prepare for another sample.

Fraser, A. S.; Wells, A. F.; Tenoso, H. J. (inventors)

1978-01-01

426

Viruses in Antarctic lakes  

NASA Technical Reports Server (NTRS)

Water samples collected from four perennially ice-covered Antarctic lakes during the austral summer of 1996-1997 contained high densities of extracellular viruses. Many of these viruses were found to be morphologically similar to double-stranded DNA viruses that are known to infect algae and protozoa. These constitute the first observations of viruses in perennially ice-covered polar lakes. The abundance of planktonic viruses and data suggesting substantial production potential (relative to bacteria] secondary and photosynthetic primary production) indicate that viral lysis may be a major factor in the regulation of microbial populations in these extreme environments. Furthermore, we suggest that Antarctic lakes may be a reservoir of previously undescribed viruses that possess novel biological and biochemical characteristics.

Kepner, R. L. Jr; Wharton, R. A. Jr; Suttle, C. A.; Wharton RA, J. r. (Principal Investigator)

1998-01-01

427

DNA Virus Replication Compartments  

PubMed Central

Viruses employ a variety of strategies to usurp and control cellular activities through the orchestrated recruitment of macromolecules to specific cytoplasmic or nuclear compartments. Formation of such specialized virus-induced cellular microenvironments, which have been termed viroplasms, virus factories, or virus replication centers, complexes, or compartments, depends on molecular interactions between viral and cellular factors that participate in viral genome expression and replication and are in some cases associated with sites of virion assembly. These virus-induced compartments function not only to recruit and concentrate factors required for essential steps of the viral replication cycle but also to control the cellular mechanisms of antiviral defense. In this review, we summarize characteristic features of viral replication compartments from different virus families and discuss similarities in the viral and cellular activities that are associated with their assembly and the functions they facilitate for viral replication. PMID:24257611

Schmid, Melanie; Speiseder, Thomas; Dobner, Thomas

2014-01-01

428

Biological Nanomachines: Viruses  

NSDL National Science Digital Library

Although nanotechnology is a new and emerging field, nanoscale structures are not new. Small molecules such as water, large molecules such as proteins, and larger, more complex objects such as viruses and nanotubes are naturally occurring and exist all around us. Viruses are particularly interesting nanoscale objects because of their precise geometrical shape, their self-assembling capability, and their fascinating ability to invade cells and alter their function. Nanoscale science researchers are studying virus properties with the aim of developing new treatments for human disease. The virus is also being studied as a model for how to make materials and engineer products at the nanoscsale through a process called "self-assembly." In this investigation, students create an icosahedral virus model and consider how virus structure and behavior could be mimicked in nanotechnology applications. This free selection includes the Table of Contents, Acknowledgments, a Dedication page, and an Introduction.

Taylor, Amy R.; Broadwell, Bethany P.; Jones, M. G.; Falvo, Michael R.

2007-01-01

429

The human oncogenic viruses  

SciTech Connect

This book contains eight selections. The titles are: Cytogenetics of the Leukemias and Lymphomas; Cytogenetics of Solid Tumors: Renal Cell Carcinoma, Malignant Melanoma, Retinoblastoma, and Wilms' Tumor; Elucidation of a Normal Function for a Human Proto-Oncogene; Detection of HSV-2 Genes and Gene Products in Cervical Neoplasia; Papillomaviruses in Anogennital Neoplasms; Human Epstein-Barr Virus and Cancer; Hepatitis B Virus and Hepatocellular Carcinoma; and Kaposi's Sarcoma: Acquired Immunodeficiency Syndrome (AIDS) and Associated Viruses.

Luderer, A.A.; Weetall, H.H

1986-01-01

430

Water system virus detection  

NASA Technical Reports Server (NTRS)

A monitoring system developed to test the capability of a water recovery system to reject the passage of viruses into the recovered water is described. A nonpathogenic marker virus, bacteriophage F2, is fed into the process stream before the recovery unit and the reclaimed water is assayed for its presence. Detection of the marker virus consists of two major components, concentration and isolation of the marker virus, and detection of the marker virus. The concentration system involves adsorption of virus to cellulose acetate filters in the presence of trivalent cations and low pH with subsequent desorption of the virus using volumes of high pH buffer. The detection of the virus is performed by a passive immune agglutination test utilizing specially prepared polystyrene particles. An engineering preliminary design was performed as a parallel effort to the laboratory development of the marker virus test system. Engineering schematics and drawings of a fully functional laboratory prototype capable of zero-G operation are presented. The instrument consists of reagent pump/metering system, reagent storage containers, a filter concentrator, an incubation/detector system, and an electronic readout and control system.

Fraser, A. S.; Wells, A. F.; Tenoso, H. J.

1975-01-01

431

Bichat guidelines for the clinical management of haemorrhagic fever viruses and bioterrorism-related haemorrhagic fever viruses.  

PubMed

Haemorrhagic fever viruses (HFVs) are a diverse group of viruses that cause a clinical disease associated with fever and bleeding disorder. HFVs that are associated with a potential biological threat are Ebola and Marburg viruses (Filoviridae), Lassa fever and New World arenaviruses (Machupo, Junin, Guanarito and Sabia viruses) (Arenaviridae), Rift Valley fever (Bunyaviridae) and yellow fever, Omsk haemorrhagic fever, and Kyanasur Forest disease (Flaviviridae). In terms of biological warfare concerning dengue, Crimean-Congo haemorrhagic fever and Hantaviruses, there is not sufficient knowledge to include them as a major biological threat. Dengue virus is the only one of these that cannot be transmitted via aerosol. Crimean-Congo haemorrhagic fever and the agents of haemorrhagic fever with renal syndrome appear difficult to weaponise. Ribavirin is recommended for the treatment and the prophylaxis of the arenaviruses and the bunyaviruses, but is not effective for the other families. All patients must be isolated and receive intensive supportive therapy. PMID:15677844

Bossi, Philippe; Tegnell, Anders; Baka, Agoritsa; Van Loock, Frank; Hendriks, Jan; Werner, Albrecht; Maidhof, Heinrich; Gouvras, Georgios

2004-12-01

432

Ebola Hemorrhagic Fever and the Current State of Vaccine Development  

PubMed Central

Current Ebola virus outbreak in West Africa already reached the total number of 1,323 including 729 deaths by July 31st. the fatality is around 55% in the southeastern area of Guinea, Sierra Leone, Liberia, and Nigeria. The number of patients with Ebola Hemorrhagic Fever (EHF) was continuously increasing even though the any effective therapeutics or vaccines has not been developed yet. The Ebola virus in Guinea showed 98% homology with Zaire Ebola Virus. Study of the pathogenesis of Ebola virus infection and assess of the various candidates of vaccine have been tried for a long time, especially in United States and some European countries. Even though the attenuated live vaccine and DNA vaccine containing Ebola viral genes were tested and showed efficacy in chimpanzees, those candidates still need clinical tests requiring much longer time than the preclinical development to be approved for the practical treatment. It can be expected to eradicate Ebola virus by a safe and efficient vaccine development similar to the case of smallpox virus which was extinguished from the world by the variola vaccine. PMID:25562048

Hong, Joo Eun; Hong, Kee-Jong; Choi, Woo Young; Lee, Won-Ja; Choi, Yeon Hwa; Jeong, Chung-Hyeon; Cho, Kwang-il

2014-01-01

433

Papaya ringspot virus (Potyviridae)  

Technology Transfer Automated Retrieval System (TEKTRAN)

Papaya ringspot virus, a member of the family Potyviridae, is single stranded RNA plant virus with a monocistronic genome of about 10,326 nucleotides that is expressed via a large polyprotein subsequently cleaved into functional proteins. It causes severe damage on cucurbit crops such as squash and...

434

Human Papilloma Virus Infections  

PubMed Central

Genital warts are believed to be caused by human papilloma viruses and to be sexually transmitted. The viruses are classified by DNA types, which appear to cause different types of disease. The choice of treatment, and usually its success rate, vary according to the type of disease and its location. PMID:21248973

Wright, V. Cecil

1989-01-01

435

Lettuce Necrotic Yellows Virus  

Microsoft Academic Search

A DESTRUCTIVE virus disease of lettuce, causing extensive crop losses sometimes as high as 100 per cent, was recognized in Victoria in 1954 as being distinct from the lettuce mosaic disease. Until 1959, however, all attempts to transmit the virus to lettuce with aphids which commonly infest lettuce, with thrips, leaf-hoppers and sap inoculation methods were unsuccessful. In that year

L. L. Stubbs; R. G. GROGAN

1963-01-01

436

Densonucleosis Virus Structural Proteins  

PubMed Central

The protein coats of two densonucleosis viruses (types 1 and 2) were examined by a variety of biophysical, biochemical, and serological techniques. The viruses were 24 nm in diameter, contained at least four polypeptides, were remarkably stable to extremes of pH and denaturing agents, and were serologically closely related. The two viruses could, however, be distinguished serologically and by differences in migration of their structural polypeptides. For each virus the “top component” (i.e., the protein coat minus DNA, found occurring naturally in infections) appeared to have a composition identical to that of the coat of the virus and was a more stable structure. Electrometric titration curves of the virus particles and top components demonstrated that the DNA phosphate in densonucleosis virus particles was neutralized by cations other than basic amino acid side chains of the protein coat. Circular dichroism studies showed that there was a conformational difference between the protein coats of top components and virus particles. Images PMID:16789202

Kelly, D. C.; Moore, N. F.; Spilling, C. R.; Barwise, A. H.; Walker, I. O.

1980-01-01

437

Positive reinforcement for viruses  

PubMed Central

Summary Virus-cell membrane fusion requires a critical transition from positive to negative membrane curvature. St. Vincent et al., in PNAS (St Vincent, et al., 2010), designed a class of antivirals that targets this transition. These Rigid Amphipathic Fusion Inhibitors are active against an array of enveloped viruses. PMID:21035726

Vigant, Frederic; Jung, Michael; Lee, Benhur

2010-01-01

438

Recombination in AIDS viruses  

Microsoft Academic Search

Recombination contributes to the generation of genetic diversity in human immunodeficiency viruses (HIV) but can only occur between viruses replicating within the same cell. Since individuals have not been found to be simultaneously coinfected with multiple divergent strains of HIV-1 or HIV-2, recombination events have been thought to be restricted to the rather closely related members of the quasispecies that

David L. Robertson; Beatrice H. Hahn; Paul M. Sharp

1995-01-01

439

What is a Virus?  

NSDL National Science Digital Library

This page is part of a web site that was created as a tutorial for an introductory virology class for college level microbiology students. It includes links to definitions of virus, virions, other virus-like-agents, and organisms, as well as the "definition of life".

Rybicki, Ed

2010-03-23

440

Cutthroat Trout Virus  

USGS Multimedia Gallery

Electron micrograph of the cutthroat trout virus (CTV) showing the small, round virions of approximately 30 nanometers in diameter containing a single-stranded RNA genome. CTV, whose genome was first characterized by USGS researchers, is being used in research into the human virus Hepatitis E....

441

Virus separation using membranes.  

PubMed

Industrial manufacturing of cell culture-derived viruses or virus-like particles for gene therapy or vaccine production are complex multistep processes. In addition to the bioreactor, such processes require a multitude of downstream unit operations for product separation, concentration, or purification. Similarly, before a biopharmaceutical product can enter the market, removal or inactivation of potential viral contamination has to be demonstrated. Given the complexity of biological solutions and the high standards on composition and purity of biopharmaceuticals, downstream processing is the bottleneck in many biotechnological production trains. Membrane-based filtration can be an economically attractive and efficient technology for virus separation. Viral clearance, for instance, of up to seven orders of magnitude has been reported for state of the art polymeric membranes under best conditions.This chapter summarizes the fundamentals of virus ultrafiltration, diafiltration, or purification with adsorptive membranes. In lieu of an impractical universally applicable protocol for virus filtration, application of these principles is demonstrated with two examples. The chapter provides detailed methods for production, concentration, purification, and removal of a rod-shaped baculovirus (Autographa californica M nucleopolyhedrovirus, about 40 × 300 nm in size, a potential vector for gene therapy, and an industrially important protein expression system) or a spherical parvovirus (minute virus of mice, 22-26 nm in size, a model virus for virus clearance validation studies). PMID:24297430

Grein, Tanja A; Michalsky, Ronald; Czermak, Peter

2014-01-01

442

Grapevine Leafroll Associated Viruses  

Technology Transfer Automated Retrieval System (TEKTRAN)

This book chapter reviews recent advances in molecular characterization of grapevine leafroll associated viruses (GLRaV), and the development and application of molecular techniques for a timely and sensitive detection of nine viruses that are associated with the leafroll disease on grapevine. To d...

443

The hepatitis B virus  

Microsoft Academic Search

DNA recombinant technology has radically changed hepatitis B virus (HBV) virology. The genetic organization, transcription and replication of the virus are basically understood, structures of integrated HBV sequences in hepatocellular carcinoma have been characterized, and new vaccines produced by recombinant DNA technique are being developed.

Pierre Tiollais; Christine Pourcel; Anne Dejean

1985-01-01

444

PATHOLOGIE VGTALE Interactions entre virus ou entre virus et leurs  

E-print Network

PATHOLOGIE V�G�TALE SYNTH�SE Interactions entre virus ou entre virus et leurs satellites chez un 84140 Montfavet R�SUM� Deux ou plusieurs virus, apparentés ou non, peuvent se multiplier ensemble dans une même plante et également dans une même cellule. Les interactions entre virus qui en résultent

Paris-Sud XI, Université de

445

Whitepox virus isolated from hamsters inoculated with monkeypox virus  

Microsoft Academic Search

SINCE the eradication of smallpox in Equatorial Africa several `new' pox viruses have been isolated in our laboratory from materials collected by WHO field workers-monkeypox virus from an affected individual and the `whitepox' viruses from apparently healthy monkeys and rodents. Monkeypox virus is not widespread but occasionally infects man and has caused death: 33 such cases have occurred in Africa,

S. S. Marennikova; E. M. Shelukhina

1978-01-01

446

Nipah virus encephalitis.  

PubMed

Nipah virus was first discovered in 1999, after a severe outbreak of viral encephalitis among pig farm workers in Malaysia. The disease is thought to spread from Pteropus bats to pigs and then to humans following close contact. The reported mortality rate in this outbreak was 40%. The main necropsy finding in patients with Nipah virus encephalitis was disseminated microinfarction associated with vasculitis and direct neuronal involvement. Relapse of encephalitis was seen in 10% of those who survived the initial illness. Since that initial report, recurrent outbreaks of Nipah virus encephalitis have been seen in Bangladesh and West Bengal, India. These outbreaks occurred between January and May, with Pteropus giganteus as a reservoir of the virus. In Bangladesh, the virus probably spread directly from bats to humans-with human to human spread as another important mode of infection-and the mortality rate was 70%. PMID:18765105

Tan, Chong-Tin; Chua, Kaw-Bing

2008-07-01

447

Tobacco Mosaic Virus  

NSDL National Science Digital Library

In this four-part laboratory exercise, learners investigate properties of Tobacco mosaic virus (TMV) including (1) symptoms induced by the virus in susceptible plants at the macroscopic and microscopic levels, (2) its stability at high temperatures, and (3) its small size. Learners first propagate tomato and pinto bean plants, and then inoculate their dried leaves with TMV. Learners observe the TMV-infected leaves as well as use a heat treatment to inactivate the virus. Learners also filter the infected sap with a bacteria-proof filter to investigate size. This lesson guide includes background information, tips for educators, and discussion questions with answers. Adult supervision is recommended. Note: The Tobacco mosaic virus is available from biological suppliers, but approval for shipping of the virus across state lines must be obtained from the USDA prior to shipment.

Rosemary Ford

2011-01-01

448

Influenza A virus reassortment.  

PubMed

Reassortment is the process by which influenza viruses swap gene segments. This genetic exchange is possible due to the segmented nature of the viral genome and occurs when two differing influenza viruses co-infect a cell. The viral diversity generated through reassortment is vast and plays an important role in the evolution of influenza viruses. Herein we review recent insights into the contribution of reassortment to the natural history and epidemiology of influenza A viruses, gained through population scale phylogenic analyses. We describe methods currently used to study reassortment in the laboratory, and we summarize recent progress made using these experimental approaches to further our understanding of influenza virus reassortment and the contexts in which it occurs. PMID:25007845

Steel, John; Lowen, Anice C

2014-01-01

449

Semliki Forest virus and Sindbis virus vectors.  

PubMed

Semliki Forest virus (SFV) and Sindbis virus (SIN) are two, positive-strand RNA viruses of the alphavirus genus. Vectors for both have been developed to express high levels of foreign genes in vitro and in vivo. Basic Protocol 1 describes the preparation of packaged SFV and SIN replicons by co-electroporation of helper and vector RNA into baby hamster kidney (BHK)-21 cells. Basic Protocol 2 describes the activation of packaged SFV replicons with a-chymotrypsin. Basic Protocol 3 provides a method for the infection of hippocampal slices. Basic Protocol 4 is a technique for the infection of primary cultures of dispersed neurons with infectious SFV and SIN replicons. The Alternate Protocol describes a method for the cotransfection of in vitro-transcribed vector and helper RNA into BHK-21 cells. Support Protocol 1 describes determining the titers of infectious SFV and SIN replicon stocks, and Support Protocol 2 for metabolic labeling of infected cells. PMID:18428324

Ehrengruber, Markus U; Lundstrom, Kenneth

2002-08-01

450

A broad-spectrum antiviral targeting entry of enveloped viruses  

PubMed Central

We describe an antiviral small molecule, LJ001, effective against numerous enveloped viruses including Influenza A, filoviruses, poxviruses, arenaviruses, bunyaviruses, paramyxoviruses, flaviviruses, and HIV-1. In sharp contrast, the compound had no effect on the infection of nonenveloped viruses. In vitro and in vivo assays showed no overt toxicity. LJ001 specifically intercalated into viral membranes, irreversibly inactivated virions while leaving functionally intact envelope proteins, and inhibited viral entry at a step after virus binding but before virus–cell fusion. LJ001 pretreatment also prevented virus-induced mortality from Ebola and Rift Valley fever viruses. Structure–activity relationship analyses of LJ001, a rhodanine derivative, implicated both the polar and nonpolar ends of LJ001 in its antiviral activity. LJ001 specifically inhibited virus–cell but not cell–cell fusion, and further studies with lipid biosynthesis inhibitors indicated that LJ001 exploits the therapeutic window that exists between static viral membranes and biogenic cellular membranes with reparative capacity. In sum, our data reveal a class of broad-spectrum antivirals effective against enveloped viruses that target the viral lipid membrane and compromises its ability to mediate virus–cell fusion. PMID:20133606

Wolf, Mike C.; Freiberg, Alexander N.; Zhang, Tinghu; Akyol-Ataman, Zeynep; Grock, Andrew; Hong, Patrick W.; Watson, Natalya F.; Fang, Angela Q.; Aguilar, Hector C.; Porotto, Matteo; Honko, Anna N.; Damoiseaux, Robert; Miller, John P.; Woodson, Sara E.; Chantasirivisal, Steven; Fontanes, Vanessa; Negrete, Oscar A.; Krogstad, Paul; Dasgupta, Asim; Moscona, Anne; Hensley, Lisa E.; Whelan, Sean P.; Faull, Kym F.; Holbrook, Michael R.; Jung, Michael E.; Lee, Benhur

2010-01-01

451

Pacui Virus, Rio Preto da Eva Virus, and Tapirape Virus, Three Distinct Viruses within the Family Bunyaviridae  

PubMed Central

Nearly complete genome sequences for three ungrouped viruses, Pacui virus (BEAN27326), Rio Preto da Eva virus (BEAR540870), and Tapirape virus (BEAN767592) isolated in the Amazon region are reported here. All three genomic segments (small, medium and large RNA) were recovered and were similar to members of the genus Orthobunyavirus. PMID:25395627

Medeiros, Daniele Barbosa de Almeida; Rodrigues, Sueli Guerreiro; Martins, Livia Caricio; de Lima, Clayton Pereira Silva; de Oliveira, Layanna Freitas; de Vasconcelos, Janaina Mota; Da Silva, Daisy Elaine; Cardoso, Jedson Ferreira; da Silva, Sandro Patroca; Vianez-Júnior, João Lídio da Silva Gonçalves; Vasconcelos, Pedro Fernando da Costa

2014-01-01

452