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1

Evolutionary history of Ebola virus.  

PubMed

SUMMARY Since Ebola virus was discovered in 1970s, the virus has persisted in Africa and sporadic fatal outbreaks in humans and non-human primates have been reported. However, the evolutionary history of Ebola virus remains unclear. In this study, 27 Ebola virus strains with complete glycoprotein genes, including five species (Zaire, Sudan, Reston, Tai Forest, Bundibugyo), were analysed. Here, we propose a hypothesis of the evolutionary history of Ebola virus which will be helpful to investigate the molecular evolution of these viruses. PMID:24040779

Li, Y H; Chen, S P

2014-06-01

2

Towards a Vaccine Against Ebola Virus.  

National Technical Information Service (NTIS)

Ebola virus infection causes hemorrhagic fever with high mortality rates in humans and nonhuman primates. Currently, there are no vaccines or therapies approved for human use. Outbreaks of Ebola virus have been infrequent, largely confined to remote locat...

T. W. Geisbert P. B. Jahrling

2003-01-01

3

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

4

Ebola virus-like particles protect from lethal Ebola virus infection  

Microsoft Academic Search

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

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

2003-01-01

5

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

6

Successful topical respiratory tract immunization of primates against Ebola virus.  

PubMed

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 highly beneficial. We evaluated a common pediatric respiratory pathogen, human parainfluenza virus type 3 (HPIV3), as a vaccine vector against Ebola virus. HPIV3 recombinants expressing the Ebola virus (Zaire species) surface glycoprotein (GP) alone or in combination with the nucleocapsid protein NP or with the cytokine adjuvant granulocyte-macrophage colony-stimulating factor were administered by the respiratory route to rhesus monkeys--in which HPIV3 infection is mild and asymptomatic--and were evaluated for immunogenicity and protective efficacy against a highly lethal intraperitoneal challenge with Ebola virus. A single immunization with any construct expressing GP was moderately immunogenic against Ebola virus and protected 88% of the animals against severe hemorrhagic fever and death caused by Ebola virus. Two doses were highly immunogenic, and all of the animals survived challenge and were free of signs of disease and of detectable Ebola virus challenge virus. These data illustrate the feasibility of immunization via the respiratory tract against the hemorrhagic fever caused by Ebola virus. To our knowledge, this is the first study in which topical immunization through respiratory tract achieved prevention of a viral hemorrhagic fever infection in a primate model. PMID:17428868

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

2007-06-01

7

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

8

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

9

Ebola virus antibody prevalence in dogs and human risk.  

PubMed

During the 2001-2002 outbreak in Gabon, we 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. PMID:15757552

Allela, Loïs; Boury, Olivier; Pouillot, Régis; Délicat, André; Yaba, Philippe; Kumulungui, Brice; Rouquet, Pierre; Gonzalez, Jean-Paul; Leroy, Eric M

2005-03-01

10

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

11

Drug Targets in Infections With Ebola and Marburg Viruses.  

National Technical Information Service (NTIS)

The development of antiviral drugs for Ebola and Marburg viruses has been slow. To date, beyond supportive care, no effective treatments, prophylactic measures, therapies or vaccines are approved to treat or prevent filovirus infections. In this review, w...

B. E. Julia G. W. Thomas M. R. Vanessa O. G. Gene W. Victoria

2009-01-01

12

Ebola virus vaccines: an overview of current approaches.  

PubMed

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

Marzi, Andrea; Feldmann, Heinz

2014-04-01

13

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

14

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

National Technical Information Service (NTIS)

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...

K. L. Warfield J. G. Perkins D. L. Swenson E. M. Deal C. M. Bosio

2004-01-01

15

Comprehensive Analysis of Ebola Virus GP1 in Viral Entry  

PubMed Central

Ebola virus infection is initiated by interactions between the viral glycoprotein GP1 and its cognate receptor(s), but little is known about the structure and function of GP1 in viral entry, partly due to the concern about safety when working with the live Ebola virus and the difficulty of manipulating the RNA genome of Ebola virus. In this study, we have used a human immunodeficiency virus-based pseudotyped virus as a surrogate system to dissect the role of Ebola virus GP1 in viral entry. Analysis of more than 100 deletion and amino acid substitution mutants of GP1 with respect to protein expression, processing, viral incorporation, and viral entry has allowed us to map the region of GP1 responsible for viral entry to the N-terminal 150 residues. Furthermore, six amino acids in this region have been identified as critical residues for early events in Ebola virus entry, and among these, three are clustered and are implicated as part of a potential receptor-binding pocket. In addition, substitutions of some 30 residues in GP1 are shown to adversely affect GP1 expression, processing, and viral incorporation, suggesting that these residues are involved in the proper folding and/or overall conformation of GP. Sequence comparison of the GP1 proteins suggests that the majority of the critical residues for GP folding and viral entry identified in Ebola virus GP1 are conserved in Marburg virus. These results provide information for elucidating the structural and functional roles of the filoviral glycoproteins and for developing potential therapeutics to block viral entry.

Manicassamy, Balaji; Wang, Jizhen; Jiang, Haiqing; Rong, Lijun

2005-01-01

16

Experimental inoculation of plants and animals with Ebola virus.  

PubMed Central

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

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

1996-01-01

17

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

PubMed

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

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

2004-01-01

18

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

19

Protection against lethal challenge by Ebola virus-like particles produced in insect cells.  

PubMed

Ebola virus-like particles (VLPs) were produced in insect cells using a recombinant baculovirus expression system and their efficacy for protection against Ebola virus infection was investigated. Two immunizations with 50 microg Ebola VLPs (high dose) induced a high level of antibodies against Ebola GP that exhibited strong neutralizing activity against GP-mediated virus infection and conferred complete protection of vaccinated mice against lethal challenge by a high dose of mouse-adapted Ebola virus. In contrast, two immunizations with 10 microg Ebola VLPs (low dose) induced 5-fold lower levels of antibodies against GP and these mice were not protected against lethal Ebola virus challenge, similar to control mice that were immunized with 50 microg SIV Gag VLPs. However, the antibody responses against GP were boosted significantly after a third immunization with 10 microg Ebola VLPs to similar levels as those induced by two immunizations with 50 microg Ebola VLPs, and vaccinated mice were also effectively protected against lethal Ebola virus challenge. Furthermore, serum viremia levels in protected mice were either below the level of detection or significantly lower compared to the viremia levels in control mice. These results show that effective protection can be achieved by immunization with Ebola VLPs produced in insect cells, which give high production yields, and lend further support to their development as an effective vaccine strategy against Ebola virus. PMID:18986663

Sun, Yuliang; Carrion, Ricardo; Ye, Ling; Wen, Zhiyuan; Ro, Young-Tae; Brasky, Kathleen; Ticer, Anysha E; Schwegler, E Ellen; Patterson, Jean L; Compans, Richard W; Yang, Chinglai

2009-01-01

20

RNA Polymerase I-Driven Minigenome System for Ebola Viruses  

Microsoft Academic Search

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

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

2005-01-01

21

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

22

TSG101 Based Antibody Therapeutic for Ebola and Related Viruses.  

National Technical Information Service (NTIS)

Functional Genetics received a contract from DARPA, No. W911NF04-C- 0039, from April 2004 to October 2006, to study TSG101 Based Antibody Therapeutic for Ebola and Related Viruses . We had set an overall goal for this contract to discover anti-TSG101 anti...

R. Duan

2006-01-01

23

VP40 Octamers Are Essential for Ebola Virus Replication  

PubMed Central

Matrix protein VP40 of Ebola virus is essential for virus assembly and budding. Monomeric VP40 can oligomerize in vitro into RNA binding octamers, and the crystal structure of octameric VP40 has revealed that residues Phe125 and Arg134 are the most important residues for the coordination of a short single-stranded RNA. Here we show that full-length wild-type VP40 octamers bind RNA upon HEK 293 cell expression. While the Phe125-to-Ala mutation resulted in reduced RNA binding, the Arg134-to-Ala mutation completely abolished RNA binding and thus octamer formation. The absence of octamer formation, however, does not affect virus-like particle (VLP) formation, as the VLPs generated from the expression of wild-type VP40 and mutated VP40 in HEK 293 cells showed similar morphology and abundance and no significant difference in size. These results strongly indicate that octameric VP40 is dispensable for VLP formation. The cellular localization of mutant VP40 was different from that of wild-type VP40. While wild-type VP40 was present in small patches predominantly at the plasma membrane, the octamer-negative mutants were found in larger aggregates at the periphery of the cell and in the perinuclear region. We next introduced the Arg134-to-Ala and/or the Phe125-to-Ala mutation into the Ebola virus genome. Recombinant wild-type virus and virus expressing the VP40 Phe125-to-Ala mutation were both rescued. In contrast, no recombinant virus expressing the VP40 Arg134-to-Ala mutation could be recovered. These results suggest that RNA binding of VP40 and therefore octamer formation are essential for the Ebola virus life cycle.

Hoenen, Thomas; Volchkov, Viktor; Kolesnikova, Larissa; Mittler, Eva; Timmins, Joanna; Ottmann, Michelle; Reynard, Olivier; Becker, Stephan; Weissenhorn, Winfried

2005-01-01

24

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

25

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

26

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

27

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

28

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

29

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

30

Epidemiology of Ebola (subtype Reston) virus in the Philippines, 1996.  

PubMed

Ebola (subtype Reston [EBO-R]) virus infection was detected in macaques imported into the United States from the Philippines in March 1996. Studies were initiated in the Philippines to identify the source of the virus among monkey-breeding and export facilities, to establish surveillance and testing, and to assess the risk and significance of EBO-R infections in humans who work in these facilities. Over a 5-month period, acutely infected animals were found at only one facility, as determined using Ebola antigen detection. Three of 1732 monkeys and 1 of 246 animal handlers tested had detectable antibodies; all were from the same facility, which was the source of infected monkeys imported to the United States. Virus transmission, which was facilitated by poor infection-control practices, continued for several months in one facility and was stopped only when the facility was depopulated. None of the 246 employees of the facilities or 4 contacts of previously antibody-positive individuals reported an Ebola-like illness. This investigation suggests that human EBO-R infection is rare. PMID:9988174

Miranda, M E; Ksiazek, T G; Retuya, T J; Khan, A S; Sanchez, A; Fulhorst, C F; Rollin, P E; Calaor, A B; Manalo, D L; Roces, M C; Dayrit, M M; Peters, C J

1999-02-01

31

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

32

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

33

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

Microsoft Academic Search

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

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

1996-01-01

34

A search for Ebola virus in animals in the Democratic Republic of the Congo and Cameroon: ecologic, virologic, and serologic surveys, 1979-1980. Ebola Virus Study Teams.  

PubMed

More than 30 years after the first outbreak of Marburg virus disease in Germany and Yugoslavia and 20 years after Ebola hemorrhagic fever first occurred in central Africa, the natural history of filoviruses remains unknown. In 1979 and 1980, animals in the Democratic Republic of the Congo and Cameroon were collected during the dry season near the site of the 1976 Ebola hemorrhagic fever epidemic. The study objectives were to identify local animals and search for evidence of Ebola virus in their tissues. A total of 1664 animals representing 117 species was collected, including >400 bats and 500 rodents. Vero and CV-1 cells and IFA and RIA were used for virus and antibody detection, respectively. No evidence of Ebola virus infection was found. This study was limited in time and animal collections and excluded insects and plants. Long-term, prospective, multidisciplinary comparative studies will yield more information than will repeat short forays on the ecology of filoviruses. PMID:9988177

Breman, J G; Johnson, K M; van der Groen, G; Robbins, C B; Szczeniowski, M V; Ruti, K; Webb, P A; Meier, F; Heymann, D L

1999-02-01

35

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

36

Viral replication and host gene expression in alveolar macrophages infected with Ebola virus (Zaire strain).  

PubMed

In order to characterize the cellular response to and identify potential diagnostic markers for the early detection of Ebola virus, an in vitro culture system involving nonhuman primate alveolar macrophages was developed. Ebola virus replication in the alveolar macrophages was characterized by plaque assay, immunohistochemical analysis, and in situ hybridization. Fluorogenic 5'-nuclease assays specific for nonhuman primate proinflammatory cytokines and chemokines were designed and used to evaluate mRNA transcription in macrophages infected with Ebola virus. Transient increases in cytokine and chemokine mRNA levels were observed immediately following exposure to Ebola virus. At 2 h postexposure, levels of cytokine and chemokine mRNAs were markedly reduced. Although Ebola virus infection of alveolar macrophages failed to induce a sustained increase in proinflammatory cytokine and chemokine mRNA transcription (potentially reducing the use of these markers as diagnostic tools), the fluorogenic 5'-nuclease assays developed may have prognostic value for individuals infected with Ebola virus. Recently published data have indicated that persons who remain asymptomatic after exposure to Ebola virus are capable of mounting an early proinflammatory cytokine response and that those who become clinically ill are not. If implemented immediately after exposure, these assays could be used to predict which individuals will be more likely to remain asymptomatic as opposed to those who will be more likely to develop clinical signs and eventually succumb to the virus. PMID:11777824

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

2002-01-01

37

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

38

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

39

Ecology of Marburg and Ebola Viruses: Speculations and Directions for Future Research  

Microsoft Academic Search

Marburg and virulent Ebola viruses are maintained in hosts that are rare and have little contact with humans or do not readily transmit virus. Bats (particularly solitary microchiropteran species) are leading contenders as reservoir hosts. Virus transfer to humans occurs by contact with the primary reservoir or via an intermediate animal that acquired infection from the reservoir and is, in

1999-01-01

40

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

41

The Cytoprotective Enzyme Heme Oxygenase-1 Suppresses Ebola Virus Replication  

PubMed Central

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

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

2013-01-01

42

Persistence in darkness of virulent alphaviruses, Ebola virus, and Lassa virus deposited on solid surfaces  

Microsoft Academic Search

Ebola, Lassa, Venezuelan equine encephalitis, and Sindbis viruses were dried onto solid surfaces, incubated for various time\\u000a periods under controlled conditions of temperature and relative humidity, and quantitatively eluted from surfaces, and viral\\u000a titers in the recovered samples were determined. The viral inactivation kinetics that were obtained indicated that viral\\u000a resistance to natural inactivation in the dark follows (in decreasing

Jose-Luis Sagripanti; Amanda M. Rom; Louis E. Holland

2010-01-01

43

Role of Ebola virus secreted glycoproteins and virus-like particles in activation of human macrophages.  

PubMed

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. Ebola virus efficiently produces four soluble glycoproteins during infection: sGP, delta peptide (Delta-peptide), GP(1), and GP(1,2Delta). While the presence of these glycoproteins has been confirmed in blood (sGP) and in vitro systems, it is hypothesized that they are of biological relevance in pathogenesis, particularly target cell activation. To gain insight into their function, we expressed the four soluble glycoproteins in mammalian cells and purified and characterized them. The role of the transmembrane glycoprotein in the context of virus-like particles was also investigated. Primary human macrophages were treated with glycoproteins and virus-like particles and subsequently tested for activation by detection of several critical proinflammatory cytokines (tumor necrosis factor alpha, interleukin-6 [IL-6], and IL-1 beta) and the chemokine IL-8. The presentation of the glycoprotein was determined to be critical since virus-like particles, but not soluble glycoproteins, induced high levels of activation. We propose that the presentation of GP(1,2) in the rigid form such as that observed on the surface of particles is critical for initiating a sufficient signal for the activation of primary target cells. The secreted glycoproteins do not appear to play any role in exogenous activation of these cells during Ebola virus infection. PMID:15681442

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

2005-02-01

44

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

45

A luciferase-based budding assay for Ebola virus.  

PubMed

The VP40 matrix protein of Ebola virus (EBOV) is capable of budding from mammalian cells as a virus-like particle (VLP) and is the major protein involved in virus egress. A functional budding assay has been developed based upon this characteristic of VP40 to assess the contributions of VP40 sequences as well as host proteins to the budding process. This well-defined assay has been modified for potential use in a high-throughput format in which the detection and quantification of firefly luciferase protein in VLPs represents a direct measure of VP40 budding efficiency. Luciferase was found to be incorporated into budding VP40 VLPs. Furthermore, co-expression of EBOV glycoprotein (GP) enhances release of VLPs containing VP40 and luciferase. In contrast, when luciferase is co-expressed with a budding deficient mutant of VP40, luciferase levels in the VLP fraction decrease significantly. This assay represents a promising high-throughput approach to identify inhibitors of EBOV budding. PMID:16837071

McCarthy, Sarah E; Licata, Jillian M; Harty, Ronald N

2006-10-01

46

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.

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

47

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

PubMed

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 therapeutic setting. A single treatment, administered 1 day after infection, is sufficient to protect animals from lethal Ebola virus challenge. Cell-based assays also identified inhibitory activity against divergent virus families, which supports a hypothesis that FGI-106 interferes with a common pathway utilized by different viruses. These findings suggest FGI-106 may provide an opportunity for targeting viral diseases. PMID:19523489

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

2009-09-01

48

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.

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

49

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

50

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

51

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

52

Ebola and Marburg Viruses Replicate in Monocyle- Derived Dendritic Cells without Inducing the Production of Cytokines and Full Maturation.  

National Technical Information Service (NTIS)

Ebola virus (EBOV) and Marburg virus (MARV) cause rapidly progressive hemorrhagic fever with high mortality and may possess specialized mechanisms to evade immune destruction. We postulated that immune evasion could be due to the ability of EBOV and MARV ...

C. M. Bosio M. J. Aman C. Grogan R. Hogan G. Ruthel

2003-01-01

53

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

National Technical Information Service (NTIS)

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 c...

C. Scully C. J. Shoemaker H. Pajouhesh K. L. Schornberg S. E. Delos

2013-01-01

54

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.

Nakayama, Eri; Saijo, Masayuki

2013-01-01

55

Animal models for Ebola and Marburg virus infections.  

PubMed

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

56

[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

57

Sensitivity to ultraviolet radiation of Lassa, vaccinia, and Ebola viruses dried on surfaces  

Microsoft Academic Search

Germicidal UV (also known as UVC) provides a means to decontaminate infected environments as well as a measure of viral sensitivity\\u000a to sunlight. The present study determined UVC inactivation slopes (and derived D37 values) of viruses dried onto nonporous (glass) surfaces. The data obtained indicate that the UV resistance of Lassa virus\\u000a is higher than that of Ebola virus. The

Jose-Luis Sagripanti; C. David Lytle

2011-01-01

58

Development and evaluation of a fluorogenic 5' nuclease assay to detect and differentiate between Ebola virus subtypes Zaire and Sudan.  

PubMed

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

Gibb, T R; Norwood, D A; Woollen, N; Henchal, E A

2001-11-01

59

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

60

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

61

Ebola Virus VP30 Is an RNA Binding Protein?  

PubMed Central

The Ebola virus (EBOV) genome encodes for several proteins that are necessary and sufficient for replication and transcription of the viral RNAs in vitro; NP, VP30, VP35, and L. VP30 acts in trans with an RNA secondary structure upstream of the first transcriptional start site to modulate transcription. Using a bioinformatics approach, we identified a region within the N terminus of VP30 with sequence features that typify intrinsically disordered regions and a putative RNA binding site. To experimentally assess the ability of VP30 to directly interact with the viral RNA, we purified recombinant EBOV VP30 to >90% homogeneity and assessed RNA binding by UV cross-linking and filter-binding assays. VP30 is a strongly acidophilic protein; RNA binding became stronger as pH was decreased. Zn2+, but not Mg2+, enhanced activity. Enhancement of transcription by VP30 requires a RNA stem-loop located within nucleotides 54 to 80 of the leader region. VP30 showed low binding affinity to the predicted stem-loop alone or to double-stranded RNA but showed a good binding affinity for the stem-loop when placed in the context of upstream and downstream sequences. To map the region responsible for interacting with RNA, we constructed, purified, and assayed a series of N-terminal deletion mutations of VP30 for RNA binding. The key amino acids supporting RNA binding activity map to residues 26 to 40, a region rich in arginine. Thus, we show for the first time the direct interaction of EBOV VP30 with RNA and the importance of the N-terminal region for binding RNA.

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

2007-01-01

62

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.

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

2002-01-01

63

Development of RNA aptamers targeting Ebola virus VP35.  

PubMed

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

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

2013-11-26

64

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

65

Successful treatment of advanced Ebola virus infection with T-705 (favipiravir) in a small animal model.  

PubMed

Outbreaks of Ebola hemorrhagic fever in sub-Saharan Africa are associated with case fatality rates of up to 90%. Currently, neither a vaccine nor an effective antiviral treatment is available for use in humans. Here, we evaluated the efficacy of the pyrazinecarboxamide derivative T-705 (favipiravir) against Zaire Ebola virus (EBOV) in vitro and in vivo. T-705 suppressed replication of Zaire EBOV in cell culture by 4log units with an IC90 of 110?M. Mice lacking the type I interferon receptor (IFNAR(-)(/)(-)) were used as in vivo model for Zaire EBOV-induced disease. Initiation of T-705 administration at day 6 post infection induced rapid virus clearance, reduced biochemical parameters of disease severity, and prevented a lethal outcome in 100% of the animals. The findings suggest that T-705 is a candidate for treatment of Ebola hemorrhagic fever. PMID:24583123

Oestereich, Lisa; Lüdtke, Anja; Wurr, Stephanie; Rieger, Toni; Muñoz-Fontela, César; Günther, Stephan

2014-05-01

66

Pathogenesis of Experimental Ebola Zaire Virus Infection in BALB\\/c Mice  

Microsoft Academic Search

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

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

2001-01-01

67

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

68

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

69

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

70

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

Microsoft Academic Search

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

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

2012-01-01

71

Ebola Virus Selectively Inhibits Responses to Interferons, but Not to Interleukin-1?, in Endothelial Cells  

PubMed Central

Ebola virus infection is highly lethal and leads to severe immunosuppression. In this study, we demonstrate that infection of human umbilical vein endothelial cells (HUVECs) with Ebola virus Zaire (EZ) suppressed basal expression of the major histocompatibility complex class I (MHC I) family of proteins and inhibited the induction of multiple genes by alpha interferon (IFN-?) and IFN-?, including those coding for MHC I proteins, 2?-5? oligoadenylate synthetase [2?-5?(A)N], and IFN regulatory factor 1 (IRF-1). Induction of interleukin-6 (IL-6) and ICAM-1 by IL-1? was not suppressed by infection with EZ, suggesting that the inhibition of IFN signaling is specific. Gel shift analysis demonstrated that infection with EZ blocked the induction by IFNs of nuclear proteins that bind to IFN-stimulated response elements, gamma activation sequences, and IFN regulatory factor binding site (IRF-E). In contrast, infection with EZ did not block activation of the transcription factor NF-?B by IL-1?. The events that lead to the blockage of IFN signaling may be critical for Ebola virus-induced immunosuppression and would play a role in the pathogenesis of Ebola virus infection.

Harcourt, Brian H.; Sanchez, Anthony; Offermann, Margaret K.

1999-01-01

72

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

73

Influences of Glycosylation on the Antigenicity, Immunogenicity, and Protective Efficacy of Ebola Virus GP DNA Vaccines.  

National Technical Information Service (NTIS)

The Ebola virus (EBOV) envelope glycoprotein (GP) is the primary target of protective immunity. Mature GP consists of two disulfide-linked subunits, GP1 and membrane-bound GP2. GP is highly glycosylated with both N- and O-linked carbohydrates. We measured...

A. R. Garrison C. Badger E. Thompson J. L. Mellquist W. Dowling

2006-01-01

74

Contribution of ebola virus glycoprotein, nucleoprotein, and VP24 to budding of VP40 virus-like particles.  

PubMed

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. We demonstrate that VP24 alone does not affect VP40 VLP release, whereas NP and GP enhance release of VP40 VLPs, individually and to a greater degree in concert. We demonstrate further the following: (i). VP40 L domains are not required for GP-mediated enhancement of budding; (ii). the membrane-bound form of GP is necessary for enhancement of VP40 VLP release; (iii). NP appears to physically interact with VP40 as judged by detection of NP in VP40-containing VLPs; and (iv). the C-terminal 50 amino acids of NP may be important for interacting with and enhancing release of VP40 VLPs. These findings provide a more complete understanding of the role of VP40 and additional Ebola virus proteins during budding. PMID:15220407

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

2004-07-01

75

Inhibition of Lassa virus and Ebola virus infection in host cells treated with the kinase inhibitors genistein and tyrphostin.  

PubMed

Arenaviruses and filoviruses are capable of causing hemorrhagic fever syndrome in humans. Limited therapeutic and/or prophylactic options are available for humans suffering from viral hemorrhagic fever. In this report, we demonstrate that pre-treatment of host cells with the kinase inhibitors genistein and tyrphostin AG1478 leads to inhibition of infection or transduction in cells infected with Ebola virus, Marburg virus, and Lassa virus. In all, the results demonstrate that a kinase inhibitor cocktail consisting of genistein and tyrphostin AG1478 is a broad-spectrum antiviral that may be used as a therapeutic or prophylactic against arenavirus and filovirus hemorrhagic fever. PMID:21947546

Kolokoltsov, Andrey A; Adhikary, Shramika; Garver, Jennifer; Johnson, Lela; Davey, Robert A; Vela, Eric M

2012-01-01

76

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

77

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

78

Enzyme Immunosorbent Assay for Ebola Virus Antigens in Tissues of Infected Primates. (Reannouncement with New Availability Information).  

National Technical Information Service (NTIS)

A sandwich enzyme immunosorbent assay (EIA) using a mixture of mouse monoclonal antibodies for antigen capture and polyclonal hyperimmune rabbit anti-Ebola virus serum for antigen detection was developed and evaluated on the tissues of monkeys naturally o...

T. G. Ksiazek P. E. Rollin P. B. Jahrling E. Johnson D. W. Dalgard

1992-01-01

79

Ebola virus glycoprotein: proteolytic processing, acylation, cell tropism, and detection of neutralizing antibodies.  

PubMed

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 GP showed no discernible effects on infectivity. Although most filoviruses are believed to target endothelial cells and hepatocytes preferentially, the GP-carrying VSV showed greater affinity for epithelial cells than for either of these cell types, indicating that Ebola virus GP does not necessarily have strong tropism toward endothelial cells and hepatocytes. Finally, when it was used to screen for neutralizing antibodies against Ebola virus GP, the VSV pseudotype system allowed us to detect strain-specific neutralizing activity that was inhibited by secretory GP (SGP). This finding provides evidence of shared neutralizing epitopes on GP and SGP molecules and indicates the potential of SGP to serve as a decoy for neutralizing antibodies. PMID:11152533

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

2001-02-01

80

A novel mechanism of immune evasion mediated by Ebola virus soluble glycoprotein.  

PubMed

Ebola viruses encode two glycoproteins (GPs): a membrane-associated GP that is present in the viral membrane and mediates viral attachment and entry into host cells; and a secreted, nonstructural glycoprotein (sGP) that is identical to GP over approximately 90% of its length. A recent study by Mohan and colleagues attributes a novel immune evasion mechanism dubbed 'antigenic subversion' to sGP. Using DNA immunization in mice, the authors demonstrate that sGP elicits antibodies that crossreact with GP, but these antibodies are non-neutralizing. Coimmunization with sGP plus GP or sequential immunizations with GP and sGP direct the host antibody response toward non-neutralizing epitopes. Therefore, the production of sGP may prevent effective neutralization of the virus during Ebola virus infection, and may reduce the effectiveness of vaccines that rely upon neutralizing antibody responses. PMID:23627853

Basler, Christopher F

2013-05-01

81

Association of Ebola Virus Matrix Protein VP40 with Microtubules.  

National Technical Information Service (NTIS)

Viruses exploit a variety of cellular components to complete their life cycles, and it has become increasingly clear that use of host cell microtubules is a vital part of the infection process for many viruses. A variety of viral proteins have been identi...

G. Ruthel G. L. Demmin G. Kallstrom M. P. Javid S. S. Badie

2005-01-01

82

The Ebola virus matrix protein deeply penetrates the plasma membrane: an important step in viral egress.  

PubMed

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

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

2013-05-01

83

Mapping of the VP40-Binding Regions of the Nucleoprotein of Ebola Virus?  

PubMed Central

Expression of Ebola virus nucleoprotein (NP) in mammalian cells leads to the formation of helical structures, which serve as a scaffold for the nucleocapsid. We recently found that NP binding with the matrix protein VP40 is important for nucleocapsid incorporation into virions (T. Noda, H. Ebihara, Y. Muramoto, K. Fujii, A. Takada, H. Sagara, J. H. Kim, H. Kida, H. Feldmann, and Y. Kawaoka, PLoS Pathog. 2:e99, 2006). To identify the region(s) on the NP molecule required for VP40 binding, we examined the interaction of a series of NP deletion mutants with VP40 biochemically and ultrastructurally. We found that both termini of NP (amino acids 2 to 150 and 601 to 739) are essential for its interaction with VP40 and for its incorporation into virus-like particles (VLPs). We also found that the C terminus of NP is important for nucleocapsid incorporation into virions. Of interest is that the formation of NP helices, which involves the N-terminal 450 amino acids of NP, is dispensable for NP incorporation into VLPs. These findings enhance our understanding of Ebola virus assembly and in so doing move us closer to the identification of targets for the development of antiviral compounds to combat Ebola virus infection.

Noda, Takeshi; Watanabe, Shinji; Sagara, Hiroshi; Kawaoka, Yoshihiro

2007-01-01

84

Assessment of the risk of Ebola virus transmission from bodily fluids and fomites.  

PubMed

Although Ebola virus (EBOV) is transmitted by unprotected physical contact with infected persons, few data exist on which specific bodily fluids are infected or on the risk of fomite transmission. Therefore, we tested various clinical specimens from 26 laboratory-confirmed cases of Ebola hemorrhagic fever, as well as environmental specimens collected from an isolation ward, for the presence of EBOV. Virus was detected by culture and/or reverse-transcription polymerase chain reaction in 16 of 54 clinical specimens (including saliva, stool, semen, breast milk, tears, nasal blood, and a skin swab) and in 2 of 33 environmental specimens. We conclude that EBOV is shed in a wide variety of bodily fluids during the acute period of illness but that the risk of transmission from fomites in an isolation ward and from convalescent patients is low when currently recommended infection control guidelines for the viral hemorrhagic fevers are followed. PMID:17940942

Bausch, Daniel G; Towner, Jonathan S; Dowell, Scott F; Kaducu, Felix; Lukwiya, Matthew; Sanchez, Anthony; Nichol, Stuart T; Ksiazek, Thomas G; Rollin, Pierre E

2007-11-15

85

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

86

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

87

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

88

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

89

Ebola Virus: The Role of Macrophages and Dendritic Cells in the Pathogenesis of Ebola Hemorrhagic Fever.  

National Technical Information Service (NTIS)

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 microphages and dendritic cells. Infect...

M. Bray T. W. Geisbert

2005-01-01

90

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

91

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

PubMed Central

Background The 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 infection. In this report, we modified the common recombinant adenovirus serotype 5-based Ebola vaccine expressing the wild-type ZEBOV glycoprotein sequence from a CMV promoter (Ad-CMVZGP). The immune response elicited by this improved expression cassette vector (Ad-CAGoptZGP) and its ability to afford protection against lethal ZEBOV challenge in mice was compared to the standard Ad-CMVZGP vector. Methodology/Principal Findings Ad-CMVZGP was previously shown to protect mice, guinea pigs and nonhuman primates from an otherwise lethal challenge of Zaire ebolavirus. The antigenic expression cassette of this vector was improved through codon optimization, inclusion of a consensus Kozak sequence and reconfiguration of a CAG promoter (Ad-CAGoptZGP). Expression of GP from Ad-CAGoptZGP was substantially higher than from Ad-CMVZGP. Ad-CAGoptZGP significantly improved T and B cell responses at doses 10 to 100-fold lower than that needed with Ad-CMVZGP. Additionally, Ad-CAGoptZGP afforded full protections in mice against lethal challenge at a dose 100 times lower than the dose required for Ad-CMVZGP. Finally, Ad-CAGoptZGP induced full protection to mice when given 30 minutes post-challenge. Conclusions/Significance We describe an improved adenovirus-based Ebola vaccine capable of affording post-exposure protection against lethal challenge in mice. The molecular modifications of the new improved vaccine also translated in the induction of significantly enhanced immune responses and complete protection at a dose 100 times lower than with the previous generation adenovirus-based Ebola vaccine. Understanding and improving the molecular components of adenovirus-based vaccines can produce potent, optimized product, useful for vaccination and post-exposure therapy.

Tran, Kaylie N.; Croyle, Maria A.; Strong, James E.; Feldmann, Heinz; Kobinger, Gary P.

2009-01-01

92

A novel mechanism for LSECtin binding to Ebola virus surface glycoprotein through truncated glycans.  

PubMed

LSECtin is a member of the C-type lectin family of glycan-binding receptors that is expressed on sinusoidal endothelial cells of the liver and lymph nodes. To compare the sugar and pathogen binding properties of LSECtin with those of related but more extensively characterized receptors, such as DC-SIGN, a soluble fragment of LSECtin consisting of the C-terminal carbohydrate-recognition domain has been expressed in bacteria. A biotin-tagged version of the protein was also generated and complexed with streptavidin to create tetramers. These forms of the carbohydrate-recognition domain were used to probe a glycan array and to characterize binding to oligosaccharide and glycoprotein ligands. LSECtin binds with high selectivity to glycoproteins terminating in GlcNAcbeta1-2Man. The inhibition constant for this disaccharide is 3.5 microm, making it one of the best low molecular weight ligands known for any C-type lectin. As a result of the selective binding of this disaccharide unit, the receptor recognizes glycoproteins with a truncated complex and hybrid N-linked glycans on glycoproteins. Glycan analysis of the surface glycoprotein of Ebola virus reveals the presence of such truncated glycans, explaining the ability of LSECtin to facilitate infection by Ebola virus. High mannose glycans are also present on the viral glycoprotein, which explains why DC-SIGN also binds to this virus. Thus, multiple receptors interact with surface glycoproteins of enveloped viruses that bear different types of relatively poorly processed glycans. PMID:17984090

Powlesland, Alex S; Fisch, Tanja; Taylor, Maureen E; Smith, David F; Tissot, Bérangère; Dell, Anne; Pöhlmann, Stefan; Drickamer, Kurt

2008-01-01

93

Prediction and identification of mouse cytotoxic T lymphocyte epitopes in Ebola virus glycoproteins  

PubMed Central

Background Ebola viruses (EBOVs) cause severe hemorrhagic fever with a high mortality rate. At present, there are no licensed vaccines or efficient therapies to combat EBOV infection. Previous studies have shown that both humoral and cellular immune responses are crucial for controlling Ebola infection. CD8+ T cells play an important role in mediating vaccine-induced protective immunity. The objective of this study was to identify H-2d-specific T cell epitopes in EBOV glycoproteins (GPs). Results Computer-assisted algorithms were used to predict H-2d-specific T cell epitopes in two species of EBOV (Sudan and Zaire) GP. The predicted peptides were synthesized and identified in BALB/c mice immunized with replication-deficient adenovirus vectors expressing the EBOV GP. Enzyme-linked immunospot assays and intracellular cytokine staining showed that the peptides RPHTPQFLF (Sudan EBOV), GPCAGDFAF and LYDRLASTV (Zaire EBOV) could stimulate splenoctyes in immunized mice to produce large amounts of interferon-gamma. Conclusion Three peptides within the GPs of two EBOV strains were identified as T cell epitopes. The identification of these epitopes should facilitate the evaluation of vaccines based on the Ebola virus glycoprotein in a BALB/c mouse model.

2012-01-01

94

Newly Discovered Ebola Virus Associated with Hemorrhagic Fever Outbreak in Uganda  

PubMed Central

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.

Towner, Jonathan S.; Sealy, Tara K.; Khristova, Marina L.; Albarino, Cesar 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.

2008-01-01

95

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

96

Characterization of host immune responses in Ebola virus infections.  

PubMed

Ebola causes highly lethal hemorrhagic fever in humans with no licensed countermeasures. Its virulence can be attributed to several immunoevasion mechanisms: an early inhibition of innate immunity started by the downregulation of type I interferon, epitope masking and subversion of the adaptive humoural immunity by secreting a truncated form of the viral glycoprotein. Deficiencies in specific and non-specific antiviral responses result in unrestricted viral replication and dissemination in the host, causing death typically within 10 days after the appearance of symptoms. This review summarizes the host immune response to Ebola infection, and highlights the short- and long-term immune responses crucial for protection, which holds implications for the design of future vaccines and therapeutics. PMID:24742338

Wong, Gary; Kobinger, Gary P; Qiu, Xiangguo

2014-06-01

97

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

PubMed

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

Scianimanico, S; Schoehn, G; Timmins, J; Ruigrok, R H; Klenk, H D; Weissenhorn, W

2000-12-15

98

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

PubMed

Ebola virus (EBOV) causes severe hemorrhagic fever in humans and nonhuman primates with high mortality rates. Rapid identification of the virus is required to prevent spread of the infection. In this study, we developed and evaluated a one-step simple reverse transcription-loop mediated isothermal amplification (RT-LAMP) assay for the rapid detection of Zaire ebolavirus (ZEBOV), the most virulent species of EBOV, targeting the trailer region of the viral genome. The assay could detect 20 copies of the artificial ZEBOV RNA in 26 min with a real time-monitoring detection, and also detect 10(-3) FFU of the cell-culture propagated viruses. The reaction time needed to detect 10(4) FFU of ZEBOV was only 20 min. In addition, the assay was highly specific for ZEBOV. The RT-LAMP assay developed in this study is rapid, simple, highly specific, and sensitive for the detection of ZEBOV, and so may be an effective diagnostic tool. Furthermore, as this technique does not require sophisticated instrumentation, it seems very suitable for diagnosis in the field or laboratories in Ebola outbreak areas such as Central Africa. PMID:17194485

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

2007-04-01

99

Comparison of the transcription and replication strategies of marburg virus and Ebola virus by using artificial replication systems.  

PubMed

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 transcription 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 minireplicon was demonstrated by reporter gene expression and detection of the transcribed and replicated RNA species. As it was shown previously for MBGV, three of the four EBOV nucleocapsid proteins, NP, VP35, and L, were essential and sufficient for replication. In contrast to MBGV, EBOV-specific transcription was dependent on the presence of the fourth nucleocapsid protein, VP30. When EBOV VP30 was replaced by MBGV VP30, EBOV-specific transcription was observed but with lower efficiency. Exchange of NP, VP35, and L between the two replication systems did not lead to detectable reporter gene expression. It was further observed that neither MBGV nor EBOV were able to replicate the heterologous minigenomes. A chimeric minigenome, however, containing the EBOV leader and the MBGV trailer was encapsidated, replicated, transcribed, and packaged by both viruses. PMID:9971816

Mühlberger, E; Weik, M; Volchkov, V E; Klenk, H D; Becker, S

1999-03-01

100

[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

101

Detection and molecular characterization of Ebola viruses causing disease in human and nonhuman primates.  

PubMed

Ebola (EBO) viruses were detected in specimens obtained during the hemorrhagic fever outbreak among humans in Kikwit, Democratic Republic of the Congo (DRC), in 1995 (subtype Zaire) and during an outbreak of disease in cynomolgus macaques in Alice, Texas, and the Philippines in 1996 (subtype Reston). Reverse transcriptase-polymerase chain reaction assays were developed and proven effective for detecting viral RNA in body fluids and tissues of infected individuals. Little change was seen in the nucleotide or deduced amino acid sequences of the glycoprotein (GP) of these EBO virus subtypes compared with those of their original representatives (i.e., the 1976 Yambuku, DRC, EBO isolate [subtype Zaire] and the 1989 Philippines and Reston, Virginia, isolates [subtype Reston]). The nonstructural secreted GP (SGP), the primary product of the GP gene, was more highly conserved than the structural GP, indicating different functional roles or evolutionary constraints for these proteins. Significant amounts of SGP were detected in acutely infected humans. PMID:9988180

Sanchez, A; Ksiazek, T G; Rollin, P E; Miranda, M E; Trappier, S G; Khan, A S; Peters, C J; Nichol, S T

1999-02-01

102

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

103

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

104

Elaboration of laboratory strains of Ebola virus and study of pathophysiological reactions of animals inoculated with these strains  

Microsoft Academic Search

Selective passages in animals and cell cultures were used to produce a set of Ebola virus (EBO) laboratory strains with changed virulence for some animal genera. Comparative study of the genomes of wild-type EBO and selected variants formed the basis for studying the molecular causes of EBO virulence. Investigation of pathophysiological reactions of the animals inoculated with these strains allowed

A. A. Chepurnov; N. M. Zubavichene; A. A. Dadaeva

2003-01-01

105

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

Microsoft Academic Search

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

Ethan Will Taylor; Chandra Sekar Ramanathan

106

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

107

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

108

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

PubMed Central

Phosphorodiamidate morpholino oligomers (PMO) are a class of uncharged single-stranded DNA analogs modified such that each subunit includes a phosphorodiamidate linkage and morpholine ring. PMO antisense agents have been reported to effectively interfere with the replication of several positive-strand RNA viruses in cell culture. The filoviruses, Marburg virus and Ebola virus (EBOV), are negative-strand RNA viruses that cause up to 90% lethality in human outbreaks. There is currently no commercially available vaccine or efficacious therapeutic for any filovirus. In this study, PMO conjugated to arginine-rich cell-penetrating peptide (P-PMO) and nonconjugated PMO were assayed for the ability to inhibit EBOV infection in cell culture and in a mouse model of lethal EBOV infection. A 22-mer P-PMO designed to base pair with the translation start site region of EBOV VP35 positive-sense RNA generated sequence-specific and time- and dose-dependent inhibition of EBOV amplification in cell culture. The same oligomer provided complete protection to mice when administered before or after an otherwise lethal infection of EBOV. A corresponding nonconjugated PMO, as well as nonconjugated truncated versions of 16 and 19 base residues, provided length-dependent protection to mice when administered prophylactically. Together, these data suggest that antisense PMO and P-PMO have the potential to control EBOV infection and are promising therapeutic candidates.

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

2006-01-01

109

Steric shielding of surface epitopes and impaired immune recognition induced by the ebola virus glycoprotein.  

PubMed

Many viruses alter expression of proteins on the surface of infected cells including molecules important for immune recognition, such as the major histocompatibility complex (MHC) class I and II molecules. Virus-induced downregulation of surface proteins has been observed to occur by a variety of mechanisms including impaired transcription, blocks to synthesis, and increased turnover. Viral infection or transient expression of the Ebola virus (EBOV) glycoprotein (GP) was previously shown to result in loss of staining of various host cell surface proteins including MHC1 and ?1 integrin; however, the mechanism responsible for this effect has not been delineated. In the present study we demonstrate that EBOV GP does not decrease surface levels of ?1 integrin or MHC1, but rather impedes recognition by steric occlusion of these proteins on the cell surface. Furthermore, steric occlusion also occurs for epitopes on the EBOV glycoprotein itself. The occluded epitopes in host proteins and EBOV GP can be revealed by removal of the surface subunit of GP or by removal of surface N- and O- linked glycans, resulting in increased surface staining by flow cytometry. Importantly, expression of EBOV GP impairs CD8 T-cell recognition of MHC1 on antigen presenting cells. Glycan-mediated steric shielding of host cell surface proteins by EBOV GP represents a novel mechanism for a virus to affect host cell function, thereby escaping immune detection. PMID:20844579

Francica, Joseph R; Varela-Rohena, Angel; Medvec, Andrew; Plesa, Gabriela; Riley, James L; Bates, Paul

2010-01-01

110

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

111

Inhibition of Heat-Shock Protein 90 Reduces Ebola Virus Replication  

PubMed Central

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 replication of several negative-strand viruses. We tested the effect of several different Hsp90 inhibitors including geldanamycin, radicicol, and 17-allylamino-17-demethoxygeldanamycin (17-AAG; a geldanamycin analog) on the replication of Zaire EBOV. Our results showed that inhibition of Hsp90 significantly reduced the replication of EBOV. Classic Hsp90 inhibitors reduced viral replication with an effective concentration at 50% (EC50) in the high nanomolar to low micromolar range, while drugs from a new class of Hsp90 inhibitors showed markedly more potent inhibition. These compounds blocked EBOV replication with an EC50 in the low nanomolar range and showed significant potency in blocking replication in primary human monocytes. These results validated that Hsp90 is an important host factor for the replication of filoviruses and suggest that Hsp90 inhibitors may be therapeutically effective in treating EBOV infection.

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

2010-01-01

112

Oligomerization of Ebola Virus VP40 Is Essential for Particle Morphogenesis and Regulation of Viral Transcription?  

PubMed Central

The morphogenesis and budding of virus particles represent an important stage in the life cycle of viruses. For Ebola virus, this process is driven by its major matrix protein, VP40. Like the matrix proteins of many other nonsegmented, negative-strand RNA viruses, VP40 has been demonstrated to oligomerize and to occur in at least two distinct oligomeric states: hexamers and octamers, which are composed of antiparallel dimers. While it has been shown that VP40 oligomers are essential for the viral life cycle, their function is completely unknown. Here we have identified two amino acids essential for oligomerization of VP40, the mutation of which blocked virus-like particle production. Consistent with this observation, oligomerization-deficient VP40 also showed impaired intracellular transport to budding sites and reduced binding to cellular membranes. However, other biological functions, such as the interaction of VP40 with the nucleoprotein, NP, remained undisturbed. Furthermore, both wild-type VP40 and oligomerization-deficient VP40 were found to negatively regulate viral genome replication, a novel function of VP40, which we have recently reported. Interestingly, while wild-type VP40 was also able to negatively regulate viral genome transcription, oligomerization-deficient VP40 was no longer able to fulfill this function, indicating that regulation of viral replication and transcription by VP40 are mechanistically distinct processes. These data indicate that VP40 oligomerization not only is a prerequisite for intracellular transport of VP40 and efficient membrane binding, and as a consequence virion morphogenesis, but also plays a critical role in the regulation of viral transcription by VP40.

Hoenen, T.; Biedenkopf, N.; Zielecki, F.; Jung, S.; Groseth, A.; Feldmann, H.; Becker, S.

2010-01-01

113

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

114

A Novel L-ficolin/Mannose-binding Lectin Chimeric Molecule with Enhanced Activity against Ebola Virus*  

PubMed Central

Ebola viruses constitute a newly emerging public threat because they cause rapidly fatal hemorrhagic fevers for which no treatment exists, and they can be manipulated as bioweapons. We targeted conserved N-glycosylated carbohydrate ligands on viral envelope surfaces using novel immune therapies. Mannose-binding lectin (MBL) and L-ficolin (L-FCN) were selected because they function as opsonins and activate complement. Given that MBL has a complex quaternary structure unsuitable for large scale cost-effective production, we sought to develop a less complex chimeric fusion protein with similar ligand recognition and enhanced effector functions. We tested recombinant human MBL and three L-FCN/MBL variants that contained the MBL carbohydrate recognition domain and varying lengths of the L-FCN collagenous domain. Non-reduced chimeric proteins formed predominantly nona- and dodecameric oligomers, whereas recombinant human MBL formed octadecameric and larger oligomers. Surface plasmon resonance revealed that L-FCN/MBL76 had the highest binding affinities for N-acetylglucosamine-bovine serum albumin and mannan. The same chimeric protein displayed superior complement C4 cleavage and binding to calreticulin (cC1qR), a putative receptor for MBL. L-FCN/MBL76 reduced infection by wild type Ebola virus Zaire significantly greater than the other molecules. Tapping mode atomic force microscopy revealed that L-FCN/MBL76 was significantly less tall than the other molecules despite similar polypeptide lengths. We propose that alterations in the quaternary structure of L-FCN/MBL76 resulted in greater flexibility in the collagenous or neck region. Similarly, a more pliable molecule might enhance cooperativity between the carbohydrate recognition domains and their cognate ligands, complement activation, and calreticulin binding dynamics. L-FCN/MBL chimeric proteins should be considered as potential novel therapeutics.

Michelow, Ian C.; Dong, Mingdong; Mungall, Bruce A.; Yantosca, L. Michael; Lear, Calli; Ji, Xin; Karpel, Marshall; Rootes, Christina L.; Brudner, Matthew; Houen, Gunnar; Eisen, Damon P.; Kinane, T. Bernard; Takahashi, Kazue; Stahl, Gregory L.; Olinger, Gene G.; Spear, Gregory T.; Ezekowitz, R. Alan B.; Schmidt, Emmett V.

2010-01-01

115

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.  

PubMed

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 suspected cases. We have established six one-step, real-time reverse transcription-PCR assays for these pathogens based on the Superscript reverse transcriptase-Platinum Taq polymerase enzyme mixture. Novel primers and/or 5'-nuclease detection probes were designed for RVFV, DENV, YFV, and CCHFV by using the latest DNA database entries. PCR products were detected in real time on a LightCycler instrument by using 5'-nuclease technology (RVFV, DENV, and YFV) or SybrGreen dye intercalation (MBGV/EBOV, LASV, and CCHFV). The inhibitory effect of SybrGreen on reverse transcription was overcome by initial immobilization of the dye in the reaction capillaries. Universal cycling conditions for SybrGreen and 5'-nuclease probe detection were established. Thus, up to three assays could be performed in parallel, facilitating rapid testing for several pathogens. All assays were thoroughly optimized and validated in terms of analytical sensitivity by using in vitro-transcribed RNA. The >or=95% detection limits as determined by probit regression analysis ranged from 1,545 to 2,835 viral genome equivalents/ml of serum (8.6 to 16 RNA copies per assay). The suitability of the assays was exemplified by detection and quantification of viral RNA in serum samples of VHF patients. PMID:12089242

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

2002-07-01

116

Digital sensing and sizing of vesicular stomatitis virus pseudotypes in complex media: a model for ebola and marburg detection.  

PubMed

Rapid, sensitive, and direct label-free capture and characterization of nanoparticles from complex media such as blood or serum will broadly impact medicine and the life sciences. We demonstrate identification of virus particles in complex samples for replication-competent wild-type vesicular stomatitis virus (VSV), defective VSV, and Ebola- and Marburg-pseudotyped VSV with high sensitivity and specificity. Size discrimination of the imaged nanoparticles (virions) allows differentiation between modified viruses having different genome lengths and facilitates a reduction in the counting of nonspecifically bound particles to achieve a limit-of-detection (LOD) of 5 × 10(3) pfu/mL for the Ebola and Marburg VSV pseudotypes. We demonstrate the simultaneous detection of multiple viruses in a single sample (composed of serum or whole blood) for screening applications and uncompromised detection capabilities in samples contaminated with high levels of bacteria. By employing affinity-based capture, size discrimination, and a "digital" detection scheme to count single virus particles, we show that a robust and sensitive virus/nanoparticle sensing assay can be established for targets in complex samples. The nanoparticle microscopy system is termed the Single Particle Interferometric Reflectance Imaging Sensor (SP-IRIS) and is capable of high-throughput and rapid sizing of large numbers of biological nanoparticles on an antibody microarray for research and diagnostic applications. PMID:24840765

Daaboul, George G; Lopez, Carlos A; Chinnala, Jyothsna; Goldberg, Bennett B; Connor, John H; Unlü, M Selim

2014-06-24

117

Ebola Virus Glycoprotein 1: Identification of Residues Important for Binding and Postbinding Events?  

PubMed Central

The filoviruses Ebola virus (EBOV) and Marburg virus (MARV) are responsible for devastating hemorrhagic fever outbreaks. No therapies are available against these viruses. An understanding of filoviral glycoprotein 1 (GP1) residues involved in entry events would facilitate the development of antivirals. Towards this end, we performed alanine scanning mutagenesis on selected residues in the amino terminus of GP1. Mutant GPs were evaluated for their incorporation onto feline immunodeficiency virus (FIV) particles, transduction efficiency, receptor binding, and ability to be cleaved by cathepsins L and B. FIV virions bearing 39 out of 63 mutant glycoproteins transduced cells efficiently, whereas virions bearing the other 24 had reduced levels of transduction. Virions pseudotyped with 23 of the poorly transducing GPs were characterized for their block in entry. Ten mutant GPs were very poorly incorporated onto viral particles. Nine additional mutant GPs (G87A/F88A, K114A/K115A, K140A, G143A, P146A/C147A, F153A/H154A, F159A, F160A, and Y162A) competed poorly with wild-type GP for binding to permissive cells. Four of these nine mutants (P146A/C147A, F153A/H154A, F159A, and F160A) were also inefficiently cleaved by cathepsins. An additional four mutant GPs (K84A, R134A, D150A, and E305/E306A) that were partially defective in transduction were found to compete effectively for receptor binding and were readily cleaved by cathepsins. This finding suggested that this latter group of mutants might be defective at a postbinding, cathepsin cleavage-independent step. In total, our study confirms the role of some GP1 residues in EBOV entry that had previously been recognized and identifies for the first time other residues that are important for productive entry.

Brindley, Melinda A.; Hughes, Laura; Ruiz, Autumn; McCray, Paul B.; Sanchez, Anthony; Sanders, David A.; Maury, Wendy

2007-01-01

118

Ebola virus glycoprotein 1: identification of residues important for binding and postbinding events.  

PubMed

The filoviruses Ebola virus (EBOV) and Marburg virus (MARV) are responsible for devastating hemorrhagic fever outbreaks. No therapies are available against these viruses. An understanding of filoviral glycoprotein 1 (GP1) residues involved in entry events would facilitate the development of antivirals. Towards this end, we performed alanine scanning mutagenesis on selected residues in the amino terminus of GP1. Mutant GPs were evaluated for their incorporation onto feline immunodeficiency virus (FIV) particles, transduction efficiency, receptor binding, and ability to be cleaved by cathepsins L and B. FIV virions bearing 39 out of 63 mutant glycoproteins transduced cells efficiently, whereas virions bearing the other 24 had reduced levels of transduction. Virions pseudotyped with 23 of the poorly transducing GPs were characterized for their block in entry. Ten mutant GPs were very poorly incorporated onto viral particles. Nine additional mutant GPs (G87A/F88A, K114A/K115A, K140A, G143A, P146A/C147A, F153A/H154A, F159A, F160A, and Y162A) competed poorly with wild-type GP for binding to permissive cells. Four of these nine mutants (P146A/C147A, F153A/H154A, F159A, and F160A) were also inefficiently cleaved by cathepsins. An additional four mutant GPs (K84A, R134A, D150A, and E305/E306A) that were partially defective in transduction were found to compete effectively for receptor binding and were readily cleaved by cathepsins. This finding suggested that this latter group of mutants might be defective at a postbinding, cathepsin cleavage-independent step. In total, our study confirms the role of some GP1 residues in EBOV entry that had previously been recognized and identifies for the first time other residues that are important for productive entry. PMID:17475648

Brindley, Melinda A; Hughes, Laura; Ruiz, Autumn; McCray, Paul B; Sanchez, Anthony; Sanders, David A; Maury, Wendy

2007-07-01

119

Detection of cell-cell fusion mediated by Ebola virus glycoproteins.  

PubMed

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 envelope with the membrane of endosomes. However, it has not yet been possible to confirm the direct role of EboV GP in membrane fusion and the requirement for low-pH activation. It was in particular not possible to induce formation of syncytia by exposing cells expressing EboV GP to acidic medium. Here, we have used an assay based on the induction of a beta-galactosidase (lacZ) reporter gene in target cells to detect cytoplasmic exchanges, indicating membrane fusion, with cells expressing EboV GP (Zaire species). Acidic activation of GP-expressing cells was required for efficient fusion with target cells. The direct role of EboV GP in this process is indicated by its inhibition by anti-GP antibodies and by the lack of activity of mutant GP normally expressed at the cell surface but defective for virus entry. Fusion was not observed when target cells underwent acidic treatment, for example, when they were placed in coculture with GP-expressing cells before the activation step. This unexpected feature, possibly related to the nature of the EboV receptor, could explain the impossibility of inducing formation of syncytia among GP-expressing cells. PMID:16501090

Bär, Séverine; Takada, Ayato; Kawaoka, Yoshihiro; Alizon, Marc

2006-03-01

120

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

PubMed

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

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

2013-08-15

121

Immunofluorescence method for detection of Ebola virus immunoglobulin g, using HeLa cells which express recombinant nucleoprotein.  

PubMed

A novel recombinant baculovirus which expresses Ebola virus (EBO) nucleoprotein (NP) under the control of the cytomegalovirus immediate-early promoter was constructed. HeLa cells abortively infected with the baculovirus expressed EBO NP, and this was used as an immunofluorescent (IF) antigen to detect EBO immunoglobulin G (IgG) antibody. This IF method has high efficacy in detecting EBO IgG antibody in clinical specimens, indicating its usefulness in the diagnosis of EBO infections and seroepidemiological studies. PMID:11158150

Saijo, M; Niikura, M; Morikawa, S; Kurane, I

2001-02-01

122

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.  

PubMed

Ebola virus 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 functional studies. Common practice is to express these proteins through transient transfection of mammalian cells. Unfortunately the transfection reagents are expensive and the process is time consuming and labour intensive. This work describes utilizing an ecdysone inducible mammalian expression system to create stable cell lines that express the Ebola virus transmembrane glycoprotein (GP), the soluble glycoprotein (sGP) and the matrix protein (VP40) individually as well as GP and VP40 simultaneously (for the production of virus like particles). These products were the same as those expressed by the transient system, by Western blot analysis and electron microscopy. The inducible system proved to be an improvement of the current technology by enhancing the cost effectiveness and simplifying the process. PMID:18242720

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

2008-03-01

123

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.

2009-01-01

124

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

125

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

126

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.

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

2011-01-01

127

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

PubMed

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

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

2014-06-01

128

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.

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

2013-01-01

129

Monoclonal antibodies combined with adenovirus-vectored interferon significantly extend the treatment window in Ebola virus-infected guinea pigs.  

PubMed

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

Qiu, Xiangguo; Wong, Gary; Fernando, Lisa; Ennis, Jane; Turner, Jeffrey D; Alimonti, Judie B; Yao, Xiaojian; Kobinger, Gary P

2013-07-01

130

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

131

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

PubMed

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

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

2005-09-01

132

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

Microsoft Academic Search

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

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

2001-01-01

133

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

134

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

135

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

Henahan, Sean

1995-01-01

136

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

PubMed Central

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

2013-01-01

137

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

PubMed

We previously described potent inhibition of Ebola virus entry by a 'C-peptide' based on the GP2 C-heptad repeat region (CHR) targeted to endosomes ('Tat-Ebo'). Here, we report the synthesis and evaluation of C-peptides conjugated to cholesterol, and Tat-Ebo analogs containing covalent side chain-side chain crosslinks to promote ?-helical conformation. We found that the cholesterol-conjugated C-peptides were potent inhibitors of Ebola virus glycoprotein (GP)-mediated cell entry (~10(3)-fold reduction in infection at 40 ?M). However, this mechanism of inhibition is somewhat non-specific because the cholesterol-conjugated peptides also inhibited cell entry mediated by vesicular stomatitis virus glycoprotein G. One side chain-side chain crosslinked peptide had moderately higher activity than the parent compound Tat-Ebo. Circular dichroism revealed that the cholesterol-conjugated peptides unexpectedly formed a strong ?-helical conformation that was independent of concentration. Side chain-side chain crosslinking enhanced ?-helical stability of the Tat-Ebo variants, but only at neutral pH. These result provide insight into mechanisms of C-peptide inhibiton of Ebola virus GP-mediated cell entry. PMID:23962564

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

2013-10-01

138

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

139

Live Virus Smallpox Vaccine  

MedlinePLUS

... for Clinicians Brucella Lab Info Surveillance & Investigation Cholera Ebola virus E. coli Food safety threats Glanders Lassa fever Marburg virus Melioidosis Plague Case Definitions and Report Forms Diagnosis & Evaluation Infection Control Lab Testing Surveillance & Investigation Publications & ...

140

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

141

Development of an immunofluorescence method for the detection of antibodies to Ebola virus subtype Reston by the use of recombinant nucleoprotein-expressing HeLa cells.  

PubMed

An indirect immunofluorescent assay (IFA) to detect Ebola virus subtype Reston (EBO-R) antibodies was developed by the use of a HeLa cell line stably expressing EBO-R nucleoprotein (NP). This IFA has a high specificity for the detection of EBO-R IgG antibodies in both hyperimmune rabbit sera and monkey sera collected during an EBO-R outbreak in the Philippines in 1996. Furthermore, this IFA showed a higher sensitivity for the detection of EBO-R antibodies than did the IFA using HeLa cells expressing the NP of Ebola virus subtype Zaire. These results suggest that this new IFA is useful for seroepidemiological studies of EBO-R infection among monkeys. PMID:12437031

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

2002-01-01

142

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

National Technical Information Service (NTIS)

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 aga...

J. B. Geisbert K. J. Davis N. J. Sullivan T. W. Geisbert W. B. Oswald

2007-01-01

143

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

144

Cross-platform evaluation of commercial real-time reverse transcription PCR master mix kits using a quantitative 5'nuclease assay for Ebola virus.  

PubMed

Selection of optimal reaction master mix reagents is essential to obtain the best performance with diagnostic real-time reverse transcription polymerase chain reaction (RT-PCR) assays. Every year the number of commercially available master mix kits increases, so it is prudent to periodically evaluate kits on the market. In this study we evaluated five commercial real-time RT-PCR master mix kits, the RealMasterMix RT-PCR ROX kit, the AgPath-ID One-Step RT-PCR kit, the SuperScript III Platinum One-step Quantitative RT-PCR system, the QuantiTect Probe RT-PCR kit, and the LightCycler RNA HybProbe amplification kit, using a 5'nuclease assay for Ebola virus. The kits were evaluated using the manufacturer's recommended conditions, as well as conditions which have been used with the Ebola virus assay during outbreaks. When evaluated for use in Ebola virus RNA detection, the AgPath-ID kit resulted in the greatest sensitivity in comparison to the other four kits. The efficacy of the AgPath-ID kit was instrument-independent in the five real-time PCR platforms tested. This study demonstrated that Ebola virus RNA detection was not equivalent among the master mix reagents studied and, thus, that this variable can affect real-time RT-PCR assay sensitivity. Furthermore, this study rates the master mix reagents for their suitability, providing diagnostic laboratories the option to select from these kits to suit their specific laboratory needs for real-time RT-PCR. PMID:20732412

Stephens, Kenyatta W; Hutchins, Rebecca J; Dauphin, Leslie A

2010-12-01

145

In vitro and in vivo characterization of recombinant Ebola viruses expressing enhanced green fluorescent protein.  

PubMed

To facilitate an understanding of the molecular aspects of the pathogenesis of Zaire ebolavirus (ZEBOV) infection, we generated 2 different recombinant viruses expressing enhanced green fluorescent protein (eGFP) from additional transcription units inserted at different positions in the virus genome. These viruses showed in vitro phenotypes similar to that of wild-type ZEBOV (wt-ZEBOV) and were stable over multiple passages. Infection with one of the viruses expressing eGFP produced only mild disease in rhesus macaques, demonstrating a marked attenuation in this animal model. However, in mice lacking signal transducer and activator of transcription 1, both viruses expressing eGFP caused lethal cases of disease that were moderately attenuated, compared with that caused by wt-ZEBOV. In mice, viral replication could be easily tracked by the detection of eGFP-positive cells in tissues, by use of flow cytometry. These findings demonstrate that the incorporation of a foreign gene will attenuate ZEBOV in vivo but that these viruses still have potential for in vitro and in vivo research applications. PMID:17940966

Ebihara, Hideki; Theriault, Steven; Neumann, Gabriele; Alimonti, Judie B; Geisbert, Joan B; Hensley, Lisa E; Groseth, Allison; Jones, Steven M; Geisbert, Thomas W; Kawaoka, Yoshihiro; Feldmann, Heinz

2007-11-15

146

The Ebola virus matrix protein penetrates into the plasma membrane: a key step in viral protein 40 (VP40) oligomerization and viral egress.  

PubMed

Ebola, a fatal virus in humans and non-human primates, has no Food and Drug Administration-approved vaccines or therapeutics. The virus from the Filoviridae family causes hemorrhagic fever, which rapidly progresses and in some cases has a fatality rate near 90%. The Ebola genome encodes seven genes, the most abundantly expressed of which is viral protein 40 (VP40), the major Ebola matrix protein that regulates assembly and egress of the virus. It is well established that VP40 assembles on the inner leaflet of the plasma membrane; however, the mechanistic details of plasma membrane association by VP40 are not well understood. In this study, we used an array of biophysical experiments and cellular assays along with mutagenesis of VP40 to investigate the role of membrane penetration in VP40 assembly and egress. Here we demonstrate that VP40 is able to penetrate specifically into the plasma membrane through an interface enriched in hydrophobic residues in its C-terminal domain. Mutagenesis of this hydrophobic region consisting of Leu(213), Ile(293), Leu(295), and Val(298) demonstrated that membrane penetration is critical to plasma membrane localization, VP40 oligomerization, and viral particle egress. Taken together, VP40 membrane penetration is an important step in the plasma membrane localization of the matrix protein where oligomerization and budding are defective in the absence of key hydrophobic interactions with the membrane. PMID:23297401

Adu-Gyamfi, Emmanuel; Soni, Smita P; Xue, Yi; Digman, Michelle A; Gratton, Enrico; Stahelin, Robert V

2013-02-22

147

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

148

Biochemical and Structural Characterization of Cathepsin L-Processed Ebola Virus Glycoprotein: Implications for Viral Entry and Immunogenicity ?  

PubMed Central

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.

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

2010-01-01

149

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.

2012-01-01

150

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.

Becquart, Pierre; Mahlakoiv, Tanel; Nkoghe, Dieudonne; Leroy, Eric M.

2014-01-01

151

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

PubMed

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

152

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

PubMed Central

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

Tamilvanan, Thangaraju; Hopper, Waheeta

2013-01-01

153

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

154

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

PubMed Central

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

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

2012-01-01

155

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

PubMed

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

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

2010-01-01

156

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

PubMed

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

Lee, Kyungae; Ren, Tao; Côté, Marceline; Gholamreza, Berahman; Misasi, John; Bruchez, Anna; Cunningham, James

2013-02-14

157

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

PubMed Central

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

Lee, Kyungae; Ren, Tao; Cote, Marceline; Gholamreza, Berahman; Misasi, John; Bruchez, Anna; Cunningham, James

2013-01-01

158

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

PubMed

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

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

1999-02-01

159

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.

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

2013-01-01

160

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

PubMed Central

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

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

2013-01-01

161

Emerging Viruses  

NSDL National Science Digital Library

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

Lee, Amy.

2002-01-01

162

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

PubMed

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

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

2013-06-01

163

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

164

The Ebola Virus Interferon Antagonist VP24 Directly Binds STAT1 and Has a Novel, Pyramidal Fold  

PubMed Central

Ebolaviruses cause hemorrhagic fever with up to 90% lethality and in fatal cases, are characterized by early suppression of the host innate immune system. One of the proteins likely responsible for this effect is VP24. VP24 is known to antagonize interferon signaling by binding host karyopherin ? proteins, thereby preventing them from transporting the tyrosine-phosphorylated transcription factor STAT1 to the nucleus. Here, we report that VP24 binds STAT1 directly, suggesting that VP24 can suppress at least two distinct branches of the interferon pathway. Here, we also report the first crystal structures of VP24, derived from different species of ebolavirus that are pathogenic (Sudan) and nonpathogenic to humans (Reston). These structures reveal that VP24 has a novel, pyramidal fold. A site on a particular face of the pyramid exhibits reduced solvent exchange when in complex with STAT1. This site is above two highly conserved pockets in VP24 that contain key residues previously implicated in virulence. These crystal structures and accompanying biochemical analysis map differences between pathogenic and nonpathogenic viruses, offer templates for drug design, and provide the three-dimensional framework necessary for biological dissection of the many functions of VP24 in the virus life cycle.

Zhang, Adrianna P. P.; Bornholdt, Zachary A.; Liu, Tong; Abelson, Dafna M.; Lee, David E.; Li, Sheng; Woods, Virgil L.; Saphire, Erica Ollmann

2012-01-01

165

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

Microsoft Academic Search

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

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

2002-01-01

166

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

PubMed

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

Malashkevich, V N; Schneider, B J; McNally, M L; Milhollen, M A; Pang, J X; Kim, P S

1999-03-16

167

The pathogenesis of Ebola hemorrhagic fever  

Microsoft Academic Search

Ebola virus causes lethal hemorrhagic disease in humans, yet there are still no satisfactory biological explanations to account for its extreme virulence. This review focuses on recent findings relevant to understanding the pathogenesis of Ebola virus infection and developing vaccines and effective therapy. The available data suggest that the envelope glycoprotein and the interaction of some viral proteins with the

Ayato Takada; Yoshihiro Kawaoka

2001-01-01

168

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.

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

169

Bat flight and zoonotic viruses.  

PubMed

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

O'Shea, Thomas J; 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

2014-05-01

170

Using next generation sequencing to identify yellow fever virus in Uganda  

Microsoft Academic Search

In October and November 2010, hospitals in northern Uganda reported patients with suspected hemorrhagic fevers. Initial tests for Ebola viruses, Marburg virus, Rift Valley fever virus, and Crimean Congo hemorrhagic fever virus were negative. Unbiased PCR amplification of total RNA extracted directly from patient sera and next generation sequencing resulted in detection of yellow fever virus and generation of 98%

Laura K. McMullan; Mike Frace; Scott A. Sammons; Trevor Shoemaker; Stephen Balinandi; Joseph F. Wamala; Julius J. Lutwama; Robert G. Downing; Ute Stroeher; Adam MacNeil; Stuart T. Nichol

171

Virus Membrane Fusion Proteins: Biological Machines that Undergo a Metamorphosis  

Microsoft Academic Search

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

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

2000-01-01

172

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

PubMed Central

Zaire ebolavirus (ZEBOV), a highly pathogenic zoonotic virus, poses serious public health, ecological and potential bioterrorism threats. Currently no specific therapy or vaccine is available. Virus entry is an attractive target for therapeutic intervention. However, current knowledge of the ZEBOV entry mechanism is limited. While it is known that ZEBOV enters cells through endocytosis, which of the cellular endocytic mechanisms used remains unclear. Previous studies have produced differing outcomes, indicating potential involvement of multiple routes but many of these studies were performed using noninfectious surrogate systems such as pseudotyped retroviral particles, which may not accurately recapitulate the entry characteristics of the morphologically distinct wild type virus. Here we used replication-competent infectious ZEBOV as well as morphologically similar virus-like particles in specific infection and entry assays to demonstrate that in HEK293T and Vero cells internalization of ZEBOV is independent of clathrin, caveolae, and dynamin. Instead the uptake mechanism has features of macropinocytosis. The binding of virus to cells appears to directly stimulate fluid phase uptake as well as localized actin polymerization. Inhibition of key regulators of macropinocytosis including Pak1 and CtBP/BARS as well as treatment with the drug EIPA, which affects macropinosome formation, resulted in significant reduction in ZEBOV entry and infection. It is also shown that following internalization, the virus enters the endolysosomal pathway and is trafficked through early and late endosomes, but the exact site of membrane fusion and nucleocapsid penetration in the cytoplasm remains unclear. This study identifies the route for ZEBOV entry and identifies the key cellular factors required for the uptake of this filamentous virus. The findings greatly expand our understanding of the ZEBOV entry mechanism that can be applied to development of new therapeutics as well as provide potential insight into the trafficking and entry mechanism of other filoviruses.

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

2010-01-01

173

Foamy Viruses  

Microsoft Academic Search

Summary Foamy viruses share complex genome organization with lentiviruses and certain oncoviruses. The open reading frame 3’ of env encodes a transcriptional transactivator. Distinct responsive sequences were identified in the long terminal repeats (LTRs) of simian (SFV-1 and SFV-3) and human foamy viruses (HFV). Transactivation of heterologous LTRs was described including those of simian and human immunodeficiency viruses. Foamy viruses

D. Neumann-Haefelin; U. Fleps; R. Renne; M. Schweizer

1993-01-01

174

Oncolytic viruses  

Microsoft Academic Search

Although the cytotoxic effects of viruses are usually viewed in terms of pathogenicity, it is possible to harness this activity for therapeutic purposes. Viral genomes are highly versatile, and can be modified to direct their cytotoxicity towards cancer cells. These viruses are known as oncolytic viruses. How are viruses engineered to become tumour specific, and can they be used to

E. Antonio Chiocca

2002-01-01

175

[Ebola fever: an emerging disease].  

PubMed

One of the most fatal diseases encountered by mankind so far is Ebola fever. Ebola fever is caused by a highly pathogenic virus from the Filoviridae family which is found in nature in four different sub-types which differ among others also by their pathogenicity for man. The hitherto detected EBO sub-types are stable do not change in the course of an epidemic nor in the course of the patient's illness, nor during passage of the virus from one subject to another. The author presents a historical review of epidemics, nosocomial and laboratory infections, spread and epizoonosis caused by the Ebola virus. The author presents a detailed clinical picture describing the frequency and evolution of different clinical symptoms and signs based on the observation of 103 patients infected with the Ebola virus in Kikwit, Zaire (nowadays Democratic Republic of Congo) in 1995. In the laboratory diagnosis individual tests are mentioned assessing the presence of the virus, viral antigens and antibodies, incl. the most recent immunohistochemical test. The author mentions the problem of patient care and his therapy, incl. available antiviral drugs and passive immunotherapy. He also discusses the possibility and probability of spread of the Ebola virus into our environment. He mentions principles for transport of subjects with suspected disease, demands for their strict isolation and maximum protection of the attending staff incl. barrier nursing technique. The author discusses also principles of epidemiological work, detection and isolation of sources, identification and follow up of contacts and epidemiological supervision of affected areas. Past epidemics made it possible to assemble many scientific findings and practical experience. These make it possible to cope nowadays with any attack of the Ebola virus not only in areas of its epizootic occurrence. PMID:11329728

Jezek, Z

2001-04-01

176

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.

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

2008-01-01

177

Virus maturation.  

PubMed

The formation of infectious virus particles is a highly complex process involving a series of sophisticated molecular events. In most cases, the assembly of virus structural elements results in the formation of immature virus particles unable to initiate a productive infection. Accordingly, for most viruses the final stage of the assembly pathway entails a set of structural transitions and/or biochemical modifications that transform inert precursor particles into fully infectious agents. In this chapter, we review the most relevant maturation mechanisms involved in the generation of infectious virions for a wide variety of viruses. PMID:23737059

Delgui, Laura R; Rodríguez, José F

2013-01-01

178

Virus Maturation  

PubMed Central

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

Veesler, David; Johnson, John E.

2013-01-01

179

[False-positive reactions in laboratory diagnosis of Lassa, Marburg, and Ebola viral hemorrhagic fevers and AIDS].  

PubMed

Sera of normal subjects and AIDS patients living in Minsk and Odessa were tested for antibodies to hazardous viral infections Lassa, Marburg, and Ebola. Four to 16% of examinees were seropositive to Ebola virus, 0.8 to 2.3% to Lassa, and up to 0.8% to Marburg virus. Common B-epitopes were found in viruses belonging to different families: Lassa, Ebola, and HIV. Antibodies specific to these viruses antigens were found in the reference sera to influenza A and B, respiratory syncytial virus, and adenovirus. Sera of convalescents after malaria and of AIDS patients contained antibodies to Lassa virus. PMID:9182402

Vladyko, A S; Za?tseva, V N; Trofimov, N M; Shkolina, T V; Scheslenok, E P; Boshchenko, Iu A; Petkevich, A S

1997-01-01

180

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.

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

2007-01-01

181

Chlorella viruses.  

PubMed

Chlorella viruses or chloroviruses are large, icosahedral, plaque-forming, double-stranded-DNA-containing viruses that replicate in certain strains of the unicellular green alga Chlorella. DNA sequence analysis of the 330-kbp genome of Paramecium bursaria chlorella virus 1 (PBCV-1), the prototype of this virus family (Phycodnaviridae), predict approximately 366 protein-encoding genes and 11 tRNA genes. The predicted gene products of approximately 50% of these genes resemble proteins of known function, including many that are completely unexpected for a virus. In addition, the chlorella viruses have several features and encode many gene products that distinguish them from most viruses. These products include: (1) multiple DNA methyltransferases and DNA site-specific endonucleases, (2) the enzymes required to glycosylate their proteins and synthesize polysaccharides such as hyaluronan and chitin, (3) a virus-encoded K(+) channel (called Kcv) located in the internal membrane of the virions, (4) a SET domain containing protein (referred to as vSET) that dimethylates Lys27 in histone 3, and (5) PBCV-1 has three types of introns; a self-splicing intron, a spliceosomal processed intron, and a small tRNA intron. Accumulating evidence indicates that the chlorella viruses have a very long evolutionary history. This review mainly deals with research on the virion structure, genome rearrangements, gene expression, cell wall degradation, polysaccharide synthesis, and evolution of PBCV-1 as well as other related viruses. PMID:16877063

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

2006-01-01

182

Biodistribution and Toxicological Safety of Adenovirus Type 5 and Type 35 Vectored Vaccines Against Human Immunodeficiency Virus-1 (HIV-1), Ebola, or Marburg Are Similar Despite Differing Adenovirus Serotype Vector, Manufacturer's Construct, or Gene Inserts  

PubMed Central

The Vaccine Research Center has developed vaccine candidates for different diseases/infectious agents (including HIV-1, Ebola, and Marburg viruses) built on an adenovirus vector platform, based on adenovirus type 5 or 35. To support clinical development of each vaccine candidate, pre-clinical studies were performed in rabbits to determine where in the body they biodistribute and how rapidly they clear, and to screen for potential toxicities (intrinsic and immunotoxicities). The vaccines biodistribute only to spleen, liver (Ad5 only), and/or iliac lymph node (Ad35 only) and otherwise remain in the site of injection muscle and overlying subcutis. Though ?1011 viral particles were inoculated, already by Day 9, all but 103 to 105 genome copies per ?g of DNA had cleared from the injection site muscle. By three months, the adenovector was cleared with, at most, a few animals retaining a small number of copies in the injection site, spleen (Ad5), or iliac lymph node (Ad35). This pattern of limited biodistribution and extensive clearance is consistent regardless of differences in adenovector type (Ad5 or 35), manufacturer's construct and production methods, or gene-insert. Repeated dose toxicology studies identified treatment-related toxicities confined primarily to the sites of injection, in certain clinical pathology parameters, and in body temperatures (Ad5 vectors) and food consumption immediately post-inoculation. Systemic reactogenicity and reactogenicity at the sites of injection demonstrated reversibility. These data demonstrate the safety and suitability for investigational human use of Ad5 or Ad35 adenovector-based vaccine candidates at doses of up to 2 × 1011 given intramuscularly to prevent various infectious diseases.

Sheets, Rebecca L.; Stein, Judith; Bailer, Robert T.; Koup, Richard A.; Andrews, Charla; Nason, Martha; He, Bin; Koo, Edward; Trotter, Holly; Duffy, Chris; Manetz, T. Scott; Gomez, Phillip

2009-01-01

183

Proposal for a revised taxonomy of the family Filoviridae: classification, names of taxa and viruses, and virus abbreviations  

PubMed Central

The taxonomy of the family Filoviridae (marburgviruses and ebolaviruses) has changed several times since the discovery of its members, resulting in a plethora of species and virus names and abbreviations. The current taxonomy has only been partially accepted by most laboratory virologists. Confusion likely arose for several reasons: species names that consist of several words or which (should) contain diacritical marks, the current orthographic identity of species and virus names, and the similar pronunciation of several virus abbreviations in the absence of guidance for the correct use of vernacular names. To rectify this problem, we suggest (1) to retain the current species names Reston ebolavirus, Sudan ebolavirus, and Zaire ebolavirus, but to replace the name Cote d'Ivoire ebolavirus [sic] with Taï Forest ebolavirus and Lake Victoria marburgvirus with Marburg marburgvirus; (2) to revert the virus names of the type marburgviruses and ebolaviruses to those used for decades in the field (Marburg virus instead of Lake Victoria marburgvirus and Ebola virus instead of Zaire ebolavirus); (3) to introduce names for the remaining viruses reminiscent of jargon used by laboratory virologists but nevertheless different from species names (Reston virus, Sudan virus, Taï Forest virus), and (4) to introduce distinct abbreviations for the individual viruses (RESTV for Reston virus, SUDV for Sudan virus, and TAFV for Taï Forest virus), while retaining that for Marburg virus (MARV) and reintroducing that used over decades for Ebola virus (EBOV). Paying tribute to developments in the field, we propose (a) to create a new ebolavirus species (Bundibugyo ebolavirus) for one member virus (Bundibugyo virus, BDBV); (b) to assign a second virus to the species Marburg marburgvirus (Ravn virus, RAVV) for better reflection of now available high-resolution phylogeny; and (c) to create a new tentative genus (Cuevavirus) with one tentative species (Lloviu cuevavirus) for the recently discovered Lloviu virus (LLOV). Furthermore, we explain the etymological derivation of individual names, their pronunciation, and their correct use, and we elaborate on demarcation criteria for each taxon and virus.

Kuhn, Jens H.; Becker, Stephan; Ebihara, Hideki; Geisbert, Thomas W.; Johnson, Karl M.; Kawaoka, Yoshihiro; Lipkin, W. Ian; Negredo, Ana I.; Netesov, Sergey V.; Nichol, Stuart T.; Palacios, Gustavo; Peters, Clarence J.; Tenorio, Antonio; Volchkov, Viktor E.; Jahrling, Peter B.

2011-01-01

184

Recombinant Vesicular Stomatitis Virus Vaccine Vectors Expressing Filovirus Glycoproteins Lack Neurovirulence in Nonhuman Primates  

Microsoft Academic Search

The filoviruses, Marburg virus and Ebola virus, cause severe hemorrhagic fever with high mortality in humans and nonhuman primates. Among the most promising filovirus vaccines under development is a system based on recombinant vesicular stomatitis virus (rVSV) that expresses an individual filovirus glycoprotein (GP) in place of the VSV glycoprotein (G). The main concern with all replication-competent vaccines, including the

Chad E. Mire; Andrew D. Miller; Angela Carville; Susan V. Westmoreland; Joan B. Geisbert; Keith G. Mansfield; Heinz Feldmann; Lisa E. Hensley; Thomas W. Geisbert

2012-01-01

185

Phytophthora viruses.  

PubMed

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

Cai, Guohong; Hillman, Bradley I

2013-01-01

186

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

187

Ebola Outbreak Killed 5000 Gorillas  

Microsoft Academic Search

Over the past decade, the Zaire strain of Ebola virus (ZEBOV) has repeatedly emerged in Gabon and Congo. Each human outbreak has been accompanied by reports of gorilla and chimpanzee carcasses in neighboring forests, but both the extent of ape mortality and the causal role of ZEBOV have been hotly debated. Here, we present data suggesting that in 2002 and

Magdalena Bermejo; José Domingo Rodríguez-Teijeiro; Germán Illera; Alex Barroso; Carles Vilà; Peter D. Walsh

2006-01-01

188

VIROLOGY: Rafting with Ebola  

NSDL National Science Digital Library

Access to the article is free, however registration and sign-in are required: Lipid rafts are microdomains in the cell plasma membrane that are enriched in cholesterol, saturated fatty acids, and certain proteins. In a Perspective, Freed discusses new work published elsewhere showing that filoviruses, including the deadly human pathogens Ebola and Marburg, use these lipid rafts to infect host cells and to assemble new virus particles.

Eric O. Freed (National Institutes of Health;National Institute of Allergy and Infectious Diseases)

2002-04-12

189

Passatempo Virus, a Vaccinia Virus Strain, Brazil  

PubMed Central

Passatempo virus was isolated during a zoonotic outbreak. Biologic features and molecular characterization of hemagglutinin, thymidine kinase, and vaccinia growth factor genes suggested a vaccinia virus infection, which strengthens the idea of the reemergence and circulation of vaccinia virus in Brazil. Molecular polymorphisms indicated that Passatempo virus is a different isolate.

Leite, Juliana A.; Drumond, Betania P.; Trindade, Giliane S.; Lobato, Zelia I.P.; da Fonseca, Flavio G.; dos Santos, Joao R.; Madureira, Marieta C.; Guedes, Maria I.M.C.; Ferreira, Jaqueline M.S.; Bonjardim, Claudio A.; Ferreira, Paulo C.P.

2005-01-01

190

Balance of power in host-virus arms races.  

PubMed

The sensing of viral RNA by the host innate immune system is mediated by RIG-I and its partner PACT. In this issue of Cell Host & Microbe, Luthra et al. (2013) show that the Ebola virus VP35 protein counteracts the action of PACT at the cost of compromising its own function in viral replication. PMID:23870307

Kok, Kin-Hang; Jin, Dong-Yan

2013-07-17

191

Marburg virus infection detected in a common African bat.  

PubMed

Marburg and Ebola viruses can cause large hemorrhagic fever (HF) outbreaks with high case fatality (80-90%) in human and great apes. Identification of the natural reservoir of these viruses is one of the most important topics in this field and a fundamental key to understanding their natural history. Despite the discovery of this virus family almost 40 years ago, the search for the natural reservoir of these lethal pathogens remains an enigma despite numerous ecological studies. Here, we report the discovery of Marburg virus in a common species of fruit bat (Rousettus aegyptiacus) in Gabon as shown by finding virus-specific RNA and IgG antibody in individual bats. These Marburg virus positive bats represent the first naturally infected non-primate animals identified. Furthermore, this is the first report of Marburg virus being present in this area of Africa, thus extending the known range of the virus. These data imply that more areas are at risk for MHF outbreaks than previously realized and correspond well with a recently published report in which three species of fruit bats were demonstrated to be likely reservoirs for Ebola virus. PMID:17712412

Towner, Jonathan S; Pourrut, Xavier; Albariño, César G; Nkogue, Chimène Nze; Bird, Brian H; Grard, Gilda; Ksiazek, Thomas G; Gonzalez, Jean-Paul; Nichol, Stuart T; Leroy, Eric M

2007-01-01

192

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

193

Constructing Computer Virus Phylogenies  

Microsoft Academic Search

There has been much recent algorithmic work on the problem of reconstructing the evolutionary history of biological species. Computer virus specialists are interested in finding the evolutionary history of computer viruses—a virus is often written using code fragments from one or more other viruses, which are its immediate ancestors. A phylogeny for a collection of computer viruses is a directed

Leslie Ann Goldberg; Paul W. Goldberg; Cynthia A. Phillips; Gregory B. Sorkin

1998-01-01

194

Ebola viral disease outbreak - west Africa, 2014.  

PubMed

On March 21, 2014, the Guinea Ministry of Health reported the outbreak of an illness characterized by fever, severe diarrhea, vomiting, and a high case-fatality rate (59%) among 49 persons. Specimens from 15 of 20 persons tested at Institut Pasteur in Lyon, France, were positive for an Ebola virus by polymerase chain reaction. Viral sequencing identified Ebola virus (species Zaïre ebolavirus), one of five viruses in the genus Ebolavirus, as the cause. Cases of Ebola viral disease (EVD) were initially reported in three southeastern districts (Gueckedou, Macenta, and Kissidougou) of Guinea and in the capital city of Conakry. By March 30, cases had been reported in Foya district in neighboring Liberia (1), and in May, the first cases identified in Sierra Leone were reported. As of June 18, the outbreak was the largest EVD outbreak ever documented, with a combined total of 528 cases (including laboratory-confirmed, probable, and suspected cases) and 337 deaths (case-fatality rate = 64%) reported in the three countries. The largest previous outbreak occurred in Uganda during 2000-2001, when 425 cases were reported with 224 deaths (case-fatality rate = 53%). The current outbreak also represents the first outbreak of EVD in West Africa (a single case caused by Taï Forest virus was reported in Côte d'Ivoire in 1994 [3]) and marks the first time that Ebola virus transmission has been reported in a capital city. PMID:24964881

Dixon, Meredith G; Schafer, Ilana J

2014-06-27

195

Constructing computer virus phylogenies.  

National Technical Information Service (NTIS)

There has been much recent algorithmic work on the problem of reconstructing the evolutionary history of biological species. Computer virus specialists are interested in finding the evolutionary history of computer viruses--a virus is often written using ...

L. A. Goldberg P. W. Goldberg C. A. Phillips G. B. Sorkin

1996-01-01

196

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

197

The viral transmembrane superfamily: possible divergence of Arenavirus and Filovirus glycoproteins from a common RNA virus ancestor  

Microsoft Academic Search

BACKGROUND: Recent studies of viral entry proteins from influenza, measles, human immunodeficiency virus, type 1 (HIV-1), and Ebola virus have shown, first with molecular modeling, and then X-ray crystallographic or other biophysical studies, that these disparate viruses share a coiled-coil type of entry protein. RESULTS: Structural models of the transmembrane glycoproteins (GP-2) of the Arenaviruses, lymphochoriomeningitis virus (LCMV) and Lassa

William R. Gallaher; Christopher DiSimone; Michael J. Buchmeier

2001-01-01

198

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

199

Virus movement maintains local virus population diversity  

PubMed Central

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.

Snyder, Jamie C.; Wiedenheft, Blake; Lavin, Matthew; Roberto, Francisco F.; Spuhler, Josh; Ortmann, Alice C.; Douglas, Trevor; Young, Mark

2007-01-01

200

Simian hemorrhagic fever virus infection of rhesus macaques as a model of viral hemorrhagic fever: Clinical characterization and risk factors for severe disease  

Microsoft Academic Search

Simian Hemorrhagic Fever Virus (SHFV) has caused sporadic outbreaks of hemorrhagic fevers in macaques at primate research facilities. SHFV is a BSL-2 pathogen that has not been linked to human disease; as such, investigation of SHFV pathogenesis in non-human primates (NHPs) could serve as a model for hemorrhagic fever viruses such as Ebola, Marburg, and Lassa viruses. Here we describe

Reed F. Johnson; Lori E. Dodd; Srikanth Yellayi; Wenjuan Gu; Jennifer A. Cann; Catherine Jett; John G. Bernbaum; Dan R. Ragland; Marisa St. Claire; Russell Byrum; Jason Paragas; Joseph E. Blaney; Peter B. Jahrling

2011-01-01

201

Targeted Transduction Patterns in the Mouse Brain by Lentivirus Vectors Pseudotyped with VSV, Ebola, Mokola, LCMV, or MuLV Envelope Proteins  

Microsoft Academic Search

Lentiviral vectors have proven to be promising tools for transduction of central nervous system (CNS) cells in vivo and in vitro. In this study, CNS transduction patterns of lentiviral vectors pseudotyped with envelope glycoproteins from Ebola virus, murine leukemia virus (MuLV), lymphocytic choriomeningitis virus (LCMV), or the rabies-related Mokola virus were compared to a vector pseudotyped with the vesicular stomatitis

Deborah J. Watson; Gary P. Kobinger; Marco A. Passini; James M. Wilson; John H. Wolfe

2002-01-01

202

Comparative Pathogenesis of Crimean-Congo Hemorrhagic Fever and Ebola Hemorrhagic Fever  

Microsoft Academic Search

Crimean-Congo hemorrhagic fever (CCHF) virus has been called “the Asian Ebola virus” – an epithet that recognizes the close\\u000a clinical resemblance of CCHF and Ebola hemorrhagic fever (EHF), and also suggests that the two illnesses share similar underlying\\u000a mechanisms [38]. CCHF and EHF both present difficult challenges to pathophysiology research, because they occur principally\\u000a in regions lacking a modern medical

Mike Bray

203

WaveLike Spread of Ebola Zaire  

Microsoft Academic Search

In the past decade the Zaire strain of Ebola virus (ZEBOV) has emerged repeatedly into human populations in central Africa and caused massive die-offs of gorillas and chimpanzees. We tested the view that emergence events are independent and caused by ZEBOV variants that have been long resident at each locality. Phylogenetic analyses place the earliest known outbreak at Yambuku, Democratic

Peter D Walsh; Roman Biek; Leslie A Real

2005-01-01

204

Salmonid viruses: Infectious pancreatic necrosis virus  

Microsoft Academic Search

Summary Epizootics occurred among young trout in France, and the behavior and symptoms suggested infectious pancreatic necrosis (IPN) virus. Specimens preserved in glycerol were sent to the U.S.A. for virological examination. Virus was isolated from four of five lots, but neutralization with antiserum against ATCC VR299 strain IPN virus was incomplete. Electron microscopy, bioassay, histopathology, and serology were used to

Ken Wolf; M. C. Quimby

1971-01-01

205

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

206

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

207

A Fusion-Inhibiting Peptide against Rift Valley Fever Virus Inhibits Multiple, Diverse Viruses  

PubMed Central

For enveloped viruses, fusion of the viral envelope with a cellular membrane is critical for a productive infection to occur. This fusion process is mediated by at least three classes of fusion proteins (Class I, II, and III) based on the protein sequence and structure. For Rift Valley fever virus (RVFV), the glycoprotein Gc (Class II fusion protein) mediates this fusion event following entry into the endocytic pathway, allowing the viral genome access to the cell cytoplasm. Here, we show that peptides analogous to the RVFV Gc stem region inhibited RVFV infectivity in cell culture by inhibiting the fusion process. Further, we show that infectivity can be inhibited for diverse, unrelated RNA viruses that have Class I (Ebola virus), Class II (Andes virus), or Class III (vesicular stomatitis virus) fusion proteins using this single peptide. Our findings are consistent with an inhibition mechanism similar to that proposed for stem peptide fusion inhibitors of dengue virus in which the RVFV inhibitory peptide first binds to both the virion and cell membranes, allowing it to traffic with the virus into the endocytic pathway. Upon acidification and rearrangement of Gc, the peptide is then able to specifically bind to Gc and prevent fusion of the viral and endocytic membranes, thus inhibiting viral infection. These results could provide novel insights into conserved features among the three classes of viral fusion proteins and offer direction for the future development of broadly active fusion inhibitors.

Koehler, Jeffrey W.; Smith, Jeffrey M.; Ripoll, Daniel R.; Spik, Kristin W.; Taylor, Shannon L.; Badger, Catherine V.; Grant, Rebecca J.; Ogg, Monica M.; Wallqvist, Anders; Guttieri, Mary C.; Garry, Robert F.; Schmaljohn, Connie S.

2013-01-01

208

Temporal Program of Peripheral Blood Gene Expression in the Response of Nonhuman Primates to Ebola Hemorrhagic Fever.  

National Technical Information Service (NTIS)

BACKGROUND: Infection with Ebola virus (EBOV) causes a fulminant and often fatal hemorrhagic fever. In order to improve our understanding of EBOV pathogenesis and EBOV-host interactions, we examined the molecular features of EBOV infection in vivo. RESULT...

H. A. Young K. H. Rubins K. M. Daddario DiCaprio L. E. Hensley V. Wahl-Jensen

2007-01-01

209

Negative-strand RNA viruses: genetic engineering and applications.  

PubMed Central

The negative-strand RNA viruses are a broad group of animal viruses that comprise several important human pathogens, including influenza, measles, mumps, rabies, respiratory syncytial, Ebola, and hantaviruses. The development of new strategies to genetically manipulate the genomes of negative-strand RNA viruses has provided us with new tools to study the structure-function relationships of the viral components and their contributions to the pathogenicity of these viruses. It is also now possible to envision rational approaches--based on genetic engineering techniques--to design live attenuated vaccines against some of these viral agents. In addition, the use of different negative-strand RNA viruses as vectors to efficiently express foreign polypeptides has also become feasible, and these novel vectors have potential applications in disease prevention as well as in gene therapy. Images Fig. 1

Palese, P; Zheng, H; Engelhardt, O G; Pleschka, S; Garcia-Sastre, A

1996-01-01

210

Viruses in the sea.  

PubMed

Viruses exist wherever life is found. They are a major cause of mortality, a driver of global geochemical cycles and a reservoir of the greatest genetic diversity on Earth. In the oceans, viruses probably infect all living things, from bacteria to whales. They affect the form of available nutrients and the termination of algal blooms. Viruses can move between marine and terrestrial reservoirs, raising the spectre of emerging pathogens. Our understanding of the effect of viruses on global systems and processes continues to unfold, overthrowing the idea that viruses and virus-mediated processes are sidebars to global processes. PMID:16163346

Suttle, Curtis A

2005-09-15

211

Trigger events: enviroclimatic coupling of Ebola hemorrhagic fever outbreaks  

NASA Technical Reports Server (NTRS)

We use spatially continuous satellite data as a correlate of precipitation within tropical Africa and show that the majority of documented Ebola hemorrhagic fever outbreaks were closely associated with sharply drier conditions at the end of the rainy season. We propose that these trigger events may enhance transmission of Ebola virus from its cryptic reservoir to humans. These findings suggest specific directions to help understand the sylvatic cycle of the virus and may provide early warning tools to detect possible future outbreaks of this enigmatic disease.

Pinzon, Jorge E.; Wilson, James M.; Tucker, Compton J.; Arthur, Ray; Jahrling, Peter B.; Formenty, Pierre

2004-01-01

212

Future directions: oncolytic viruses.  

PubMed

Oncolytic viruses offer a promising new modality for cancer treatment. The strategy of this therapy is to develop viruses capable of selectively infecting and replicating in malignant tumor cells. Oncolytic viruses can spread and destroy malignant tumors without deleterious effects in normal tissues. These viruses are genetically engineered based on both the biology of replicating viruses and the major genetic defects in human cancer cells, so that they can replicate in cancer cells but not in normal cells. The key to the development of such viruses is the identification of viral genes, the deletion or modification of which enables tumor-specific cell destruction. Several clinical trials have demonstrated the safety of oncolytic viruses as cancer therapy and have also shown some encouraging results. Much evidence suggests that oncolytic viral therapy works in synergy with standard cancer therapies. In this review, we will focus on the oncolytic viruses that may be beneficial to patients with lung cancer in the near future. PMID:14967074

You, Liang; He, Biao; Xu, Zhidong; McCormick, Frank; Jablons, David M

2004-01-01

213

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

214

Cytotoxicity of Virus.  

National Technical Information Service (NTIS)

Cytotoxic effects through virus capable of propagation such as those of the pox group inactivated by ultraviolet exposure, were produced under high virus-cell ratios in various cell cultures. In the inoculated culture systems, these effects do not propaga...

H. Mahnel

1968-01-01

215

Viruses and Breast Cancer  

PubMed Central

Viruses are the accepted cause of many important cancers including cancers of the cervix and anogenital area, the liver, some lymphomas, head and neck cancers and indirectly human immunodeficiency virus associated cancers. For over 50 years, there have been serious attempts to identify viruses which may have a role in breast cancer. Despite these efforts, the establishment of conclusive evidence for such a role has been elusive. However, the development of extremely sophisticated new experimental techniques has allowed the recent development of evidence that human papilloma virus, Epstein-Barr virus, mouse mammary tumor virus and bovine leukemia virus may each have a role in the causation of human breast cancers. This is potentially good news as effective vaccines are already available to prevent infections from carcinogenic strains of human papilloma virus, which causes cancer of the uterine cervix.

Lawson, James S.; Heng, Benjamin

2010-01-01

216

Viruses and human cancer  

SciTech Connect

This book contains papers on the following topics: Immunology and Epidemiology, Biology and Pathogenesis, Models of Pathogenesis and Treatment, Simian and Bovine Retroviruses, Human Papilloma Viruses, EBV and Herpesvirus, and Hepatitis B Virus.

Gallo, R.C.; Haseltine, W.; Klein, G.; Zur Hausen, H.

1987-01-01

217

[Viruses and mammary carcinogenesis].  

PubMed

Bittner virus has been extensively studied by recent electron microscopy and molecular biology techniques. The structure, the biochemical, physical and antigenic properties of the RNA tumor viruses - i.e. the mouse mammary tumor virus (MMTV) - are well known. Recent observations in human tissues of particles similar to animal viruses that are known to be oncogenic have raised the hypothesis of the role of viruses in human cancer. In mice, breast cancer can be caused by a virus - the Bittner virus or MMTV - that is usually transmitted from mother to offspring in the milk. The discovery of such virus particles in human milks and breast cancer tissues could provide data about a viral aetiology of human breast cancer. PMID:172551

Vokaer, A

1975-01-01

218

Advances in virus research  

SciTech Connect

This book contains eight chapters. Some of the titles are: Initiation of viral DNA replication; Vaccinia: virus, vector, vaccine; The pre-S region of hepadnavirus envelope proteins; and Archaebacterial viruses.

Maramorosch, K. (Rutgers--the State Univ., New Brunswick, NJ (USA)); Murphy, F.A. (Centers for Disease Control, Atlanta, GA (USA)); Shatkin, A.J. (Rutgers-UMDNJ, Piscataway, NJ (US))

1988-01-01

219

[Mumps vaccine virus transmission].  

PubMed

In this work we report the mumps vaccine virus shedding based on the laboratory confirmed cases of the mumps virus (MuV) infection. The likely epidemiological sources of the transmitted mumps virus were children who were recently vaccinated with the mumps vaccine containing Leningrad-Zagreb or Leningrad-3 MuV. The etiology of the described cases of the horizontal transmission of both mumps vaccine viruses was confirmed by PCR with the sequential restriction analysis. PMID:24772647

Otrashevskaia, E V; Kulak, M V; Otrashevskaia, A V; Karpov, I A; Fisenko, E G; Ignat'ev, G M

2013-01-01

220

An Undetectable Computer Virus  

Microsoft Academic Search

One of the few solid theoretical results in the study of computer viruses is Cohen's 1987 demonstration that there is no algorithm that can perfectly detect all possible viruses [1]. This brief paper adds to the bad news, by pointing out that there are computer viruses which no algorithm can detect, even under a somewhat more liberal definition of detection.

David M. Chess; Steve R. White

2000-01-01

221

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...

222

Constructing Computer Virus Phylogenies  

Microsoft Academic Search

. There has been much recent algorithmic work on the problemof reconstructing the evolutionary history of biological species. Computervirus specialists are interested in finding the evolutionary history of computerviruses --- a virus is often written using code fragments from one ormore other viruses, which are its immediate ancestors. A phylogeny fora collection of computer viruses is a directed acyclic graph

Leslie Ann Goldberg; Paul W. Goldberg; Cynthia A. Phillips; Gregory B. Sorkin

1996-01-01

223

Lipids of Archaeal Viruses  

PubMed Central

Archaeal viruses represent one of the least known territory of the viral universe and even less is known about their lipids. Based on the current knowledge, however, it seems that, as in other viruses, archaeal viral lipids are mostly incorporated into membranes that reside either as outer envelopes or membranes inside an icosahedral capsid. Mechanisms for the membrane acquisition seem to be similar to those of viruses infecting other host organisms. There are indications that also some proteins of archaeal viruses are lipid modified. Further studies on the characterization of lipids in archaeal viruses as well as on their role in virion assembly and infectivity require not only highly purified viral material but also, for example, constant evaluation of the adaptability of emerging technologies for their analysis. Biological membranes contain proteins and membranes of archaeal viruses are not an exception. Archaeal viruses as relatively simple systems can be used as excellent tools for studying the lipid protein interactions in archaeal membranes.

Roine, Elina; Bamford, Dennis H.

2012-01-01

224

Elastic Properties of Viruses  

PubMed Central

Viruses are compact biological nanoparticles whose elastic and dynamical properties are hardly known. Inelastic (Brillouin) light scattering was used to characterize these properties, from microcrystals of the Satellite Tobacco Mosaic Virus, a nearly spherical plant virus of 17-nm diameter. Longitudinal sound velocities in wet and dry Satellite Tobacco Mosaic Virus crystals were determined and compared to that of the well-known protein crystal, lysozyme. Localized vibrational modes of the viral particles (i.e., particle modes) were sought in the relevant frequency ranges, as derived assuming the viruses as full free nanospheres. Despite very favorable conditions, regarding virus concentration and expected low damping in dry microcrystals, no firm evidence of virus particle modes could be detected.

Stephanidis, B.; Adichtchev, S.; Gouet, P.; McPherson, A.; Mermet, A.

2007-01-01

225

Abacá mosaic virus: A distinct strain of Sugarcane mosaic virus  

Microsoft Academic Search

Abacá mosaic virus (AbaMV) is related to members of the sugarcane mosaic virus subgroup of the genus Potyvirus. The ?2 kb 3? terminal region of the viral genome was sequenced and, in all areas analysed, found to be most similar to Sugarcane mosaic virus (SCMV) and distinct from Johnsongrass mosaic virus (JGMV), Maize dwarf mosaic virus (MDMV) and Sorghum mosaic

C. F. Gambley; J. E. Thomas; L. V. Magnaye; L. Herradura

2004-01-01

226

TIM-family proteins promote infection of multiple enveloped viruses through virion-associated phosphatidylserine.  

PubMed

Human T-cell Immunoglobulin and Mucin-domain containing proteins (TIM1, 3, and 4) specifically bind phosphatidylserine (PS). TIM1 has been proposed to serve as a cellular receptor for hepatitis A virus and Ebola virus and as an entry factor for dengue virus. Here we show that TIM1 promotes infection of retroviruses and virus-like particles (VLPs) pseudotyped with a range of viral entry proteins, in particular those from the filovirus, flavivirus, New World arenavirus and alphavirus families. TIM1 also robustly enhanced the infection of replication-competent viruses from the same families, including dengue, Tacaribe, Sindbis and Ross River viruses. All interactions between TIM1 and pseudoviruses or VLPs were PS-mediated, as demonstrated with liposome blocking and TIM1 mutagenesis experiments. In addition, other PS-binding proteins, such as Axl and TIM4, promoted infection similarly to TIM1. Finally, the blocking of PS receptors on macrophages inhibited the entry of Ebola VLPs, suggesting that PS receptors can contribute to infection in physiologically relevant cells. Notably, infection mediated by the entry proteins of Lassa fever virus, influenza A virus and SARS coronavirus was largely unaffected by TIM1 expression. Taken together our data show that TIM1 and related PS-binding proteins promote infection of diverse families of enveloped viruses, and may therefore be useful targets for broad-spectrum antiviral therapies. PMID:23555248

Jemielity, Stephanie; Wang, Jinyize J; Chan, Ying Kai; Ahmed, Asim A; Li, Wenhui; Monahan, Sheena; Bu, Xia; Farzan, Michael; Freeman, Gordon J; Umetsu, Dale T; Dekruyff, Rosemarie H; Choe, Hyeryun

2013-03-01

227

Internet computer virus protection policy  

Microsoft Academic Search

Organizations and individuals today need to have a comprehensive virus protection policy to face the growing threats of Internet computer viruses. The purpose of this paper is to introduce to the reader the threats that Internet computer viruses can cause and provide guidelines on how organizations or individuals can protect themselves against these viruses. Discusses the full set of virus

H. Joseph Wen

1998-01-01

228

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

229

Wild animal mortality monitoring and human Ebola outbreaks, Gabon and Republic of Congo, 2001-2003.  

PubMed

All human Ebola virus outbreaks during 2001-2003 in the forest zone between Gabon and Republic of Congo resulted from handling infected wild animal carcasses. After the first outbreak, we created an Animal Mortality Monitoring Network in collaboration with the Gabonese and Congolese Ministries of Forestry and Environment and wildlife organizations (Wildlife Conservation Society and Programme de Conservation et Utilisation Rationnelle des Ecosystemes Forestiers en Afrique Centrale) to predict and possibly prevent human Ebola outbreaks. Since August 2001, 98 wild animal carcasses have been recovered by the network, including 65 great apes. Analysis of 21 carcasses found that 10 gorillas, 3 chimpanzees, and 1 duiker tested positive for Ebola virus. Wild animal outbreaks began before each of the 5 human Ebola outbreaks. Twice we alerted the health authorities to an imminent risk for human outbreaks, weeks before they occurred. PMID:15752448

Rouquet, Pierre; Froment, Jean-Marc; Bermejo, Magdalena; Kilbourn, Annelisa; Karesh, William; Reed, Patricia; Kumulungui, Brice; Yaba, Philippe; Délicat, André; Rollin, Pierre E; Leroy, Eric M

2005-02-01

230

The Acute bee paralysis virus–Kashmir bee virus–Israeli acute paralysis virus complex  

Microsoft Academic Search

Acute bee paralysis virus (ABPV), Kashmir bee virus (KBV) and Israeli acute paralysis virus (IAPV) are part of a complex of closely related viruses from the Family Dicistroviridae. These viruses have a widespread prevalence in honey bee (Apis mellifera) colonies and a predominantly sub-clinical etiology that contrasts sharply with the extremely virulent pathology encountered at elevated titres, either artificially induced

Joachim R. de Miranda; Guido Cordoni; Giles Budge

2010-01-01

231

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

232

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

233

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.

Schmid, Melanie; Speiseder, Thomas; Dobner, Thomas

2014-01-01

234

Viruses, masters at downsizing.  

PubMed

Viruses are the smallest fruits on the tree of life. Dwarfed by their bacterial and cellular hosts, viruses and their close relatives have long been considered the smallest microbes. The genome of a virus may contain no more than three thousand nucleotides, compared to the three billion base pairs in human genomes. (Lest we feel superior, though, the genomes of some other organisms are much larger than our own.). PMID:22704616

DiMaio, Daniel

2012-06-14

235

Rabies virus receptors  

Microsoft Academic Search

There is convincing in vitro evidence that the muscular form of the nicotinic acetylcholine receptor (nAChR), the neuronal cell adhesion molecule (NCAM),\\u000a and the p75 neurotrophin receptor (p75NTR) bind rabies virus and\\/or facilitate rabies virus entry into cells. Other components\\u000a of the cell membrane, such as gangliosides, may also participate in the entry of rabies virus. However, little is known

Monique Lafon

2005-01-01

236

Viruses for tumor therapy.  

PubMed

Oncolytic virotherapy exploits live viruses with selective tropism for cancerous cells and tissues to treat cancer. As discussed here, the field has progressed considerably as a result of both the successes and failures of previous and on-going clinical trials for various cancers. These studies indicate that oncolytic viruses are remarkably safe and more efficacious when virus replication stimulates sustained antitumor immune responses. In the future, virotherapy should be combined with immunomodulatory reagents that target immune tolerance to established cancers. PMID:24629333

Bell, John; McFadden, Grant

2014-03-12

237

Avian Influenza A Virus Infections in Humans  

MedlinePLUS

... Google Bookmarks Avian Influenza A Virus Infections in Humans On this Page Avian Influenza A Virus Infections ... A Viruses Avian Influenza A Virus Infections in Humans Although avian influenza A viruses usually do not ...

238

Ebola outbreak killed 5000 gorillas.  

PubMed

Over the past decade, the Zaire strain of Ebola virus (ZEBOV) has repeatedly emerged in Gabon and Congo. Each human outbreak has been accompanied by reports of gorilla and chimpanzee carcasses in neighboring forests, but both the extent of ape mortality and the causal role of ZEBOV have been hotly debated. Here, we present data suggesting that in 2002 and 2003 ZEBOV killed about 5000 gorillas in our study area. The lag between neighboring gorilla groups in mortality onset was close to the ZEBOV disease cycle length, evidence that group-to-group transmission has amplified gorilla die-offs. PMID:17158318

Bermejo, Magdalena; Rodríguez-Teijeiro, José Domingo; Illera, Germán; Barroso, Alex; Vilà, Carles; Walsh, Peter D

2006-12-01

239

Tracking a Virus  

NSDL National Science Digital Library

Students simulate the spread of a virus such as HIV through a population by "sharing" (but not drinking) the water in a plastic cup with several classmates. Although invisible, the water in a few of the cups has already be tainted with the "virus" (sodium carbonate). After all the students have shared their liquids, the contents of the cups are tested for the virus with phenolphthalein, a chemical that causes a striking color change in the presence of sodium carbonate. Students then set about trying to determine which of their classmates were the ones originally infected with the virus.

Engineering K-Phd Program

240

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

241

Viruses in artichoke.  

PubMed

Most of the 25 viruses found in globe artichoke (Cynara scolymus L.) and cardoon (Cynara cardunculus L.) were recorded from Europe and the Mediterranean basin, where they decrease both the productivity and the quality of the crop. Although, sometimes, these viruses are agents of diseases of different severity, most often their infections are symptomless. These conditions have contributed to spread virus-infected material since farmers multiply traditional artichoke types vegetatively with no effective selection of virus-free plants. This review reports the main properties of these viruses and the techniques used for their detection and identification. ELISA kits are commercially available for most of the viruses addressed in this review but have seldom been used for their detection in artichoke. Conversely, nucleic acid-based diagnostic reagents, some of which are commercially available, have successfully been employed to identify some viruses in artichoke sap. Control measures mainly use virus-free stocks for new plantations. A combined procedure of meristem-tip culture and thermotherapy proved useful for producing virus-free regenerants of the reflowering southern Italian cultivar Brindisino, which kept earliness and typical heads shape. PMID:22682171

Gallitelli, Donato; Mascia, Tiziana; Martelli, Giovanni P

2012-01-01

242

DC-SIGN and DC-SIGNR Bind Ebola Glycoproteins and Enhance Infection of Macrophages and Endothelial Cells  

Microsoft Academic Search

Ebola virus exhibits a broad cellular tropism in vitro. In humans and animal models, virus is found in most tissues and organs during the latter stages of infection. In contrast, a more restricted cell and tissue tropism is exhibited early in infection where macrophages, liver, lymph node, and spleen are major initial targets. This indicates that cellular factors other than

Graham Simmons; Jacqueline D. Reeves; Case C. Grogan; Luk H. Vandenberghe; Frédéric Baribaud; J. Charles Whitbeck; Emily Burke; Michael J. Buchmeier; Elizabeth J. Soilleux; James L. Riley; Robert W. Doms; Paul Bates; Stefan Pöhlmann

2003-01-01

243

Small molecule inhibitors of ER ?-glucosidases are active against multiple hemorrhagic fever viruses.  

PubMed

Host cellular endoplasmic reticulum ?-glucosidases I and II are essential for the maturation of viral glycosylated envelope proteins that use the calnexin mediated folding pathway. Inhibition of these glycan processing enzymes leads to the misfolding and degradation of these viral glycoproteins and subsequent reduction in virion secretion. We previously reported that, CM-10-18, an imino sugar ?-glucosidase inhibitor, efficiently protected the lethality of dengue virus infection of mice. In the current study, through an extensive structure-activity relationship study, we have identified three CM-10-18 derivatives that demonstrated superior in vitro antiviral activity against representative viruses from four viral families causing hemorrhagic fever. Moreover, the three novel imino sugars significantly reduced the mortality of two of the most pathogenic hemorrhagic fever viruses, Marburg virus and Ebola virus, in mice. Our study thus proves the concept that imino sugars are promising drug candidates for the management of viral hemorrhagic fever caused by variety of viruses. PMID:23578725

Chang, Jinhong; Warren, Travis K; Zhao, Xuesen; Gill, Tina; Guo, Fang; Wang, Lijuan; Comunale, Mary Ann; Du, Yanming; Alonzi, Dominic S; Yu, Wenquan; Ye, Hong; Liu, Fei; Guo, Ju-Tao; Mehta, Anand; Cuconati, Andrea; Butters, Terry D; Bavari, Sina; Xu, Xiaodong; Block, Timothy M

2013-06-01

244

Requirements for budding of paramyxovirus simian virus 5 virus-like particles.  

PubMed

Enveloped viruses are released from infected cells after coalescence of viral components at cellular membranes and budding of membranes to release particles. For some negative-strand RNA viruses (e.g., vesicular stomatitis virus and Ebola virus), the viral matrix (M) protein contains all of the information needed for budding, since virus-like particles (VLPs) are efficiently released from cells when the M protein is expressed from cDNA. To investigate the requirements for budding of the paramyxovirus simian virus 5 (SV5), its M protein was expressed in mammalian cells, and it was found that SV5 M protein alone could not induce vesicle budding and was not secreted from cells. Coexpression of M protein with the viral hemagglutinin-neuraminidase (HN) or fusion (F) glycoproteins also failed to result in significant VLP release. It was found that M protein in the form of VLPs was only secreted from cells, with an efficiency comparable to authentic virus budding, when M protein was coexpressed with one of the two glycoproteins, HN or F, together with the nucleocapsid (NP) protein. The VLPs appeared similar morphologically to authentic virions by electron microscopy. CsCl density gradient centrifugation indicated that almost all of the NP protein in the cells had assembled into nucleocapsid-like structures. Deletion of the F and HN cytoplasmic tails indicated an important role of these cytoplasmic tails in VLP budding. Furthermore, truncation of the HN cytoplasmic tail was found to be inhibitory toward budding, since it prevented coexpressed wild-type (wt) F protein from directing VLP budding. Conversely, truncation of the F protein cytoplasmic tail was not inhibitory and did not affect the ability of coexpressed wt HN protein to direct the budding of particles. Taken together, these data suggest that multiple viral components, including assembled nucleocapsids, have important roles in the paramyxovirus budding process. PMID:11907235

Schmitt, Anthony P; Leser, George P; Waning, David L; Lamb, Robert A

2002-04-01

245

Duration of Maternal Antibodies against Canine Distemper Virus and Hendra Virus in Pteropid Bats  

PubMed Central

Old World frugivorous bats have been identified as natural hosts for emerging zoonotic viruses of significant public health concern, including henipaviruses (Nipah and Hendra virus), Ebola virus, and Marburg virus. Epidemiological studies of these viruses in bats often utilize serology to describe viral dynamics, with particular attention paid to juveniles, whose birth increases the overall susceptibility of the population to a viral outbreak once maternal immunity wanes. However, little is understood about bat immunology, including the duration of maternal antibodies in neonates. Understanding duration of maternally derived immunity is critical for characterizing viral dynamics in bat populations, which may help assess the risk of spillover to humans. We conducted two separate studies of pregnant Pteropus bat species and their offspring to measure the half-life and duration of antibodies to 1) canine distemper virus antigen in vaccinated captive Pteropus hypomelanus; and 2) Hendra virus in wild-caught, naturally infected Pteropus alecto. Both of these pteropid bat species are known reservoirs for henipaviruses. We found that in both species, antibodies were transferred from dam to pup. In P. hypomelanus pups, titers against CDV waned over a mean period of 228.6 days (95% CI: 185.4–271.8) and had a mean terminal phase half-life of 96.0 days (CI 95%: 30.7–299.7). In P. alecto pups, antibodies waned over 255.13 days (95% CI: 221.0–289.3) and had a mean terminal phase half-life of 52.24 days (CI 95%: 33.76–80.83). Each species showed a duration of transferred maternal immunity of between 7.5 and 8.5 months, which was longer than has been previously estimated. These data will allow for more accurate interpretation of age-related Henipavirus serological data collected from wild pteropid bats.

Zambrana-Torrelio, Carlos; Middleton, Deborah; Barr, Jennifer A.; DuBovi, Edward; Boyd, Victoria; Pope, Brian; Todd, Shawn; Crameri, Gary; Walsh, Allyson; Pelican, Katey; Fielder, Mark D.; Davies, Angela J.; Wang, Lin-Fa; Daszak, Peter

2013-01-01

246

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

247

Studies on Arbor Viruses.  

National Technical Information Service (NTIS)

Brain antigens from Chikungunya, Semliki, St. Louis, West Nile, and Ntaya viruses as well as antigens from Sindbis virus prepared from the brain tissue of suckling mice and from culture fluid after inoculation of a trypsinized culture of chick embryo fibr...

V. D. Neustroev T. A. Salagova T. A. Rezepova K. S. Kulikov

1968-01-01

248

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

249

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

250

Deformed wing virus  

Microsoft Academic Search

Deformed wing virus (DWV; Iflaviridae) is one of many viruses infecting honeybees and one of the most heavily investigated due to its close association with honeybee colony collapse induced by Varroadestructor. In the absence of V.destructor DWV infection does not result in visible symptoms or any apparent negative impact on host fitness. However, for reasons that are still not fully

Joachim R. de Miranda; Elke Genersch

2010-01-01

251

Computer Virus Propagation Models  

Microsoft Academic Search

The availability of reliable models of computer virus propa- gation would prove useful in a number of ways, in order both to predict future threats, and to develop new containment measures. In this pa- per, we review the most popular models of virus propagation, analyzing the underlying assumptions of each of them, their strengths and their weaknesses. We also introduce

Giuseppe Serazzi; Stefano Zanero

2003-01-01

252

Introduction to computer viruses.  

National Technical Information Service (NTIS)

This report on computer viruses is based upon a thesis written for the Master of Science degree in Computer Science from the University of Tennessee in December 1989 by David R. Brown. This thesis is entitled An Analysis of Computer Virus Construction, Pr...

D. R. Brown

1992-01-01

253

Schmallenberg Virus as Possible Ancestor of Shamonda Virus  

PubMed Central

Schmallenberg virus (SBV), an orthobunyavirus of the Simbu serogroup, recently emerged in Europe and has been suggested to be a Shamonda/Sathuperi virus reassortant. Results of full-genome and serologic investigations indicate that SBV belongs to the species Sathuperi virus and is a possible ancestor of the reassortant Shamonda virus.

Goller, Katja V.; Hoper, Dirk; Schirrmeier, Horst; Mettenleiter, Thomas C.

2012-01-01

254

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.

Ford, Rosemary; Evans, Tom

2011-01-01

255

Hepatitis B Virus Biology  

PubMed Central

Hepadnaviruses (hepatitis B viruses) cause transient and chronic infections of the liver. Transient infections run a course of several months, and chronic infections are often lifelong. Chronic infections can lead to liver failure with cirrhosis and hepatocellular carcinoma. The replication strategy of these viruses has been described in great detail, but virus-host interactions leading to acute and chronic disease are still poorly understood. Studies on how the virus evades the immune response to cause prolonged transient infections with high-titer viremia and lifelong infections with an ongoing inflammation of the liver are still at an early stage, and the role of the virus in liver cancer is still elusive. The state of knowledge in this very active field is therefore reviewed with an emphasis on past accomplishments as well as goals for the future.

Seeger, Christoph; Mason, William S.

2000-01-01

256

Rapid Detection of Enveloped Viruses.  

National Technical Information Service (NTIS)

M-protein of influenza virus is a type-specific antigen and the most invariant protein of the virus. A rapid virus detection system based on M-protein detection would detect all type A influenza viruses and be independent of antigenic shift and drift. To ...

D. J. Bucher

1988-01-01

257

Evolution of avian influenza viruses  

Microsoft Academic Search

Although influenza viruses can infect a wide variety of birds and mammals, the natural host of the virus is wild waterfowl, shorebirds, and gulls. When other species of animals, including chickens, turkeys, swine, horses, and humans, are infected with influenza viruses, they are considered aberrant hosts. The distinction between the normal and aberrant host is important when describing virus evolution

David L. Suarez

2000-01-01

258

Virus-PEDOT Biocomposite Films  

PubMed Central

Virus-poly(3,4-ethylenedioxythiophene) (virus-PEDOT) biocomposite films are prepared by electropolymerizing 3,4-ethylenedioxythiophene (EDOT) in aqueous electrolytes containing 12 mM LiClO4 and the bacteriophage M13. The concentration of virus in these solutions, [virus]soln, is varied from 3 nM to 15 nM. A quartz crystal microbalance is used to directly measure the total mass of the biocomposite film during its electrodeposition. In combination with a measurement of the electrodeposition charge, the mass of the virus incorporated into the film is calculated. These data show that concentration of the M13 within the electropolymerized film, [virus]film, increases linearly with [virus]soln. The incorporation of virus particles into the PEDOT film from solution is efficient, resulting in a concentration ratio: [virus]film:[virus]soln ?450. Virus incorporation into the PEDOT causes roughening of the film topography that is observed using scanning electron microscopy and atomic force microscopy (AFM). The electrical conductivity of the virus-PEDOT film, measured perpendicular to the plane of the film using conductive tip AFM, decreases linearly with virus loading, from 270 ?S/cm for pure PE-DOT films to 50 ?S/cm for films containing 100 ?M virus. The presence on the virus surface of displayed affinity peptides did not significantly influence the efficiency of incorporation into virus-PEDOT biocomposite films.

Donavan, Keith C.; Arter, Jessica A.

2012-01-01

259

A Virus in Turbo Pascal.  

ERIC Educational Resources Information Center

Addresses why the authors feel it is not inappropriate to teach about viruses in the how-to, hands-on fashion. Identifies the special features of Turbo Pascal that have to be used for the creation of an effective virus. Defines virus, derives its structure, and from this structure is derived the implemented virus. (PR)

Teleky, Heidi Ann; And Others

1993-01-01

260

Computer Viruses: Pathology and Detection.  

ERIC Educational Resources Information Center

Explains how computer viruses were originally created, how a computer can become infected by a virus, how viruses operate, symptoms that indicate a computer is infected, how to detect and remove viruses, and how to prevent a reinfection. A sidebar lists eight antivirus resources. (four references) (LRW)

Maxwell, John R.; Lamon, William E.

1992-01-01

261

An enzymatic virus-like particle assay for sensitive detection of virus entry.  

PubMed

A viral entry assay where a beta-lactamase reporter protein fused to the influenza matrix protein-1 (BlaM1) is packaged as a structural component into influenza virus-like particles (VLPs) is described. The Bla reporter is released upon fusion with target cells and can be detected in live cells by flow cytometry, microscopy, or fluorometric plate reader for utility in high-throughput screening approaches. The production of BlaM1 VLPs and subsequent transfer of Bla activity to target cells requires the presence of influenza hemagglutinin (HA) and neuraminidase (NA). In addition, transfer of Bla by the VLPs can be blocked by an influenza neutralizing antibody, is impeded by a chemical inhibitor of influenza virus entry, and requires HA that is cleaved by a protease specific for its cleavage site. An analogous VLP system also was developed for Ebola (EBOV) and Marburg (MARV) viruses, demonstrating that this straightforward assay has broad application for studying the entry steps of enveloped viruses, especially those that require high levels of biosafety containment. PMID:19879300

Tscherne, Donna M; Manicassamy, Balaji; García-Sastre, Adolfo

2010-02-01

262

Ocular Tropism of Respiratory Viruses  

PubMed Central

SUMMARY Respiratory viruses (including adenovirus, influenza virus, respiratory syncytial virus, coronavirus, and rhinovirus) cause a broad spectrum of disease in humans, ranging from mild influenza-like symptoms to acute respiratory failure. While species D adenoviruses and subtype H7 influenza viruses are known to possess an ocular tropism, documented human ocular disease has been reported following infection with all principal respiratory viruses. In this review, we describe the anatomical proximity and cellular receptor distribution between ocular and respiratory tissues. All major respiratory viruses and their association with human ocular disease are discussed. Research utilizing in vitro and in vivo models to study the ability of respiratory viruses to use the eye as a portal of entry as well as a primary site of virus replication is highlighted. Identification of shared receptor-binding preferences, host responses, and laboratory modeling protocols among these viruses provides a needed bridge between clinical and laboratory studies of virus tropism.

Rota, Paul A.; Tumpey, Terrence M.

2013-01-01

263

Enteric hepatitis viruses  

PubMed Central

Hepatitis viruses are infectious agents that can infect liver and cause inflammation. The infection triggers immune response against infected cells that leads to the destruction of hepatic cells. This destruction has two consequences: leaking ALT and AST liver enzymes which increases during the course of disease and accumulation of bilirubin- a red pigmented compound released from dead red cells- which causes the yellow coloration of eyes and skin. These viruses transmit through diverse routes i.e. blood transfusion, sexual contacts and consuming water or food contaminated by feces. Enteric hepatitis viruses use the latter route for transmission; hence their outbreaks are more common in underdeveloped countries. There are currently two distinguished enteric hepatitis viruses, hepatitis A and hepatitis E. These viruses belong to different family of viruses and their epidemiological characteristics are different. These infections can be diagnosed by an ELISA for IgM antibody. A vaccine has been developed in last decade of twentieth century for hepatitis A virus, which is administered mostly in the developed world i.e. U.S and Japan. Treatment for these infections is mostly supportive; however, in the case of fulminant hepatitis the liver transplantation might be necessary.

Tahaei, Seyed Mohammad Ebrahim; Zali, Mohammad Reza

2012-01-01

264

Expression of an immunogenic Ebola immune complex in Nicotiana benthamiana  

PubMed Central

Summary Filoviruses (Ebola and Marburg viruses) cause severe and often fatal hemorrhagic fever in humans and non-human primates. The US Centers for Disease Control identify Ebola and Marburg viruses as “category A” pathogens (defined as posing a risk to national security as bioterrorism agents), which has lead to a search for vaccines that could prevent the disease. Because the use of such vaccines would be in the service of public health, the cost of production is an important component of their development. The use of plant biotechnology is one possible way to cost-effectively produce subunit vaccines. In this work, a geminiviral replicon system was used to produce an Ebola immune complex (EIC) in Nicotiana benthamiana. Ebola glycoprotein (GP1) was fused at the C-terminus of the heavy chain of humanized 6D8 IgG monoclonal antibody, which specifically binds to a linear epitope on GP1. Co-expression of the GP1-heavy chain fusion and the 6D8 light chain using a geminiviral vector in leaves of Nicotiana benthamiana produced assembled immunoglobulin, which was purified by ammonium sulfate precipitation and protein G affinity chromatography. Immune complex formation was confirmed by assays to show that the recombinant protein bound the complement factor C1q. Size measurements of purified recombinant protein by dynamic light scattering and size exclusion chromatography also indicated complex formation. Subcutaneous immunization of BALB/C mice with purified EIC resulted in anti-Ebola virus antibody production at levels comparable to those obtained with a GP1 virus-like particle. These results show excellent potential for a plant-expressed EIC as a human vaccine.

Bhoo, Seong Hee; Lai, Huafang; Ma, Julian; Arntzen, Charles J.; Chen, Qiang; Mason, Hugh S.

2014-01-01

265

Cucumber mosaic virus.  

PubMed

Cucumber mosaic virus (CMV) is an important virus because of its agricultural impact in the Mediterranean Basin and worldwide, and also as a model for understanding plant-virus interactions. This review focuses on those areas where most progress has been made over the past decade in our understanding of CMV. Clearly, a deep understanding of the role of the recently described CMV 2b gene in suppression of host RNA silencing and viral virulence is the most important discovery. These findings have had an impact well beyond the virus itself, as the 2b gene is an important tool in the studies of eukaryotic gene regulation. Protein 2b was shown to be involved in most of the steps of the virus cycle and to interfere with several basal host defenses. Progress has also been made concerning the mechanisms of virus replication and movement. However, only a few host proteins that interact with viral proteins have been identified, making this an area of research where major efforts are still needed. Another area where major advances have been made is CMV population genetics, where contrasting results were obtained. On the one hand, CMV was shown to be prone to recombination and to show high genetic diversity based on sequence data of different isolates. On the other hand, populations did not exhibit high genetic variability either within plants, or even in a field and the nearby wild plants. The situation was partially clarified with the finding that severe bottlenecks occur during both virus movement within a plant and transmission between plants. Finally, novel studies were undertaken to elucidate mechanisms leading to selection in virus population, according to the host or its environment, opening a new research area in plant-virus coevolution. PMID:22682176

Jacquemond, Mireille

2012-01-01

266

Polyoma BK Virus: An Oncogenic Virus?  

PubMed Central

We report a case of a 65-year-old gentleman with a history of end stage renal disease who underwent a successful cadaveric donor kidney transplant four years ago. He subsequently developed BK virus nephropathy related to chronic immunosuppressant therapy. Three years later, misfortune struck again, and he developed adenocarcinoma of the bladder.

Hassan, Syed; Alirhayim, Zaid; Ahmed, Syed; Amer, Syed

2013-01-01

267

Genome of Horsepox Virus  

PubMed Central

Here we present the genomic sequence of horsepox virus (HSPV) isolate MNR-76, an orthopoxvirus (OPV) isolated in 1976 from diseased Mongolian horses. The 212-kbp genome contained 7.5-kbp inverted terminal repeats and lacked extensive terminal tandem repetition. HSPV contained 236 open reading frames (ORFs) with similarity to those in other OPVs, with those in the central 100-kbp region most conserved relative to other OPVs. Phylogenetic analysis of the conserved region indicated that HSPV is closely related to sequenced isolates of vaccinia virus (VACV) and rabbitpox virus, clearly grouping together these VACV-like viruses. Fifty-four HSPV ORFs likely represented fragments of 25 orthologous OPV genes, including in the central region the only known fragmented form of an OPV ribonucleotide reductase large subunit gene. In terminal genomic regions, HSPV lacked full-length homologues of genes variably fragmented in other VACV-like viruses but was unique in fragmentation of the homologue of VACV strain Copenhagen B6R, a gene intact in other known VACV-like viruses. Notably, HSPV contained in terminal genomic regions 17 kbp of OPV-like sequence absent in known VACV-like viruses, including fragments of genes intact in other OPVs and approximately 1.4 kb of sequence present only in cowpox virus (CPXV). HSPV also contained seven full-length genes fragmented or missing in other VACV-like viruses, including intact homologues of the CPXV strain GRI-90 D2L/I4R CrmB and D13L CD30-like tumor necrosis factor receptors, D3L/I3R and C1L ankyrin repeat proteins, B19R kelch-like protein, D7L BTB/POZ domain protein, and B22R variola virus B22R-like protein. These results indicated that HSPV contains unique genomic features likely contributing to a unique virulence/host range phenotype. They also indicated that while closely related to known VACV-like viruses, HSPV contains additional, potentially ancestral sequences absent in other VACV-like viruses.

Tulman, E. R.; Delhon, G.; Afonso, C. L.; Lu, Z.; Zsak, L.; Sandybaev, N. T.; Kerembekova, U. Z.; Zaitsev, V. L.; Kutish, G. F.; Rock, D. L.

2006-01-01

268

[Enigmatic archaeal viruses].  

PubMed

Viruses infecting microorganisms of the third domain of life, Archaea, are still poorly characterized: to date, only about fifty of these viruses have been isolated. Their hosts are hyperthermophilic, acidothermophilic, and extreme halophilic or methanogenic archaea. Their morphotypes are highly diverse and their gene content is very specific. Some of these viruses have developed extraordinary mechanisms to open the cell wall thanks to the formation of exceptional pyramidal nanostructures. The still limited knowledge about the biology of archaeoviruses should develop rapidly in the coming years. PMID:24330970

Bize, Ariane; Sezonov, Guennadi; Prangishvili, David

2013-01-01

269

Virus templated metallic nanoparticles.  

PubMed

Plant viruses are considered as nanobuilding blocks that can be used as synthons or templates for novel materials. Cowpea mosaic virus (CPMV) particles have been shown to template the fabrication of metallic nanoparticles by an electroless deposition metallization process. Palladium ions were electrostatically bound to the virus capsid and, when reduced, acted as nucleation sites for the subsequent metal deposition from solution. The method, although simple, produced highly monodisperse metallic nanoparticles with a diameter of ca. ?35 nm. CPMV-templated particles were prepared with cobalt, nickel, iron, platinum, cobalt-platinum and nickel-iron. PMID:20877898

Aljabali, Alaa A A; Barclay, J Elaine; Lomonossoff, George P; Evans, David J

2010-12-01

270

Respiratory syncytial virus (RSV)  

MedlinePLUS

... often spreads very rapidly in crowded households and day care centers. The virus can live for a half ... The following increase the risk for RSV: Attending day care Being near tobacco smoke Having school-aged brothers ...

271

Viruses causing gastroenteritis.  

PubMed

Acute gastroenteritis is one of the most common diseases in humans worldwide. Viruses are recognized as important causes of this disease, particularly in children. Since the Norwalk virus was identified as a cause of gastroenteritis, the number of viral agents associated with diarrheal disease in humans has steadily increased. Rotavirus is the most common cause of severe diarrhea in children under 5 years of age. Astrovirus, calicivirus and enteric adenovirus are also important etiologic agents of acute gastroenteritis. Other viruses, such as toroviruses, coronaviruses, picobirnaviruses and pestiviruses, are increasingly being identified as causative agents of diarrhea. In recent years, the availability of diagnostic tests, mainly immunoassays or molecular biology techniques, has increased our understanding of this group of viruses. The future development of a safe and highly effective vaccine against rotavirus could prevent, at least, cases of severe diarrhea and reduce mortality from this disease. PMID:12667234

Wilhelmi, I; Roman, E; Sánchez-Fauquier, A

2003-04-01

272

Hepatitis B virus (image)  

MedlinePLUS

Hepatitis B is also known as serum hepatitis and is spread through blood and sexual contact. It is ... population. This photograph is an electronmicroscopic image of hepatitis B virus particles. (Image courtesy of the Centers for ...

273

Respiratory Syncytial Virus (RSV)  

MedlinePLUS

... and between 12 and 15 months. What is hepatitis B? Hepatitis B is caused by the hepatitis B virus. It can lead to serious liver disease. Signs of hepatitis B infection include belly pain, joint pain, dark urine, ...

274

The influenza viruses  

Microsoft Academic Search

Human epidemic influenza is caused by influenza type A and B viruses, which continually undergo antigenic change in their surface antigens, haemagglutinin (H) and neuraminidase (N). • Influenza epidemics are the consequence of small, ongoing antigenic changes known as \\

Alan W Hampson; John S Mackenzie

2006-01-01

275

Virus Ultra Structure  

NSDL National Science Digital Library

Linda Stannard of the University of Capetown, South Africa, has composed a page which, although it was intended to serve as an introductory manual for students of virology, can be appreciated by a wide audience. A section on the principles of virus architecture uses text and outstanding graphics to provide an introduction to why viruses look the way they do. Other parts of the site emphasize how virus shapes and structures are "seen" and recorded with sections on negative staining and electron microscopy of DNA- and RNA-containing viruses. This site's success relies on the use of well-chosen graphics and the inclusion of interesting factoids such as the following: "The head of a dress-maker's pin can provide seating accommodation for five hundred million rhinoviruses (cause of the common cold)!".

276

Smaller Fleas: Viruses of Microorganisms  

PubMed Central

Life forms can be roughly differentiated into those that are microscopic versus those that are not as well as those that are multicellular and those that, instead, are unicellular. Cellular organisms seem generally able to host viruses, and this propensity carries over to those that are both microscopic and less than truly multicellular. These viruses of microorganisms, or VoMs, in fact exist as the world's most abundant somewhat autonomous genetic entities and include the viruses of domain Bacteria (bacteriophages), the viruses of domain Archaea (archaeal viruses), the viruses of protists, the viruses of microscopic fungi such as yeasts (mycoviruses), and even the viruses of other viruses (satellite viruses). In this paper we provide an introduction to the concept of viruses of microorganisms, a.k.a., viruses of microbes. We provide broad discussion particularly of VoM diversity. VoM diversity currently spans, in total, at least three-dozen virus families. This is roughly ten families per category—bacterial, archaeal, fungal, and protist—with some virus families infecting more than one of these microorganism major taxa. Such estimations, however, will vary with further discovery and taxon assignment and also are dependent upon what forms of life one includes among microorganisms.

Hyman, Paul; Abedon, Stephen T.

2012-01-01

277

Detection of Nipah Virus RNA in Fruit Bat (Pteropus giganteus) from India  

PubMed Central

The study deals with the survey of different bat populations (Pteropus giganteus, Cynopterus sphinx, and Megaderma lyra) in India for highly pathogenic Nipah virus (NiV), Reston Ebola virus, and Marburg virus. Bats (n = 140) from two states in India (Maharashtra and West Bengal) were tested for IgG (serum samples) against these viruses and for virus RNAs. Only NiV RNA was detected in a liver homogenate of P. giganteus captured in Myanaguri, West Bengal. Partial sequence analysis of nucleocapsid, glycoprotein, fusion, and phosphoprotein genes showed similarity with the NiV sequences from earlier outbreaks in India. A serum sample of this bat was also positive by enzyme-linked immunosorbent assay for NiV-specific IgG. This is the first report on confirmation of Nipah viral RNA in Pteropus bat from India and suggests the possible role of this species in transmission of NiV in India.

Yadav, Pragya D.; Raut, Chandrashekhar G.; Shete, Anita M.; Mishra, Akhilesh C.; Towner, Jonathan S.; Nichol, Stuart T.; Mourya, Devendra T.

2012-01-01

278

Virus templated metallic nanoparticles  

NASA Astrophysics Data System (ADS)

Plant viruses are considered as nanobuilding blocks that can be used as synthons or templates for novel materials. Cowpea mosaic virus (CPMV) particles have been shown to template the fabrication of metallic nanoparticles by an electroless deposition metallization process. Palladium ions were electrostatically bound to the virus capsid and, when reduced, acted as nucleation sites for the subsequent metal deposition from solution. The method, although simple, produced highly monodisperse metallic nanoparticles with a diameter of ca. <=35 nm. CPMV-templated particles were prepared with cobalt, nickel, iron, platinum, cobalt-platinum and nickel-iron.Plant viruses are considered as nanobuilding blocks that can be used as synthons or templates for novel materials. Cowpea mosaic virus (CPMV) particles have been shown to template the fabrication of metallic nanoparticles by an electroless deposition metallization process. Palladium ions were electrostatically bound to the virus capsid and, when reduced, acted as nucleation sites for the subsequent metal deposition from solution. The method, although simple, produced highly monodisperse metallic nanoparticles with a diameter of ca. <=35 nm. CPMV-templated particles were prepared with cobalt, nickel, iron, platinum, cobalt-platinum and nickel-iron. Electronic supplementary information (ESI) available: Additional experimental detail, agarose gel electrophoresis results, energy dispersive X-ray spectra, ?-potential measurements, dynamic light scattering data, nanoparticle tracking analysis and an atomic force microscopy image of Ni-CPMV. See DOI: 10.1039/c0nr00525h

Aljabali, Alaa A. A.; Barclay, J. Elaine; Lomonossoff, George P.; Evans, David J.

2010-12-01

279

Oncogenic Viruses of Nonhuman Primates: A Review.  

National Technical Information Service (NTIS)

Oncogenic viruses of nonhuman primates were reviewed. Viruses of nonhuman primate origin oncogenic in other nonhuman primates includes Herpesvirus saimiri and ateles, simian sarcoma virus, Yaba poxvirus, and oral papilloma virus. SV-40 and simian adenovir...

C. P. Raflo

1975-01-01

280

Recombinant Vaccinia Virus: Immunization against Multiple Pathogens  

NASA Astrophysics Data System (ADS)

The coding sequences for the hepatitis B virus surface antigen, the herpes simplex virus glycoprotein D, and the influenza virus hemagglutinin were inserted into a single vaccinia virus genome. Rabbits inoculated intravenously or intradermally with this polyvalent vaccinia virus recombinant produced antibodies reactive to all three authentic foreign antigens. In addition, the feasibility of multiple rounds of vaccination with recombinant vaccinia virus was demonstrated.

Perkus, Marion E.; Piccini, Antonia; Lipinskas, Bernard R.; Paoletti, Enzo

1985-09-01

281

Durability of a vesicular stomatitis virus-based marburg virus vaccine in nonhuman primates.  

PubMed

The filoviruses, Marburg virus (MARV) and Ebola virus, causes severe hemorrhagic fever with high mortality in humans and nonhuman primates. A promising filovirus vaccine under development is based on a recombinant vesicular stomatitis virus (rVSV) that expresses individual filovirus glycoproteins (GPs) in place of the VSV glycoprotein (G). These vaccines have shown 100% efficacy against filovirus infection in nonhuman primates when challenge occurs 28-35 days after a single injection immunization. Here, we examined the ability of a rVSV MARV-GP vaccine to provide protection when challenge occurs more than a year after vaccination. Cynomolgus macaques were immunized with rVSV-MARV-GP and challenged with MARV approximately 14 months after vaccination. Immunization resulted in the vaccine cohort of six animals having anti-MARV GP IgG throughout the pre-challenge period. Following MARV challenge none of the vaccinated animals showed any signs of clinical disease or viremia and all were completely protected from MARV infection. Two unvaccinated control animals exhibited signs consistent with MARV infection and both succumbed. Importantly, these data are the first to show 100% protective efficacy against any high dose filovirus challenge beyond 8 weeks after final vaccination. These findings demonstrate the durability of VSV-based filovirus vaccines. PMID:24759889

Mire, Chad E; Geisbert, Joan B; Agans, Krystle N; Satterfield, Benjamin A; Versteeg, Krista M; Fritz, Elizabeth A; Feldmann, Heinz; Hensley, Lisa E; Geisbert, Thomas W

2014-01-01

282

Durability of a Vesicular Stomatitis Virus-Based Marburg Virus Vaccine in Nonhuman Primates  

PubMed Central

The filoviruses, Marburg virus (MARV) and Ebola virus, causes severe hemorrhagic fever with high mortality in humans and nonhuman primates. A promising filovirus vaccine under development is based on a recombinant vesicular stomatitis virus (rVSV) that expresses individual filovirus glycoproteins (GPs) in place of the VSV glycoprotein (G). These vaccines have shown 100% efficacy against filovirus infection in nonhuman primates when challenge occurs 28–35 days after a single injection immunization. Here, we examined the ability of a rVSV MARV-GP vaccine to provide protection when challenge occurs more than a year after vaccination. Cynomolgus macaques were immunized with rVSV-MARV-GP and challenged with MARV approximately 14 months after vaccination. Immunization resulted in the vaccine cohort of six animals having anti-MARV GP IgG throughout the pre-challenge period. Following MARV challenge none of the vaccinated animals showed any signs of clinical disease or viremia and all were completely protected from MARV infection. Two unvaccinated control animals exhibited signs consistent with MARV infection and both succumbed. Importantly, these data are the first to show 100% protective efficacy against any high dose filovirus challenge beyond 8 weeks after final vaccination. These findings demonstrate the durability of VSV-based filovirus vaccines.

Mire, Chad E.; Geisbert, Joan B.; Agans, Krystle N.; Satterfield, Benjamin A.; Versteeg, Krista M.; Fritz, Elizabeth A.; Feldmann, Heinz; Hensley, Lisa E.; Geisbert, Thomas W.

2014-01-01

283

Multiple virus infections in the honey bee and genome divergence of honey bee viruses  

Microsoft Academic Search

Using uniplex RT-PCR we screened honey bee colonies for the presence of several bee viruses, including black queen cell virus (BQCV), deformed wing virus (DWV), Kashmir bee virus (KBV), and sacbrood virus (SBV), and described the detection of mixed virus infections in bees from these colonies. We report for the first time that individual bees can harbor four viruses simultaneously.

Yanping Chen; Yan Zhao; John Hammond; Hei-ti Hsu; Jay Evans; Mark Feldlaufer

2004-01-01

284

Characterization of K virus and its comparison with polyoma virus.  

PubMed Central

The antigenic relationship between the two murine papovaviruses, K virus and polyoma virus, was examined by serological techniques to determine whether they shared any antigenic components. No cross-reactivity was found associated with the viral (V) antigens by the indirect immunofluorescence, neutralization, or hemagglutination-inhibition tests. The tumor (T) antigens expressed in transformed cells or cells productively infected by either K or polyoma virus did not cross-react by indirect immunofluorescence. An antigenic relationship was detected, however, among the late proteins of K virus, polyoma virus, simian virus 40, and the human papovavirus BKV, when tested with either hyperimmune sera prepared against polyoma virus and simian virus 40 or sera prepared against disrupted virions. The nucleic acids of K and polyoma viruses were compared by agarose gel electrophoresis and restriction endonuclease analysis. No nucleotide sequence homology between the genomes of these two viruses was detectable by DNA-DNA hybridization techniques under stringent conditions. The genome of K virus was found to be slightly smaller than that of polyoma virus, and the cleavage patterns of the viral DNAs with six restriction endonucleases were different. These findings indicate that there is little relationship between these two murine papovaviruses. Images

Bond, S B; Howley, P M; Takemoto, K K

1978-01-01

285

Immunology of hepatitis B virus and hepatitis C virus infection  

Microsoft Academic Search

More than 500 million people worldwide are persistently infected with the hepatitis B virus (HBV) and\\/or hepatitis C virus (HCV) and are at risk of developing chronic liver disease, cirrhosis and hepatocellular carcinoma. Despite many common features in the pathogenesis of HBV- and HCV-related liver disease, these viruses markedly differ in their virological properties and in their immune escape and

Michelina Nascimbeni; Barbara Rehermann

2005-01-01

286

Production of virus resistant plants  

DOEpatents

A method of suppressing virus gene expression in plants using untranslatable plus sense RNA is disclosed. The method is useful for the production of plants that are resistant to virus infection. 9 figs.

Dougherty, W.G.; Lindbo, J.A.

1996-12-10

287

Chlorella viruses isolated in China  

SciTech Connect

Plaque-forming viruses of the unicellular, eukaryotic, exsymbiotic, Chlorella-like green algae strain NC64A, which are common in the United States, were also present in fresh water collected in the People's Republic of China. Seven of the Chinese viruses were examined in detail and compared with the Chlorella viruses previously isolated in the United States. Like the American viruses, the Chinese viruses were large polyhedra and sensitive to chloroform. They contained numerous structural proteins and large double-stranded DNA genomes of at least 300 kilobase pairs. Each of the DNAs from the Chinese viruses contained 5-methyldeoxycytosine, which varied from 12.6 to 46.7% of the deoxycytosine, and N{sup 6}-methyldeoxyadenosine, which varied from 2.2 to 28.3% of the deoxyadenosine. Four of the Chinese virus DNAs hybridized extensively with {sup 32}P-labeled DNA from the American virus PBCV-1, and three hybridized poorly.

Zhang, Y.; Burbank, D.E.; Van Etten, J.L. (Univ. of Nebraska, Lincoln (USA))

1988-09-01

288

Viruses and Multiple Sclerosis  

PubMed Central

Multiple sclerosis (MS) is a chronic demyelinating disorder of unknown etiology, possibly caused by a virus or virus-triggered immunopathology. The virus might reactivate after years of latency and lyse oligodendrocytes, as in progressive multifocal leukoencephalopathy, or initiate immunopathological demyelination, as in animals infected with Theiler’s murine encephalomyelitis virus or coronaviruses. The argument for a viral cause of MS is supported by epidemiological analyses and studies of MS in identical twins, indicating that disease is acquired. However, the most important evidence is the presence of bands of oligoclonal IgG (OCBs) in MS brain and CSF that persist throughout the lifetime of the patient. OCBs are found almost exclusively in infectious CNS disorders, and antigenic targets of OCBs represent the agent that causes disease. Here, the authors review past attempts to identify an infectious agent in MS brain cells and discuss the promise of using recombinant antibodies generated from clonally expanded plasma cells in brain and CSF to identify disease-relevant antigens. They show how this strategy has been used successfully to analyze antigen specificity in subacute sclerosing panencephalitis, a chronic encephalitis caused by measles virus, and in neuromyelitis optica, a chronic autoimmune demyelinating disease produced by antibodies directed against the aquaporin-4 water channel.

Owens, Gregory P.; Gilden, Don; Burgoon, Mark P.; Yu, Xiaoli; Bennett, Jeffrey L.

2012-01-01

289

Viruses and multiple sclerosis.  

PubMed

Multiple sclerosis (MS) is a chronic demyelinating disorder of unknown etiology, possibly caused by a virus or virus-triggered immunopathology. The virus might reactivate after years of latency and lyse oligodendrocytes, as in progressive multifocal leukoencephalopathy, or initiate immunopathological demyelination, as in animals infected with Theiler's murine encephalomyelitis virus or coronaviruses. The argument for a viral cause of MS is supported by epidemiological analyses and studies of MS in identical twins, indicating that disease is acquired. However, the most important evidence is the presence of bands of oligoclonal IgG (OCBs) in MS brain and CSF that persist throughout the lifetime of the patient. OCBs are found almost exclusively in infectious CNS disorders, and antigenic targets of OCBs represent the agent that causes disease. Here, the authors review past attempts to identify an infectious agent in MS brain cells and discuss the promise of using recombinant antibodies generated from clonally expanded plasma cells in brain and CSF to identify disease-relevant antigens. They show how this strategy has been used successfully to analyze antigen specificity in subacute sclerosing panencephalitis, a chronic encephalitis caused by measles virus, and in neuromyelitis optica, a chronic autoimmune demyelinating disease produced by antibodies directed against the aquaporin-4 water channel. PMID:22130640

Owens, Gregory P; Gilden, Don; Burgoon, Mark P; Yu, Xiaoli; Bennett, Jeffrey L

2011-12-01

290

Nongenital herpes simplex virus.  

PubMed

Nongenital herpes simplex virus type 1 is a common infection usually transmitted during childhood via nonsexual contact. Most of these infections involve the oral mucosa or lips (herpes labialis). The diagnosis of an infection with herpes simplex virus type 1 is usually made by the appearance of the lesions (grouped vesicles or ulcers on an erythematous base) and patient history. However, if uncertain, the diagnosis of herpes labialis can be made by viral culture, polymerase chain reaction, serology, direct fluorescent antibody testing, or Tzanck test. Other nonoral herpes simplex virus type 1 infections include herpetic keratitis, herpetic whitlow, herpes gladiatorum, and herpetic sycosis of the beard area. The differential diagnosis of nongenital herpes simplex virus infection includes aphthous ulcers, acute paronychia, varicella-zoster virus infection, herpangina, herpes gestationis (pemphigoid gestationis), pemphigus vulgaris, and Behçet syndrome. Oral acyclovir suspension is an effective treatment for children with primary herpetic gingivostomatitis. Oral acyclovir, valacyclovir, and famciclovir are effective in treating acute recurrence of herpes labialis (cold sores). Recurrences of herpes labialis may be diminished with daily oral acyclovir or valacyclovir. Topical acyclovir, penciclovir, and docosanol are optional treatments for recurrent herpes labialis, but they are less effective than oral treatment. PMID:21121552

Usatine, Richard P; Tinitigan, Rochelle

2010-11-01

291

Virus Evolution and Population Dynamics  

Microsoft Academic Search

It is intuitive that the field of virology is a discipline integral to the medical sciences. The affiliation of virology with population and conservation biology may not be as apparent. However, viruses, and in particular, virus evolution, may both contribute to and be a significant tool to understand changes in host population structure. The impact of viruses is most notable

Mary Poss; Roman Biek; Allen Rodrigo

292

Rhabdomyolysis Associated with Parainfluenza Virus  

PubMed Central

Influenza virus is the most frequently reported viral cause of rhabdomyolysis. A 7-year-old child is presented with rhabdomyolysis associated with parainfluenza type 2 virus. Nine cases of rhabdomyolysis associated with parainfluenza virus have been reported. Complications may include electrolyte disturbances, acute renal failure, and compartment syndrome.

Kielbasa, Johanna M.; Chandrasekharan, Gopal M.; Holmes, Cynthia L.; Gomez, Michael R.

2013-01-01

293

Novel avian influenza virus vaccines  

Microsoft Academic Search

Summary Current vaccines against avian influenza (AI) virus infections are primarily based on classical inactivated whole-virus preparations. Although administration of these vaccines can protect poultry from clinical disease, sterile immunity is not achieved under field conditions, allowing for undetected virus spread and evolution under immune cover. Therefore, there is an urgent need for a robust and reliable system of differentiation

W. Fuchs; A. Römer-Oberdörfer; J. Veits; T. C. Mettenleiter

2009-01-01

294

Virus Necrosis of Tobacco Veins.  

National Technical Information Service (NTIS)

Virus necrosis of tobacco veins (browning of tobacco veins) occurs all over Poland and causes major economic losses. Studies of a number of orders show that the necrosis of tobacco veins is caused by a virus, which belongs to the group of potato virus Y (...

J. Berbec

1964-01-01

295

An introduction to computer viruses  

SciTech Connect

This report on computer viruses is based upon a thesis written for the Master of Science degree in Computer Science from the University of Tennessee in December 1989 by David R. Brown. This thesis is entitled An Analysis of Computer Virus Construction, Proliferation, and Control and is available through the University of Tennessee Library. This paper contains an overview of the computer virus arena that can help the reader to evaluate the threat that computer viruses pose. The extent of this threat can only be determined by evaluating many different factors. These factors include the relative ease with which a computer virus can be written, the motivation involved in writing a computer virus, the damage and overhead incurred by infected systems, and the legal implications of computer viruses, among others. Based upon the research, the development of a computer virus seems to require more persistence than technical expertise. This is a frightening proclamation to the computing community. The education of computer professionals to the dangers that viruses pose to the welfare of the computing industry as a whole is stressed as a means of inhibiting the current proliferation of computer virus programs. Recommendations are made to assist computer users in preventing infection by computer viruses. These recommendations support solid general computer security practices as a means of combating computer viruses.

Brown, D.R.

1992-03-01

296

Deformed wing virus.  

PubMed

Deformed wing virus (DWV; Iflaviridae) is one of many viruses infecting honeybees and one of the most heavily investigated due to its close association with honeybee colony collapse induced by Varroadestructor. In the absence of V.destructor DWV infection does not result in visible symptoms or any apparent negative impact on host fitness. However, for reasons that are still not fully understood, the transmission of DWV by V.destructor to the developing pupae causes clinical symptoms, including pupal death and adult bees emerging with deformed wings, a bloated, shortened abdomen and discolouration. These bees are not viable and die soon after emergence. In this review we will summarize the historical and recent data on DWV and its relatives, covering the genetics, pathobiology, and transmission of this important viral honeybee pathogen, and discuss these within the wider theoretical concepts relating to the genetic variability and population structure of RNA viruses, the evolution of virulence and the development of disease symptoms. PMID:19909976

de Miranda, Joachim R; Genersch, Elke

2010-01-01

297

Neuroinvasion by Chandipura virus.  

PubMed

Chandipura virus (CHPV) is an arthropod borne rhabdovirus associated with acute encephalitis in children below the age of 15 years in the tropical states of India. Although the entry of the virus into the nervous system is among the crucial events in the pathogenesis of CHPV, the exact mechanism allowing CHPV to invade the central nervous system (CNS) is currently poorly understood. In the present review, based on the knowledge of host interactors previously predicted for CHPV, along with the support from experimental data available for other encephalitic viruses, the authors have speculated the various plausible modes by which CHPV could surpass the blood-brain barrier and invade the CNS to cause encephalitis whilst evading the host immune surveillance. Collectively, this review provides a conservative set of potential interactions that can be employed for future experimental validation with a view to better understand the neuropathogenesis of CHPV. PMID:24713200

Rajasekharan, Sreejith; Rana, Jyoti; Gulati, Sahil; Gupta, Vandana; Gupta, Sanjay

2014-07-01

298

Viruses in water  

PubMed Central

Attention is drawn in this paper to the increasing problem of viral contamination of water and shellfish, particularly since growing demands for available water resources by a rising world population and expanding industry will make the recycling of wastewater almost inevitable in the future. The problem of eliminating viruses pathogenic for man from water is considered in the light of present water treatment procedures, which are often inadequate for that purpose. Man may be exposed to waterborne viruses through the consumption of contaminated water, shellfish, or crops, as a result of recreational activities involving water, or from aerosols following the spraying of crops with liquid wastes. Physical and chemical methods of eliminating viruses from water are discussed.

Melnick, Joseph L.; Gerba, Charles P.; Wallis, Craig

1978-01-01

299

Bagaza virus and Israel turkey meningoencephalomyelitis virus are a single virus species.  

PubMed

Bagaza virus (BAGV) and Israel turkey meningoencephalomyelitis virus (ITV) are classified in the genus Flavivirus of the family Flaviviridae. Serologically, they are closely related, belonging to the Ntaya serocomplex. Nucleotide sequences available to date consist of several complete sequences of BAGV isolates, but only partial sequences of ITV isolates. Sequence comparisons of partial envelope (E) and NS5 regions reveal a close genetic relationship between these viruses. Despite this, BAGV and ITV are considered as separate virus species in the database of the International Committee on Taxonomy of Viruses. In this work, complete nucleotide sequences for five ITV isolates are provided, thereby permitting a phylogenetic comparison with other complete sequences of flaviviruses in the Ntaya serogroup. We conclude that BAGV and ITV are the same virus species and propose that both viruses be designated by a new unified name: Avian meningoencephalomyelitis virus. PMID:24457974

Fernández-Pinero, Jovita; Davidson, Irit; Elizalde, Maia; Perk, Shimon; Khinich, Yevgeny; Jiménez-Clavero, Miguel Angel

2014-04-01

300

West Nile virus.  

PubMed

West Nile virus infection has quickly become a feared cause of neurologic disability and death, particularly when it presents with encephalitis. Recent epidemics in endemic regions of Eurasia and Africa, as well as its recent spread to North America, have highlighted the need for all physicians to be aware of its clinical presentation and course. In particular, because of the increased susceptibility of West Nile virus infection during outdoor activities, as well as during travel to the Middle East and Southeastern Europe, military physicians should be informed about case recognition, management, and prevention to maintain the health of soldiers and their families. PMID:15132225

Brandt, Antonio L; Martyak, Nicholas; Westhoff, John; Kang, Christopher

2004-04-01

301

Autophagy by hepatitis B virus and for hepatitis B virus.  

PubMed

Autophagy is a catabolic process by which cells remove unwanted proteins and damaged organelles. It is important for maintaining cellular homeostasis and can also be used by cells to remove intracellular microbial pathogens. As such, some viruses such as herpes simplex virus-1 (HSV-1) have evolved mechanisms to suppress autophagy for their survival. In contrast, other viruses such as poliovirus, hepatitis C virus (HCV) and dengue viruses have instead evolved mechanisms to use this pathway to enhance their replication. Recently, we demonstrated that hepatitis B virus (HBV), a DNA virus that infects hepatocytes, could enhance and use autophagy for its DNA replication. This enhancement of autophagy is mediated by its X protein, which binds to and activates phosphatidylinositol-3-kinase class 3 (PI3KC3), an enzyme important for the initiation of autophagy. The persistent activation of autophagy in hepatocytes by HBV during chronic infection may play an important role in HBV pathogenesis. PMID:20305390

Sir, Donna; Ann, David K; Ou, Jing-Hsiung James

2010-05-01

302

Progress in recombinant DNA-derived vaccines for Lassa virus and filoviruses.  

PubMed

Developing vaccines for highly pathogenic viruses such as those causing Lassa, Ebola, and Marburg hemorrhagic fevers is a daunting task due to both scientific and logistical constraints. Scientific hurdles to overcome include poorly defined relationships between pathogenicity and protective immune responses, genetic diversity of viruses, and safety in a target population that includes a large number of individuals with compromised immune systems. Logistical obstacles include the requirement for biosafety level-4 containment to study the authentic viruses, the poor public health infrastructure of the endemic disease areas, and the cost of developing these vaccines for use in non-lucrative markets. Recombinant DNA-based vaccine approaches offer promise of overcoming some of these issues. In this review, we consider the status of various recombinant DNA candidate vaccines against Lassa virus and filoviruses which have been tested in animals. PMID:21925552

Grant-Klein, Rebecca J; Altamura, Louis A; Schmaljohn, Connie S

2011-12-01

303

Interaction of Venezuelan Equine Encephalomyelitis Virus with Neutralizing Antibody: II. The Persistent Virus Fraction.  

National Technical Information Service (NTIS)

The persistent virus fraction that results from the interaction of Venezuelan equine encephalomyelitis (VEE) virus with antiviral serum is an infectious virus-antibody complex (sensitized virus) that can be neutralized by anti-IgG serum. The quantities of...

N. Hahon

1969-01-01

304

Biology of parainfluenza viruses.  

PubMed Central

Parainfluenza virus types 1 to 4 (PIV1 to PIV4) are important human pathogens that cause upper and lower respiratory tract infections, especially in infants and children. PIV1, PIV2, and PIV3 are second only to respiratory syncytial virus as a cause of croup in young children. Although some clinical symptoms are typical of PIVs, etiologic diagnosis always requires detection of infectious virus, viral components, or an antibody response. PIVs are typical paramyxoviruses, causing a syncytial cytopathic effect in cell cultures; virus growth can be confirmed either by hemadsorption or by using immunological reagents. Currently, PIV is most often diagnosed by demonstrating viral antigens in clinical specimens by rapid and highly sensitive immunoassays. More recently, PCR has been used for the detection of PIVs. Serological diagnosis is made by detecting a rising titer of immunoglobulin G or by demonstrating immunoglobulin M antibodies. PIVs infect species other than humans, and animal models are used to study the pathogenesis of PIV infections and to test candidate vaccines. Accumulating knowledge on the molecular structure and mechanisms of replication of PIVs has accelerated research on prevention and treatment. Several strategies for vaccine development, such as the use of live attenuated, inactivated, recombinant, and subunit vaccines, have been investigated, and it may become possible to prevent PIV infections in the near future.

Vainionpaa, R; Hyypia, T

1994-01-01

305

From Shakespeare to Viruses  

SciTech Connect

Berkeley Lab scientists have created a unique new tool for analyzing and comparing long sets of data, be it the genomes of mammals or viruses, or the works of Shakespeare. The results of the Shakespeare analysis surprised scholars with their accuracy

Sung-Hou Kim

2009-02-09

306

Yellow Fever Virus Infection  

PubMed Central

A sequential and quantitative survey of brain and liver of suckling mice for infective virus and complement-fixing antigen, after infection with yellow fever virus, showed that while there was progressive increase of infective virus content in both organs, only the brain showed a corresponding rise in CF antigen. Histopathological examination revealed that the liver was not significantly involved. The target organ was the brain, where the progressive pathological changes culminated in an acute encephalitis by the 3rd day of experiment. Organ destruction began with the molecular layer of the grey matter. But by the 4th day after infection the entire cerebral cortex was involved. At the initial stages the hippocampus was particularly affected. Tissue damage did not appear to be entirely due to the differential quantitative localization of infective virus. It was hypothesized that the CF antigen acting singly or in conjunction with some hypothetical proteins may be principally involved in the pathological outcome of the disease. ImagesFigs. 7-9Figs. 3-6

David-West, Tam. S.; Smith, J. A.

1971-01-01

307

Virus Inactivation Kinetics  

Microsoft Academic Search

At the session of the Research Group of the Standing Technical Committee of the European Commission for the Control of Foot-and-Mouth Disease in Gerzensee, Berne, Switzerland in September 2003 a review of methods for describing the effect of temperature and time upon virus survival in products was presented (Have, 2003). The Research Group recommended that \\

Soren Alexandersen

308

Cold Facts about Viruses.  

ERIC Educational Resources Information Center

Provides ways for students to demonstrate their understanding of scientific concepts and skills. Describes a mini-unit around the cold in which students can relate humans to viruses. Includes activities and a modified simulation that provides questions to guide students. Discusses ways that allows students to apply prior knowledge, take ownership…

Pea, Celeste; Sterling, Donna R.

2002-01-01

309

Turnip Yellow Mosaic Virus  

NASA Technical Reports Server (NTRS)

The bumpy exterior of the turnip yellow mosaic virus (TYMV) protein coat, or capsid, was defined in detail by Dr. Alexander McPherson of the University of California, Irvin using proteins crystallized in space for analysis on Earth. TYMV is an icosahedral virus constructed from 180 copies of the same protein arranged into 12 clusters of five proteins (pentamers), and 20 clusters of six proteins (hexamers). The final TYMV structure led to the unexpected hypothesis that the virus releases its RNA by essentially chemical-mechanical means. Most viruses have fairly flat coats, but in TYNV, the fold in each protein, called the jellyroll, is clustered at the points where the protein pentamers and hexamers join. The jellyrolls are almost standing on end, producing a bumpy surface with knobs at all of the pentamers and hexamers. At the inside surface of the pentamers is a void that is not present at the hexamers. The coating had been seen in early stuties of TYMV, but McPherson's atomic structure shows much more detail. The inside surface is strikingly, and unexpectedly, different than the outside. While the pentamers contain a central void on the inside, the hexameric units contain peptides linked to each other, forming a ring or, more accurately, rings to fill the void. Credit: Dr. Alexander McPherson, University of California, Irvine

2000-01-01

310

West Nile Virus, Guadeloupe  

PubMed Central

To determine whether West Nile virus (WNV) had reached the archipelago of Guadeloupe, a serologic study in horses and birds was conducted in 2002. Immunoglobulin (Ig) G, IgM, enzyme-linked immunosorbent assay, and seroneutralization tests identified WNV infection in horses and chickens. Six months later, a high rate of seroconversion was observed in horses.

Quirin, Rene; Salas, Michel; Zientara, Stephan; Zeller, Herve; Labie, Jacques; Murri, Severine; Lefrancois, Thierry; Petitclerc, Martial

2004-01-01

311

Viruses and autophagy  

PubMed Central

SUMMARY Autophagy is an evolutionarily conserved intracellular process by which bulk cytoplasm is enveloped inside a double-membraned vesicle and shuttled to lysosomes for degradation. Within the last 15 years, the genes necessary for the execution of autophagy have been identified and the number of tools for studying this process has grown. Autophagy is essential for tissue homeostasis and development and defective autophagy is associated with a number of diseases. As intracellular parasites, during the course of an infection, viruses encounter autophagy and interact with the proteins that execute this process. Autophagy and/or autophagy genes likely play both anti-viral and proviral roles in the life cycles and pathogenesis of many different virus families. With respect to anti-viral roles, the autophagy proteins function in targeting viral components or virions for lysosomal degradation in a process termed xenophagy, and they also play a role in the initiation of innate and adaptive immune system responses to viral infections. Consistent with this anti-viral role of host autophagy, some viruses encode virulence factors that interact with the host autophagy machinery and block the execution of autophagy. In contrast, other viruses appear to utilise components of the autophagic machinery to foster their own intracellular growth or non-lytic cellular egress. As the details of the role(s) of autophagy in viral pathogenesis become clearer, new anti-viral therapies could be developed to inhibit the beneficial and enhance the destructive aspects of autophagy on the viral life cycle.

Kudchodkar, Sagar B.; Levine, Beth

2010-01-01

312

Viruses and bacteriophages.  

PubMed

Many of the enteric viruses which are transmitted from person to person by the fecal-oral route are found in raw and treated wastewater, and because of their persistence under adverse conditions may also be found in slightly polluted waters. There is no routine examination procedure of water and wastewater for enteroviruses, mainly because of the cumbersome isolation techniques, high cost and the need for highly skilled laboratory personnel. Phages are specific to single species of bacteria, are known for many enteric bacteria, and are very often used for final identification of enteric pathogenic bacteria. Coliphages are prevalent in raw and treated sewage as well as in polluted water, where enteric viruses may also be found. Coliphages were often mentioned as possible viral indicators in polluted water. To be a perfect indicator, they should comply with minimum criteria as follows: (a) they should be present wherever human enteric viruses are present; (b) the coliphage numbers recovered should be equal to or larger than those of enteric viruses recovered; (c) the coliphages should be at least as resistant as enteric viruses to adverse environmental conditions; (d) isolation and quantification of the coliphage should be faster and less expensive than isolation of the enteroviruses. Comparative studies show that the coliphage to enterovirus ratio in wastewater is about 10(3):1. Levels of poliovirus 1 (attenuated) to coliphage f2 remained stable for a few months in oxidation pond effluents. f2 coliphage exhibited higher resistance to chlorination than poliovirus 1 (attenuated). When the two strains were kept in water of different quality, f2 survived longer. In addition, all coliphage counts were completed within 24 h. while those of enteroviruses required about a week. Results indicate very strongly that coliphages can be used as viral indicators and this is already the practice in a few European and other countries. PMID:6262909

Kott, Y

1981-04-01

313

Nonstructural Protein 3 of Bluetongue Virus Assists Virus Release by Recruiting ESCRT-I Protein Tsg101  

PubMed Central

The release of Bluetongue virus (BTV) and other members of the Orbivirus genus from infected host cells occurs predominantly by cell lysis, and in some cases, by budding from the plasma membrane. Two nonstructural proteins, NS3 and NS3A, have been implicated in this process. Here we show that both proteins bind to human Tsg101 and its ortholog from Drosophila melanogaster with similar strengths in vitro. This interaction is mediated by a conserved PSAP motif in NS3 and appears to play a role in virus release. The depletion of Tsg101 with small interfering RNA inhibits the release of BTV and African horse sickness virus, a related orbivirus, from HeLa cells up to fivefold and threefold, respectively. Like most other viral proteins which recruit Tsg101, NS3 also harbors a PPXY late-domain motif that allows NS3 to bind NEDD4-like ubiquitin ligases in vitro. However, the late-domain motifs in NS3 do not function as effectively in facilitating the release of mini Gag virus-like particles from 293T cells as the late domains from human immunodeficiency virus type 1, human T-cell leukemia virus, and Ebola virus. A mutagenesis study showed that the arginine residue in the PPRY motif is responsible for the low activity of the NS3 late-domain motifs. Our data suggest that the BTV late-domain motifs either recruit an antagonist that interferes with budding or fail to recruit an agonist which is different from NEDD4.

Wirblich, Christoph; Bhattacharya, Bishnupriya; Roy, Polly

2006-01-01

314

Newcastle disease virus (NDV)-based assay demonstrates interferon-antagonist activity for the NDV V protein and the Nipah virus V, W, and C proteins.  

PubMed

We have generated a recombinant Newcastle disease virus (NDV) that expresses the green fluorescence protein (GFP) in infected chicken embryo fibroblasts (CEFs). This virus is interferon (IFN) sensitive, and pretreatment of cells with chicken alpha/beta IFN (IFN-alpha/beta) completely blocks viral GFP expression. Prior transfection of plasmid DNA induces an IFN response in CEFs and blocks NDV-GFP replication. However, transfection of known inhibitors of the IFN-alpha/beta system, including the influenza A virus NS1 protein and the Ebola virus VP35 protein, restores NDV-GFP replication. We therefore conclude that the NDV-GFP virus could be used to screen proteins expressed from plasmids for the ability to counteract the host cell IFN response. Using this system, we show that expression of the NDV V protein or the Nipah virus V, W, or C proteins rescues NDV-GFP replication in the face of the transfection-induced IFN response. The V and W proteins of Nipah virus, a highly lethal pathogen in humans, also block activation of an IFN-inducible promoter in primate cells. Interestingly, the amino-terminal region of the Nipah virus V protein, which is identical to the amino terminus of Nipah virus W, is sufficient to exert the IFN-antagonist activity. In contrast, the anti-IFN activity of the NDV V protein appears to be located in the carboxy-terminal region of the protein, a region implicated in the IFN-antagonist activity exhibited by the V proteins of mumps virus and human parainfluenza virus type 2. PMID:12502864

Park, Man-Seong; Shaw, Megan L; Muñoz-Jordan, Jorge; Cros, Jerome F; Nakaya, Takaaki; Bouvier, Nicole; Palese, Peter; García-Sastre, Adolfo; Basler, Christopher F

2003-01-01

315

Recombinant Vaccinia Virus: Immunization against Multiple Pathogens  

Microsoft Academic Search

The coding sequences for the hepatitis B virus surface antigen, the herpes simplex virus glycoprotein D, and the influenza virus hemagglutinin were inserted into a single vaccinia virus genome. Rabbits inoculated intravenously or intradermally with this polyvalent vaccinia virus recombinant produced antibodies reactive to all three authentic foreign antigens. In addition, the feasibility of multiple rounds of vaccination with recombinant

Marion E. Perkus; Antonia Piccini; Bernard R. Lipinskas; Enzo Paoletti

1985-01-01

316

Neural networks for computer virus recognition  

Microsoft Academic Search

We have developed a neural network for generic detection of a particular class of computer viruses-the so called boot sector viruses that infect the boot sector of a floppy disk or a hard drive. This is an important and relatively tractable subproblem of generic virus detection. Only about 5% of all known viruses are boot sector viruses, yet they account

G. J. Tesauro; J. O. Kephart; G. B. Sorkin

1996-01-01

317

Measuring and modeling computer virus prevalence  

Microsoft Academic Search

To understand the current extent of the computer virus problem and predict its future course, the authors have conducted a statistical analysis of computer virus incidents in a large, stable sample population of PCs and developed new epidemiological models of computer virus spread. Only a small fraction of all known viruses have appeared in real incidents, partly because many viruses

Jeffrey O. Kephart; Steve R. White

1993-01-01

318

Virus entry mediated by hepatitis B virus envelope proteins  

PubMed Central

Hepatitis B virus (HBV), a major cause of human liver disease worldwide, encodes three envelope proteins needed for the attachment and entry of the virus into susceptible host cells. A second virus, hepatitis delta virus, which is known to enhance liver disease in HBV infected patients, diverts the same HBV envelope proteins to achieve its own assembly and infection. In the lab, lentiviral vectors based on human immunodeficiency virus type 1 can be assembled using the HBV envelope proteins, and will similarly infect susceptible cells. This article provides a partial review and some personal reflections of how these three viruses infect and of how recipient cells become susceptible, along with some consideration of questions that remain to be answered.

Taylor, John M

2013-01-01

319

Tetherin-mediated restriction of filovirus budding is antagonized by the Ebola glycoprotein.  

PubMed

Mammalian cells employ numerous innate cellular mechanisms to inhibit viral replication and spread. Tetherin, also known as Bst-2 or CD317, is a recently identified, IFN-induced, cellular response factor that blocks release of HIV-1 and other retroviruses from infected cells. The means by which tetherin retains retroviruses on the cell surface, as well as the mechanism used by the HIV-1 accessory protein Vpu to antagonize tetherin function and promote HIV-1 release, are unknown. Here, we document that tetherin functions as a broadly acting antiviral factor by demonstrating that both human and murine tetherin potently inhibit the release of the filovirus, Ebola, from the surface of cells. Expression of the Ebola glycoprotein (GP) antagonized the antiviral effect of human and murine tetherin and facilitated budding of Ebola particles, as did the HIV-1 Vpu protein. Conversely, Ebola GP could substitute for Vpu to promote HIV-1 virion release from tetherin-expressing cells, demonstrating a common cellular target for these divergent viral proteins. Ebola GP efficiently coimmunoprecipitated with tetherin, suggesting that the viral glycoprotein directly interferes with this host antiviral factor. These results demonstrate that tetherin is a cellular antiviral factor that restricts budding of structurally diverse enveloped viruses. Additionally, Ebola has evolved a highly effective strategy to combat this antiviral response elicited in the host during infection. PMID:19179289

Kaletsky, Rachel L; Francica, Joseph R; Agrawal-Gamse, Caroline; Bates, Paul

2009-02-24

320

Active virus filter for enrichment and manipulation of virus  

Microsoft Academic Search

We developed an active virus filter (AVF) that was able to virus enrichment and distribution for single virus manipulation by using the insulator based dielectrophoresis (iDEP). The design of constricted flow channel enabled the microfluidic chip to produce iDEP force. We utilized maskless photolithography to achieve the precise 3D gray-scale exposure for constricted flow channel. When we applied sinusoidal wave

T. Masuda; H. Maruyama; A. Honda; F. Arai

2011-01-01

321

Human herpes virus 8: a new virus discloses its face  

Microsoft Academic Search

The human herpes virus 8 (HHV8) or Kaposi’s sarcoma-associated herpes virus (KSHV) is present in all Kaposi’s sarcoma, and\\u000a the detection of the virus using polymerase chain reaction or in situ hybridization is a highly sensitive and specific diagnostic\\u000a test for the diagnosis of this neoplasm. HHV8 is furthermore invariably present in primary effusion lymphoma (PEL) and has\\u000a also been

Gieri Cathomas

2000-01-01

322

An optofluidic nanoplasmonic biosensor for direct detection of live viruses from biological media.  

PubMed

Fast and sensitive virus detection techniques, which can be rapidly deployed at multiple sites, are essential to prevent and control future epidemics and bioterrorism threats. In this Letter, we demonstrate a label-free optofluidic nanoplasmonic sensor that can directly detect intact viruses from biological media at clinically relevant concentrations with little to no sample preparation. Our sensing platform is based on an extraordinary light transmission effect in plasmonic nanoholes and utilizes group-specific antibodies for highly divergent strains of rapidly evolving viruses. So far, the questions remain for the possible limitations of this technique for virus detection, as the penetration depths of the surface plasmon polaritons are comparable to the dimensions of the pathogens. Here, we demonstrate detection and recognition of small enveloped RNA viruses (vesicular stomatitis virus and pseudotyped Ebola) as well as large enveloped DNA viruses (vaccinia virus) within a dynamic range spanning 3 orders of magnitude. Our platform, by enabling high signal to noise measurements without any mechanical or optical isolation, opens up opportunities for detection of a broad range of pathogens in typical biology laboratory settings. PMID:21053965

Yanik, Ahmet A; Huang, Min; Kamohara, Osami; Artar, Alp; Geisbert, Thomas W; Connor, John H; Altug, Hatice

2010-12-01

323

Public health awareness of emerging zoonotic viruses of bats: a European perspective.  

PubMed

Bats classified in the order Chiroptera are the most abundant and widely distributed non-human mammalian species in the world. Several bat species are reservoir hosts of zoonotic viruses and therefore can be a public health hazard. Lyssaviruses of different genotypes have emerged from bats in America (Genotype 1 rabies virus; RABV), Europe (European bat lyssavirus; EBLV), and Australia (Australian bat lyssavirus; ABLV), whereas Nipah virus is the most important recent zoonosis of bat origin in Asia. Furthermore, some insectivorous bat species may be important reservoirs of SARS coronavirus, whereas Ebola virus has been detected in some megachiropteran fruit bats. Thus far, European bat lyssavirus (EBLV) is the only zoonotic virus that has been detected in bats in Europe. New zoonotic viruses may emerge from bat reservoirs and known ones may spread to a wider geographical range. To assess future threats posed by zoonotic viruses of bats, there is a need for accurate knowledge of the factors underlying disease emergence, for an effective surveillance programme, and for a rapid response system. In Europe, primary efforts should be focussed on the implementation of effective passive and active surveillance systems for EBLVs in the Serotine bat, Eptesicus serotinus, and Myotis species (i.e., M. daubentonii and M. dasycneme). Apart from that, detection methods for zoonotic viruses that may emerge from bats should be implemented. Analyses of data from surveillance studies can shed more light on the dynamics of bat viruses, (i.e., population persistence of viruses in bats). Subsequently, studies will have to be performed to assess the public health hazards of such viruses (i.e., infectivity and risk of infection to people). With the knowledge generated from this kind of research, a rapid response system can be set up to enhance public health awareness of emerging zoonotic viruses of bats. PMID:17187565

van der Poel, Wim H M; Lina, Peter H C; Kramps, Johannes A

2006-01-01

324

Viruses from extreme thermal environments  

PubMed Central

Viruses of extreme thermophiles are of great interest because they serve as model systems for understanding the biochemistry and molecular biology required for life at high temperatures. In this work, we report the discovery, isolation, and preliminary characterization of viruses and virus-like particles from extreme thermal acidic environments (70–92°C, pH 1.0–4.5) found in Yellowstone National Park. Six unique particle morphologies were found in Sulfolobus enrichment cultures. Three of the particle morphologies are similar to viruses previously isolated from Sulfolobus species from Iceland and/or Japan. Sequence analysis of their viral genomes suggests that they are related to the Icelandic and Japanese isolates. In addition, three virus particle morphologies that had not been previously observed from thermal environments were found. These viruses appear to be completely novel in nature.

Rice, George; Stedman, Kenneth; Snyder, Jamie; Wiedenheft, Blake; Willits, Debbie; Brumfield, Susan; McDermott, Timothy; Young, Mark J.

2001-01-01

325

Proteorhodopsin genes in giant viruses.  

PubMed

Viruses with large genomes encode numerous proteins that do not directly participate in virus biogenesis but rather modify key functional systems of infected cells. We report that a distinct group of giant viruses infecting unicellular eukaryotes that includes Organic Lake Phycodnaviruses and Phaeocystis globosa virus encode predicted proteorhodopsins that have not been previously detected in viruses. Search of metagenomic sequence data shows that putative viral proteorhodopsins are extremely abundant in marine environments. Phylogenetic analysis suggests that giant viruses acquired proteorhodopsins via horizontal gene transfer from proteorhodopsin-encoding protists although the actual donor(s) could not be presently identified. The pattern of conservation of the predicted functionally important amino acid residues suggests that viral proteorhodopsin homologs function as sensory rhodopsins. We hypothesize that viral rhodopsins modulate light-dependent signaling, in particular phototaxis, in infected protists. PMID:23036091

Yutin, Natalya; Koonin, Eugene V

2012-01-01

326

Introducing Virological Concepts Using an Insect Virus.  

ERIC Educational Resources Information Center

A technique is presented which utilizes wax moth larvae in a laboratory investigation of an insect virus. Describes how an insect virus can be used to introduce undergraduate biology students to laboratory work on viruses and several virological concepts. (SA)

Sheppard, Roger F.

1980-01-01

327

Studies of Respiratory Syncytial Virus Vaccines.  

National Technical Information Service (NTIS)

Studies of Respiratory Syncytial virus vaccines included both biological and physical aspects with the principle objective being a study of the banding of RS virus in the density gradient ultracentrifuge. Various studies on virus propagation both in the B...

R. N. Hull C. B. Reimer L. F. Ellis

1966-01-01

328

NATIONAL RESPIRATORY AND ENTERIC VIRUS SURVEILLANCE SYSTEM  

EPA Science Inventory

The National Respiratory and Enteric Virus Surveillance System is a lab based system which monitors temporal and geographic patterns associated with the detection of respiratory syncytial virus (RSV), human parainfluenza viruses (HPIV), respiratory and enteric adenoviruses, and r...

329

Tobacco mosaic virus virulence and avirulence.  

PubMed Central

In celebration of a century of research on tobacco mosaic virus that initiated the science of virology, I review recent progress relative to earlier contributions concerning how viruses cause diseases of plants and how plants defend themselves from viruses.

Dawson, W O

1999-01-01

330

NIAID's Role in Addressing West Nile Virus  

MedlinePLUS

... repellants and other ways to prevent mosquito bites. World Reference Center for Emerging Viruses and Arboviruses (WRCEVA) ... virus when it replicates. NIAID also supports the World Reference Center for Emerging Viruses and Arboviruses (WRCEVA) , ...

331

Virus-Related Antigens Associated with Cancer.  

National Technical Information Service (NTIS)

Contents: Virus-associated antigens and human breast cancer; Virus-associated antigens and experimental mammary cancer; Viral antigens associated with leukemias and lymphomas; Cell surface and other virus-induced antigens associated with leukemias and lym...

1977-01-01

332

Equine arteritis virus.  

PubMed

Equine arteritis virus (EAV) is the causative agent of equine viral arteritis (EVA), a respiratory and reproductive disease of equids. There has been significant recent progress in understanding the molecular biology of EAV and the pathogenesis of its infection in horses. In particular, the use of contemporary genomic techniques, along with the development and reverse genetic manipulation of infectious cDNA clones of several strains of EAV, has generated significant novel information regarding the basic molecular biology of the virus. Therefore, the objective of this review is to summarize current understanding of EAV virion architecture, replication, evolution, molecular epidemiology and genetic variation, pathogenesis including the influence of host genetics on disease susceptibility, host immune response, and potential vaccination and treatment strategies. PMID:23891306

Balasuriya, Udeni B R; Go, Yun Young; MacLachlan, N James

2013-11-29

333

West Nile Virus  

PubMed Central

Overview Since its isolation in Uganda in 1937, West Nile virus (WNV) has been responsible for thousands of cases of morbidity and mortality in birds, horses, and humans. Historically, epidemics were localized to Europe, Africa, the Middle East, and parts of Asia, and primarily caused a mild febrile illness in humans. However, in the late 1990’s, the virus became more virulent and expanded its geographical range to North America. In humans, the clinical presentation ranges from asymptomatic (approximately 80% of infections) to encephalitis/paralysis and death (less than 1% of infections). There is no FDA-licensed vaccine for human use, and the only recommended treatment is supportive care. Individuals that survive infection often have a long recovery period. This article will review the current literature summarizing the molecular virology, epidemiology, clinical manifestations, pathogenesis, diagnosis, treatment, immunology, and protective measures against WNV and WNV infections in humans.

Rossi, Shannan L.; Ross, Ted M.; Evans, Jared D.

2010-01-01

334

The encephalomyocarditis virus  

PubMed Central

The encephalomyocarditis virus (EMCV) is a small non-enveloped single-strand RNA virus, the causative agent of not only myocarditis and encephalitis, but also neurological diseases, reproductive disorders and diabetes in many mammalian species. EMCV pathogenesis appears to be viral strain- and host-specific, and a better understanding of EMCV virulence factors is increasingly required. Indeed, EMCV is often used as a model for diabetes and viral myocarditis, and is also widely used in immunology as a double-stranded RNA stimulus in the study of Toll-like as well as cytosolic receptors. However, EMCV virulence and properties have often been neglected. Moreover, EMCV is able to infect humans albeit with a low morbidity. Progress on xenografts, such as pig heart transplantation in humans, has raised safety concerns that need to be explored. In this review we will highlight the biology of EMCV and all known and potential virulence factors.

Carocci, Margot; Bakkali-Kassimi, Labib

2012-01-01

335

Hetdex: Virus Instrument  

NASA Astrophysics Data System (ADS)

The Visible Integral-field-unit Replicable Unit Spectrograph (VIRUS) instrument is made up of 150+ individually compact and identical spectrographs, each fed by a fiber integral-field unit. The instrument provides integral field spectroscopy at wavelengths between 350nm and 550nm of over 33,600 spatial elements per observation, each 1.8 sq. arcsec on the sky, at R 700. The instrument will be fed by a new wide-field corrector (WFC) of the Hobby-Eberly Telescope (HET) with increased science field of view as large as 22arcmin diameter and telescope aperture of 10m. This will enable the HETDEX, a large area blind survey of Lyman-alpha emitting galaxies at redshift z < 3.5. The status of VIRUS instrument construction is summarized.

Lee, Hanshin; Hill, G. J.; DePoy, D. L.; Tuttle, S.; Marshall, J. L.; Vattiat, B. L.; Prochaska, T.; Chonis, T. S.; Allen, R.; HETDEX Collaboration

2012-01-01

336

Interferon-? therapy prolongs survival in rhesus macaque models of Ebola and Marburg hemorrhagic fever.  

PubMed

There is a clear need for novel, effective therapeutic approaches to hemorrhagic fever due to filoviruses. Ebola virus hemorrhagic fever is associated with robust interferon (IFN)-? production, with plasma concentrations of IFN-? that greatly (60- to 100-fold) exceed those seen in other viral infections, but little IFN-? production. While all of the type I IFNs signal through the same receptor complex, both quantitative and qualitative differences in biological activity are observed after stimulation of the receptor complex with different type I IFNs. Taken together, this suggested potential for IFN-? therapy in filovirus infection. Here we show that early postexposure treatment with IFN-? significantly increased survival time of rhesus macaques infected with a lethal dose of Ebola virus, although it failed to alter mortality. Early treatment with IFN-? also significantly increased survival time after Marburg virus infection. IFN-? may have promise as an adjunctive postexposure therapy in filovirus infection. PMID:23255566

Smith, Lauren M; Hensley, Lisa E; Geisbert, Thomas W; Johnson, Joshua; Stossel, Andrea; Honko, Anna; Yen, Judy Y; Geisbert, Joan; Paragas, Jason; Fritz, Elizabeth; Olinger, Gene; Young, Howard A; Rubins, Kathleen H; Karp, Christopher L

2013-07-15

337

Viruses from the Hypersaline Environment  

Microsoft Academic Search

\\u000a Halophilic environments such as solar salterns and salt lakes are enriched in organisms belonging to the domain Archaea. The\\u000a number of virus-like particles has also been shown to be high. Although most of the described haloarchaeal viruses are head–tail\\u000a viruses, direct microscopic examination of environmental samples suggests more diversity. In this chapter, we shortly review\\u000a the existing knowledge of the

Elina Roine; Hanna M. Oksanen

338

Reverse Genetics with Animal Viruses  

Microsoft Academic Search

New strategies to genetically manipulate the genomes of several important animal pathogens have been established in recent\\u000a years. This article focuses on the reverse genetics techniques, which enables genetic manipulation of the genomes of non-segmented\\u000a negative-sense RNA viruses. Recovery of a negative-sense RNA virus entirely from cDNA was first achieved for rabies virus\\u000a in 1994. Since then, reverse genetic systems

Teshome Mebatsion

339

Tracking the West Nile Virus  

NSDL National Science Digital Library

How can viral sequences help us establish the origin of the virus that appeared in the US in 1999? Epidemiologists have adopted bioinformatics approaches using sequence data from strains of pathogens to track the movement of bacteria and viruses from continent to continent. * explore a data set of West Nile Virus sequences from all over the world that date from the mid-20th century to the present

Erica Suchmann (University of California - San Diego;Biology); Mark Gallo (Niagara University;Biology)

2006-05-20

340

Viruses in extreme environments  

Microsoft Academic Search

The tolerance limits of extremophiles in term of temperature, pH, salinity, desiccation, hydrostatic pressure, radiation,\\u000a anaerobiosis far exceed what can support non-extremophilic organisms. Like all other organisms, extremophiles serve as hosts\\u000a for viral replication. Many lines of evidence suggest that viruses could no more be regarded as simple infectious “fragments\\u000a of life” but on the contrary as one of the

Marc Le Romancer; Mélusine Gaillard; Claire Geslin; Daniel Prieur

341

Human Immunodeficiency Virus  

Microsoft Academic Search

Oral health is an integral component of overall health and well-being in all patients. However, for an immunocompromised patient,\\u000a many common oral conditions may have a significant impact on quality of life. Intraoral pain, which is a common complaint\\u000a among patients with human immunodeficiency virus (HIV), will compromise patients’ ability to maintain adequate and appropriate\\u000a oral intake. Furthermore, the polypharmacopeia

Anita Patel; Michael Glick

342

Depletion of GTP pool is not the predominant mechanism by which ribavirin exerts its antiviral effect on Lassa virus.  

PubMed

Ribavirin (1-?-d-ribofuranosyl-1,2,4-triazole-3-carboxamide) is the standard treatment for Lassa fever, though its mode of action is unknown. One possibility is depletion of the intracellular GTP pool via inhibition of the cellular enzyme inosine monophosphate dehydrogenase (IMPDH). This study compared the anti-arenaviral effect of ribavirin with that of two other IMPDH inhibitors, mycophenolic acid (MPA) and 5-ethynyl-1-?-d-ribofuranosylimidazole-4-carboxamide (EICAR). All three compounds were able to inhibit Lassa virus replication by ?2 log units in cell culture. Restoring the intracellular GTP pool by exogenous addition of guanosine reversed the inhibitory effects of MPA and EICAR, while ribavirin remained fully active. Analogous experiments performed with Zaire Ebola virus showed that IMPDH inhibitors are also active against this virus, although to a lesser extent than against Lassa virus. In conclusion, the experiments with MPA and EICAR indicate that replication of Lassa and Ebola virus is sensitive to depletion of the GTP pool mediated via inhibition of IMPDH. However, this is not the predominant mechanism by which ribavirin exerts its in-vitro antiviral effect on Lassa virus. PMID:21616094

Ölschläger, Stephan; Neyts, Johan; Günther, Stephan

2011-08-01

343

Hepatitis delta virus.  

PubMed

Hepatitis delta virus (HDV) is a sub-viral agent that is dependent for its life cycle on hepatitis B virus (HBV). The help it obtains from HBV is limited to the sharing of envelope proteins. These proteins are needed to facilitate the assembly of the HDV genome into new virus particles, and in turn, to allow the attachment and entry of HDV into new host cells. In other respects, the replication of the small single-stranded circular RNA genome of HDV is independent of HBV. HDV genome replication produces two forms of a RNA-binding protein known as the long and small delta antigens (Ag). All other proteins needed for HDV genome replication, especially the RNA-directed RNA polymerase activity, are provided by the host cell. This mini-review article is a mixture of personal perspective and speculations about the future of HDV research. It starts with a brief overview of HDV and its replication, notes some of the major unresolved questions, and directs the interested reader to more detailed reviews. PMID:16364738

Taylor, John M

2006-01-01

344

STUDIES ON NEWCASTLE DISEASE VIRUS  

PubMed Central

1. It is likely that certain tailed and filamentous particles seen on electron microscope examination of partially purified saline suspensions of Newcastle virus are the individual virus particles because: (a) They have a highly characteristic shape not seen in other virus preparations. (b) They are present whenever the virus is present in high concentration. (c) Their size agrees with the size of the virus as calculated from light scattering and centrifuge data. (d) They are agglutinated by specific antisera. (e) Infection may be produced in the embryo by relatively few of these particles. 2. It is possible that these filamentous forms have been derived from spherical forms without loss of activity because: (a) Such filamentous forms are not found in the original allantoic fluid when this contains a comparable amount of virus. (b) Filamentous forms appeared in the original allantoic fluid when it was dialyzed against saline solution. (c) Filamentous forms were produced at certain hydrogen ion concentrations but not at others, in solutions maintaining the same infectivity for the embryo. (d) Spherical forms were obtained by suspending the partially purified virus in water instead of saline. In this the virus remained moderately stable. (e) These round forms could apparently be converted into tailed and filamentous forms by the addition of saline, again without loss of activity. (f) This "conversion" could be inhibited by partial inactivation of the water suspension of virus.

Bang, F. B.

1948-01-01

345

Structure of Flexible Filamentous Plant Viruses  

SciTech Connect

Flexible filamentous viruses make up a large fraction of the known plant viruses, but in comparison with those of other viruses, very little is known about their structures. We have used fiber diffraction, cryo-electron microscopy, and scanning transmission electron microscopy to determine the symmetry of a potyvirus, soybean mosaic virus; to confirm the symmetry of a potexvirus, potato virus X; and to determine the low-resolution structures of both viruses. We conclude that these viruses and, by implication, most or all flexible filamentous plant viruses share a common coat protein fold and helical symmetry, with slightly less than 9 subunits per helical turn.

Kendall, Amy; McDonald, Michele; Bian, Wen; Bowles, Timothy; Baumgarten, Sarah C.; Shi, Jian; Stewart, Phoebe L.; Bullitt, Esther; Gore, David; Irving, Thomas C.; Havens, Wendy M.; Ghabrial, Said A.; Wall, Joseph S.; Stubbs, Gerald (IIT); (BU-M); (Vanderbilt); (Kentucky); (BNL)

2008-10-23

346

Computer virus information update CIAC-2301  

SciTech Connect

While CIAC periodically issues bulletins about specific computer viruses, these bulletins do not cover all the computer viruses that affect desktop computers. The purpose of this document is to identify most of the known viruses for the MS-DOS and Macintosh platforms and give an overview of the effects of each virus. The authors also include information on some windows, Atari, and Amiga viruses. This document is revised periodically as new virus information becomes available. This document replaces all earlier versions of the CIAC Computer virus Information Update. The date on the front cover indicates date on which the information in this document was extracted from CIAC`s Virus database.

Orvis, W.J.

1994-01-15

347

Evolutionary relationship of alfalfa mosaic virus with cucumber mosaic virus and brome mosaic virus  

Microsoft Academic Search

The amino acid sequences of the non-structural protein (molecular weight 35,000; 3a protein) from three plant viruses — cucumber\\u000a mosaic, brome mosaic and alfalfa mosaic have been systematically compared using the partial genomic sequences for these three\\u000a viruses already available. The 3a protein of cucumber mosaic virus has an amino acid sequence homology of 33.7% with the corresponding\\u000a protein of

H. S. Savithri; M. R. N. Murthy

1983-01-01

348

Cowpea mosaic virus: the plant virus-based biotechnology workhorse.  

PubMed

In the 50 years since it was first described, Cowpea mosaic virus (CPMV) has become one of the most intensely studied plant viruses. Research in the past 15 to 20 years has shifted from studying the underlying genetics and structure of the virus to focusing on ways in which it can be exploited in biotechnology. This work led first to the use of virus particles to present peptides, then to the creation of a variety of replicating virus vectors and finally to the development of a highly efficient protein expression system that does not require viral replication. The circle has been completed by the use of the latter system to create empty particles for peptide presentation and other novel uses. The history of CPMV in biotechnology can be likened to an Ouroborus, an ancient symbol depicting a snake or dragon swallowing its own tail, thus forming a circle. PMID:20455698

Sainsbury, Frank; Cañizares, M Carmen; Lomonossoff, George P

2010-01-01

349

Hepatitis C Virus and Cardiomyopathy  

Microsoft Academic Search

The importance of hepatitis C virus infection has been recently noted in patients with hypertrophic cardiomyopathy or dilated cardiomyopathy. In a collaborative research project of the Committees for the Study of Idiopathic Cardiomyopathy, hepatitis C virus antibody was found in 74 of 697 patients (10.65) with hypertrophic cardiomyopathy and in 42 of 663 patients (6.3%) with dilated cardiomyopathy; these prevalences

Akira Matsumori

2000-01-01

350

Influenza virus assembly and budding.  

PubMed

Influenza A virus causes seasonal epidemics, sporadic pandemics and is a significant global health burden. Influenza virus is an enveloped virus that contains a segmented negative strand RNA genome. Assembly and budding of progeny influenza virions is a complex, multi-step process that occurs in lipid raft domains on the apical membrane of infected cells. The viral proteins hemagglutinin (HA) and neuraminidase (NA) are targeted to lipid rafts, causing the coalescence and enlargement of the raft domains. This clustering of HA and NA may cause a deformation of the membrane and the initiation of the virus budding event. M1 is then thought to bind to the cytoplasmic tails of HA and NA where it can then polymerize and form the interior structure of the emerging virion. M1, bound to the cytoplasmic tails of HA and NA, additionally serves as a docking site for the recruitment of the viral RNPs and may mediate the recruitment of M2 to the site of virus budding. M2 initially stabilizes the site of budding, possibly enabling the polymerization of the matrix protein and the formation of filamentous virions. Subsequently, M2 is able to alter membrane curvature at the neck of the budding virus, causing membrane scission and the release of the progeny virion. This review investigates the latest research on influenza virus budding in an attempt to provide a step-by-step analysis of the assembly and budding processes for influenza viruses. PMID:21237476

Rossman, Jeremy S; Lamb, Robert A

2011-03-15

351

Human viruses: discovery and emergence  

PubMed Central

There are 219 virus species that are known to be able to infect humans. The first of these to be discovered was yellow fever virus in 1901, and three to four new species are still being found every year. Extrapolation of the discovery curve suggests that there is still a substantial pool of undiscovered human virus species, although an apparent slow-down in the rate of discovery of species from different families may indicate bounds to the potential range of diversity. More than two-thirds of human viruses can also infect non-human hosts, mainly mammals, and sometimes birds. Many specialist human viruses also have mammalian or avian origins. Indeed, a substantial proportion of mammalian viruses may be capable of crossing the species barrier into humans, although only around half of these are capable of being transmitted by humans and around half again of transmitting well enough to cause major outbreaks. A few possible predictors of species jumps can be identified, including the use of phylogenetically conserved cell receptors. It seems almost inevitable that new human viruses will continue to emerge, mainly from other mammals and birds, for the foreseeable future. For this reason, an effective global surveillance system for novel viruses is needed.

Woolhouse, Mark; Scott, Fiona; Hudson, Zoe; Howey, Richard; Chase-Topping, Margo

2012-01-01

352

How Viruses Enter Animal Cells  

Microsoft Academic Search

Viruses replicate within living cells and use the cellular machinery for the synthesis of their genome and other components. To gain access, they have evolved a variety of elegant mechanisms to deliver their genes and accessory proteins into the host cell. Many animal viruses take advantage of endocytic pathways and rely on the cell to guide them through a complex

Alicia E. Smith; Ari Helenius

2004-01-01

353

Virioplankton: Viruses in Aquatic Ecosystems†  

PubMed Central

The discovery that viruses may be the most abundant organisms in natural waters, surpassing the number of bacteria by an order of magnitude, has inspired a resurgence of interest in viruses in the aquatic environment. Surprisingly little was known of the interaction of viruses and their hosts in nature. In the decade since the reports of extraordinarily large virus populations were published, enumeration of viruses in aquatic environments has demonstrated that the virioplankton are dynamic components of the plankton, changing dramatically in number with geographical location and season. The evidence to date suggests that virioplankton communities are composed principally of bacteriophages and, to a lesser extent, eukaryotic algal viruses. The influence of viral infection and lysis on bacterial and phytoplankton host communities was measurable after new methods were developed and prior knowledge of bacteriophage biology was incorporated into concepts of parasite and host community interactions. The new methods have yielded data showing that viral infection can have a significant impact on bacteria and unicellular algae populations and supporting the hypothesis that viruses play a significant role in microbial food webs. Besides predation limiting bacteria and phytoplankton populations, the specific nature of virus-host interaction raises the intriguing possibility that viral infection influences the structure and diversity of aquatic microbial communities. Novel applications of molecular genetic techniques have provided good evidence that viral infection can significantly influence the composition and diversity of aquatic microbial communities.

Wommack, K. Eric; Colwell, Rita R.

2000-01-01

354

Virus Removal by Chemical Coagulation.  

National Technical Information Service (NTIS)

Using bacterial viruses (Bacteriophages T4 and MS2 against Escherichia coli) as models and aluminum as the coagulant metal ion, it was shown that removal of viruses from water by chemical coagulation and flocculation with aluminum sulfate consists of a pr...

R. S. Engelbrecht M. Chaudhuri

1969-01-01

355

Sunshine virus in Australian pythons.  

PubMed

Sunshine virus is a recently discovered novel paramyxovirus that is associated with illness in snakes. It does not phylogenetically cluster within either of the two currently accepted paramyxoviral subfamilies. It is therefore only distantly related to the only other known genus of reptilian paramyxoviruses, Ferlavirus, which clusters within the Paramyxovirinae subfamily. Clinical and diagnostic aspects associated with Sunshine virus are as yet undescribed. The objective of this paper was to report the clinical presentation, virus isolation, PCR testing and pathology associated with Sunshine virus infection. Clinical records and samples from naturally occurring cases were obtained from two captive snake collections and the archives of a veterinary diagnostic laboratory. The clinical signs that are associated with Sunshine virus infection are localised to the neurorespiratory systems or are non-specific (e.g. lethargy, inappetence). Out of 15 snakes that were infected with Sunshine virus (detected in any organ by either virus isolation or PCR), the virus was isolated from four out of ten (4/10) sampled brains, 3/10 sampled lungs and 2/7 pooled samples of kidney and liver. In these same 15 snakes, PCR was able to successfully detect Sunshine virus in fresh-frozen brain (11/11), kidney (7/8), lung (8/11) and liver (5/8); and various formalin-fixed paraffin-embedded tissues (7/8). During a natural outbreak of Sunshine virus in a collection of 32 snakes, the virus could be detected in five out of 39 combined oral-cloacal swabs that were collected from 23 of these snakes over a 105 day period. All snakes that were infected with Sunshine virus were negative for reovirus and ferlavirus by PCR. Snakes infected with Sunshine virus reliably exhibited hindbrain white matter spongiosis and gliosis with extension to the surrounding grey matter and neuronal necrosis evident in severe cases. Five out of eight infected snakes also exhibited mild bronchointerstitial pneumonia. Infection with Sunshine virus should be considered by veterinarians investigating disease outbreaks in snakes, particularly those that are associated with neurorespiratory disease. PMID:22883310

Hyndman, Timothy H; Shilton, Cathy M; Doneley, Robert J T; Nicholls, Philip K

2012-12-28

356

Marine Viruses: Truth or Dare  

NASA Astrophysics Data System (ADS)

Over the past two decades, marine virology has progressed from a curiosity to an intensely studied topic of critical importance to oceanography. At concentrations of approximately 10 million viruses per milliliter of surface seawater, viruses are the most abundant biological entities in the oceans. The majority of these viruses are phages (viruses that infect bacteria). Through lysing their bacterial hosts, marine phages control bacterial abundance, affect community composition, and impact global biogeochemical cycles. In addition, phages influence their hosts through selection for resistance, horizontal gene transfer, and manipulation of bacterial metabolism. Recent work has also demonstrated that marine phages are extremely diverse and can carry a variety of auxiliary metabolic genes encoding critical ecological functions. This review is structured as a scientific "truth or dare," revealing several well-established "truths" about marine viruses and presenting a few "dares" for the research community to undertake in future studies.

Breitbart, Mya

2012-01-01

357

Virus assembly, allostery, and antivirals  

PubMed Central

Assembly of virus capsids and surface proteins must be regulated to ensure that the resulting complex is an infectious virion. Here we examine assembly of virus capsids, focusing on hepatitis B virus and bacteriophage MS2, and formation of glycoproteins in the alphaviruses. These systems are structurally and biochemically well-characterized and are simplest-case paradigms of self-assembly. Published data suggest that capsid and glycoprotein assembly is subject to allosteric regulation, that is, regulation at the level of conformational change. The hypothesis that allostery is a common theme in viruses suggests that deregulation of capsid and glycoprotein assembly by small molecule effectors will be an attractive antiviral strategy, as has been demonstrated with hepatitis B virus.

Zlotnick, Adam; Mukhopadhyay, Suchetana

2010-01-01

358

Hiding the evidence: two strategies for innate immune evasion by hemorrhagic fever viruses.  

PubMed

The innate immune system is one of the first lines of defense against invading pathogens. Pathogens have, in turn, evolved different strategies to counteract these responses. Recent studies have illuminated how the hemorrhagic fever viruses Ebola and Lassa fever prevent host sensing of double-stranded RNA (dsRNA), a key hallmark of viral infection. The ebolavirus protein VP35 adopts a unique bimodal configuration to mask key cellular recognition sites on dsRNA. Conversely, the Lassa fever virus nucleoprotein actually digests the dsRNA signature. Collectively, these structural and functional studies shed new light on the mechanisms of pathogenesis of these viruses and provide new targets for therapeutic intervention. PMID:22482712

Hastie, Kathryn M; Bale, Shridhar; Kimberlin, Christopher R; Saphire, Erica Ollmann

2012-04-01

359

Do viruses require the cytoskeleton?  

PubMed Central

Background It is generally thought that viruses require the cytoskeleton during their replication cycle. However, recent experiments in our laboratory with rubella virus, a member of the family Togaviridae (genus rubivirus), revealed that replication proceeded in the presence of drugs that inhibit microtubules. This study was done to expand on this observation. Findings The replication of three diverse viruses, Sindbis virus (SINV; family Togaviridae family), vesicular stomatitis virus (VSV; family Rhabdoviridae), and Herpes simplex virus (family Herpesviridae), was quantified by the titer (plaque forming units/ml; pfu/ml) produced in cells treated with one of three anti-microtubule drugs (colchicine, noscapine, or paclitaxel) or the anti-actin filament drug, cytochalasin D. None of these drugs affected the replication these viruses. Specific steps in the SINV infection cycle were examined during drug treatment to determine if alterations in specific steps in the virus replication cycle in the absence of a functional cytoskeletal system could be detected, i.e. redistribution of viral proteins and replication complexes or increases/decreases in their abundance. These investigations revealed that the observable impacts were a colchicine-mediated fragmentation of the Golgi apparatus and concomitant intracellular redistribution of the virion structural proteins, along with a reduction in viral genome and sub-genome RNA levels, but not double-stranded RNA or protein levels. Conclusions The failure of poisons affecting the cytoskeleton to inhibit the replication of a diverse set of viruses strongly suggests that viruses do not require a functional cytoskeletal system for replication, either because they do not utilize it or are able to utilize alternate pathways when it is not available.

2013-01-01

360

Virus nomenclature below the species level: a standardized nomenclature for natural variants of viruses assigned to the family Filoviridae  

PubMed Central

The task of international expert groups is to recommend the classification and naming of viruses. The ICTV Filoviridae Study Group and other experts have recently established an almost consistent classification and nomenclature for filoviruses. Here, further guidelines are suggested to include their natural genetic variants. First, this term is defined. Second, a template for full-length virus names (such as “Ebola virus H.sapiens-tc/COD/1995/Kikwit-9510621”) is proposed. These names contain information on the identity of the virus (e.g., Ebola virus), isolation host (e.g., members of the species Homo sapiens), sampling location (e.g., Democratic Republic of the Congo (COD)), sampling year, genetic variant (e.g., Kikwit), and isolate (e.g., 9510621). Suffixes are proposed for individual names that clarify whether a given genetic variant has been characterized based on passage zero material (-wt), has been passaged in tissue/cell culture (-tc), is known from consensus sequence fragments only (-frag), or does (most likely) not exist anymore (-hist). We suggest that these comprehensive names are to be used specifically in the methods section of publications. Suitable abbreviations, also proposed here, could then be used throughout the text, while the full names could be used again in phylograms, tables, or figures if the contained information aids the interpretation of presented data. The proposed system is very similar to the well-known influenzavirus nomenclature and the nomenclature recently proposed for rotaviruses. If applied consistently, it would considerably simplify retrieval of sequence data from electronic databases and be a first important step toward a viral genome annotation standard as sought by the National Center for Biotechnology Information (NCBI). Furthermore, adoption of this nomenclature would increase the general understanding of filovirus-related publications and presentations and improve figures such as phylograms, alignments, and diagrams. Most importantly, it would counter the increasing confusion in genetic variant naming due to the identification of ever more sequences through technological breakthroughs in high-throughput sequencing and environmental sampling.

Kuhn, Jens H.; Bao, Yiming; Bavari, Sina; Becker, Stephan; Bradfute, Steven; Brister, J. Rodney; Bukreyev, Alexander A.; Chandran, Kartik; Davey, Robert A.; Dolnik, Olga; Dye, John M.; Enterlein, Sven; Hensley, Lisa; Honko, Anna N.; Jahrling, Peter B.; Johnson, Karl M.; Kobinger, Gary; Leroy, Eric M.; Lever, Mark S.; Muhlberger, Elke; Netesov, Sergey V.; Olinger, Gene G.; Palacios, Gustavo; Patterson, Jean L.; Paweska, Janusz T.; Pitt, Louise; Radoshitzky, Sheli R.; Saphire, Erica Ollmann; Smither, Sophie J.; Swanepoel, Robert; Towner, Jonathan S.; van der Groen, Guido; Volchkov, Viktor E.; Wahl-Jensen, Victoria; Warren, Travis; Weidmann, Manfred; Nichol, Stuart T.

2012-01-01

361

Infectious vaccinia virus recombinants that express hepatitis B virus surface antigen  

NASA Astrophysics Data System (ADS)

Potential live vaccines against hepatitis B virus have been produced. The coding sequence for hepatitis B virus surface antigen (HBsAg) has been inserted into the vaccinia virus genome under control of vaccinia virus early promoters. Cells infected with these vaccinia virus recombinants synthesize and excrete HBsAg and vaccinated rabbits rapidly produce antibodies to HBsAg.

Smith, Geoffrey L.; Mackett, Michael; Moss, Bernard

1983-04-01

362

The Acute bee paralysis virus-Kashmir bee virus-Israeli acute paralysis virus complex.  

PubMed

Acute bee paralysis virus (ABPV), Kashmir bee virus (KBV) and Israeli acute paralysis virus (IAPV) are part of a complex of closely related viruses from the Family Dicistroviridae. These viruses have a widespread prevalence in honey bee (Apis mellifera) colonies and a predominantly sub-clinical etiology that contrasts sharply with the extremely virulent pathology encountered at elevated titres, either artificially induced or encountered naturally. These viruses are frequently implicated in honey bee colony losses, especially when the colonies are infested with the parasitic mite Varroa destructor. Here we review the historical and recent literature of this virus complex, covering history and origins; the geographic, host and tissue distribution; pathology and transmission; genetics and variation; diagnostics, and discuss these within the context of the molecular and biological similarities and differences between the viruses. We also briefly discuss three recent developments relating specifically to IAPV, concerning its association with Colony Collapse Disorder, treatment of IAPV infection with siRNA and possible honey bee resistance to IAPV. PMID:19909972

de Miranda, Joachim R; Cordoni, Guido; Budge, Giles

2010-01-01

363

42 CFR 73.3 - HHS select agents and toxins.  

Code of Federal Regulations, 2010 CFR

...Ebola viruses Francisella tularensis Lassa fever virus Marburg virus Monkeypox virus Reconstructed...seizure of Botulinum neurotoxins, Ebola viruses, Francisella tularensis, Lassa fever virus, Marburg virus, South American...

2009-10-01

364

42 CFR 73.3 - HHS select agents and toxins.  

Code of Federal Regulations, 2010 CFR

...Ebola viruses Francisella tularensis Lassa fever virus Marburg virus Monkeypox virus Reconstructed...seizure of Botulinum neurotoxins, Ebola viruses, Francisella tularensis, Lassa fever virus, Marburg virus, South American...

2010-10-01

365

Influenza: a virus of our times  

PubMed Central

Viruses are successful and omnipresent. Influenza A is a particularly important virus of humans. The article reviews the 2009 emergence of the pandemic influenza A virus, focusing on the potential origin of the virus and the distinctive clinical and epidemiological impact of the 2009 pandemic.

McCaughey, Conall

2010-01-01

366

Immunogenicity of combination DNA vaccines for Rift Valley fever virus, tick-borne encephalitis virus, Hantaan virus, and Crimean Congo hemorrhagic fever virus  

Microsoft Academic Search

DNA vaccines for Rift Valley fever virus (RVFV), Crimean Congo hemorrhagic fever virus (CCHFV), tick-borne encephalitis virus (TBEV), and Hantaan virus (HTNV), were tested in mice alone or in various combinations. The bunyavirus vaccines (RVFV, CCHFV, and HTNV) expressed Gn and Gc genes, and the flavivirus vaccine (TBEV) expressed the preM and E genes. All vaccines were delivered by gene

Kristin Spik; Amy Shurtleff; Anita K. McElroy; Mary C. Guttieri; Jay W. Hooper; Connie Schmaljohn

2006-01-01

367

Biologically Inspired Defenses Against Computer Viruses  

Microsoft Academic Search

Today's anti-virus technology, based largely on analysis of existing viruses by human experts, is just barely able to keep pace with the more than three new computer viruses that are writ­ ten daily. In a few years, intelligent agents nav­ igating through highly connected networks are likely to form an extremely fertile medium for a new breed of viruses. At

Jeffrey O. Kephart; Gregory B. Sorkin; William C. Arnold; David M. Chess; Gerald Tesauro; Steve R. White

1995-01-01

368

Safe Computing: An Overview of Viruses.  

ERIC Educational Resources Information Center

A computer virus is a program that replicates itself, in conjunction with an additional program that can harm a computer system. Common viruses include boot-sector, macro, companion, overwriting, and multipartite. Viruses can be fast, slow, stealthy, and polymorphic. Anti-virus products are described. (MLH)

Wodarz, Nan

2001-01-01

369

Smallpox vaccination and bioterrorism with pox viruses  

Microsoft Academic Search

Bioterrorist attacks occupy a special place amongst the innumerable potential types of terrorist attack, with the intentional release of pox viruses being especially feared in this connection. Apart from the variola virus, the agent responsible for smallpox in humans, the monkeypox virus and numerous other animal pox viruses pose potential risks for humans and animals. This risk scenario also includes

Anton Mayr

2003-01-01

370

Hepatitis E virus infection.  

PubMed

Hepatitis E virus (HEV) infection is a worldwide disease. An improved understanding of the natural history of HEV infection has been achieved within the last decade. Several reservoirs and transmission modes have been identified. Hepatitis E is an underdiagnosed disease, in part due to the use of serological assays with low sensitivity. However, diagnostic tools, including nucleic acid-based tests, have been improved. The epidemiology and clinical features of hepatitis E differ between developing and developed countries. HEV infection is usually an acute self-limiting disease, but in developed countries it causes chronic infection with rapidly progressive cirrhosis in organ transplant recipients, patients with hematological malignancy requiring chemotherapy, and individuals with HIV. HEV also causes extrahepatic manifestations, including a number of neurological syndromes and renal injury. Acute infection usually requires no treatment, but chronic infection should be treated by reducing immunosuppression in transplant patients and/or the use of antiviral therapy. In this comprehensive review, we summarize the current knowledge about the virus itself, as well as the epidemiology, diagnostics, natural history, and management of HEV infection in developing and developed countries. PMID:24396139

Kamar, Nassim; Dalton, Harry R; Abravanel, Florence; Izopet, Jacques

2014-01-01

371

Hepatitis E virus.  

PubMed

Hepatitis E virus (HEV) is responsible for major outbreaks of acute hepatitis in developing countries where it was first described as a waterborne disease, transmitted by drinking water contaminated with feces. Attention was focused on HEV in developed countries and its associated diseases in recent years as a result of increasing reports of autochthonous infections. Hepatitis E is the zoonotic cause of these acute infections, and mainly in men over 50 years of age. The clinical manifestations and laboratory abnormalities of hepatitis E infections in immunocompetent patients cannot be distinguished from those caused by other hepatitis viruses. HEV is a major public health concern in immunocompromised patients because their infections can become chronic. The specific etiology of cases of hepatitis E infection can be diagnosed by serological testing and detecting viral RNA. Ribavirin is currently the reference treatment for HEV infections in immunocompromised patients. Several vaccines have proved safe and effective in clinical trials, but none have been approved for use in Europe yet. PMID:23608595

Abravanel, F; Lhomme, S; Dubois, M; Peron, J-M; Alric, L; Kamar, N; Izopet, J

2013-07-01

372

Virus interactions with human signal transduction pathways  

PubMed Central

Viruses depend on their hosts at every stage of their life cycles and must therefore communicate with them via Protein-Protein Interactions (PPIs). To investigate the mechanisms of communication by different viruses, we overlay reported pairwise human-virus PPIs on human signalling pathways. Of 671 pathways obtained from NCI and Reactome databases, 355 are potentially targeted by at least one virus. The majority of pathways are linked to more than one virus. We find evidence supporting the hypothesis that viruses often interact with different proteins depending on the targeted pathway. Pathway analysis indicates overrepresentation of some pathways targeted by viruses. The merged network of the most statistically significant pathways shows several centrally located proteins, which are also hub proteins. Generally, hub proteins are targeted more frequently by viruses. Numerous proteins in virus-targeted pathways are known drug targets, suggesting that these might be exploited as potential new approaches to treatments against multiple viruses.

Zhao, Zhongming; Xia, Junfeng; Tastan, Oznur; Singh, Irtisha; Kshirsagar, Meghana; Carbonell, Jaime; Klein-Seetharaman, Judith

2011-01-01

373

Transmitting Plant Viruses Using Whiteflies  

PubMed Central

Whiteflies, Hemiptera: Aleyrodidae, Bemisia tabaci, a complex of morphologically indistinquishable species5, are vectors of many plant viruses. Several genera of these whitefly-transmitted plant viruses (Begomovirus, Carlavirus, Crinivirus, Ipomovirus, Torradovirus) include several hundred species of emerging and economically significant pathogens of important food and fiber crops (reviewed by9,10,16). These viruses do not replicate in their vector but nevertheless are moved readily from plant to plant by the adult whitefly by various means (reviewed by2,6,7,9,10,11,17). For most of these viruses whitefly feeding is required for acquisition and inoculation, while for others only probing is required. Many of these viruses are unable or cannot be easily transmitted by other means. Therefore maintenance of virus cultures, biological and molecular characterization (identification of host range and symptoms)3,13, ecology2,12, require that the viruses be transmitted to experimental hosts using the whitefly vector. In addition the development of new approaches to management, such as evaluation of new chemicals14 or compounds15, new cultural approaches1,4,19, or the selection and development of resistant cultivars7,8,18, requires the use of whiteflies for virus transmission. The use of whitefly transmission of plant viruses for the selection and development of resistant cultivars in breeding programs is particularly challenging7. Effective selection and screening for resistance employs large numbers of plants and there is a need for 100% of the plants to be inoculated in order to find the few genotypes which possess resistance genes. These studies use very large numbers of viruliferous whiteflies, often several times per year. Whitefly maintenance described here can generate hundreds or thousands of adult whiteflies on plants each week, year round, without the contamination of other plant viruses. Plants free of both whiteflies and virus must be produced to introduce into the whitefly colony each week. Whitefly cultures must be kept free of whitefly pathogens, parasites, and parasitoids that can reduce whitefly populations and/or reduce the transmission efficiency of the virus. Colonies produced in the manner described can be quickly scaled to increase or decrease population numbers as needed, and can be adjusted to accommodate the feeding preferences of the whitefly based on the plant host of the virus. There are two basic types of whitefly colonies that can be maintained: a nonviruliferous and a viruliferous whitefly colony. The nonviruliferous colony is composed of whiteflies reared on virus-free plants and allows the weekly availability of whiteflies which can be used to transmit viruses from different cultures. The viruliferous whitefly colony, composed of whiteflies reared on virus-infected plants, allows weekly availability of whiteflies which have acquired the virus thus omitting one step in the virus transmission process.

Polston, Jane E.; Capobianco, H.

2013-01-01

374

Viruses and Interactomes in Translation*  

PubMed Central

A decade of high-throughput screenings for intraviral and virus-host protein-protein interactions led to the accumulation of data and to the development of theories on laws governing interactome organization for many viruses. We present here a computational analysis of intraviral protein networks (EBV, FLUAV, HCV, HSV-1, KSHV, SARS-CoV, VACV, and VZV) and virus-host protein networks (DENV, EBV, FLUAV, HCV, and VACV) from up-to-date interaction data, using various mathematical approaches. If intraviral networks seem to behave similarly, they are clearly different from the human interactome. Viral proteins target highly central human proteins, which are precisely the Achilles' heel of the human interactome. The intrinsic structural disorder is a distinctive feature of viral hubs in virus-host interactomes. Overlaps between virus-host data sets identify a core of human proteins involved in the cellular response to viral infection and in the viral capacity to hijack the cell machinery for viral replication. Host proteins that are strongly targeted by a virus seem to be particularly attractive for other viruses. Such protein-protein interaction networks and their analysis represent a powerful resource from a therapeutic perspective.

Meyniel-Schicklin, Laurene; de Chassey, Benoit; Andre, Patrice; Lotteau, Vincent

2012-01-01

375

21 CFR 866.3360 - Lymphocytic choriomeningitis virus serological reagents.  

Code of Federal Regulations, 2013 CFR

... false Lymphocytic choriomeningitis virus serological reagents. 866.3360 Section...866.3360 Lymphocytic choriomeningitis virus serological reagents. (a) Identification. Lymphocytic choriomeningitis virus serological reagents are devices...

2013-04-01

376

Influenza Viruses in Animal Wildlife Populations  

Microsoft Academic Search

Influenza viruses belong to the family Orthomyxoviridae. Genus Influenza A viruses are true zoonotic agents with many animal reservoirs, whereas genus Influenza B viruses are generally\\u000a considered to be a virus of humans. The genome of influenza A viruses consists of eight unique segments of single-stranded\\u000a RNA of negative polarity; they are typed according to their surface proteins, hemagglutinin (HA)

R. J. Webby; R. G. Webster; Jürgen A. Richt

377

Fish Viruses: A Double-Stranded RNA Icosahedral Virus from a North American Cyprinid.  

National Technical Information Service (NTIS)

A previously unreported virus disease of cultured golden shiners (Notemigonus crysoleucas) is described. The condition is called golden shiner virus (GSV) disease. The virus is icosahedral, measures approximately 70 nm, is ether and heat resistant, stable...

J. A. Plumb P. R. Bowser J. M. Grizzle A. J. Mitchell

1978-01-01

378

78 FR 29755 - Human Immunodeficiency Virus Patient-Focused Drug Development and Human Immunodeficiency Virus...  

Federal Register 2010, 2011, 2012, 2013

...FDA-2013-N-0473] Human Immunodeficiency Virus Patient-Focused Drug Development and Human Immunodeficiency Virus...for public comment on human immunodeficiency virus...Patient-Focused Drug Development and HIV Cure...

2013-05-21

379

78 FR 46969 - Human Immunodeficiency Virus Patient-Focused Drug Development and Human Immunodeficiency Virus...  

Federal Register 2010, 2011, 2012, 2013

...FDA-2013-N-0473] Human Immunodeficiency Virus Patient-Focused Drug Development and Human Immunodeficiency Virus...meeting entitled ``Human Immunodeficiency Virus...Patient-Focused Drug Development and HIV Cure...

2013-08-02

380

9 CFR 113.215 - Bovine Virus Diarrhea Vaccine, Killed Virus.  

Code of Federal Regulations, 2010 CFR

...2009-01-01 2009-01-01 false Bovine Virus Diarrhea Vaccine, Killed Virus. 113.215 Section 113.215 Animals and...INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS;...

2009-01-01

381

Virus infection and knee injury.  

PubMed Central

Serological evidence of virus infection was sought in 31 consecutive patients presenting with knee swelling and compared with age/sex-matched controls. In a normal age/sex-matched control group, 42% of patients had evidence of recent or past infection with Coxsackie B virus, emphasising the care required in the evaluation of the significance of Coxsackie B neutralization titres in individual patients. Of 12 patients presenting with knee swelling and a history of a twisting injury, eight had serological evidence of recent or past infection with Coxsackie B virus, and one had evidence of a current adenovirus infection.

Driscoll, P; Venner, R; Clements, G B

1987-01-01

382

Model for Vesicular Stomatitis Virus  

PubMed Central

Vesicular stomatitis virus contains single-stranded ribonucleic acid of molecular weight 3.6 × 106 and three major proteins with molecular weights of 75 × 103, 57 × 103, and 32.5 × 103. The proteins have been shown to be subunits of the surface projections, ribonucleoprotein, and matrix protein, respectively. From these values and from estimates of the proportions of the individual proteins, it has been calculated that the virus has approximately 500 surface projections, 1,100 protein units on the ribonucleoprotein strand, and 1,600 matrix protein units. Possible models of the virus are proposed in which the proteins are interrelated. Images

Cartwright, B.; Smale, C. J.; Brown, F.; Hull, R.

1972-01-01

383

Xenotropic Murine Leukemia Virus-related Virus (XMRV) Backgrounder  

Cancer.gov

Researchers have not found evidence that XMRV causes any diseases in humans or in animals. The presence of an infectious agent, such as a virus, in diseased tissue does not mean that the agent causes the disease.

384

Evolution of Computer Virus Concealment and AntiVirus Techniques: A Short Survey  

Microsoft Academic Search

This paper presents a general overview on evolution of concealment methods in computer viruses and defensive techniques employed by anti-virus products. In order to stay far from the anti-virus scanners, computer viruses gradually improve their codes to make them invisible. On the other hand, anti-virus technologies continually follow the virus tricks and methodologies to overcome their threats. In this process,

Babak Bashari Rad; Maslin Masrom; Suhaimi Ibrahim

2011-01-01

385

Antiviral Drugs for Viruses Other Than Human Immunodeficiency Virus  

PubMed Central

Most viral diseases, with the exception of those caused by human immunodeficiency virus, are self-limited illnesses that do not require specific antiviral therapy. The currently available antiviral drugs target 3 main groups of viruses: herpes, hepatitis, and influenza viruses. With the exception of the antisense molecule fomivirsen, all antiherpes drugs inhibit viral replication by serving as competitive substrates for viral DNA polymerase. Drugs for the treatment of influenza inhibit the ion channel M2 protein or the enzyme neuraminidase. Combination therapy with Interferon-? and ribavirin remains the backbone treatment for chronic hepatitis C; the addition of serine protease inhibitors improves the treatment outcome of patients infected with hepatitis C virus genotype 1. Chronic hepatitis B can be treated with interferon or a combination of nucleos(t)ide analogues. Notably, almost all the nucleos(t) ide analogues for the treatment of chronic hepatitis B possess anti–human immunodeficiency virus properties, and they inhibit replication of hepatitis B virus by serving as competitive substrates for its DNA polymerase. Some antiviral drugs possess multiple potential clinical applications, such as ribavirin for the treatment of chronic hepatitis C and respiratory syncytial virus and cidofovir for the treatment of cytomegalovirus and other DNA viruses. Drug resistance is an emerging threat to the clinical utility of antiviral drugs. The major mechanisms for drug resistance are mutations in the viral DNA polymerase gene or in genes that encode for the viral kinases required for the activation of certain drugs such as acyclovir and ganciclovir. Widespread antiviral resistance has limited the clinical utility of M2 inhibitors for the prevention and treatment of influenza infections. This article provides an overview of clinically available antiviral drugs for the primary care physician, with a special focus on pharmacology, clinical uses, and adverse effects.

Razonable, Raymund R.

2011-01-01

386

Antiviral drugs for viruses other than human immunodeficiency virus.  

PubMed

Most viral diseases, with the exception of those caused by human immunodeficiency virus, are self-limited illnesses that do not require specific antiviral therapy. The currently available antiviral drugs target 3 main groups of viruses: herpes, hepatitis, and influenza viruses. With the exception of the antisense molecule fomivirsen, all antiherpes drugs inhibit viral replication by serving as competitive substrates for viral DNA polymerase. Drugs for the treatment of influenza inhibit the ion channel M(2) protein or the enzyme neuraminidase. Combination therapy with Interferon-? and ribavirin remains the backbone treatment for chronic hepatitis C; the addition of serine protease inhibitors improves the treatment outcome of patients infected with hepatitis C virus genotype 1. Chronic hepatitis B can be treated with interferon or a combination of nucleos(t)ide analogues. Notably, almost all the nucleos(t) ide analogues for the treatment of chronic hepatitis B possess anti-human immunodeficiency virus properties, and they inhibit replication of hepatitis B virus by serving as competitive substrates for its DNA polymerase. Some antiviral drugs possess multiple potential clinical applications, such as ribavirin for the treatment of chronic hepatitis C and respiratory syncytial virus and cidofovir for the treatment of cytomegalovirus and other DNA viruses. Drug resistance is an emerging threat to the clinical utility of antiviral drugs. The major mechanisms for drug resistance are mutations in the viral DNA polymerase gene or in genes that encode for the viral kinases required for the activation of certain drugs such as acyclovir and ganciclovir. Widespread antiviral resistance has limited the clinical utility of M(2) inhibitors for the prevention and treatment of influenza infections. This article provides an overview of clinically available antiviral drugs for the primary care physician, with a special focus on pharmacology, clinical uses, and adverse effects. PMID:21964179

Razonable, Raymund R

2011-10-01

387

Role of the Phosphatidylserine Receptor TIM-1 in Enveloped-Virus Entry  

PubMed Central

The cell surface receptor T cell immunoglobulin mucin domain 1 (TIM-1) dramatically enhances filovirus infection of epithelial cells. Here, we showed that key phosphatidylserine (PtdSer) binding residues of the TIM-1 IgV domain are critical for Ebola virus (EBOV) entry through direct interaction with PtdSer on the viral envelope. PtdSer liposomes but not phosphatidylcholine liposomes competed with TIM-1 for EBOV pseudovirion binding and transduction. Further, annexin V (AnxV) substituted for the TIM-1 IgV domain, supporting a PtdSer-dependent mechanism. Our findings suggest that TIM-1-dependent uptake of EBOV occurs by apoptotic mimicry. Additionally, TIM-1 enhanced infection of a wide range of enveloped viruses, including alphaviruses and a baculovirus. As further evidence of the critical role of enveloped-virion-associated PtdSer in TIM-1-mediated uptake, TIM-1 enhanced internalization of pseudovirions and virus-like proteins (VLPs) lacking a glycoprotein, providing evidence that TIM-1 and PtdSer-binding receptors can mediate virus uptake independent of a glycoprotein. These results provide evidence for a broad role of TIM-1 as a PtdSer-binding receptor that mediates enveloped-virus uptake. Utilization of PtdSer-binding receptors may explain the wide tropism of many of these viruses and provide new avenues for controlling their virulence.

Moller-Tank, Sven; Kondratowicz, Andrew S.; Davey, Robert A.; Rennert, Paul D.

2013-01-01

388

Adeno-associated virus: from defective virus to effective vector  

PubMed Central

The initial discovery of adeno-associated virus (AAV) mixed with adenovirus particles was not a fortuitous one but rather an expression of AAV biology. Indeed, as it came to be known, in addition to the unavoidable host cell, AAV typically needs a so-called helper virus such as adenovirus to replicate. Since the AAV life cycle revolves around another unrelated virus it was dubbed a satellite virus. However, the structural simplicity plus the defective and non-pathogenic character of this satellite virus caused recombinant forms to acquire centre-stage prominence in the current constellation of vectors for human gene therapy. In the present review, issues related to the development of recombinant AAV (rAAV) vectors, from the general principle to production methods, tropism modifications and other emerging technologies are discussed. In addition, the accumulating knowledge regarding the mechanisms of rAAV genome transduction and persistence is reviewed. The topics on rAAV vectorology are supplemented with information on the parental virus biology with an emphasis on aspects that directly impact on vector design and performance such as genome replication, genetic structure, and host cell entry.

Goncalves, Manuel AFV

2005-01-01

389

Adeno-associated virus: from defective virus to effective vector.  

PubMed

The initial discovery of adeno-associated virus (AAV) mixed with adenovirus particles was not a fortuitous one but rather an expression of AAV biology. Indeed, as it came to be known, in addition to the unavoidable host cell, AAV typically needs a so-called helper virus such as adenovirus to replicate. Since the AAV life cycle revolves around another unrelated virus it was dubbed a satellite virus. However, the structural simplicity plus the defective and non-pathogenic character of this satellite virus caused recombinant forms to acquire centre-stage prominence in the current constellation of vectors for human gene therapy. In the present review, issues related to the development of recombinant AAV (rAAV) vectors, from the general principle to production methods, tropism modifications and other emerging technologies are discussed. In addition, the accumulating knowledge regarding the mechanisms of rAAV genome transduction and persistence is reviewed. The topics on rAAV vectorology are supplemented with information on the parental virus biology with an emphasis on aspects that directly impact on vector design and performance such as genome replication, genetic structure, and host cell entry. PMID:15877812

Gonçalves, Manuel A F V

2005-01-01

390

Human immunodeficiency virus endocrinopathy  

PubMed Central

Human immunodeficiency virus (HIV) endocrinopathy encompasses a broad spectrum of disorders. Almost all the endocrine organs are virtually affected by HIV infection. HIV can directly alter glandular function. More commonly secondary endocrine dysfunction occurs due to opportunistic infections and neoplasms in immunocompromised state. The complex interaction between HIV infection and endocrine system may be manifested as subtle biochemical and hormonal perturbation to overt glandular failure. Antiretroviral therapy as well as other essential medications often result in adverse endocrinal consequences. Apart from adrenal insufficiency, hypogonadism, diabetes and bone loss, AIDS wasting syndrome and HIV lipodystrophy need special reference. Endocrinal evaluation should proceed as in other patients with suspected endocrine dysfunction. Available treatment options have been shown to improve quality of life and long-term mortality in AIDS patients.

Sinha, Uma; Sengupta, Nilanjan; Mukhopadhyay, Prasanta; Roy, Keshab Sinha

2011-01-01

391

Hepatitis C virus kinetics.  

PubMed

The balance of virus production and clearance for untreated patients with chronic hepatitis C virus (HCV) results in a decline of viraemia when initiating active antiviral treatment. During the first phase of interferon-alpha therapy, after a delay of about 8-9 h, the kinetics of the viral load is characterized by a rapid dose-dependent decline. This early response can be observed for almost all patients treated with interferon-alpha. After about 24-48 h, the viral decline enters a second phase of relatively slow exponential decay during the following weeks of therapy. Non-responding patients, however, show constant viraemia or even a rebound during this second phase. The rate of the exponential decline of the viral load in responding patients in this second phase is less sensitive to the dose of interferon-alpha and varies considerably among patients. Furthermore, combination therapy with interferon-alpha plus ribavirin does not significantly improve the initial viral decay, although it may prevent more patients from rebounding. Mathematical modelling of viral dynamics reveals high turnover rates of pre-treatment viral production and clearance, and permits the estimation of in vivo half-lives of a few hours for free HCV virions and of 1-70 days for productively infected cells. Infected cell death rate, which determines the second phase decline slope, is predictive of response to treatment. Current models indicate that the early biphasic viral decline is explained if interferon-alpha partially blocks virion production from infected cells, yet they do not rule out additional antiviral or immunological effects. Therapeutic implications are the advisability of use of frequent (daily) and comparatively high initial doses. In conclusion, kinetic analysis of the viral decay during the first weeks of treatment permits the prediction of response at the end-of-therapy and might help to evaluate new drugs and to optimize therapy. PMID:10971860

Herrmann, E; Neumann, A U; Schmidt, J M; Zeuzem, S

2000-06-01

392

[An update on Lassa virus].  

PubMed

Lassa virus, the etiologic agent of Lassa hemorrhagic fever, infects 100,000 to 300,000 people every year in West Africa with an overall mortality rate ranging from 1 to 2%. It was discovered in 1969 and remains a significant public health risk in endemic areas. Because airborne transmission is possible and mortality can be high under certain conditions, Lassa virus has been classified as a category A bioterrorism agent. Early diagnosis is difficult due to insidious non-specific onset and to the great genetic divergence of the virus that makes RT-PCR assays unreliable. The lack of proper diagnostic tools promotes nosocomial infection and diminishes the efficacy of treatment. Recently, numerous advances have been made in the development of both diagnostic and vaccination techniques. The purpose of this review is to present an update on that research as well as the current epidemiology of Lassa virus. PMID:22393616

Leparc-Goffart, I; Emonet, S F

2011-12-01

393

Virus Transport through Solid Beds.  

National Technical Information Service (NTIS)

A theoretical model for predicting the breakthrough curve of viruses from solid beds is developed. This model includes the percolation of contaminated water through clean solid beds (saturation) and of uncontaminated water through contaminated beds (eluti...

S. Sundaram

1977-01-01

394

Novel vaccines against influenza viruses  

PubMed Central

Killed and live attenuated influenza virus vaccines are effective in preventing and curbing the spread of influenza epidemics when the strains present in the vaccines are closely matched with the predicted epidemic strains. These vaccines are primarily targeted to induce immunity to the variable major target antigen, hemagglutinin (HA) of influenza virus. However, current vaccines are not effective in preventing the emergence of new pandemic or highly virulent viruses. New approaches are being investigated to develop universal influenza virus vaccines as well as to apply more effective vaccine delivery methods. Conserved vaccine targets including the influenza M2 ion channel protein and HA stalk domains are being developed using recombinant technologies to improve the level of cross protection. In addition, recent studies provide evidence that vaccine supplements can provide avenues to further improve current vaccination.

Kang, Sang-Moo; Song, Jae-Min; Compans, Richard W.

2011-01-01

395

Viruses of eukaryotice green algae  

SciTech Connect

The primary objective of our research was to develop the Chlorella-PBCV-1 virus system so that it can be used as a model system for studying gene expression in a photosynthetic eukaryote. We have made considerable progress and have learned much about PBCV-1 and its replication cycle. In addition, several significant discoveries were made in the last 3 to 4 years. These discoveries include: (i) the finding that morphologically similar, plaque forming, dsDNA containing viruses are common in nature and can be isolated readily from fresh water, (ii) the finding that all of these Chlorella viruses contain methylated bases which range in concentration from 0.1% to 47.5% m{sup 5}dC and 0 to 37% m{sup 6}dA and (iii) the discovery that infection with at least some of these viruses induces the appearance of DNA modification/restriction systems. 26 refs.

Van Etten, J.L.

1989-01-01

396

Coronavirus avian infectious bronchitis virus  

Microsoft Academic Search

Infectious bronchitis virus (IBV), the coronavirus of the chicken (Gallus gallus), is one of the foremost causes of economic loss within the poultry industry, affecting the performance of both meat-type and egg-laying birds. The virus replicates not only in the epithelium of upper and lower respiratory tract tissues, but also in many tissues along the alimentary tract and elsewhere e.g.

Dave Cavanagh

2007-01-01

397

Movement of Viruses between Biomes  

Microsoft Academic Search

Viruses are abundant in all known ecosystems. In the present study, we tested the possibility that viruses from one biome can successfully propagate in another. Viral concentrates were prepared from different near-shore marine sites, lake water, marine sediments, and soil. The concentrates were added to microcosms containing dissolved organic matter as a food source (after filtration to allow 100-kDa particles

Emiko Sano; Suzanne Carlson; Linda Wegley; Forest Rohwer

2004-01-01

398

Membrane Proteins in Plant Viruses  

Microsoft Academic Search

It is clear that MPs play an essential role in the pathogenesis and movement within the plant of many plant viruses. However,\\u000a studies of the structure and function of such proteins are still in their infancy. Substantial progress may be expected in\\u000a the next few years, particularly in the area of cell-to-cell movement where viruses are proving useful tools to

Michael J. Adams; John F. Antoniw

399

Determinants of virulence of influenza A virus  

PubMed Central

Influenza A viruses cause yearly seasonal epidemics and occasional global pandemics in humans. In the last century, four human influenza A virus pandemics have occured. Ocasionally, influenza A viruses that circulate in other species, cross the species barrier and infect humans. Virus re-assortment (i.e. mixing of gene segments of multiple viruses) and the accumulation of mutations contribute to the emergence of new influenza A virus variants. Fortunately, most of these variants do not have the ability to spread among humans and subsequently cause a pandemic. In this review we focus on the threat of animal influenza A viruses which have shown the ability to infect humans. In addition, genetic factors which could alter the virulence of influenza A viruses are discussed. Identification and characterization of these factors may provide insights into genetic traits which change virulence and help us to understand which genetic determinants are of importance for the pandemic potential of animal influenza A viruses.

Schrauwen, Eefje J.A.; de Graaf, Miranda; Herfst, Sander; Rimmelzwaan, Guus F.; Osterhaus, Albert D.M.E.; Fouchier, Ron A.M.

2013-01-01

400

DC-SIGN mediates avian H5N1 influenza virus infection in cis and in trans  

SciTech Connect

DC-SIGN, a C-type lectin receptor expressed in dendritic cells (DCs), has been identified as a receptor for human immunodeficiency virus type 1, hepatitis C virus, Ebola virus, cytomegalovirus, dengue virus, and the SARS coronavirus. We used H5N1 pseudotyped and reverse-genetics (RG) virus particles to study their ability to bind with DC-SIGN. Electronic microscopy and functional assay results indicate that pseudotyped viruses containing both HA and NA proteins express hemagglutination and are capable of infecting cells expressing {alpha}-2,3-linked sialic acid receptors. Results from a capture assay show that DC-SIGN-expressing cells (including B-THP-1/DC-SIGN and T-THP-1/DC-SIGN) and peripheral blood dendritic cells are capable of transferring H5N1 pseudotyped and RG virus particles to target cells; this action can be blocked by anti-DC-SIGN monoclonal antibodies. In summary, (a) DC-SIGN acts as a capture or attachment molecule for avian H5N1 virus, and (b) DC-SIGN mediates infections in cis and in trans.

Wang, S.-F.; Huang, Jason C. [Department of Biotechnology and Laboratory Science in Medicine, School of Medicine, National Yang-Ming University, Taipei 112, Taiwan (China); AIDS Prevention and Research Center, School of Medicine, National Yang-Ming University, Taipei 112, Taiwan (China); Lee, Y.-M. [Division of Preventive Medicine, Institute of Public Health, School of Medicine, National Yang-Ming University, Taipei 112, Taiwan (China); Division of Clinical Virology, Department of Pathology and Laboratory Medicine, Taipei Veterans General Hospital, Taipei, Taiwan (China); Liu, S.-J. [Vaccine Research and Development Center, National Health Research Institutes, Taiwan (China); Chan, Yu-Jiun [Division of Preventive Medicine, Institute of Public Health, School of Medicine, National Yang-Ming University, Taipei 112, Taiwan (China); Division of Clinical Virology, Department of Pathology and Laboratory Medicine, Taipei Veterans General Hospital, Taipei, Taiwan (China); Division of Infectious Diseases, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan (China); Chau, Y.-P. [Institute of Anatomy and Cell Biology, School of Medicine, National Yang-Ming University, Taipei 112, Taiwan (China); Chong, P. [Vaccine Research and Development Center, National Health Research Institutes, Taiwan (China); Chen, Y.-M.A. [AIDS Prevention and Research Center, School of Medicine, National Yang-Ming University, Taipei 112, Taiwan (China) and Division of Preventive Medicine, Institute of Public Health, School of Medicine, National Yang-Ming University, Taipei 112, Taiwan (China); Department of Microbiology, School of Medicine, National Yang-Ming University, AIDS Prevention and Research Center, No. 155, Linong Street, Section 2, Taipei 112, Taiwan (China)], E-mail: arthur@ym.edu.tw

2008-09-05

401

PC viruses: How do they do that  

SciTech Connect

The topic of PC Viruses has been an issue for a number of years now. They've been reported in every major newspaper, tabloids, television and radio. People from all fields get viruses: government, private sector businesses, home computers, schools, computer software suppliers. A definition is proposed to introduce the virus phenomenon. Virus authors come from a variety of communities. Motives and ideologies of authors are discussed, and examples of viruses are offered. Also mentioned is the growing number of viruses developed, isolated, and never distributed to the public at large, but kept within the antivirus research community. Virus examples are offered as well. Viruses are distributed not only through bulletin boards and shareware, but also from areas previously assumed to be safe, including the threat of receiving a virus through a standard in-house function, such as an in-house hardware maintenance shop. Three categories of viruses are presented: File Infecter viruses, Boot Sector Infecters, and the new category of Directory Entry Infecter virus. Also discussed are crossover viruses, that is, viruses which utilize a variety of techniques to ensure survival. An explanation of what is occurring within every stage of various viruses is given. Replication strategies common to all three types is noted, mainly the two different replication strategies of memory resident infecters and active selection infecters. A detailed definition, description and application of a stealth virus is presented. Detection strategies are discussed as each topic in this section is completed; a high level schemata of the operation of various virus detection programs ispresented. Since most eradication today is done using virus detection/eradication software, this paper attempts to reveal the techniques used by these packages.Included in the paper is the topic of manual eradication.

Pichnarczyk, K.

1992-07-01

402

PC viruses: How do they do that?  

SciTech Connect

The topic of PC Viruses has been an issue for a number of years now. They`ve been reported in every major newspaper, tabloids, television and radio. People from all fields get viruses: government, private sector businesses, home computers, schools, computer software suppliers. A definition is proposed to introduce the virus phenomenon. Virus authors come from a variety of communities. Motives and ideologies of authors are discussed, and examples of viruses are offered. Also mentioned is the growing number of viruses developed, isolated, and never distributed to the public at large, but kept within the antivirus research community. Virus examples are offered as well. Viruses are distributed not only through bulletin boards and shareware, but also from areas previously assumed to be safe, including the threat of receiving a virus through a standard in-house function, such as an in-house hardware maintenance shop. Three categories of viruses are presented: File Infecter viruses, Boot Sector Infecters, and the new category of Directory Entry Infecter virus. Also discussed are crossover viruses, that is, viruses which utilize a variety of techniques to ensure survival. An explanation of what is occurring within every stage of various viruses is given. Replication strategies common to all three types is noted, mainly the two different replication strategies of memory resident infecters and active selection infecters. A detailed definition, description and application of a stealth virus is presented. Detection strategies are discussed as each topic in this section is completed; a high level schemata of the operation of various virus detection programs ispresented. Since most eradication today is done using virus detection/eradication software, this paper attempts to reveal the techniques used by these packages.Included in the paper is the topic of manual eradication.

Pichnarczyk, K.

1992-07-01

403

Circulating avian influenza viruses closely related to the 1918 virus have pandemic potential.  

PubMed

Wild birds harbor a large gene pool of influenza A viruses that have the potential to cause influenza pandemics. Foreseeing and understanding this potential is important for effective surveillance. Our phylogenetic and geographic analyses revealed the global prevalence of avian influenza virus genes whose proteins differ only a few amino acids from the 1918 pandemic influenza virus, suggesting that 1918-like pandemic viruses may emerge in the future. To assess this risk, we generated and characterized a virus composed of avian influenza viral segments with high homology to the 1918 virus. This virus exhibited pathogenicity in mice and ferrets higher than that in an authentic avian influenza virus. Further, acquisition of seven amino acid substitutions in the viral polymerases and the hemagglutinin surface glycoprotein conferred respiratory droplet transmission to the 1918-like avian virus in ferrets, demonstrating that contemporary avian influenza viruses with 1918 virus-like proteins may have pandemic potential. PMID:24922572

Watanabe, Tokiko; Zhong, Gongxun; Russell, Colin A; Nakajima, Noriko; Hatta, Masato; Hanson, Anthony; McBride, Ryan; Burke, David F; Takahashi, Kenta; Fukuyama, Satoshi; Tomita, Yuriko; Maher, Eileen A; Watanabe, Shinji; Imai, Masaki; Neumann, Gabriele; Hasegawa, Hideki; Paulson, James C; Smith, Derek J; Kawaoka, Yoshihiro

2014-06-11

404

Foodborne viruses: an emerging problem.  

PubMed

Several groups of viruses may infect persons after ingestion and then are shed via stool. Of these, the norovirus (NoV) and hepatitis A virus (HAV) are currently recognised as the most important human foodborne pathogens with regard to the number of outbreaks and people affected in the Western world. NoV and HAV are highly infectious and may lead to widespread outbreaks. The clinical manifestation of NoV infection, however, is relatively mild. Asymptomatic infections are common and may contribute to the spread of the infection. Introduction of NoV in a community or population (a seeding event) may be followed by additional spread because of the highly infectious nature of NoV, resulting in a great number of secondary infections (50% of contacts). Hepatitis A is an increasing problem because of the decrease in immunity of populations in countries with high standards of hygiene. Molecular-based methods can detect viruses in shellfish but are not yet available for other foods. The applicability of the methods currently available for monitoring foods for viral contamination is unknown. No consistent correlation has been found between the presence of indicator microorganisms (i.e. bacteriophages, E. coli) and viruses. NoV and HAV are highly infectious and exhibit variable levels of resistance to heat and disinfection agents. However, they are both inactivated at 100 degrees C. No validated model virus or model system is available for studies of inactivation of NoV, although investigations could make use of structurally similar viruses (i.e. canine and feline caliciviruses). In the absence of a model virus or model system, food safety guidelines need to be based on studies that have been performed with the most resistant enteric RNA viruses (i.e. HAV, for which a model system does exist) and also with bacteriophages (for water). Most documented foodborne viral outbreaks can be traced to food that has been manually handled by an infected foodhandler, rather than to industrially processed foods. The viral contamination of food can occur anywhere in the process from farm to fork, but most foodborne viral infections can be traced back to infected persons who handle food that is not heated or otherwise treated afterwards. Therefore, emphasis should be on stringent personal hygiene during preparation. If viruses are present in food preprocessing, residual viral infectivity may be present after some industrial processes. Therefore, it is key that sufficient attention be given to good agriculture practice (GAP) and good manufacturing practice (GMP) to avoid introduction of viruses onto the raw material and into the food-manufacturing environment, and to HACCP to assure adequate management of (control over) viruses present during the manufacturing process. If viruses are present in foods after processing, they remain infectious in most circumstances and in most foods for several days or weeks, especially if kept cooled (at 4 degrees C). Therefore, emphasis should be on stringent personal hygiene during preparation. For the control of foodborne viral infections, it is necessary to: Heighten awareness about the presence and spread of these viruses by foodhandlers; Optimise and standardise methods for the detection of foodborne viruses; Develop laboratory-based surveillance to detect large, common-source outbreaks at an early stage; and Emphasise consideration of viruses in setting up food safety quality control and management systems (GHP, GMP, HACCP). PMID:14672828

Koopmans, Marion; Duizer, Erwin

2004-01-01

405

Ebola Virus Replication in Macrophages and its Relation to the Virus Pathogeneicity.  

National Technical Information Service (NTIS)

Any infectious disease is a result of complicated interplay of both pathogen and organism factors. Identification of the most important events, which determine development of the disease is necessary for understanding of the basic mechanisms of infection....

E. I. Ryabchikova J. N. Rassadkin M. P. Smolina

2001-01-01

406

40 CFR 174.514 - Coat Protein of Watermelon Mosaic Virus-2 and Zucchini Yellow Mosaic Virus; exemption from the...  

Code of Federal Regulations, 2013 CFR

...2013-07-01 false Coat Protein of Watermelon Mosaic Virus-2 and Zucchini Yellow Mosaic Virus; exemption from the requirement for a tolerance...174.514 Coat Protein of Watermelon Mosaic Virus-2 and Zucchini Yellow Mosaic Virus;...

2013-07-01

407

Engineered resistance in potato against potato leafroll virus, potato virus A and potato virus Y.  

PubMed

Transgenic potato plants of Solanum tuberosum cultivar Vales Sovereign were generated that expressed fused, tandem, 200 bp segments derived from the capsid protein coding sequences of potato virus Y (PVY strain O) and potato leafroll virus (PLRV), as well as the cylindrical inclusion body coding sequences of potato virus A (PVA), as inverted repeat double-stranded RNAs, separated by an intron. The orientation of the expressed double-stranded RNAs was either sense-intron-antisense or antisense-intron-sense RNAs, and the double-stranded RNAs were processed into small RNAs. Four lines of such transgenic potato plants were assessed for resistance to infection by PVY-O, PLRV, or PVA, all transmitted by a natural vector, the green-peach aphid, Myzus persicae. Resistance was assessed by the absence of detectable virus accumulation in the foliage. All four transgenic potato lines tested showed 100% resistance to infection by either PVY-O or PVA, but variable resistance to infection by PLRV, ranging from 72 to 96% in different lines. This was regardless of the orientation of the viral inserts in the construct used to generate the transgenic plants and the gene copy number of the transgene. This demonstrates the potential for using tandem, fused viral segments and the inverted-repeat expression system to achieve multiple virus resistance to viruses transmitted by aphids in potato. PMID:23526159

Chung, Bong Nam; Yoon, Ju-Yeon; Palukaitis, Peter

2013-08-01

408

Immunological Memory after Exposure to Variola Virus, Monkeypox Virus, and Vaccinia Virus  

PubMed Central

We compared cellular and humoral immunity to vaccinia virus (VV) in individuals exposed to 3 different orthopoxviruses: 154 individuals previously vaccinated with VV, 7 individuals with a history of monkeypox virus infection, and 8 individuals with a history of variola virus infection. Among individuals vaccinated >20 years prior, 9 (14%) of 66 individuals demonstrated VV-specific interferon (IFN)-? enzyme-linked immunospot (ELISPOT) assay responses; 21 (50%) of 42 had lymphoproliferative (LP) responses, and 29 (97%) of 30 had VV-specific neutralizing antibodies. One year after monkeypox virus infection, 6 of 7 individuals had IFN-? ELISPOT responses, all had VV-specific LP responses, and 3 of 7 had VV-specific neutralizing antibodies. Of 8 individuals with a history of variola virus infection, 1 had a VV-specific IFN-? ELISPOT response, 4 had LP responses against whole VV, 7 had LP responses against heat-denatured vaccinia antigen, and 7 had VV-specific neutralizing antibodies. Survivors of variola virus infection demonstrated VV-specific CD4 memory cell responses and neutralizing antibodies >40 years after infection.

Sivapalasingam, Sumathi; Kennedy, Jeffrey S.; Borkowsky, William; Valentine, Fred; Zhan, Ming-Xia; Pazoles, Pamela; Paolino, Anna; Ennis, Francis A.; Steigbigel, Neal H.

2007-01-01

409

Comparison of cowpox-like viruses isolated from European zoos  

Microsoft Academic Search

Summary Poxviruses isolated from captive carnivores in Russia (Moscow virus) and elephants in Germany (elephant virus) were very closely-related to cowpox virus. Immunological analysis with absorbed sera separated elephant virus but not cowpox and Moscow virus, whereas polypeptide analysis separated cowpox but not elephant and Moscow virus. A combination of biological tests separated all three. The epidemiological implications are briefly

D. Baxby; W. B. Shackleton; Jean Wheeler; A. Turner

1979-01-01

410

Performance of Virus Resistant Transgenic Yellow Summer Squash in Alabama  

Microsoft Academic Search

Production of summer squash in Alabama and the southeastern United States is generally limited to spring and early summer due to the abundance of aphid transmitted viruses during the late summer and fall. Cucumber mosaic virus (CMV), Watermelon mosaic virus (WMV), Zucchini yellow mosaic virus (ZYMV), and Papaya ring spot virus (PRSV) are the most common viruses affecting Cucurbits in

Edward J. Sikora; John F. Murphy; Jason Burkett

2006-01-01

411

A decade after the generation of a negative-sense RNA virus from cloned cDNA - what have we learned?  

PubMed

Since the first generation of a negative-sense RNA virus entirely from cloned cDNA in 1994, similar reverse genetics systems have been established for members of most genera of the Rhabdo- and Paramyxoviridae families, as well as for Ebola virus (Filoviridae). The generation of segmented negative-sense RNA viruses was technically more challenging and has lagged behind the recovery of nonsegmented viruses, primarily because of the difficulty of providing more than one genomic RNA segment. A member of the Bunyaviridae family (whose genome is composed of three RNA segments) was first generated from cloned cDNA in 1996, followed in 1999 by the production of influenza virus, which contains eight RNA segments. Thus, reverse genetics, or the de novo synthesis of negative-sense RNA viruses from cloned cDNA, has become a reliable laboratory method that can be used to study this large group of medically and economically important viruses. It provides a powerful tool for dissecting the virus life cycle, virus assembly, the role of viral proteins in pathogenicity and the interplay of viral proteins with components of the host cell immune response. Finally, reverse genetics has opened the way to develop live attenuated virus vaccines and vaccine vectors. PMID:12388800

Neumann, Gabriele; Whitt, Michael A; Kawaoka, Yoshihiro

2002-11-01

412

Viruses and viruslike particles of eukaryotic algae.  

PubMed Central

Until recently there was little interest or information on viruses and viruslike particles of eukaryotic algae. However, this situation is changing. In the past decade many large double-stranded DNA-containing viruses that infect two culturable, unicellular, eukaryotic green algae have been discovered. These viruses can be produced in large quantities, assayed by plaque formation, and analyzed by standard bacteriophage techniques. The viruses are structurally similar to animal iridoviruses, their genomes are similar to but larger (greater than 300 kbp) than that of poxviruses, and their infection process resembles that of bacteriophages. Some of the viruses have DNAs with low levels of methylated bases, whereas others have DNAs with high concentrations of 5-methylcytosine and N6-methyladenine. Virus-encoded DNA methyltransferases are associated with the methylation and are accompanied by virus-encoded DNA site-specific (restriction) endonucleases. Some of these enzymes have sequence specificities identical to those of known bacterial enzymes, and others have previously unrecognized specificities. A separate rod-shaped RNA-containing algal virus has structural and nucleotide sequence affinities to higher plant viruses. Quite recently, viruses have been associated with rapid changes in marine algal populations. In the next decade we envision the discovery of new algal viruses, clarification of their role in various ecosystems, discovery of commercially useful genes in these viruses, and exploitation of algal virus genetic elements in plant and algal biotechnology. Images

Van Etten, J L; Lane, L C; Meints, R H

1991-01-01

413

Adaptive Mutations in Sindbis Virus E2 and Ross River Virus E1 That Allow Efficient Budding of Chimeric Viruses  

Microsoft Academic Search

Alphavirus glycoproteins E2 and E1 form a heterodimer that is required for virus assembly. We have studied adaptive mutations in E2 of Sindbis virus (SIN) and E1 of Ross River virus (RR) that allow these two glycoproteins to interact more efficiently in a chimeric virus that has SIN E2 but RR E1. These mutations include K129E, K131E, and V237F in

KYONGMIN HWANG KIM; ELLEN G. STRAUSS; JAMES H. STRAUSS

2000-01-01

414

Virus nomenclature below the species level: a standardized nomenclature for filovirus strains and variants rescued from cDNA.  

PubMed

Specific alterations (mutations, deletions, insertions) of virus genomes are crucial for the functional characterization of their regulatory elements and their expression products, as well as a prerequisite for the creation of attenuated viruses that could serve as vaccine candidates. Virus genome tailoring can be performed either by using traditionally cloned genomes as starting materials, followed by site-directed mutagenesis, or by de novo synthesis of modified virus genomes or parts thereof. A systematic nomenclature for such recombinant viruses is necessary to set them apart from wild-type and laboratory-adapted viruses, and to improve communication and collaborations among researchers who may want to use recombinant viruses or create novel viruses based on them. A large group of filovirus experts has recently proposed nomenclatures for natural and laboratory animal-adapted filoviruses that aim to simplify the retrieval of sequence data from electronic databases. Here, this work is extended to include nomenclature for filoviruses obtained in the laboratory via reverse genetics systems. The previously developed template for natural filovirus genetic variant naming, <virus name> (/)///-, is retained, but we propose to adapt the type of information added to each field for cDNA clone-derived filoviruses. For instance, the full-length designation of an Ebola virus Kikwit variant rescued from a plasmid developed at the US Centers for Disease Control and Prevention could be akin to "Ebola virus H.sapiens-rec/COD/1995/Kikwit-abc1" (with the suffix "rec" identifying the recombinant nature of the virus and "abc1" being a placeholder for any meaningful isolate designator). Such a full-length designation should be used in databases and the methods section of publications. Shortened designations (such as "EBOV H.sap/COD/95/Kik-abc1") and abbreviations (such as "EBOV/Kik-abc1") could be used in the remainder of the text, depending on how critical it is to convey information contained in the full-length name. "EBOV" would suffice if only one EBOV strain/variant/isolate is addressed. PMID:24190508

Kuhn, Jens H; Bào, Y?míng; Bavari, Sina; Becker, Stephan; Bradfute, Steven; Brauburger, Kristina; Rodney Brister, J; Bukreyev, Alexander A; Caì, Yíngyún; Chandran, Kartik; Davey, Robert A; Dolnik, Olga; Dye, John M; Enterlein, Sven; Gonzalez, Jean-Paul; Formenty, Pierre; Freiberg, Alexander N; Hensley, Lisa E; Hoenen, Thomas; Honko, Anna N; Ignatyev, Georgy M; Jahrling, Peter B; Johnson, Karl M; Klenk, Hans-Dieter; Kobinger, Gary; Lackemeyer, Matthew G; Leroy, Eric M; Lever, Mark S; Mühlberger, Elke; Netesov, Sergey V; Olinger, Gene G; Palacios, Gustavo; Patterson, Jean L; Paweska, Janusz T; Pitt, Louise; Radoshitzky, Sheli R; Ryabchikova, Elena I; Saphire, Erica Ollmann; Shestopalov, Aleksandr M; Smither, Sophie J; Sullivan, Nancy J; Swanepoel, Robert; Takada, Ayato; Towner, Jonathan S; van der Groen, Guido; Volchkov, Viktor E; Volchkova, Valentina A; Wahl-Jensen, Victoria; Warren, Travis K; Warfield, Kelly L; Weidmann, Manfred; Nichol, Stuart T

2014-05-01

415

Recovery of Virus Samples from Various Surfaces with the Integrated Virus Detection System.  

National Technical Information Service (NTIS)

Viruses are known to survive in environmental settings over various time periods. This study will show that certain viruses survive for a 24 h period, and certain viruses do not survive, depending on the substrate with which the viruses are in contact.

C. H. Wick P. E. McCubbin

2010-01-01

416

Avian-human reassortant influenza A viruses derived by mating avian and human influenza A viruses.  

PubMed

Reassortant influenza A viruses were produced by mating an avian virus (A/Mallard/NY/78, A/Mallard/Alberta/78, or A/Pintail/Alberta/79) with a wild-type human influenza A virus. From each mating a reassortant virus was obtained that contained the genes coding for the hemagglutinin and neuraminidase surface antigens of the human influenza A wild-type virus and the six other RNA segments ("internal genes") of the avian influenza A virus parent. The avian-human reassortant influenza viruses produced resembled their avian virus parent in that they produced plaques on MDCK monolayers at 42 C, a temperature restrictive for the human influenza viruses. In the trachea of squirrel monkeys, each avian-human reassortant influenza virus was as restricted in its replication as was its avian influenza virus parent. Thus, one or more of the six internal genes of each avian parent virus was responsible for restriction of the reassortant virus in monkeys. The A/Washington/80 X A/Mallard/NY/78 reassortant virus retained its phenotype of restricted replication in monkeys after five serial passages in vivo. It also failed to transmit to cagemates or induce resistance to wild-type virus challenge, and it did not initiate a systemic or enteric infection. These findings form the basis for evaluation of these attenuated avian-human reassortant influenza A viruses as live attenuated vaccines for humans. PMID:6501928

Murphy, B R; Buckler-White, A J; London, W T; Harper, J; Tierney, E L; Miller, N T; Reck, L J; Chanock, R M; Hinshaw, V S

1984-12-01

417

Genetic Diversity in RNA Virus Quasispecies Is Controlled by Host-Virus Interactions  

Microsoft Academic Search

Many RNA viruses have genetically diverse populations known as quasispecies. Important biological char- acteristics may be related to the levels of diversity in the quasispecies (quasispecies cloud size), including adaptability and host range. Previous work using Tobacco mosaic virus and Cucumber mosaic virus indicated that evolutionarily related viruses have very different levels of diversity in a common host. The quasispecies

WILLIAM L. SCHNEIDER; MARILYN J. ROOSSINCK

2001-01-01

418

Mouse Neuroinvasive Phenotype of West Nile Virus Strains Varies Depending upon Virus Genotype  

Microsoft Academic Search

Despite recent advances in the genetics of West Nile (WN) virus, relatively little is known about the molecular basis of virulence of this virus. In particular, although the genotype of the WN virus strain that was recently introduced into North America has been determined, there have been few experimental studies on the virulence phenotype of the virus. We compared genetic

David W. C. Beasley; Li Li; Miguel T. Suderman; Alan D. T. Barrett

2002-01-01

419

Coping with Computer Viruses: General Discussion and Review of Symantec Anti-Virus for the Macintosh.  

ERIC Educational Resources Information Center

Discusses computer viruses that attack the Macintosh and describes Symantec AntiVirus for Macintosh (SAM), a commercial program designed to detect and eliminate viruses; sample screen displays are included. SAM is recommended for use in library settings as well as two public domain virus protection programs. (four references) (MES)

Primich, Tracy

1992-01-01

420

Dengue viruses - an overview  

PubMed Central

Dengue viruses (DENVs) cause the most common arthropod-borne viral disease in man with 50–100 million infections per year. Because of the lack of a vaccine and antiviral drugs, the sole measure of control is limiting the Aedes mosquito vectors. DENV infection can be asymptomatic or a self-limited, acute febrile disease ranging in severity. The classical form of dengue fever (DF) is characterized by high fever, headache, stomach ache, rash, myalgia, and arthralgia. Severe dengue, dengue hemorrhagic fever (DHF), and dengue shock syndrome (DSS) are accompanied by thrombocytopenia, vascular leakage, and hypotension. DSS, which can be fatal, is characterized by systemic shock. Despite intensive research, the underlying mechanisms causing severe dengue is still not well understood partly due to the lack of appropriate animal models of infection and disease. However, even though it is clear that both viral and host factors play important roles in the course of infection, a fundamental knowledge gap still remains to be filled regarding host cell tropism, crucial host immune response mechanisms, and viral markers for virulence.

Back, Anne Tuiskunen; Lundkvist, Ake

2013-01-01

421

Hepatitis B virus morphogenesis  

PubMed Central

The hepatitis B virus (HBV) particle consists of an envelope containing three related surface proteins and probably lipid and an icosahedral nucleocapsid of approximately 30 nm diameter enclosing the viral DNA genome and DNA polymerase. The capsid is formed in the cytosol of the infected cell during packaging of an RNA pregenome replication complex by multiple copies of a 21-kDa C protein. The capsid gains the ability to bud during synthesis of the viral DNA genome by reverse transcription of the pregenome in the lumen of the particle. The three envelope proteins S, M, and L shape a complex transmembrane fold at the endoplasmic reticulum, and form disulfide-linked homo- and heterodimers. The transmembrane topology of a fraction of the large envelope protein L changes post-translationally, therefore, the N terminal domain of L (preS) finally appears on both sides of the membrane. During budding at an intracellular membrane, a short linear domain in the cytosolic preS region interacts with binding sites on the capsid surface. The virions are subsequently secreted into the blood. In addition, the surface proteins can bud in the absence of capsids and form subviral lipoprotein particles of 20 nm diameter which are also secreted.

Bruss, Volker

2007-01-01

422

Hepatitis B virus replication  

PubMed Central

Hepadnaviruses, including human hepatitis B virus (HBV), replicate through reverse transcription of an RNA intermediate, the pregenomic RNA (pgRNA). Despite this kinship to retroviruses, there are fundamental differences beyond the fact that hepadnavirions contain DNA instead of RNA. Most peculiar is the initiation of reverse transcription: it occurs by protein-priming, is strictly committed to using an RNA hairpin on the pgRNA, ?, as template, and depends on cellular chaperones; moreover, proper replication can apparently occur only in the specialized environment of intact nucleocapsids. This complexity has hampered an in-depth mechanistic understanding. The recent successful reconstitution in the test tube of active replication initiation complexes from purified components, for duck HBV (DHBV), now allows for the analysis of the biochemistry of hepadnaviral replication at the molecular level. Here we review the current state of knowledge at all steps of the hepadnaviral genome replication cycle, with emphasis on new insights that turned up by the use of such cell-free systems. At this time, they can, unfortunately, not be complemented by three-dimensional structural information on the involved components. However, at least for the ? RNA element such information is emerging, raising expectations that combining biophysics with biochemistry and genetics will soon provide a powerful integrated approach for solving the many outstanding questions. The ultimate, though most challenging goal, will be to visualize the hepadnaviral reverse transcriptase in the act of synthesizing DNA, which will also have strong implications for drug development.

Beck, Juergen; Nassal, Michael

2007-01-01

423

Induction of protective immunity in swine by recombinant bamboo mosaic virus expressing foot-and-mouth disease virus epitopes  

Microsoft Academic Search

BACKGROUND: Plant viruses can be employed as versatile vectors for the production of vaccines by expressing immunogenic epitopes on the surface of chimeric viral particles. Although several viruses, including tobacco mosaic virus, potato virus X and cowpea mosaic virus, have been developed as vectors, we aimed to develop a new viral vaccine delivery system, a bamboo mosaic virus (BaMV), that

Chung-Da Yang; Jia-Teh Liao; Chen-Yen Lai; Ming-Hwa Jong; Chi-Ming Liang; Yeou-Liang Lin; Na-Sheng Lin; Yau-Heiu Hsu; Shu-Mei Liang

2007-01-01

424

Multiple roles of the coagulation protease cascade during virus infection.  

PubMed

The coagulation cascade is activated during viral infections. This response may be part of the host defense system to limit spread of the pathogen. However, excessive activation of the coagulation cascade can be deleterious. In fact, inhibition of the tissue factor/factor VIIa complex reduced mortality in a monkey model of Ebola hemorrhagic fever. Other studies showed that incorporation of tissue factor into the envelope of herpes simplex virus increases infection of endothelial cells and mice. Furthermore, binding of factor X to adenovirus serotype 5 enhances infection of hepatocytes but also increases the activation of the innate immune response to the virus. Coagulation proteases activate protease-activated receptors (PARs). Interestingly, we and others found that PAR1 and PAR2 modulate the immune response to viral infection. For instance, PAR1 positively regulates TLR3-dependent expression of the antiviral protein interferon ?, whereas PAR2 negatively regulates expression during coxsackievirus group B infection. These studies indicate that the coagulation cascade plays multiple roles during viral infections. PMID:24632711

Antoniak, Silvio; Mackman, Nigel

2014-04-24

425

Autophagic machinery activated by dengue virus enhances virus replication  

SciTech Connect

Autophagy is a cellular response against stresses which include the infection of viruses and bacteria. We unravel that Dengue virus-2 (DV2) can trigger autophagic process in various infected cell lines demonstrated by GFP-LC3 dot formation and increased LC3-II formation. Autophagosome formation was also observed under the transmission electron microscope. DV2-induced autophagy further enhances the titers of extracellular and intracellular viruses indicating that autophagy can promote viral replication in the infected cells. Moreover, o