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1

Ebola Virus Antibodies in Fruit Bats, Bangladesh  

PubMed Central

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

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

2013-01-01

2

Successful Topical Respiratory Tract Immunization of Primates against Ebola Virus  

Microsoft Academic Search

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

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

2007-01-01

3

Reemerging Sudan Ebola Virus Disease in Uganda, 2011  

PubMed Central

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

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

2012-01-01

4

The natural history of Ebola virus in Africa  

Microsoft Academic Search

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

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

2005-01-01

5

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

6

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

7

Recombinant vesicular stomatitis virus-based vaccines against Ebola and Marburg virus infections.  

PubMed

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

Geisbert, Thomas W; Feldmann, Heinz

2011-11-01

8

Ebola virus: immune mechanisms of protection and vaccine development.  

PubMed

Vaccination is one of our most powerful antiviral strategies. Despite the emergence of deadly viruses such as Ebola virus, vaccination efforts have focused mainly on childhood communicable diseases. Although Ebola virus was once believed to be limited to isolated outbreaks in distant lands, forces of globalization potentiate outbreaks anywhere in the world through incidental transmission. Moreover, since this virus has already been transformed into weapon-grade material, the potential exists for it to be used as a biological weapon with catastrophic consequences for any population vulnerable to attack. Ebola hemorrhagic fever (EHF) is a syndrome that can rapidly lead to death within days of symptom onset. The disease directly affects the immune system and vascular bed, with correspondingly high mortality rates. Patients with severe disease produce dangerously high levels of inflammatory cytokines, which destroy normal tissue and microcirculation, leading to profound capillary leakage, renal failure, and disseminated intravascular coagulation. Vaccine development has been fraught with obstacles, primarily of a biosafety nature. Case reports of acutely ill patients with EHF showing improvement with the transfusion of convalescent plasma are at odds with animal studies demonstrating further viral replication with the same treatment. Using mRNA extracted from bone marrow of Ebola survivors, human monoclonal antibodies against Ebola virus surface protein have been experimentally produced and now raise the hope for the development of a safe vaccine. PMID:12698920

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

2003-04-01

9

Short report: lack of virus replication in arthropods after intrathoracic inoculation of Ebola Reston virus.  

PubMed

To evaluate the potential for arthropods to serve as reservoir hosts of Ebola virus, three mosquito species, Aedes albopictus, Aedes taeniorhynchus, and Culex pipiens, and a soft tick, Ornithodoros sonrai, were inoculated with 1O2.5 plaque-forming units of Ebola Reston virus. After incubation at 22 degrees C for 11 days, at least six specimens of each species were triturated and examined for evidence of viral replication by enzyme-linked immunosorbent assay and plaque assay. There was no evidence of viral replication in any of the arthropods tested. Because intrathoracic inoculation bypasses various barriers to viral infection, the lack of replication of Ebola Reston virus in these inoculated arthropods indicates that these mosquito species and soft ticks probably are not involved as natural reservoirs of Ebola virus. PMID:8702028

Turell, M J; Bressler, D S; Rossi, C A

1996-07-01

10

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

11

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

Microsoft Academic Search

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

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

2009-01-01

12

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

Microsoft Academic Search

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

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

2011-01-01

13

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

14

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

15

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

Microsoft Academic Search

We used an ELISA to determine the prevalence of IgG antibodies specific for the Zaire subtype of Ebola virus in 790 nonhuman primates, belonging to 20 species, studied between 1985 and 2000 in Cameroon, Gabon, and the Republic of Congo. The seroprevalence rate of Ebola antibody in wild-born chimpanzees was 12.9%, indicating that (1) Ebola virus circulates in the forests

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

2004-01-01

16

Ebola virus outbreaks in Africa: Past and present.  

PubMed

Ebola haemorrhagic fever (EHF) is a zoonosis affecting both human and non-human primates (NHP). Outbreaks in Africa occur mainly in the Congo and Nile basins. The first outbreaks of EHF occurred nearly simultaneously in 1976 in the Democratic Republic of the Congo (DRC, former Zaire) and Sudan with very high case fatality rates of 88% and 53%, respectively. The two outbreaks were caused by two distinct species of Ebola virus named Zaire ebolavirus (ZEBOV) and Sudan ebolavirus (SEBOV). The source of transmission remains unknown. After a long period of silence (1980-1993), EHF outbreaks in Africa caused by the two species erupted with increased frequency and new species were discovered, namely Côte d'Ivoire ebolavirus (CIEBOV) in 1994 in the Ivory Coast and Bundibugyo ebolavirus (BEBOV) in 2007 in Uganda. The re-emergence of EHF outbreaks in Gabon and Republic of the Congo were concomitant with an increase in mortality amongst gorillas and chimpanzees infected with ZEBOV. The human outbreaks were related to multiple, unrelated index cases who had contact with dead gorillas or chimpanzees. However, in areas where NHP were rare or absent, as in Kikwit (DRC) in 1995, Mweka (DRC) in 2007, Gulu (Uganda) in 2000 and Yambio (Sudan) in 2004, the hunting and eating of fruit bats may have resulted in the primary transmission of Ebola virus to humans. Human-to-human transmission is associated with direct contact with body fluids or tissues from an infected subject or contaminated objects. Despite several, often heroic field studies, the epidemiology and ecology of Ebola virus, including identification of its natural reservoir hosts, remains a formidable challenge for public health and scientific communities. PMID:23327370

Muyembe-Tamfum, J J; Mulangu, S; Masumu, Justin; Kayembe, J M; Kemp, A; Paweska, Janusz T

2012-06-20

17

Vaccine to Confer to Nonhuman Primates Complete Protection Against Multistrain Ebola and Marburg Virus Infections.  

National Technical Information Service (NTIS)

Filoviruses (Ebola and Marburg viruses) are among the deadliest viruses known to mankind with mortality rates nearing 90%. These pathogens are highly infectious through contact with infected body fluids and can be easily aerosolized. Additionally, there a...

D. Wang D. L. Swenson J. Woraratanadharm K. L. Warfield M. Luo

2008-01-01

18

Prospects for immunisation against Marburg and Ebola viruses.  

PubMed

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

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

2010-11-01

19

Productive replication of Ebola virus is regulated by the c-Abl1 tyrosine kinase.  

PubMed

Ebola virus causes a fulminant infection in humans resulting in diffuse bleeding, vascular instability, hypotensive shock, and often death. Because of its high mortality and ease of transmission from human to human, Ebola virus remains a biological threat for which effective preventive and therapeutic interventions are needed. An understanding of the mechanisms of Ebola virus pathogenesis is critical for developing antiviral therapeutics. Here, we report that productive replication of Ebola virus is modulated by the c-Abl1 tyrosine kinase. Release of Ebola virus-like particles (VLPs) in a cell culture cotransfection system was inhibited by c-Abl1-specific small interfering RNA (siRNA) or by Abl-specific kinase inhibitors and required tyrosine phosphorylation of the Ebola matrix protein VP40. Expression of c-Abl1 stimulated an increase in phosphorylation of tyrosine 13 (Y(13)) of VP40, and mutation of Y(13) to alanine decreased the release of Ebola VLPs. Productive replication of the highly pathogenic Ebola virus Zaire strain was inhibited by c-Abl1-specific siRNAs or by the Abl-family inhibitor nilotinib by up to four orders of magnitude. These data indicate that c-Abl1 regulates budding or release of filoviruses through a mechanism involving phosphorylation of VP40. This step of the virus life cycle therefore may represent a target for antiviral therapy. PMID:22378924

García, Mayra; Cooper, Arik; Shi, Wei; Bornmann, William; Carrion, Ricardo; Kalman, Daniel; Nabel, Gary J

2012-02-29

20

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

Microsoft Academic Search

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

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

2005-01-01

21

Serological Evidence of Ebola Virus Infection in Indonesian Orangutans  

PubMed Central

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

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

2012-01-01

22

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

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 (VSV) that expresses a single filovirus glycoprotein (GP) in place of the VSV glycoprotein (G). Here, we performed a proof-of-concept study in order to

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

2009-01-01

23

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

Microsoft Academic Search

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

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

2008-01-01

24

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

25

Vaccine To Confer to Nonhuman Primates Complete Protection against Multistrain Ebola and Marburg Virus Infections?  

PubMed Central

Filoviruses (Ebola and Marburg viruses) are among the deadliest viruses known to mankind, with mortality rates nearing 90%. These pathogens are highly infectious through contact with infected body fluids and can be easily aerosolized. Additionally, there are currently no licensed vaccines available to prevent filovirus outbreaks. Their high mortality rates and infectious capabilities when aerosolized and the lack of licensed vaccines available to prevent such infectious make Ebola and Marburg viruses serious bioterrorism threats, placing them both on the category A list of bioterrorism agents. Here we describe a panfilovirus vaccine based on a complex adenovirus (CAdVax) technology that expresses multiple antigens from five different filoviruses de novo. Vaccination of nonhuman primates demonstrated 100% protection against infection by two species of Ebola virus and three Marburg virus subtypes, each administered at 1,000 times the lethal dose. This study indicates the feasibility of vaccination against all current filovirus threats in the event of natural hemorrhagic fever outbreak or biological attack.

Swenson, Dana L.; Wang, Danher; Luo, Min; Warfield, Kelly L.; Woraratanadharm, Jan; Holman, David H.; Dong, John Y.; Pratt, William D.

2008-01-01

26

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

27

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

Microsoft Academic Search

Considerable progress has been made over the last decade in developing candidate preventive vaccines that can protect nonhuman primates against Ebola and Marburg viruses. A vaccine based on recombinant vesicular stomatitis virus (VSV) seems to be particularly robust as it can also confer protection when administered as a postexposure treatment. While filoviruses are not thought to be transmitted by aerosol

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

2008-01-01

28

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

PubMed Central

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

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

2001-01-01

29

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

PubMed Central

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

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

2011-01-01

30

Activation of Triggering Receptor Expressed on Myeloid Cells-1 on Human Neutrophils by Marburg and Ebola Viruses.  

National Technical Information Service (NTIS)

Marburg virus (MARV) and Ebola virus (EBOV), members of the viral family Filoviridae, cause fatal hemorrhagic fevers in humans and nonhuman primates. High viral burden is coincident with inadequate adaptive immune responses and robust inflammatory respons...

M. Mohamadzadeh S. S. Coberley G. G. Olinger W. V. Kalina G. Ruthel

2006-01-01

31

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

32

141. Adenovirus Vaccine to Ebola Virus: Mechanism of Protection and Impact of Pre-Existing Immunity to the Vaccine Carrier  

Microsoft Academic Search

A number of viral pathogens could be used as agents for biological warfare or bioterrorism. The Zaire strain of Ebola virus, with mortality rate of up to 90%, often with death occurring in less than 20 days after infection, represents one of the most dangerous viral pathogen. The profile of Ebola virus infections that makes it such a dangerous pathogen

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

2005-01-01

33

[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

34

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

Microsoft Academic Search

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

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

2011-01-01

35

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

36

Evasion of interferon responses by Ebola and Marburg viruses.  

PubMed

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

Basler, Christopher F; Amarasinghe, Gaya K

2009-09-01

37

Evasion of Interferon Responses by Ebola and Marburg Viruses  

PubMed Central

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

Amarasinghe, Gaya K.

2009-01-01

38

Detection of Cell-Cell Fusion Mediated by Ebola Virus Glycoproteins  

Microsoft Academic Search

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

Severine Bar; Ayato Takada; Yoshihiro Kawaoka; Marc Alizon

2006-01-01

39

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

PubMed Central

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.

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

2001-01-01

40

A New Ebola Virus Nonstructural Glycoprotein Expressed through RNA Editing?  

PubMed Central

Ebola virus (EBOV), an enveloped, single-stranded, negative-sense RNA virus, causes severe hemorrhagic fever in humans and nonhuman primates. The EBOV glycoprotein (GP) gene encodes the nonstructural soluble glycoprotein (sGP) but also produces the transmembrane glycoprotein (GP1,2) through transcriptional editing. A third GP gene product, a small soluble glycoprotein (ssGP), has long been postulated to be produced also as a result of transcriptional editing. To identify and characterize the expression of this new EBOV protein, we first analyzed the relative ratio of GP gene-derived transcripts produced during infection in vitro (in Vero E6 cells or Huh7 cells) and in vivo (in mice). The average percentages of transcripts encoding sGP, GP1,2, and ssGP were approximately 70, 25, and 5%, respectively, indicating that ssGP transcripts are indeed produced via transcriptional editing. N-terminal sequence similarity with sGP, the absence of distinguishing antibodies, and the abundance of sGP made it difficult to identify ssGP through conventional methodology. Optimized 2-dimensional (2D) gel electrophoresis analyses finally verified the expression and secretion of ssGP in tissue culture during EBOV infection. Biochemical analysis of recombinant ssGP characterized this protein as a disulfide-linked homodimer that was exclusively N glycosylated. In conclusion, we have identified and characterized a new EBOV nonstructural glycoprotein, which is expressed as a result of transcriptional editing of the GP gene. While ssGP appears to share similar structural properties with sGP, it does not appear to have the same anti-inflammatory function on endothelial cells as sGP.

Mehedi, Masfique; Falzarano, Darryl; Seebach, Jochen; Hu, Xiaojie; Carpenter, Michael S.; Schnittler, Hans-Joachim; Feldmann, Heinz

2011-01-01

41

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

Microsoft Academic Search

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

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

2004-01-01

42

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

43

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

Microsoft Academic Search

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

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

2011-01-01

44

Impact of Ebola mucin-like domain on antiglycoprotein antibody responses induced by Ebola virus-like particles.  

PubMed

Ebola virus (EBOV) glycoprotein (GP), responsible for mediating host-cell attachment and membrane fusion, contains a heavily glycosylated mucin-like domain hypothesized to shield GP from neutralizing antibodies. To test whether the mucin-like domain inhibits the production and function of anti-GP antibodies, we vaccinated mice with Ebola virus-like particles (VLPs) that express vesicular stomatitis virus G, wild-type EBOV GP (EBGP), EBOV GP without its mucin-like domain (?MucGP), or EBOV GP with a Crimean-Congo hemorrhagic fever virus mucin-like domain substituted for the EBOV mucin-like domain (CMsubGP). EBGP-VLP immunized mice elicited significantly higher serum antibody titers toward EBGP or its mutants, as detected by western blot analysis, than did VLP-?MucGP. However, EBGP-, ?MucGP- and CMsubGP-VLP immunized mouse sera contained antibodies that bound to cell surface-expressed GP at similar levels. Furthermore, low but similar neutralizing antibody titers, measured against a vesicular stomatitis virus (VSV) expressing EBGP or ?MucGP, were present in EBGP, ?MucGP, and CMsubGP sera, although a slightly higher neutralizing titer (2- to 2.5-fold) was detected in ?MucGP sera. We conclude that the EBOV GP mucin-like domain can increase relative anti-GP titers, however these titers appear to be directed, at least partly, to denatured GP. Furthermore, removing the mucin-like domain from immunizing VLPs has modest impact on neutralizing antibody titers in serum. PMID:21987758

Martinez, Osvaldo; Tantral, Lee; Mulherkar, Nirupama; Chandran, Kartik; Basler, Christopher F

2011-11-01

45

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

PubMed Central

Ebola viruses represent a class of filoviruses that causes severe hemorrhagic fever with high mortality. Recognized first in 1976 in the Democratic Republic of Congo, outbreaks continue to occur in equatorial Africa. A safe and effective Ebola virus vaccine is needed because of its continued emergence and its potential for use for biodefense. We report the safety and immunogenicity of an Ebola virus vaccine in its first phase I human study. A three-plasmid DNA vaccine encoding the envelope glycoproteins (GP) from the Zaire and Sudan/Gulu species as well as the nucleoprotein was evaluated in a randomized, placebo-controlled, double-blinded, dose escalation study. Healthy adults, ages 18 to 44 years, were randomized to receive three injections of vaccine at 2 mg (n = 5), 4 mg (n = 8), or 8 mg (n = 8) or placebo (n = 6). Immunogenicity was assessed by enzyme-linked immunosorbent assay (ELISA), immunoprecipitation-Western blotting, intracellular cytokine staining (ICS), and enzyme-linked immunospot assay. The vaccine was well-tolerated, with no significant adverse events or coagulation abnormalities. Specific antibody responses to at least one of the three antigens encoded by the vaccine as assessed by ELISA and CD4+ T-cell GP-specific responses as assessed by ICS were detected in 20/20 vaccinees. CD8+ T-cell GP-specific responses were detected by ICS assay in 6/20 vaccinees. This Ebola virus DNA vaccine was safe and immunogenic in humans. Further assessment of the DNA platform alone and in combination with replication-defective adenoviral vector vaccines, in concert with challenge and immune data from nonhuman primates, will facilitate evaluation and potential licensure of an Ebola virus vaccine under the Animal Rule.

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

2006-01-01

46

Functional characterization of Ebola virus L-domains using VSV recombinants  

Microsoft Academic Search

VSV recombinants containing the overlapping L-domain sequences from Ebola virus VP40 (PTAPPEY) were recovered by reverse-genetics. Replication kinetics of M40-WT, M40-P24L, and M40-Y30A were indistinguishable from VSV-WT in BHK-21 cells, whereas the double mutant (M40-P2728A) was defective in budding. Insertion of the Ebola L-domain region into VSV M protein was sufficient to alter the dependence on host proteins for efficient

Takashi Irie; Jillian M. Licata; Ronald N. Harty

2005-01-01

47

Role of Endosomal Cathepsins in Entry Mediated by the Ebola Virus Glycoprotein  

PubMed Central

Using chemical inhibitors and small interfering RNA (siRNA), we have confirmed roles for cathepsin B (CatB) and cathepsin L (CatL) in Ebola virus glycoprotein (GP)-mediated infection. Treatment of Ebola virus GP pseudovirions with CatB and CatL converts GP1 from a 130-kDa to a 19-kDa species. Virus with 19-kDa GP1 displays significantly enhanced infection and is largely resistant to the effects of the CatB inhibitor and siRNA, but it still requires a low-pH-dependent endosomal/lysosomal function. These and other results support a model in which CatB and CatL prime GP by generating a 19-kDa intermediate that can be acted upon by an as yet unidentified endosomal/lysosomal enzyme to trigger fusion.

Schornberg, Kathryn; Matsuyama, Shutoku; Kabsch, Kirsten; Delos, Sue; Bouton, Amy; White, Judith

2006-01-01

48

Vaccine to confer to nonhuman primates complete protection against multistrain Ebola and Marburg virus infections.  

PubMed

Filoviruses (Ebola and Marburg viruses) are among the deadliest viruses known to mankind, with mortality rates nearing 90%. These pathogens are highly infectious through contact with infected body fluids and can be easily aerosolized. Additionally, there are currently no licensed vaccines available to prevent filovirus outbreaks. Their high mortality rates and infectious capabilities when aerosolized and the lack of licensed vaccines available to prevent such infectious make Ebola and Marburg viruses serious bioterrorism threats, placing them both on the category A list of bioterrorism agents. Here we describe a panfilovirus vaccine based on a complex adenovirus (CAdVax) technology that expresses multiple antigens from five different filoviruses de novo. Vaccination of nonhuman primates demonstrated 100% protection against infection by two species of Ebola virus and three Marburg virus subtypes, each administered at 1,000 times the lethal dose. This study indicates the feasibility of vaccination against all current filovirus threats in the event of natural hemorrhagic fever outbreak or biological attack. PMID:18216185

Swenson, Dana L; Wang, Danher; Luo, Min; Warfield, Kelly L; Woraratanadharm, Jan; Holman, David H; Dong, John Y; Pratt, William D

2008-01-23

49

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

50

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

PubMed

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

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

2011-02-15

51

The rhetorical construction of the predatorial virus: a Burkian analysis of nonfiction accounts of the Ebola virus.  

PubMed

Over the past 5 years, a new subgenre of horror films, referred to as plague films, has turned our focus to the threat of a hemorrhagic viral pandemic, comparable to the Spanish Flu epidemic of 1916. Based on the Ebola viral outbreaks of 1976, various writers have presented their accounts under the guise of increasing interest and prevention strategies. Disregarding inappropriate health care practices as the cause of these epidemics, accountability is refocused onto the rhetorically constructed, predatory nature of the virus. By employing Burke's theory of dramatism and pentadic analysis, the author examines this rhetorical construction of Ebola as a predatorial virus and its implications for public perceptions of public health endeavors. PMID:11147163

Weldon, R A

2001-01-01

52

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

PubMed Central

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

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

2010-01-01

53

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

PubMed Central

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

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

2008-01-01

54

Chemical Modifications of Antisense Morpholino Oligomers Enhance Their Efficacy against Ebola Virus Infection?  

PubMed Central

Phosphorodiamidate morpholino oligomers (PMOs) are uncharged nucleic acid-like molecules designed to inactivate the expression of specific genes via the antisense-based steric hindrance of mRNA translation. PMOs have been successful at knocking out viral gene expression and replication in the case of acute viral infections in animal models and have been well tolerated in human clinical trials. We propose that antisense PMOs represent a promising class of therapeutic agents that may be useful for combating filoviral infections. We have previously shown that mice treated with a PMO whose sequence is complementary to a region spanning the start codon of VP24 mRNA were protected against lethal Ebola virus challenge. In the present study, we report on the abilities of two additional VP24-specific PMOs to reduce the cell-free translation of a VP24 reporter, to inhibit the in vitro replication of Ebola virus, and to protect mice against lethal challenge when the PMOs are delivered prior to infection. Additionally, structure-activity relationship evaluations were conducted to assess the enhancement of antiviral efficacy associated with PMO chemical modifications that included conjugation with peptides of various lengths and compositions, positioning of conjugated peptides to either the 5? or the 3? terminus, and the conferring of charge modifications by the addition of piperazine moieties. Conjugation with arginine-rich peptides greatly enhanced the antiviral efficacy of VP24-specific PMOs in infected cells and mice during lethal Ebola virus challenge.

Swenson, Dana L.; Warfield, Kelly L.; Warren, Travis K.; Lovejoy, Candace; Hassinger, Jed N.; Ruthel, Gordon; Blouch, Robert E.; Moulton, Hong M.; Weller, Dwight D.; Iversen, Patrick L.; Bavari, Sina

2009-01-01

55

A nonreplicating subunit vaccine protects mice against lethal Ebola virus challenge  

PubMed Central

Ebola hemorrhagic fever is an acute and often deadly disease caused by Ebola virus (EBOV). The possible intentional use of this virus against human populations has led to design of vaccines that could be incorporated into a national stockpile for biological threat reduction. We have evaluated the immunogenicity and efficacy of an EBOV vaccine candidate in which the viral surface glycoprotein is biomanufactured as a fusion to a monoclonal antibody that recognizes an epitope in glycoprotein, resulting in the production of Ebola immune complexes (EICs). Although antigen–antibody immune complexes are known to be efficiently processed and presented to immune effector cells, we found that codelivery of the EIC with Toll-like receptor agonists elicited a more robust antibody response in mice than did EIC alone. Among the compounds tested, polyinosinic:polycytidylic acid (PIC, a Toll-like receptor 3 agonist) was highly effective as an adjuvant agent. After vaccinating mice with EIC plus PIC, 80% of the animals were protected against a lethal challenge with live EBOV (30,000 LD50 of mouse adapted virus). Surviving animals showed a mixed Th1/Th2 response to the antigen, suggesting this may be important for protection. Survival after vaccination with EIC plus PIC was statistically equivalent to that achieved with an alternative viral vector vaccine candidate reported in the literature. Because nonreplicating subunit vaccines offer the possibility of formulation for cost-effective, long-term storage in biothreat reduction repositories, EIC is an attractive option for public health defense measures.

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

2011-01-01

56

Discovery and Early Development of AVI-7537 and AVI-7288 for the Treatment of Ebola Virus and Marburg Virus Infections  

PubMed Central

There are no currently approved treatments for filovirus infections. In this study we report the discovery process which led to the development of antisense Phosphorodiamidate Morpholino Oligomers (PMOs) AVI-6002 (composed of AVI-7357 and AVI-7539) and AVI-6003 (composed of AVI-7287 and AVI-7288) targeting Ebola virus and Marburg virus respectively. The discovery process involved identification of optimal transcript binding sites for PMO based RNA-therapeutics followed by screening for effective viral gene target in mouse and guinea pig models utilizing adapted viral isolates. An evolution of chemical modifications were tested, beginning with simple Phosphorodiamidate Morpholino Oligomers (PMO) transitioning to cell penetrating peptide conjugated PMOs (PPMO) and ending with PMOplus containing a limited number of positively charged linkages in the PMO structure. The initial lead compounds were combinations of two agents targeting separate genes. In the final analysis, a single agent for treatment of each virus was selected, AVI-7537 targeting the VP24 gene of Ebola virus and AVI-7288 targeting NP of Marburg virus, and are now progressing into late stage clinical development as the optimal therapeutic candidates.

Iversen, Patrick L.; Warren, Travis K.; Wells, Jay B.; Garza, Nicole L.; Mourich, Dan V.; Welch, Lisa S.; Panchal, Rekha G.; Bavari, Sina

2012-01-01

57

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

Microsoft Academic Search

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

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

2008-01-01

58

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

Microsoft Academic Search

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

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

1998-01-01

59

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

60

How Ebola and Marburg Viruses Battle the Immune System.  

National Technical Information Service (NTIS)

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 ...

M. Mohamadzadeh L. Chen A. L. Schmaljohn

2007-01-01

61

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

PubMed Central

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. In order 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 GlcNAc?1-2Man. The inhibition constant for this disaccharide is 3.5 ?M, 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 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.

Powlesland, Alex S.; Fisch, Tanja; Taylor, Maureen E.; Smith, David F.; Tissot, Berangere; Dell, Anne; Pohlmann, Stefan; Drickamer, Kurt

2008-01-01

62

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

2007-11-05

63

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

64

Structural and functional characterization of Reston Ebola virus VP35 interferon inhibitory domain.  

PubMed

Ebolaviruses are causative agents of lethal hemorrhagic fever in humans and nonhuman primates. Among the filoviruses characterized thus far, Reston Ebola virus (REBOV) is the only Ebola virus that is nonpathogenic to humans despite the fact that REBOV can cause lethal disease in nonhuman primates. Previous studies also suggest that REBOV is less effective at inhibiting host innate immune responses than Zaire Ebola virus (ZEBOV) or Marburg virus. Virally encoded VP35 protein is critical for immune suppression, but an understanding of the relative contributions of VP35 proteins from REBOV and other filoviruses is currently lacking. In order to address this question, we characterized the REBOV VP35 interferon inhibitory domain (IID) using structural, biochemical, and virological studies. These studies reveal differences in double-stranded RNA binding and interferon inhibition between the two species. These observed differences are likely due to increased stability and loss of flexibility in REBOV VP35 IID, as demonstrated by thermal shift stability assays. Consistent with this finding, the 1.71-A crystal structure of REBOV VP35 IID reveals that it is highly similar to that of ZEBOV VP35 IID, with an overall backbone r.m.s.d. of 0.64 A, but contains an additional helical element at the linker between the two subdomains of VP35 IID. Mutations near the linker, including swapping sequences between REBOV and ZEBOV, reveal that the linker sequence has limited tolerance for variability. Together with the previously solved ligand-free and double-stranded-RNA-bound forms of ZEBOV VP35 IID structures, our current studies on REBOV VP35 IID reinforce the importance of VP35 in immune suppression. Functional differences observed between REBOV and ZEBOV VP35 proteins may contribute to observed differences in pathogenicity, but these are unlikely to be the major determinant. However, the high level of similarity in structure and the low tolerance for sequence variability, coupled with the multiple critical roles played by Ebola virus VP35 proteins, highlight the viability of VP35 as a potential target for therapeutic development. PMID:20399790

Leung, Daisy W; Shabman, Reed S; Farahbakhsh, Mina; Prins, Kathleen C; Borek, Dominika M; Wang, Tianjiao; Mühlberger, Elke; Basler, Christopher F; Amarasinghe, Gaya K

2010-04-24

65

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

PubMed

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

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

2011-12-05

66

604. Comparative Analysis of Different Methods for Quantitative Evaluation of Neutralizing Antibody to Ebola Virus in a Biosafety Level 2 or 4 Environment  

Microsoft Academic Search

Ebola hemorrhagic fever virus can be modeled in different animal species such as mice, Guinea pigs and nonhuman primates. Several vaccine strategies were evaluated using DNA-, protein-based and\\/or viral vectors and found to protect mice against challenge with a lethal dose of mouse-adapted Ebola virus. However, only a few strategies involving DNA, Adenovirus or Vesicular Stomatitis virus (VSV), alone or

Hideki Ebihara; Xiangguo Qiu; Steven Theriault; Matthew Klassen; Ute Stroeher; Jim Strong; Steven Jones; James M. Wilson; Heinz Feldmann; Gary Kobinger

2006-01-01

67

Single-injection vaccine protects nonhuman primates against infection with marburg virus and three species of ebola virus.  

PubMed

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

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

2009-04-22

68

A strategy to simultaneously eradicate the natural reservoirs of rabies and Ebola virus.  

PubMed

The efficacy of a recombinant live-attenuated or chemically inactivated bivalent vaccine against rabies virus (RABV) and Ebola virus (EBOV) infection was evaluated in a lethal mouse model of infection. The vaccines were derived from the live-attenuated Street Alabama Dufferin B19 RABV platform already approved for veterinary use, where intramuscular, intranasal and intraperitoneal administration of the recombinant vaccines were avirulent in adult mice. Significant levels of serum RABV- and EBOV-specific antibodies were observed postvaccination, with levels that correlated with protection in vaccinated mice post-RABV or -EBOV challenge. These results justify further studies in guinea pigs and nonhuman primates, and highlight a promising strategy to eradicate the natural reservoirs of RABV and EBOV. PMID:22309665

Wong, Gary; Kobinger, Gary

2012-02-01

69

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

PubMed Central

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; Raaben, Matthijs; de la Torre, Juan Carlos; Whelan, Sean P.; Chandran, Kartik

2011-01-01

70

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

PubMed Central

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

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

2013-01-01

71

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

PubMed

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

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

2013-06-07

72

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

Microsoft Academic Search

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

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

2003-01-01

73

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

PubMed Central

Human infections with Ebola virus (EBOV) result in a deadly viral disease known as Ebola hemorrhagic fever. Up to 90% of infected patients die, and there is no available treatment or vaccine. The sporadic human outbreaks are believed to result when EBOV “jumps” from an infected animal to a person and is subsequently transmitted between persons by direct contact with infected blood or body fluids. This study was undertaken to investigate the mechanism by which EBOV can persistently infect and then escape from model cell and animal reservoir systems. We report a model system in which infection of mouse and bat cell lines with EBOV leads to persistence, which can be broken with low levels of lipopolysaccharide or phorbol-12-myristate-13-acetate (PMA). This reactivation depends on the Ras/MAPK pathway through inhibition of RNA-dependent protein kinase and eukaryotic initiation factor 2? phosphorylation and occurs at the level of protein synthesis. EBOV also can be evoked from mice 7 days after infection by PMA treatment, indicating that a similar mechanism occurs in vivo. Our findings suggest that EBOV may persist in nature through subclinical infection of a reservoir species, such as bats, and that appropriate physiological stimulation may result in increased replication and transmission to new hosts. Identification of a presumptive mechanism responsible for EBOV emergence from its reservoir underscores the “hit-and-run” nature of the initiation of human and/or nonhuman primate EBOV outbreaks and may provide insight into possible countermeasures to interfere with transmission.

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

2008-01-01

74

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

PubMed

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

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

2008-10-18

75

Ebola Virus Exploits a Monocyte Differentiation Program To Promote Its Entry  

PubMed Central

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

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

2013-01-01

76

Ebola Virus Enters Host Cells by Macropinocytosis and Clathrin-Mediated Endocytosis  

PubMed Central

Virus entry into host cells is the first step of infection and a crucial determinant of pathogenicity. Here we show that Ebola virus-like particles (EBOV-VLPs) composed of the glycoprotein GP1,2 and the matrix protein VP40 use macropinocytosis and clathrin-mediated endocytosis to enter cells. EBOV-VLPs applied to host cells induced actin-driven ruffling and enhanced FITC-dextran uptake, which indicated macropinocytosis as the main entry mechanism. This was further supported by inhibition of entry through inhibitors of actin polymerization (latrunculin A), Na+/H+-exchanger (EIPA), and PI3-kinase (wortmannin). A fraction of EBOV-VLPs, however, colocalized with clathrin heavy chain (CHC), and VLP uptake was reduced by CHC small interfering RNA transfection and expression of the dominant negative dynamin II–K44A mutant. In contrast, we found no evidence that EBOV-VLPs enter cells via caveolae. This work identifies macropinocytosis as the major, and clathrin-dependent endocytosis as an alternative, entry route for EBOV particles. Therefore, EBOV seems to utilize different entry pathways depending on both cell type and virus particle size.

Aleksandrowicz, Paulina; Marzi, Andrea; Biedenkopf, Nadine; Beimforde, Nadine; Becker, Stephan; Hoenen, Thomas; Feldmann, Heinz

2011-01-01

77

Tyro3 Family-Mediated Cell Entry of Ebola and Marburg Viruses  

PubMed Central

Filoviruses, represented by the genera Ebolavirus and Marburgvirus, cause a lethal hemorrhagic fever in humans and in nonhuman primates. Although filovirus can replicate in various tissues or cell types in these animals, the molecular mechanisms of its broad tropism remain poorly understood. Here we show the involvement of members of the Tyro3 receptor tyrosine kinase family—Axl, Dtk, and Mer—in cell entry of filoviruses. Ectopic expression of these family members in lymphoid cells, which otherwise are highly resistant to filovirus infection, enhanced infection by pseudotype viruses carrying filovirus glycoproteins on their envelopes. This enhancement was reduced by antibodies to Tyro3 family members, Gas6 ligand, or soluble ectodomains of the members. Live Ebola viruses infected both Axl- and Dtk-expressing cells more efficiently than control cells. Antibody to Axl inhibited infection of pseudotype viruses in a number of Axl-positive cell lines. These results implicate each Tyro3 family member as a cell entry factor in filovirus infection.

Shimojima, Masayuki; Takada, Ayato; Ebihara, Hideki; Neumann, Gabriele; Fujioka, Kouki; Irimura, Tatsuro; Jones, Steven; Feldmann, Heinz; Kawaoka, Yoshihiro

2006-01-01

78

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

79

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

80

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

81

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

2007-05-02

82

Vesicular stomatitis virus-based ebola vaccine is well-tolerated and protects immunocompromised nonhuman primates.  

PubMed

Ebola virus (EBOV) is a significant human pathogen that presents a public health concern as an emerging/re-emerging virus and as a potential biological weapon. Substantial progress has been made over the last decade in developing candidate preventive vaccines that can protect nonhuman primates against EBOV. Among these prospects, a vaccine based on recombinant vesicular stomatitis virus (VSV) is particularly robust, as it can also confer protection when administered as a postexposure treatment. A concern that has been raised regarding the replication-competent VSV vectors that express EBOV glycoproteins is how these vectors would be tolerated by individuals with altered or compromised immune systems such as patients infected with HIV. This is especially important as all EBOV outbreaks to date have occurred in areas of Central and Western Africa with high HIV incidence rates in the population. In order to address this concern, we evaluated the safety of the recombinant VSV vector expressing the Zaire ebolavirus glycoprotein (VSVDeltaG/ZEBOVGP) in six rhesus macaques infected with simian-human immunodeficiency virus (SHIV). All six animals showed no evidence of illness associated with the VSVDeltaG/ZEBOVGP vaccine, suggesting that this vaccine may be safe in immunocompromised populations. While one goal of the study was to evaluate the safety of the candidate vaccine platform, it was also of interest to determine if altered immune status would affect vaccine efficacy. The vaccine protected 4 of 6 SHIV-infected macaques from death following ZEBOV challenge. Evaluation of CD4+ T cells in all animals showed that the animals that succumbed to lethal ZEBOV challenge had the lowest CD4+ counts, suggesting that CD4+ T cells may play a role in mediating protection against ZEBOV. PMID:19043556

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

2008-11-28

83

DRBP76 associates with Ebola virus VP35 and suppresses viral polymerase function.  

PubMed

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

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

2011-11-01

84

DRBP76 Associates With Ebola Virus VP35 and Suppresses Viral Polymerase Function  

PubMed Central

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

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

2011-01-01

85

An Upstream Open Reading Frame Modulates Ebola Virus Polymerase Translation and Virus Replication  

PubMed Central

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

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

2013-01-01

86

Immune Protection of Nonhuman Primates against Ebola Virus with Single Low-Dose Adenovirus Vectors Encoding Modified GPs  

PubMed Central

Background Ebola virus causes a hemorrhagic fever syndrome that is associated with high mortality in humans. In the absence of effective therapies for Ebola virus infection, the development of a vaccine becomes an important strategy to contain outbreaks. Immunization with DNA and/or replication-defective adenoviral vectors (rAd) encoding the Ebola glycoprotein (GP) and nucleoprotein (NP) has been previously shown to confer specific protective immunity in nonhuman primates. GP can exert cytopathic effects on transfected cells in vitro, and multiple GP forms have been identified in nature, raising the question of which would be optimal for a human vaccine. Methods and Findings To address this question, we have explored the efficacy of mutant GPs from multiple Ebola virus strains with reduced in vitro cytopathicity and analyzed their protective effects in the primate challenge model, with or without NP. Deletion of the GP transmembrane domain eliminated in vitro cytopathicity but reduced its protective efficacy by at least one order of magnitude. In contrast, a point mutation was identified that abolished this cytopathicity but retained immunogenicity and conferred immune protection in the absence of NP. The minimal effective rAd dose was established at 1010 particles, two logs lower than that used previously. Conclusions Expression of specific GPs alone vectored by rAd are sufficient to confer protection against lethal challenge in a relevant nonhuman primate model. Elimination of NP from the vaccine and dose reductions to 1010 rAd particles do not diminish protection and simplify the vaccine, providing the basis for selection of a human vaccine candidate.

Geisbert, Joan B; Shedlock, Devon J; Xu, Ling; Lamoreaux, Laurie; Custers, Jerome H. H. V; Popernack, Paul M; Yang, Zhi-Yong; Pau, Maria G; Roederer, Mario; Koup, Richard A; Goudsmit, Jaap; Jahrling, Peter B; Nabel, Gary J

2006-01-01

87

Cathepsin Cleavage Potentiates the Ebola Virus Glycoprotein To Undergo a Subsequent Fusion-Relevant Conformational Change  

PubMed Central

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

Brecher, Matthew; Schornberg, Kathryn L.; Delos, Sue E.; Fusco, Marnie L.; Saphire, Erica Ollmann

2012-01-01

88

Ebola and Marburg haemorrhagic fever viruses: major scientific advances, but a relatively minor public health threat for Africa.  

PubMed

Ebola and Marburg viruses are the only members of the Filoviridae family (order Mononegavirales), a group of viruses characterized by a linear, non-segmented, single-strand negative RNA genome. They are among the most virulent pathogens for humans and great apes, causing acute haemorrhagic fever and death within a matter of days. Since their discovery 50 years ago, filoviruses have caused only a few outbreaks, with 2317 clinical cases and 1671 confirmed deaths, which is negligible compared with the devastation caused by malnutrition and other infectious diseases prevalent in Africa (malaria, cholera, AIDS, dengue, tuberculosis …). Yet considerable human and financial resourses have been devoted to research on these viruses during the past two decades, partly because of their potential use as bioweapons. As a result, our understanding of the ecology, host interactions, and control of these viruses has improved considerably. PMID:21722250

Leroy, E M; Gonzalez, J-P; Baize, S

2011-07-01

89

Ebola virus entry requires the host-programmed recognition of an intracellular receptor  

PubMed Central

Ebola and Marburg filoviruses cause deadly outbreaks of haemorrhagic fever. Despite considerable efforts, no essential cellular receptors for filovirus entry have been identified. We showed previously that Niemann-Pick C1 (NPC1), a lysosomal cholesterol transporter, is required for filovirus entry. Here, we demonstrate that NPC1 is a critical filovirus receptor. Human NPC1 fulfills a cardinal property of viral receptors: it confers susceptibility to filovirus infection when expressed in non-permissive reptilian cells. The second luminal domain of NPC1 binds directly and specifically to the viral glycoprotein, GP, and a synthetic single-pass membrane protein containing this domain has viral receptor activity. Purified NPC1 binds only to a cleaved form of GP that is generated within cells during entry, and only viruses containing cleaved GP can utilize a receptor retargeted to the cell surface. Our findings support a model in which GP cleavage by endosomal cysteine proteases unmasks the binding site for NPC1, and GP–NPC1 engagement within lysosomes promotes a late step in entry proximal to viral escape into the host cytoplasm. NPC1 is the first known viral receptor that recognizes its ligand within an intracellular compartment and not at the plasma membrane.

Miller, Emily Happy; Obernosterer, Gregor; Raaben, Matthijs; Herbert, Andrew S; Deffieu, Maika S; Krishnan, Anuja; Ndungo, Esther; Sandesara, Rohini G; Carette, Jan E; Kuehne, Ana I; Ruthel, Gordon; Pfeffer, Suzanne R; Dye, John M; Whelan, Sean P; Brummelkamp, Thijn R; Chandran, Kartik

2012-01-01

90

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

91

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

92

Mouse LSECtin as a model for a human Ebola virus receptor.  

PubMed

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

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

2011-01-21

93

Ebola virus entry requires the host-programmed recognition of an intracellular receptor.  

PubMed

Ebola and Marburg filoviruses cause deadly outbreaks of haemorrhagic fever. Despite considerable efforts, no essential cellular receptors for filovirus entry have been identified. We showed previously that Niemann-Pick C1 (NPC1), a lysosomal cholesterol transporter, is required for filovirus entry. Here, we demonstrate that NPC1 is a critical filovirus receptor. Human NPC1 fulfills a cardinal property of viral receptors: it confers susceptibility to filovirus infection when expressed in non-permissive reptilian cells. The second luminal domain of NPC1 binds directly and specifically to the viral glycoprotein, GP, and a synthetic single-pass membrane protein containing this domain has viral receptor activity. Purified NPC1 binds only to a cleaved form of GP that is generated within cells during entry, and only viruses containing cleaved GP can utilize a receptor retargeted to the cell surface. Our findings support a model in which GP cleavage by endosomal cysteine proteases unmasks the binding site for NPC1, and GP-NPC1 engagement within lysosomes promotes a late step in entry proximal to viral escape into the host cytoplasm. NPC1 is the first known viral receptor that recognizes its ligand within an intracellular compartment and not at the plasma membrane. PMID:22395071

Miller, Emily Happy; Obernosterer, Gregor; Raaben, Matthijs; Herbert, Andrew S; Deffieu, Maika S; Krishnan, Anuja; Ndungo, Esther; Sandesara, Rohini G; Carette, Jan E; Kuehne, Ana I; Ruthel, Gordon; Pfeffer, Suzanne R; Dye, John M; Whelan, Sean P; Brummelkamp, Thijn R; Chandran, Kartik

2012-03-06

94

Antibody-mediated Neutralization of Ebola Virus Can Occur by Two Distinct Mechanisms  

PubMed Central

Human Ebola virus (EBOV) 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 non-essential 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.; Bailey, Michael A.; Popernack, Paul M.; Cunningham, James M.; Burton, Dennis R.; Sullivan, Nancy J.

2010-01-01

95

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

PubMed Central

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

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

2007-01-01

96

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

PubMed Central

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

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

2012-01-01

97

Influences of glycosylation on antigenicity, immunogenicity, and protective efficacy of ebola virus GP DNA vaccines.  

PubMed

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 the influences of GP glycosylation on antigenicity, immunogenicity, and protection by testing DNA vaccines comprised of GP genes with deleted N-linked glycosylation sites or with deletions in the central hypervariable mucin region. We showed that mutation of one of the two N-linked GP2 glycosylation sites was highly detrimental to the antigenicity and immunogenicity of GP. Our data indicate that this is likely due to the inability of GP2 and GP1 to dimerize at the cell surface and suggest that glycosylation at this site is required for achieving the conformational integrity of GP2 and GP1. In contrast, mutation of two N-linked sites on GP1, which flank previously defined protective antibody epitopes on GP, may enhance immunogenicity, possibly by unmasking epitopes. We further showed that although deleting the mucin region apparently had no effect on antigenicity in vitro, it negatively impacted the elicitation of protective immunity in mice. In addition, we confirmed the presence of previously identified B-cell and T-cell epitopes in GP but show that when analyzed individually none of them were neither absolutely required nor sufficient for protective immunity to EBOV. Finally, we identified other potential regions of GP that may contain relevant antibody or T-cell epitopes. PMID:17151111

Dowling, William; Thompson, Elizabeth; Badger, Catherine; Mellquist, Jenny L; Garrison, Aura R; Smith, Jeffery M; Paragas, Jason; Hogan, Robert J; Schmaljohn, Connie

2006-12-06

98

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

PubMed Central

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 the influences of GP glycosylation on antigenicity, immunogenicity, and protection by testing DNA vaccines comprised of GP genes with deleted N-linked glycosylation sites or with deletions in the central hypervariable mucin region. We showed that mutation of one of the two N-linked GP2 glycosylation sites was highly detrimental to the antigenicity and immunogenicity of GP. Our data indicate that this is likely due to the inability of GP2 and GP1 to dimerize at the cell surface and suggest that glycosylation at this site is required for achieving the conformational integrity of GP2 and GP1. In contrast, mutation of two N-linked sites on GP1, which flank previously defined protective antibody epitopes on GP, may enhance immunogenicity, possibly by unmasking epitopes. We further showed that although deleting the mucin region apparently had no effect on antigenicity in vitro, it negatively impacted the elicitation of protective immunity in mice. In addition, we confirmed the presence of previously identified B-cell and T-cell epitopes in GP but show that when analyzed individually none of them were neither absolutely required nor sufficient for protective immunity to EBOV. Finally, we identified other potential regions of GP that may contain relevant antibody or T-cell epitopes.

Dowling, William; Thompson, Elizabeth; Badger, Catherine; Mellquist, Jenny L.; Garrison, Aura R.; Smith, Jeffery M.; Paragas, Jason; Hogan, Robert J.; Schmaljohn, Connie

2007-01-01

99

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

PubMed

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

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

2012-08-24

100

Delayed treatment of Ebola virus infection with plant-derived monoclonal antibodies provides protection in rhesus macaques  

PubMed Central

Filovirus infections can cause a severe and often fatal disease in humans and nonhuman primates, including great apes. Here, three anti-Ebola virus mouse/human chimeric mAbs (c13C6, h-13F6, and c6D8) were produced in Chinese hamster ovary and in whole plant (Nicotiana benthamiana) cells. In pilot experiments testing a mixture of the three mAbs (MB-003), we found that MB-003 produced in both manufacturing systems protected rhesus macaques from lethal challenge when administered 1 h postinfection. In a pivotal follow-up experiment, we found significant protection (P < 0.05) when MB-003 treatment began 24 or 48 h postinfection (four of six survived vs. zero of two controls). In all experiments, surviving animals that received MB-003 experienced little to no viremia and had few, if any, of the clinical symptoms observed in the controls. The results represent successful postexposure in vivo efficacy by a mAb mixture and suggest that this immunoprotectant should be further pursued as a postexposure and potential therapeutic for Ebola virus exposure.

Olinger, Gene Garrard; Pettitt, James; Kim, Do; Working, Cara; Bohorov, Ognian; Bratcher, Barry; Hiatt, Ernie; Hume, Steven D.; Johnson, Ashley K.; Morton, Josh; Pauly, Michael; Whaley, Kevin J.; Lear, Calli M.; Biggins, Julia E.; Scully, Corinne; Hensley, Lisa; Zeitlin, Larry

2012-01-01

101

Mutations abrogating VP35 interaction with double-stranded RNA render Ebola virus avirulent in guinea pigs.  

PubMed

Ebola virus (EBOV) protein VP35 is a double-stranded RNA (dsRNA) binding inhibitor of host interferon (IFN)-alpha/beta responses that also functions as a viral polymerase cofactor. Recent structural studies identified key features, including a central basic patch, required for VP35 dsRNA binding activity. To address the functional significance of these VP35 structural features for EBOV replication and pathogenesis, two point mutations, K319A/R322A, that abrogate VP35 dsRNA binding activity and severely impair its suppression of IFN-alpha/beta production were identified. Solution nuclear magnetic resonance (NMR) spectroscopy and X-ray crystallography reveal minimal structural perturbations in the K319A/R322A VP35 double mutant and suggest that loss of basic charge leads to altered function. Recombinant EBOVs encoding the mutant VP35 exhibit, relative to wild-type VP35 viruses, minimal growth attenuation in IFN-defective Vero cells but severe impairment in IFN-competent cells. In guinea pigs, the VP35 mutant virus revealed a complete loss of virulence. Strikingly, the VP35 mutant virus effectively immunized animals against subsequent wild-type EBOV challenge. These in vivo studies, using recombinant EBOV viruses, combined with the accompanying biochemical and structural analyses directly correlate VP35 dsRNA binding and IFN inhibition functions with viral pathogenesis. Moreover, these studies provide a framework for the development of antivirals targeting this critical EBOV virulence factor. PMID:20071589

Prins, Kathleen C; Delpeut, Sebastien; Leung, Daisy W; Reynard, Olivier; Volchkova, Valentina A; Reid, St Patrick; Ramanan, Parameshwaran; Cárdenas, Washington B; Amarasinghe, Gaya K; Volchkov, Viktor E; Basler, Christopher F

2010-01-13

102

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

PubMed Central

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

Prins, Kathleen C.; Delpeut, Sebastien; Leung, Daisy W.; Reynard, Olivier; Volchkova, Valentina A.; Reid, St. Patrick; Ramanan, Parameshwaran; Cardenas, Washington B.; Amarasinghe, Gaya K.; Volchkov, Viktor E.; Basler, Christopher F.

2010-01-01

103

Ebola hemorrhagic fever  

MedlinePLUS

... Ebola-Sudan virus, and Ebola-Ivory Coast virus. The human disease has so far been limited to parts of ... virus has recently been found in the Philippines. The disease can be passed to humans from infected animals and animal materials. Ebola can ...

104

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

PubMed Central

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

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

2013-01-01

105

Ebola Virus Genome Plasticity as a Marker of Its Passaging History: A Comparison of In Vitro Passaging to Non-Human Primate Infection  

PubMed Central

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

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

2012-01-01

106

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

PubMed Central

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

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

2011-01-01

107

A small-molecule oxocarbazate inhibitor of human cathepsin L blocks severe acute respiratory syndrome and ebola pseudotype virus infection into human embryonic kidney 293T cells.  

PubMed

A tetrahydroquinoline oxocarbazate (PubChem CID 23631927) was tested as an inhibitor of human cathepsin L (EC 3.4.22.15) and as an entry blocker of severe acute respiratory syndrome (SARS) coronavirus and Ebola pseudotype virus. In the cathepsin L inhibition assay, the oxocarbazate caused a time-dependent 17-fold drop in IC(50) from 6.9 nM (no preincubation) to 0.4 nM (4-h preincubation). Slowly reversible inhibition was demonstrated in a dilution assay. A transient kinetic analysis using a single-step competitive inhibition model provided rate constants of k(on) = 153,000 M(-1)s(-1) and k(off) = 4.40 x 10(-5) s(-1) (K(i) = 0.29 nM). The compound also displayed cathepsin L/B selectivity of >700-fold and was nontoxic to human aortic endothelial cells at 100 muM. The oxocarbazate and a related thiocarbazate (PubChem CID 16725315) were tested in a SARS coronavirus (CoV) and Ebola virus-pseudotype infection assay with the oxocarbazate but not the thiocarbazate, demonstrating activity in blocking both SARS-CoV (IC(50) = 273 +/- 49 nM) and Ebola virus (IC(50) = 193 +/- 39 nM) entry into human embryonic kidney 293T cells. To trace the intracellular action of the inhibitors with intracellular cathepsin L, the activity-based probe biotin-Lys-C5 alkyl linker-Tyr-Leu-epoxide (DCG-04) was used to label the active site of cysteine proteases in 293T lysates. The reduction in active cathepsin L in inhibitor-treated cells correlated well with the observed potency of inhibitors observed in the virus pseudotype infection assay. Overall, the oxocarbazate CID 23631927 was a subnanomolar, slow-binding, reversible inhibitor of human cathepsin L that blocked SARS-CoV and Ebola pseudotype virus entry in human cells. PMID:20466822

Shah, Parag P; Wang, Tianhua; Kaletsky, Rachel L; Myers, Michael C; Purvis, Jeremy E; Jing, Huiyan; Huryn, Donna M; Greenbaum, Doron C; Smith, Amos B; Bates, Paul; Diamond, Scott L

2010-05-13

108

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

Microsoft Academic Search

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

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

2004-01-01

109

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

PubMed Central

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

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

2012-01-01

110

Anti-Tetherin Activities of HIV-1 Vpu and Ebola Virus Glycoprotein Do Not Involve Removal of Tetherin from Lipid Rafts  

PubMed Central

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

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

2012-01-01

111

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

PubMed Central

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

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

2013-01-01

112

Ebola fever: The African emergency  

Microsoft Academic Search

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

J. Bruce; P. Brysiewicz

2002-01-01

113

Ebola haemorrhagic fever  

PubMed Central

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

Feldmann, Heinz; Geisbert, Thomas W

2012-01-01

114

Ebola haemorrhagic fever.  

PubMed

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

Feldmann, Heinz; Geisbert, Thomas W

2011-03-01

115

Ebola virus-like particle-induced activation of NF-?B and Erk signaling in human dendritic cells requires the glycoprotein mucin domain  

PubMed Central

Dendritic cells (DCs), important early targets of Ebola virus (EBOV) infection in vivo, are activated by Ebola virus-like particles (VLPs). To better understand this phenomenon, we have systematically assessed the response of DCs to VLPs of different compositions. VLPs containing the viral matrix protein (VP40) and the viral glycoprotein (GP), were found to induce a proinflammatory response highly similar to a prototypical DC activator, LPS. This response included the production of several proinflammatory cytokines, activation of numerous transcription factors including NF-kappaB, the functional importance of which was demonstrated by employing inhibitors of NF-kappaB activation, and activation of ERK1/2 MAP kinase. In contrast, VLPs constituted with a mutant GP lacking the heavily glycosylated mucin domain showed impaired NF-kappaB and Erk activation and induced less DC cytokine production. We conclude that the GP mucin domain is required for VLPs to stimulate human dendritic cells through NF-kappaB and MAPK signaling pathways.

Martinez, Osvaldo; Valmas, Charalampos; Basler, Christopher F.

2007-01-01

116

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

PubMed Central

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

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

2011-01-01

117

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

Microsoft Academic Search

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

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

2004-01-01

118

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

PubMed

The cynomolgus macaque, Macaca fascicularis, is frequently used in immunological and other biomedical research as a model for man; understanding it's antibody repertoire is, therefore, of fundamental interest. The expressed variable-region gene repertoire of a single M. fascicularis, which was immune to the Ebola virus, was studied. Using 5' rapid amplification of cDNA ends with immunoglobulin (Ig)G-specific primers, we obtained 30 clones encoding full-length variable, diversity, and joining domains. Similar to the human V(H) repertoire, the M. fascicularis repertoire utilized numerous immunoglobulin heavy variable (IGHV) gene fragments, with the V(H)3 (41%), V(H)4 (39%), and V(H)1 (14%) subgroups used more frequently than the V(H)5 (3.9%) or V(H)7 (1.7%) subgroups. Diverse immunoglobulin heavy joining (IGHJ) fragments also appeared to be utilized, including a putative homolog of JH5beta gene segment identified in the related species Macaca mulatta, Rhesus macaque, but not in humans. Although the diverse V region genes in the IgG antibody repertoire of M. fascicularis had likely undergone somatic hypermutations (SHMs), they nevertheless showed high nucleotide identity with the corresponding human germline genes, 80-89% for IGHV and 72-92% for IGHJ. M. fascicularis and human V(H) genes were also similar in other aspects: length of complementarity-determining regions and framework regions, and distribution of consensus sites for SHMs. Finally, we demonstrated that monoclonal antibodies (mAbs) specific for an Ebola protein could be obtained from M. fascicularis tissue samples by phage display technology. In summary, the study provides new insight into the M. fascicularis V region gene repertoire and further supports the idea that macaque-derived mAbs may be of therapeutic value to humans. PMID:16215733

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

2005-11-08

119

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

PubMed Central

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

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

2008-01-01

120

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

PubMed Central

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

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

2013-01-01

121

Functional expression of mouse relaxin and mouse relaxin-3 in the lung from an Ebola virus glycoprotein-pseudotyped lentivirus via tracheal delivery.  

PubMed

The peptide hormone relaxin is a known modulator of connective tissue and the extracellular matrix by virtue of its ability to regulate matrix metalloproteinases (MMPs). Relaxin knockout mice exhibit age-related pulmonary fibrosis, and delivery of recombinant human H2 relaxin ameliorates fibrotic-like conditions in the mouse lung. We investigated whether lentiviral vectors (LVs) engineering the expression of murine relaxins could induce MMP activity in the mouse lung. Mouse relaxin and mouse relaxin-3 peptides engineered by recombinant LVs were biologically active as shown by stimulation of cAMP from both THP-1 and 293T cells stably expressing relaxin receptor LGR7 and by up-regulation of MMP-2 activity from primary C57BL/6 lung cell cultures. To provide the virions with enhanced tropism for the lung, LVs were pseudotyped with the Zaire strain of the Ebola virus glycoprotein (EboZ GP) and delivered by endotracheal intubation. LVs engineering luciferase pseudotyped with EboZ GP, but not with vesicular stomatitis virus glycoprotein resulted in successful LV transduction and transgene expression in C57BL/6 mouse lung by as early as d 4. Mice treated via tracheal delivery with EboZ GP pseudotyped LVs that engineered expression of mouse relaxins exhibited increased MMP-2 and MMP-9 activity in lung tissue up until the end of our study at d 21. Taken together, this study provides proof-of- principle that relaxin gene expression targeted to the mouse lungs can result in enhanced MMP activity offering potential for alleviating disease conditions characterized by dysregulation of extracellular matrix protein accumulation. PMID:16709614

Silvertown, Josh D; Walia, Jagdeep S; Summerlee, Alastair J; Medin, Jeffrey A

2006-05-18

122

Antivirals for High Hazard Viruses,  

National Technical Information Service (NTIS)

In large areas of the world there exist extremely high hazard viruses for which there are no vaccines for prophylaxis and no effective drugs for therapy. Examples of such viruses are Ebola, Argentine, Bolivian, Crimean-Congo, and Korean hemorrhagic fevers...

P. G. Canonico

1988-01-01

123

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

124

Clinical Manifestations and Case Management of Ebola Haemorrhagic Fever Caused by a Newly Identified Virus Strain, Bundibugyo, Uganda, 2007-2008  

PubMed Central

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

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

2012-01-01

125

Virus Resistance  

Technology Transfer Automated Retrieval System (TEKTRAN)

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

126

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

Microsoft Academic Search

Identifying microbial pathogens with zoonotic potential in wild-living primates can be important to human health, as evidenced by human immunodeficiency viruses types 1 and 2 (HIV-1 and HIV-2) and Ebola virus. Simian foamy viruses (SFVs) are ancient retroviruses that infect Old and New World monkeys and apes. Although not known to cause disease, these viruses are of public health interest

Weimin Liu; Michael Worobey; Yingying Li; Brandon F. Keele; Frederic Bibollet-Ruche; Yuanyuan Guo; Paul A. Goepfert; Mario L. Santiago; Jean-Bosco N. Ndjango; Cecile Neel; Stephen L. Clifford; Crickette Sanz; Shadrack Kamenya; Michael L. Wilson; Anne E. Pusey; Nicole Gross-Camp; Christophe Boesch; Vince Smith; Koichiro Zamma; Michael A. Huffman; John C. Mitani; David P. Watts; Martine Peeters; George M. Shaw; William M. Switzer; Paul M. Sharp; Beatrice H. Hahn

2008-01-01

127

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

128

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

129

Hepadna viruses  

SciTech Connect

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

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

1987-01-01

130

Camelpox virus  

Microsoft Academic Search

Camelpox virus (CMLV) causes a smallpox-like illness in a unique host, the camel. The disease is enzootic in almost all regions where camel husbandry is practiced, and is responsible for severe economic losses. Although it is genetically the closest known virus to variola virus, the etiologic agent of smallpox, CMLV remains poorly studied. It is characterized by a narrow host

Sophie Duraffour; Hermann Meyer; Graciela Andrei; Robert Snoeck

2011-01-01

131

Differential requirements for clathrin endocytic pathway components in cellular entry by Ebola and Marburg glycoprotein pseudovirions  

Microsoft Academic Search

Clathrin-mediated endocytosis was previously implicated as one of the cellular pathways involved in filoviral glycoprotein mediated viral entry into target cells. Here we have further dissected the requirements for different components of this pathway in Ebola versus Marburg virus glycoprotein (GP) mediated viral infection. Although a number of these components were involved in both cases; Ebola GP-dependent viral entry specifically

Suchita Bhattacharyya; Thomas J. Hope; John A. T. Young

2011-01-01

132

Ebola Goes Pop: The Filovirus from Literature into Film  

Microsoft Academic Search

Semmler examines Virus and Outbreak, two contemporary films about the Ebola virus. The essay carefully establishes the connections between the films and Robin Cook's novel Outbreak and Richard Preston's nonfictional book The Hot Zone. Semmler's essay looks at food, war, and jungle imagery in the two movies as a way to begin questioning the scientific accuracy of the films and

Iliana Alexandra Semmler

1998-01-01

133

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

134

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

135

Ganjam virus.  

PubMed

Ganjam virus (GANV), a member of genus Nairovirus of family Bunyavirdae is of considerable veterinary importance in India. Though, predominantly tick borne, GANV was also isolated from mosquitoes, man and sheep. Neutralizing and complement fixing antibodies to GANV have been detected in animal and human sera collected from different parts of the country. Thirty three strains of GANV have been isolated from India, mainly from Haemaphysalis ticks. The virus replicated in certain vertebrate and mosquito cell lines and found pathogenic to laboratory animals. One natural infection and five laboratory-acquired infections in men were also reported. GANV is antigenically related to Nairobi sheep disease virus (NSDV) of Africa, which is highly pathogenic for sheep and goats causing 70-90 per cent mortality among the susceptible population. Recent molecular studies have demonstrated that GANV is an Asian variant of NSDV and both these viruses are related to the dreaded Crimean Congo haemorrhagic fever (CCHF) group viruses. The versatility of the virus to replicate in different arthropod species, its ability to infect sheep, goat and man makes it an important zoonotic agent. PMID:20090098

Sudeep, A B; Jadi, R S; Mishra, A C

2009-11-01

136

West Nile Virus  

MedlinePLUS

... virus is a virus that can infect humans, birds, horses and mosquitoes. Infection from this virus is ... spread by mosquitoes. Mosquitoes become infected by biting birds that carry the virus. People can get West ...

137

Marburg Virus Infection Detected in a Common African Bat  

PubMed Central

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.

Towner, Jonathan S.; Pourrut, Xavier; Albarino, Cesar G.; Nkogue, Chimene Nze; Bird, Brian H.; Grard, Gilda; Ksiazek, Thomas G.; Gonzalez, Jean-Paul; Nichol, Stuart T.; Leroy, Eric M.

2007-01-01

138

Current Ebola vaccines  

PubMed Central

Introduction Ebolaviruses cause severe viral hemorrhagic fever in humans and non-human primates, with case fatality rates of up to 90%. Currently, neither a specific treatment nor a vaccine licensed for use in humans is available. However, a number of vaccine candidates have been developed in the last decade that are highly protective in non-human primates, the gold standard animal model for Ebola hemorrhagic fever. Areas covered This review analyzes a number of scenarios for the use of ebolavirus vaccines, discusses the requirements for ebolavirus vaccines in these scenarios, and describes current ebolavirus vaccines. Among these vaccines are recombinant Adenoviruses, recombinant Vesicular Stomatitis viruses, recombinant Human Parainfluenza viruses and virus-like particles. Interestingly, one of these vaccine platforms, based on recombinant Vesicular Stomatitis viruses, has also demonstrated post-exposure protection in non-human primates. Expert opinion The most pressing remaining challenge is now to move these vaccine candidates forward into human trials and towards licensure. In order to achieve this, it will be necessary to establish the mechanisms and correlates of protection for these vaccines, and to continue to demonstrate their safety, particularly in potentially immunocompromised populations. However, already now there is sufficient evidence that, from a scientific perspective, a vaccine protective against ebolaviruses is possible.

Hoenen, Thomas; Groseth, Allison; Feldmann, Heinz

2012-01-01

139

Parainfluenza Viruses  

PubMed Central

Human parainfluenza viruses (HPIV) were first discovered in the late 1950s. Over the last decade, considerable knowledge about their molecular structure and function has been accumulated. This has led to significant changes in both the nomenclature and taxonomic relationships of these viruses. HPIV is genetically and antigenically divided into types 1 to 4. Further major subtypes of HPIV-4 (A and B) and subgroups/genotypes of HPIV-1 and HPIV-3 have been described. HPIV-1 to HPIV-3 are major causes of lower respiratory infections in infants, young children, the immunocompromised, the chronically ill, and the elderly. Each subtype can cause somewhat unique clinical diseases in different hosts. HPIV are enveloped and of medium size (150 to 250 nm), and their RNA genome is in the negative sense. These viruses belong to the Paramyxoviridae family, one of the largest and most rapidly growing groups of viruses causing significant human and veterinary disease. HPIV are closely related to recently discovered megamyxoviruses (Hendra and Nipah viruses) and metapneumovirus.

Henrickson, Kelly J.

2003-01-01

140

Laboratory Diagnostic Systems for Ebola and Marburg Hemorrhagic Fevers Developed with Recombinant Proteins  

Microsoft Academic Search

Ebola virus and Marburg virus (EBOV and MARV, respec- tively) of the family Filoviridae cause hemorrhagic fever with high mortality rates, sometimes reaching 50 to 90% of infected individuals, in humans and nonhuman primates (10, 16, 47). EBOV consists of four species, Zaire EBOV, Sudan EBOV, Ivory Coast EBOV, and Reston EBOV, which were first iso- lated in the Democratic

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

2006-01-01

141

Wild Animal Mortality Monitoring and Human Ebola Outbreaks, Gabon and Republic of Congo, 2001-2003  

PubMed Central

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 Ecosystèmes 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.

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

2005-01-01

142

Pathogenesis of Ebola Hemorrhagic Fever in Cynomolgus Macaques.  

National Technical Information Service (NTIS)

Ebola virus (EBOV) infection causes a severe and fatal hemorrhagic disease that in many ways appears to be similar in humans and nonhuman primates; however, little is known about the development of EBOV hemorrhagic fever. In the present study, 21 cynomolg...

T. W. Geisbert L. E. Hensley T. Larsen H. A. Young D. S. Reed

2003-01-01

143

Camelpox virus.  

PubMed

Camelpox virus (CMLV) causes a smallpox-like illness in a unique host, the camel. The disease is enzootic in almost all regions where camel husbandry is practiced, and is responsible for severe economic losses. Although it is genetically the closest known virus to variola virus, the etiologic agent of smallpox, CMLV remains poorly studied. It is characterized by a narrow host range, the capacity to induce giant cells in culture and to counteract host immune defenses; however, the genetic bases associated with these features are not understood. Also, it still needs to be demonstrated whether CMLV strains of variable virulence circulate and how arthropod vectors might be involved in virus transmission. Current evidence indicates that, under certain circumstances, CMLV can be mildly pathogenic in humans. A reservoir host other than camels is unlikely to exist. We review here current knowledge of CMLV, including clinical and laboratory aspects of the disease. We also discuss prevention and therapy by use of vaccines and antiviral treatments, as well as the possibility of camelpox eradication. PMID:21945248

Duraffour, Sophie; Meyer, Hermann; Andrei, Graciela; Snoeck, Robert

2011-09-16

144

Vesicular Stomatitis Virus Disease  

NSDL National Science Digital Library

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

American Society For Microbiology;

2007-01-09

145

Attenuated Influenza A Virus.  

National Technical Information Service (NTIS)

An attenuated influenza virus of a first strain is described together with a method for preparing the attenuated influenza virus. The attenuated influenza virus of the first strain comprises a sufficient number of single strand RNA segments of negative po...

P. Palese T. Muster B. R. Murphy M. Enami M. Bergmann

1992-01-01

146

Plant virus treatment  

US Patent & Trademark Office Database

It has been found that plant viruses and viroids can be inhibited by treating plants infected with or exposed to viruses or viroids with a virus-inhibiting amount of a maleic acid, maleic anhydride or fumaric acid copolymer.

1976-12-07

147

Preventing West Nile Virus  

MedlinePLUS

... carriers of the virus by feeding on infected birds. Although other animals have been infected with the virus—including horses, bats, squirrels, and domestic animals—birds are the most common reservoir. Once the virus ...

148

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

149

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

PubMed

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. PMID:24069485

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

2013-09-12

150

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

151

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

152

Advances in Virus-Like Particle Vaccines for Filoviruses  

PubMed Central

Ebola virus (EBOV) and Marburg virus (MARV) are among the deadliest human pathogens, with no vaccines or therapeutics available. Multiple vaccine platforms have been tested for efficacy as prophylactic pretreatments or therapeutics for prevention of filovirus hemorrhagic fever. Most successful vaccines are based on a virus-vectored approach expressing the protective glycoprotein (GP); protein-based subunit and DNA vaccines have been tested with moderate success. Virus-like particle (VLP) vaccines have realized promising results when tested in both rodents and nonhuman primates. VLPs rely on the natural properties of the viral matrix protein (VP) 40 to drive budding of filamentous particles that can also incorporate ?1 other filovirus protein, including GP, VP24, and nucleoprotein (NP). Filovirus VLP vaccines have used particles containing 2 or 3 (GP and VP40, with or without NP) viral proteins generated in either mammalian or insect cells. Early studies successfully demonstrated efficacy of bivalent VLP vaccines in rodents; more recent studies have shown the ability of the VLP vaccines containing GP, NP, and VP40 to confer complete homologous protection against Ebola virus and Marburg virus in a prophylactic setting against in macaques. This review will discuss published work to date regarding development of the VLP vaccines for prevention of lethal filovirus hemorrhagic fever.

Aman, M. Javad

2011-01-01

153

Viruses in cancer treatment.  

PubMed

Soon after the discovery that viruses cause human disease, started the idea of using viruses to treat cancer. After the initial indiscriminate use, crude preparations of each novel virus in the early twentieth century, a second wave of virotherapy blossomed in the 60s with purified and selected viruses. Responses were rare and short-lived. Immune rejection of the oncolytic viruses was identified as the major problem and virotherapy was abandoned. During the past two decades virotherapy has re-emerged with engineered viruses, with a trend towards using them as tumor-debulking immunostimulatory agents combined with radio or chemotherapy. Currently, oncolytic Reovirus, Herpes, and Vaccinia virus are in late phase clinical trials. Despite the renewed hope, efficacy will require improving systemic tumor targeting, overcoming stroma barriers for virus spread, and selectively stimulating immune responses against tumor antigens but not against the virus. Virotherapy history, viruses, considerations for clinical trials, and hurdles are briefly overviewed. PMID:23143950

Alemany, R

2012-11-10

154

West Nile Virus  

Microsoft Academic Search

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

Vassil St. Georgiev

155

The Family of Influenza Viruses and of Pneumotropic Animal Viruses.  

National Technical Information Service (NTIS)

Influenza viruses and pneumotropic animal viruses are characterized. The morphology, pathology and immunology of these viruses are discussed. A classification of species and types is given for the pneumotropic animal viruses. The epidemiology and mode of ...

V. M. Zhadanov

1969-01-01

156

A broad-spectrum antiviral targeting entry of enveloped viruses  

PubMed Central

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

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

2010-01-01

157

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

158

Viruses in the sea  

NASA Astrophysics Data System (ADS)

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.

Suttle, Curtis A.

2005-09-01

159

Chimeric Dengue Viruses.  

National Technical Information Service (NTIS)

The invention relates, in general, to chimeric dengue viruses. In particular, the invention relates to chimeric dengue viruses and vaccines comprising same. Further, the invention relates to segments of dengue viral DNA.

C. J. Lai M. Bray

1991-01-01

160

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

161

Human B Lymphotropic Virus.  

National Technical Information Service (NTIS)

The invention is related generally to the isolation and characterization of a new virus. More particularly, it is related to providing a biologically pure, isolated human B lymphotropic virus, molecular clones, nucleic acid, distinctive antigenic proteins...

S. Salahuddin

1988-01-01

162

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

163

Viruses and cancer  

SciTech Connect

This book contains 14 selections. Some of the titles are: Immortalising gene(s) encoded by Epstein-Barr Virus; Adenovirus genes involved in transformation. What determines the oncogenic phenotype.; Oncogenesis by mouse mammary tumour virus; and Transforming ras genes.

Rigby, P.W.J.; Wilkie, N.M.

1985-01-01

164

West Nile Virus  

NSDL National Science Digital Library

Good introduction and synopsis of West Nile Virus. Briefly reporting on such topics as geographic distribution, symptoms and treatment, transmission and prevention. The article includes a list of references for further investigation into the West Nile Virus.

0002-11-30

165

West Nile virus  

MedlinePLUS

West Nile virus is a disease spread by mosquitoes. The condition ranges from mild to severe. ... West Nile virus was first identified in 1937 in Uganda in eastern Africa. It was first discovered in ...

166

West Nile Virus  

MedlinePLUS

West Nile virus (WNV) is an infectious disease that first appeared in the United States in 1999. Infected ... and usually go away on their own. If West Nile virus enters the brain, however, it can be ...

167

West Nile Virus  

MedlinePLUS

... West Nile virus has been found in animals, birds, and humans in all continental states in the ... picked up the virus after feeding on infected birds. Pets and other animals can also become infected ...

168

Wave-Like Spread of Ebola Zaire  

PubMed Central

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 Republic of Congo, very near to the root of the ZEBOV tree, suggesting that viruses causing all other known outbreaks evolved from a Yambuku-like virus after 1976. The tendency for earlier outbreaks to be directly ancestral to later outbreaks suggests that outbreaks are epidemiologically linked and may have occurred at the front of an advancing wave. While the ladder-like phylogenetic structure could also bear the signature of positive selection, our statistical power is too weak to reach a conclusion in this regard. Distances among outbreaks indicate a spread rate of about 50 km per year that remains consistent across spatial scales. Viral evolution is clocklike, and sequences show a high level of small-scale spatial structure. Genetic similarity decays with distance at roughly the same rate at all spatial scales. Our analyses suggest that ZEBOV has recently spread across the region rather than being long persistent at each outbreak locality. Controlling the impact of Ebola on wild apes and human populations may be more feasible than previously recognized.

2005-01-01

169

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

170

[Viruses as biological weapons].  

PubMed

The destruction made by nuclear, biological and chemical weapons used by governments and terrorist groups in the near history is posing anxiety and fear for human being. Rumour about the possible use of these agents leads to the development of serious negative effects on populations. Since there are no vaccine and therapy for most viral agents and cost of production as biological weapons is low, interest rate is rising for viruses. In this review, general characteristics, diagnosis, therapy and protective measures for viral agents such as variola virus, hemorrhagic fever viruses, encephalitis viruses, Hantaviruses and Nipah viruses, those can be used as biological weapon, have been summarized. PMID:16358499

Akçali, Alper

2005-07-01

171

Overview of Musa virus diseases  

Microsoft Academic Search

Bananas and other Musa spp. are affected by fi ve known, relatively well-characterized viruses: these are Banana bunchy top virus (BBTV) genus Nanavirus; Banana streak virus (BSV) genus Badnavirus, Cucumber mosaic virus (CMV) genus Cucumovi- rus, Banana bract mosaic virus (BBrMV) genus Potyvirus, and Abaca mosaic virus (AbaMV) genus Potyvirus. Recently, new fi lamentous virus particles have been noted in

G. Pietersen; J. E. Thomas

172

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

173

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

174

Molecular approaches for the treatment of hemorrhagic fever virus infections.  

PubMed

Viruses causing hemorrhagic fevers in man belong to the following virus groups: togavirus (Chikungunya), flavivirus (dengue, yellow fever, Kyasanur Forest disease, Omsk hemorrhagic fever), arenavirus (Argentinian hemorrhagic fever, Bolivian hemorrhagic fever, Lassa fever), filovirus (Ebola, Marburg), phlebovirus (Rift Valley fever), nairovirus (Crimian-Congo hemorrhagic fever) and hantavirus (hemorrhagic fever with renal syndrome, nephropathic epidemia). Hemorrhagic fever virus infections can be approached by different therapeutic strategies: (i) vaccination; (ii) administration of high-titered antibodies; and (iii) treatment with antiviral drugs. Depending on the molecular target of their interaction, antiviral agents could be classified as follows: IMP dehydrogenase inhibitors (i.e., ribavirin and its derivatives); OMP decarboxylase inhibitors (i.e., pyrazofurin); CTP synthetase inhibitors (i.e., cyclopentylcytosine and cyclopentenylcytosine); SAH hydrolase inhibitors (i.e., neplanocin A); polyanionic substances (i.e., sulfated polymers); interferon and immunomodulators. PMID:8250543

Andrei, G; De Clercq, E

1993-09-01

175

Encephalitis due to emerging viruses: CNS innate immunity and potential therapeutic targets.  

PubMed

The emerging viruses represent a group of pathogens that are intimately connected to a diverse range of animal vectors. The recent escalation of air travel climate change and urbanization has meant humans will have increased risk of contacting these pathogens resulting in serious CNS infections. Many RNA viruses enter the CNS by evading the BBB due to axonal transport from the periphery. The systemic adaptive and CNS innate immune systems express pattern recognition receptors PRR (TLRs, RiG-1 and MDA-5) that detect viral nucleic acids and initiate host antiviral response. However, several emerging viruses (West Nile Fever, Influenza A, Enterovirus 71 Ebola) are recognized and internalized by host cell receptors (TLR, MMR, DC-SIGN, CD162 and Scavenger receptor B) and escape immuno surveillance by the host systemic and innate immune systems. Many RNA viruses express viral proteins WNF (E protein), Influenza A (NS1), EV71 (protein 3C), Rabies (Glycoprotein), Ebola proteins (VP24 and VP 35) that inhibit the host cell anti-virus Interferon type I response promoting virus replication and encephalitis. The therapeutic use of RNA interference methodologies to silence gene expression of viral peptides and treat emerging virus infection of the CNS is discussed. PMID:22484271

Denizot, M; Neal, J W; Gasque, P

2012-04-04

176

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

177

Viruses in Antarctic lakes.  

PubMed

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. PMID:11543124

Kepner, R L; Wharton, R A; Suttle, C A

1998-11-01

178

Constructing computer virus phylogenies  

SciTech Connect

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 acyclic graph whose nodes are the viruses and whose edges map ancestors to descendants and satisfy the property that each code fragment is ``invented`` only once. To provide a simple explanation for the data, we consider the problem of constructing such a phylogeny with a minimal number of edges. In general, this optimization problem cannot be solved in quasi-polynomial time unless NQP=QP; we present positive and negative results for associated approximated problems. When tree solutions exist, they can be constructed and randomly sampled in polynomial time.

Goldberg, L.A. [Warwick Univ., Coventry (United Kingdom) Dept. of Computer Science; Goldberg, P.W. [Aston Univ., Birmingham (United Kingdom) Dept. of Applied Mathematics; Phillips, C.A. [Sandia National Labs., Albuquerque, NM (United States); Sorkin, G.B. [International Business Machines Corp., Yorktown Heights, NY (United States). Thomas J. Watson Research Center

1996-03-01

179

Recombinant vaccinia viruses  

Microsoft Academic Search

The technologies of recombinant gene expression have greatly enhanced the structural and functional analyses of genetic elements\\u000a and proteins. Vaccinia virus, a large double-stranded DNA virus and the prototypic and best characterized member of the poxvirus\\u000a family, has been an instrumental tool among these technologies and the recombinant vaccinia virus system has been widely employed\\u000a to express genes from eukaryotic,

Christopher C. Broder; Patricia L. Earl

1999-01-01

180

Origins of Viruses  

NSDL National Science Digital Library

This page contains lecture notes on the origins and evolution of viruses. The primary topics covered are the diversity of extant viruses, the probability of multiple origins, and host-virus co-evolution. There are links to definitions and further explanations by the author, as well as to articles or discussions in Scientific American, MicrobiologyBytes, and Viroblogy. This page originates from an undergraduate course, but most information would be accessible to high school students.

Rybicki, Ed; Town, University O.

181

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

182

CDC: West Nile Virus  

NSDL National Science Digital Library

This Web site contains the most recent West Nile virus data from the Centers for Disease Control. The main features include a 2003 Human Case Count and updated maps representing the spread of the virus. A downloadable document outlines the CDC's West Nile virus surveillance and control program, which involves weekly data collection for wild birds, sentinel chicken flocks, human cases, veterinary cases, and mosquito surveillance. The site also provides links to general information about the virus, from the ecology and virology of West Nile to epidemiological and laboratory issues.

2008-06-26

183

Papaya Ringspot Virus  

Technology Transfer Automated Retrieval System (TEKTRAN)

The term papaya ringspot virus (PRSV) was coined by Jensen in 1949, to describe a papaya disease in Hawaii. Later work showed that diseases such as papaya mosaic and watermelon mosaic virus-1 were caused by PRSV. The primary host range of PRSV is papaya and cucurbits, with Chenopium amaranticolor ...

184

Papaya ringspot virus (Potyviridae)  

Technology Transfer Automated Retrieval System (TEKTRAN)

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

185

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

186

Bovine viral diarrhea viruses  

Technology Transfer Automated Retrieval System (TEKTRAN)

Infections with bovine viral diarrhea viruses (BVDV) result in significant economic losses for beef and dairy producers worldwide. BVDV is actually an umbrella term for two species of viruses, BVDV1 and BVDV2, within the Pestivirus genus of the Flavivirus family. While denoted as a bovine pathogen...

187

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

188

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

189

What is a Virus?  

NSDL National Science Digital Library

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

Rybicki, Ed

2010-03-23

190

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

191

Human Papilloma Virus Infections  

PubMed Central

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

Wright, V. Cecil

1989-01-01

192

Virus persistence in groundwater.  

PubMed Central

More than 50% of the outbreaks of waterborne disease in the United States are due to the consumption of contaminated groundwater. An estimated 65% of the cases in these outbreaks are caused by enteric viruses. Little, however, is known about the persistence of viruses in groundwater. The purpose of this study was to determine whether measurable chemical and physical factors correlate with virus survival in groundwater. Groundwater samples were obtained from 11 sites throughout the United States. Water temperature was measured at the time of collection. Several physical and chemical characteristics, including pH, nitrates, turbidity, and hardness, were determined for each sample. Separate water samples were inoculated with each of three viruses (poliovirus 1, echovirus 1, and MS-2 coliphage) and incubated at the in situ groundwater temperature; selected samples were also incubated at other temperatures. Assays were performed at predetermined intervals over a 30-day period to determine the number of infective viruses remaining. Multiple regression analysis revealed that temperature was the only variable significantly correlated with the decay rates of all three viruses. No significant differences were found among the decay rates of the three viruses, an indication that MS-2 coliphage might be used as a model of animal virus survival in groundwater.

Yates, M V; Gerba, C P; Kelley, L M

1985-01-01

193

Differential requirements for clathrin endocytic pathway components in cellular entry by Ebola and Marburg glycoprotein pseudovirions.  

PubMed

Clathrin-mediated endocytosis was previously implicated as one of the cellular pathways involved in filoviral glycoprotein mediated viral entry into target cells. Here we have further dissected the requirements for different components of this pathway in Ebola versus Marburg virus glycoprotein (GP) mediated viral infection. Although a number of these components were involved in both cases; Ebola GP-dependent viral entry specifically required the cargo recognition proteins Eps15 and DAB2 as well as the clathrin adaptor protein AP-2. In contrast, Marburg GP-mediated infection was independent of these three proteins and instead required beta-arrestin 1 (ARRB1). These findings have revealed an unexpected difference between the clathrin pathway requirements for Ebola GP versus Marburg GP pseudovirion infection. Anthrax toxin also uses a clathrin-, and ARRB1-dependent pathway for cellular entry, indicating that the mechanism used by Marburg GP pseudovirions may be more generally important for pathogen entry. PMID:21855102

Bhattacharyya, Suchita; Hope, Thomas J; Young, John A T

2011-08-19

194

Giant Viruses: Conflicts in Revisiting the Virus Concept  

Microsoft Academic Search

The current paradigm on the nature of viruses is based on early work of the ‘phage group’ (the pro-phage concept) and molecular biologists working on tumour viruses (the proto-oncogene concept). It posits that viruses evolved from either prokaryotic or eukaryotic cellular genes that became infectious via their association with capsid genes. In this view, after their emergence viruses continued to

Patrick Forterre

2010-01-01

195

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

196

Cytosolic sensing of viruses.  

PubMed

Cells are equipped with mechanisms that allow them to rapidly detect and respond to viruses. These defense mechanisms rely partly on receptors that monitor the cytosol for the presence of atypical nucleic acids associated with virus infection. RIG-I-like receptors detect RNA molecules that are absent from the uninfected host. DNA receptors alert the cell to the abnormal presence of that nucleic acid in the cytosol. Signaling by RNA and DNA receptors results in the induction of restriction factors that prevent virus replication and establish cell-intrinsic antiviral immunity. In light of these formidable obstacles, viruses have evolved mechanisms of evasion, masking nucleic acid structures recognized by the host, sequestering themselves away from the cytosol or targeting host sensors, and signaling adaptors for deactivation or degradation. Here, we detail recent advances in the molecular understanding of cytosolic nucleic acid detection and its evasion by viruses. PMID:23706667

Goubau, Delphine; Deddouche, Safia; Reis E Sousa, Caetano

2013-05-23

197

Virus discovery and recent insights into virus diversity in arthropods.  

PubMed

Recent studies on virus discovery have focused mainly on mammalian and avian viruses. Arbovirology with its long tradition of ecologically oriented investigation is now catching up, with important novel insights into the diversity of arthropod-associated viruses. Recent discoveries include taxonomically outlying viruses within the families Flaviviridae, Togaviridae, and Bunyaviridae, and even novel virus families within the order Nidovirales. However, the current focusing of studies on blood-feeding arthropods has restricted the range of arthropod hosts analyzed for viruses so far. Future investigations should include species from other arthropod taxa than Ixodita, Culicidae and Phlebotominae in order to shed light on the true diversity of arthropod viruses. PMID:23850098

Junglen, Sandra; Drosten, Christian

2013-07-11

198

Realms of the Viruses Online  

ERIC Educational Resources Information Center

|Viruses have evolved strategies for infecting all taxa, but most viruses are highly specific about their cellular host. In humans, viruses cause diverse diseases, from chronic but benign warts, to acute and deadly hemorrhagic fever. Viruses have entertaining names like Zucchini Yellow Mosaic, Semliki Forest, Coxsackie, and the original…

Liu, Dennis

2007-01-01

199

Hepatitis B Virus in Pregnancy  

MedlinePLUS

What is hepatitis B virus? Hepatitis B virus is one of a number of hepatitis viruses that attack and damage the liver. Other types include hepatitis A, ... upper-right side of your abdomen. How is hepatitis B transmitted? Hepatitis B virus is passed from ...

200

Oncolytic viruses in cancer therapy.  

PubMed

Oncolytic virotherapy is a promising form of gene therapy for cancer, employing nature's own agents to find and destroy malignant cells. The purpose of this review is to provide an introduction to this very topical field of research and to point out some of the current observations, insights and ideas circulating in the literature. We have strived to acknowledge as many different oncolytic viruses as possible to give a broader picture of targeting cancer using viruses. Some of the newest additions to the panel of oncolytic viruses include the avian adenovirus, foamy virus, myxoma virus, yaba-like disease virus, echovirus type 1, bovine herpesvirus 4, Saimiri virus, feline panleukopenia virus, Sendai virus and the non-human coronaviruses. Although promising, virotherapy still faces many obstacles that need to be addressed, including the emergence of virus-resistant tumor cells. PMID:17383089

Vähä-Koskela, Markus J V; Heikkilä, Jari E; Hinkkanen, Ari E

2007-03-23

201

The Role of the Charged Residues of the GP2 Helical Regions in Ebola Entry*  

PubMed Central

The glycoprotein (GP) of Ebola is the sole structural protein that forms the spikes on the viral envelope. The GP contains two subunits, GP1 and GP2, linked by a disulfide bond, which are responsible for receptor binding and membrane fusion, respectively. In this study, the full length of GP gene of Ebola Zaire species, 2028 base pairs in length, was synthesized using 38 overlapping oligonucleotides by multiple rounds of polymerase chain reaction (PCR). The synthesized GP gene was shown to be efficiently expressed in mammalian cells. Furthermore, an efficient HIV-based pseudotyping system was developed using the synthetic GP gene, providing a safe approach to dissecting the entry mechanism of Ebola viruses. Using this pseudotyping system and mutational analysis, the role of the charged residues in the GP2 helical regions was examined. It was found that substitutions of the most charged residues in the regions did not adversely affect GP expression, processing, or viral incorporation, however, most of the mutations greatly impaired the ability of GP to mediate efficient viral infection. These results demonstrate that these charged residues of GP2 play an important role in GP-mediated Ebola entry into its host cells. We propose that these charged residues are involved in forming the intermediate conformation(s) of GP in membrane fusion and Ebola entry.

Jiang, Haiqing; Wang, Jizhen; Manicassamy, Balaji; Manicassamy, Santhakumar; Caffrey, Michael; Rong, Lijun

2009-01-01

202

Tracking a Virus  

NSDL National Science Digital Library

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

Engineering K-Ph.d. Program

203

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

Code of Federal Regulations, 2010 CFR

...Diarrhea Vaccine, Killed Virus. Bovine Virus Diarrhea Vaccine...this paragraph. (i) Eight bovine virus diarrhea susceptible...after the last vaccination, blood samples shall be drawn and the...samples inactivated and tested for bovine virus diarrhea virus...

2009-01-01

204

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

Code of Federal Regulations, 2010 CFR

...Diarrhea Vaccine, Killed Virus. Bovine Virus Diarrhea Vaccine...this paragraph. (i) Eight bovine virus diarrhea susceptible...after the last vaccination, blood samples shall be drawn and the...samples inactivated and tested for bovine virus diarrhea virus...

2010-01-01

205

The dengue viruses.  

PubMed Central

Dengue, a major public health problem throughout subtropical and tropical regions, is an acute infectious disease characterized by biphasic fever, headache, pain in various parts of the body, prostration, rash, lymphadenopathy, and leukopenia. In more severe or complicated dengue, patients present with a severe febrile illness characterized by abnormalities of hemostasis and increased vascular permeability, which in some instances results in a hypovolemic shock. Four distinct serotypes of the dengue virus (dengue-1, dengue-2, dengue-3, and dengue-4) exist, with numerous virus strains found worldwide. Molecular cloning methods have led to a greater understanding of the structure of the RNA genome and definition of virus-specific structural and nonstructural proteins. Progress towards producing safe, effective dengue virus vaccines, a goal for over 45 years, has been made. Images

Henchal, E A; Putnak, J R

1990-01-01

206

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)!".

207

Influenza Virus Vaccine Actions  

Center for Biologics Evaluation and Research (CBER)

... Approval of new bulk manufacturing facility for production of Influenza Virus Vaccine. -. Key Resources. ... Key Links. Flu.gov. -. Contact FDA. ... More results from www.fda.gov/biologicsbloodvaccines/safetyavailability/vaccinesafety

208

Rubella Virus Vaccine Live  

Center for Biologics Evaluation and Research (CBER)

... Rubella Virus Vaccine Live. -. Product. MERUVAX II Merck & Co, Inc. -. Contact FDA. (800) 835-4709. (301) 827-1800. ocod ... More results from www.fda.gov/biologicsbloodvaccines/vaccines/approvedproducts

209

Simian hemorrhagic fever virus  

Technology Transfer Automated Retrieval System (TEKTRAN)

This book chapter describes the taxonomic classification of Simian hemorrhagic fever virus (SHFV). Included are: host, genome, classification, morphology, physicochemical and physical properties, nucleic acid, proteins, lipids, carbohydrates, geographic range, phylogenetic properties, biological pro...

210

What's West Nile Virus?  

MedlinePLUS

... Baseball Injuries Jellyfish The Pink Locker Society What's West Nile Virus? KidsHealth > Kids > Illnesses & Injuries > Aches, Pains & Injuries > ... are most at risk for the infection. Continue West Nile Symptoms Most of the time, symptoms of West ...

211

Selective Precipitation of Viruses.  

National Technical Information Service (NTIS)

The invention provides new methods for purifying and concentrating viruses. The inventors have discovered that high molecular weight proteoglycans present in retroviral stocks are co-concentrated with the retroviruses, and can inhibit retroviral transduct...

J. M. LeDoux M. L. Yarmush J. R. Morgan

2005-01-01

212

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 ...

213

AVG Anti-Virus  

NSDL National Science Digital Library

Those who wish for an antivirus program that is both versatile and reliable should definitely consider this latest iteration of the AVG Anti-Virus program. With this program, visitors can be assured that AVG will look for new virus definitions on a daily basis and that it will also create an effective rescue disk in case a dire situation emerges. This website features a number of archived versions of the AVG software for users to choose from.

2008-01-01

214

West nile virus encephalitis  

Microsoft Academic Search

West Nile virus (WNV) is a small RNA virus. It was first isolated in the blood of a febrile woman in the West Nile district\\u000a of Uganda in 1937. Although WNV has caused human disease in Africa and Europe since its identification, the first documented\\u000a human infections occurred in the United States in 1999. Wild birds are the reservoir for

James L. Dean; Brandon J. Palermo

2005-01-01

215

Bacterial Indicators of Viruses  

Microsoft Academic Search

The association between human enteric viruses and disease is well established. However, determining the presence of all of\\u000a the many types of viruses that are pathogenic to humans in food and water is not practical at this time. Because enteric bacteria\\u000a are usual inhabitants of the human intestinal tract, they have been used as indicators of fecal pollution and the

Samuel R. Farrah

216

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

217

Clarifying Bunyamwera virus riddles of the past.  

PubMed

Pyrosequencing data and phylogenetic analysis for the full genome of Ilesha virus, Ngari virus and Calovo virus are described clarifying their much discussed relationship within the species Bunyamwera virus of the genus Orthobunyavirus of the Bunyaviridae. PMID:23686694

Dilcher, Meik; Sall, Amadou A; Hufert, Frank T; Weidmann, Manfred

2013-05-18

218

Molecular detection of respiratory viruses.  

PubMed

Over the past several years a wide variety of molecular assays for the detection of respiratory viruses has reached the market. The tests described herein range from kits containing primers and probes detecting specific groups of viruses, to self-contained systems requiring specialized instruments that extract nucleic acids and perform the polymerase chain reaction with little operator input. Some of the tests target just the viruses involved in large yearly epidemics such as influenza, or specific groups of viruses such as the adenoviruses or parainfluenza viruses; others can detect most of the known respiratory viruses and some bacterial agents. PMID:23931834

Buller, Richard S

2013-09-01

219

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

220

Bovine Leukemia Virus: An Exogenous RNA Oncogenic Virus  

Microsoft Academic Search

Short-term cultures of bovine leukemic lymphocytes release virus particles with biochemical properties of RNA oncogenic viruses. These particles, tentatively called bovine leukemia virus (BLV), have a high molecular weight RNA-reverse transcriptase complex and a density of 1.155 g\\/ml in sucrose solutions. Molecular hybridizations between BLV [3H]cDNA and several viral RNAs show that BLV is not related to Mason-Pfizer monkey virus,

R. Kettmann; D. Portetelle; M. Mammerickx; Y. Cleuter; D. Dekegel; M. Galoux; J. Ghysdael; A. Burny; H. Chantrenne

1976-01-01

221

[Hemorrhagic (Marburg, Ebola, Lassa, and Bolivian) fevers: epidemiology, clinical pictures, and treatment].  

PubMed

The evaluation of the biological and epidemiological properties of Ebola, Marburg, Lassa, and Machupo viruses suggests that they are of social importance for health care authorities. The studies have created prerequisites to the development of reliable biosafety means against these pathogens. Particular emphasis is laid on the methods for infection diagnosis and on the studies to design specific protective agents--immunoglobulins and inactivated vaccines. PMID:17087059

Borisevich, I V; Markin, V A; Firsova, I V; Evseev, A A; Khamitov, R A; Maksimov, V A

222

Maternal recognition of foetal infection with bovine virus diarrhoea virus (BVDV)—the bovine pestivirus  

Microsoft Academic Search

Background: Pestiviruses are the veterinary viruses with genome homology to human hepatitis C virus (HCV). This group includes classical swine fever virus (CSFV), border disease virus of sheep (BDV) and bovine virus diarrhoea virus (BVDV). There are some similarities in the pathology of all three virus infections; in utero transmission to the foetus can cause early embryonic losses, severe congenital

J Brownlie; L. B Hooper; I Thompson; M. E Collins

1998-01-01

223

Pseudotypes of Vesicular Stomatitis Virus with the Coat of Murine Leukaemia and of Avian Myeloblastosis Viruses  

Microsoft Academic Search

SUMMARY Vesicular stomatitis virus (VSV) grown in mouse embryo cells pre-infected with murine sarcoma virus or in chicken cells pre-infected with avian myeloblastosis virus contains, in contrast to virus grown in corresponding control cells, a proportion of virus resistant to antiserum against VSV. Infectivity of this virus fraction can specifically be neutralized with antiserum against murine leukaemia virus (MLV) and

J. Zavada

1972-01-01

224

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

225

Glycyrrhizic acid inhibits virus growth and inactivates virus particles  

Microsoft Academic Search

Screening investigations in antiviral action of plant extracts have revealed that a component of Glycyrrhiza glabra roots, found to be glycyrrhizic acid, is active against viruses. We report here that this drug inhibits growth and cytopathology of several unrelated DNA and RNA viruses, while not affecting cell activity and ability to replicate. In addition, glycyrrhizic acid inactivates herpes simplex virus

Raffaello Pompei; Ornella Flore; Maria Antonietta Marccialis; Alessandra Pani; Bernardo Loddo

1979-01-01

226

Emerging issues in virus taxonomy.  

PubMed

Viruses occupy a unique position in biology. Although they possess some of the properties of living systems such as having a genome, they are actually nonliving infectious entities and should not be considered microorganisms. A clear distinction should be drawn between the terms virus, virion, and virus species. Species is the most fundamental taxonomic category used in all biological classification. In 1991, the International Committee on Taxonomy of Viruses (ICTV) decided that the category of virus species should be used in virus classification together with the categories of genus and family. More than 50 ICTV study groups were given the task of demarcating the 1,550 viral species that were recognized in the 7th ICTV report, which was published in 2000. We briefly describe the changes in virus classification that were introduced in that report. We also discuss recent proposals to introduce a nonlatinized binomial nomenclature for virus species. PMID:15078590

van Regenmortel, Marc H V; Mahy, Brian W J

2004-01-01

227

Studies Relating to Virus Control.  

National Technical Information Service (NTIS)

Contents: Fifty years' effort to control virus infections in the USSR; Thirtieth anniversary of the discovery of the causative agent of tick-borne encephalitis; Relationship between the effect of ionizing radiation on the course of virus infections and th...

O. V. Baroyan E. N. Levkovich A. G. Moroz

1968-01-01

228

Replication of Japanese Encephalitis Virus.  

National Technical Information Service (NTIS)

Gene expression in the flavivirus Japanese encephalitis virus (JEV) was studied by three different approaches. Virus-specific RNA in infected cells was radiolabeled in the presence of actinomycin D, and analyzed by sucrose gradient sedimentation and agaro...

C. D. Blair

1981-01-01

229

Respiratory syncytial virus bronchiolitis.  

PubMed Central

Respiratory syncytial virus, the most common cause of bronchiolitis, is the leading cause of infant hospitalization in developed countries and accounts for substantial mortality and morbidity in developing countries. Children at increased risk of developing severe bronchiolitis are those <6 weeks of age, those born prematurely and those with an underlying cardiopulmonary disorder or immunodeficiency. Approximately 80% of cases occur in the first year of life. By two years of age, virtually all children have been infected by at least one strain of the virus. Classically, respiratory syncytial virus bronchiolitis manifests as cough, wheezing and respiratory distress. The mainstay of treatment is supportive care, consisting of adequate fluid intake, antipyretics to control fever and use of supplemental oxygen if necessary. Frequent and meticulous hand-washing is the best measure to prevent secondary spread. Treatment of respiratory syncytial virus bronchiolitis beyond supportive care should be individualized. Palivizumab has been shown to be effective in preventing severe respiratory syncytial virus bronchiolitis in high-risk children when given prophylactically. In the majority of cases, the disease is usually self-limited. The mortality rate is <1% and occurs predominantly in children at high risk for severe disease.

Leung, Alexander K. C.; Kellner, James D.; Davies, H. Dele

2005-01-01

230

Diagnosis of influenza virus.  

PubMed

The laboratory diagnosis of influenza uses a wide range of techniques including rapid immunoassays, immunofluorescence techniques, virus culture methods, and increasingly sophisticated molecular assays. The potential utility of each of these methods has changed over the years, most dramatically perhaps with the emergence of the pandemic H1N1 2009 influenza virus. While rapid immunoassays had previously been widely used in clinics and emergency departments, their poor detection sensitivity for the 2009 subtype brought their application into question. Concerns were also raised about the detection sensitivities of antibody reagents used in immunofluorescence methods, and the safety of virus culture was initially questioned with regard to the newly emerged subtype. Early molecular detection techniques had been labor intensive, and required separate facilities in order to prevent contamination. Those techniques have largely been supplanted by more modern methods, most notably real-time reverse transcription PCR assays, which are currently the method of choice in many laboratories for the detection and subtyping of influenza viruses. Suspension and low-density array assays are also increasingly used, in an effort to detect larger numbers of viruses in a single assay, and microarrays have proven valuable for outbreak analysis and pathogen discovery. Each laboratory must assess the optimal methods for its situation and the best application of each technique, taking into account numerous factors including its budget, equipment, staff expertise, the patient population that it serves, the needs of its submitting clinicians, and its surveillance and public health responsibilities. PMID:22528153

George, Kirsten St

2012-01-01

231

Molluscum contagiosum virus infection.  

PubMed

Molluscum contagiosum virus is an important human skin pathogen: it can cause disfigurement and suffering in children, in adults it is less common and often sexually transmitted. Extensive and persistent skin infection with the virus can indicate underlying immunodeficiency. Traditional ablative therapies have not been compared directly with newer immune-modulating and specific antiviral therapies. Advances in research raise the prospect of new approaches to treatment informed by the biology of the virus; in human skin, the infection is localised in the epidermal layers, where it induces a typical, complex hyperproliferative lesion with an abundance of virus particles but a conspicuous absence of immune effectors. Functional studies of the viral genome have revealed effects on cellular pathways involved in the cell cycle, innate immunity, inflammation, and cell death. Extensive lesions caused by molluscum contagiosum can occur in patients with DOCK8 deficiency-a genetic disorder affecting migration of dendritic and specialised T cells in skin. Sudden disappearance of lesions is the consequence of a vigorous immune response in healthy people. Further study of the unique features of infection with molluscum contagiosum virus could give fundamental insight into the nature of skin immunity. PMID:23972567

Chen, Xiaoying; Anstey, Alex V; Bugert, Joachim J

2013-08-21

232

Infectious salmon anaemia virus.  

PubMed

Infectious salmon anaemia virus (ISAV) is a commercially important orthomyxovirus causing disease in farmed Atlantic salmon. The cumulative mortality in a net pen during an outbreak may vary from insignificant to more than 90%. The infection is spread by management activity such as well-boat traffic, but possibly also through contact with wild fish. In many of its aspects, including the structure of the virus particle and replication strategy, the ISAV is similar to the influenza viruses. Variations between ISAV and the influenza viruses can mostly be related to differences in the temperature at which replication occurs and the immune response of their respective host animals. ISAV shows both haemagglutinating and receptor-destroying activity. The variability of the ISAV haemagglutinin molecule is concentrated around a small domain close to the transmembrane region. The function of this variable region is unknown, but it may be related to a recent or ongoing crossing of a species barrier. Alignment studies based on genetic data indicate that the phylogenetic relationship to the influenza viruses is distant, and that ISAV therefore could possibly warrant a new genus within Orthomyxoviridae. PMID:12076262

Rimstad, Espen; Mjaaland, Siri

2002-04-01

233

Measles virus 1998-2002: progress and controversy.  

PubMed

Despite the extensive media exposure that viruses such as West Nile, Norwalk, and Ebola have received lately, and the emerging threat that old pathogens may reappear as new agents of terrorism, measles virus (MV) persists as one of the leading causes of death by infectious agents worldwide, approaching the annual mortality rate of human immunodeficiency virus (HIV)-1. For most MV victims, fatality is indirect: Virus-induced transient immunosuppression predisposes the individual to opportunistic infections that, left untreated, can result in mortality. In rare cases, MV may also cause progressive neurodegenerative disease. During the past five years (1998-2002), development of animal models and the application of reverse genetics and immunological assays have collectively contributed to major progress in our understanding of MV biology and pathogenesis. Nevertheless, questions and controversies remain that are the basis for future research. In this review, major advances and current debates are discussed, including MV receptor usage, the cellular basis of immunosuppression, the suspected role of MV in "nonviral" diseases such as multiple sclerosis and Paget's disease, and the controversy surrounding MV vaccine safety. PMID:14527283

Rall, Glenn F

2003-01-01

234

Dissecting virus entry via endocytosis  

Microsoft Academic Search

Numerous virus families utilize endocytosis to infect host cells, mediating virus internalization as well as trafficking to the site of replication. Recent research has demonstrated that viruses employ the full endocytic capabilities of the cell. The endocytic pathways utilized include clathrin-mediated endocytosis, caveolae, macropinocytosis and novel non-clathrin, non-caveolae pathways. The tools to study endocytosis and, consequently, virus entry are becoming

Sara B. Sieczkarski; Gary R. Whittaker

2002-01-01

235

Virus load and antigenic diversity  

Microsoft Academic Search

In this paper, we analyse mathematical models for the interaction between virus replication and immune responses. We show\\u000a that the immune system can provide selection pressure for or against viral diversity. The paper provides new insights into\\u000a the relationship between virus load (=the abundance of virus in an infected individual) and antigenic diversity. Antigenic\\u000a variation can increase virus load during

Barbara Bittner; Sebastian Bonhoeffer; Martin A. Nowak

1997-01-01

236

Measles Virus for Cancer Therapy  

Microsoft Academic Search

Measles virus offers an ideal platform from which to build a new generation of safe, effective oncolytic viruses. Occasional\\u000a so-called spontaneous tumor regressions have occurred during natural measles infections, but common tumors do not express\\u000a SLAM, the wild-type MV receptor, and are therefore not susceptible to the virus. Serendipitously, attenuated vaccine strains\\u000a of measles virus have adapted to use CD46,

S. J. Russell; K. W. Peng

237

Nipah virus outbreak in Malaysia  

Microsoft Academic Search

Nipah virus, a novel paramyxovirus, closely related to Hendra virus emerged in northern part of Peninsular Malaysia in 1998. The virus caused an outbreak of severe febrile encephalitis in humans with a high mortality rate, whereas, in pigs, encephalitis and respiratory diseases but with a relatively low mortality rate. The outbreak subsequently spread to various regions of the country and

Kaw Bing Chua

2003-01-01

238

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

239

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

240

Soy isoflavones and virus infections  

Microsoft Academic Search

Isoflavones and their related flavonoid compounds exert antiviral properties in vitro and in vivo against a wide range of viruses. Genistein is, by far, the most studied soy isoflavone in this regard, and it has been shown to inhibit the infectivity of enveloped or nonenveloped viruses, as well as single-stranded or double-stranded RNA or DNA viruses. At concentrations ranging from

Aline Andres; Sharon M. Donovan; Mark S. Kuhlenschmidt

2009-01-01

241

Raspberry latent virus in Rubus  

Technology Transfer Automated Retrieval System (TEKTRAN)

Raspberry latent virus (RpLV) is a recently characterized virus reported from the Pacific Northwest, including Oregon and Washington in the United States and British Columbia in Canada. The virus appears to spread rapidly in the Fraser River Valley (northwest Washington and southwest British Columb...

242

Epidemiological Studies of Amapari Virus.  

National Technical Information Service (NTIS)

A new virus, named Amapari virus, was isolated from forest rodents and their mites caught in Amapa, Brazil. Through August 1970, more than 350 isolations of MAPARI VIRUS HAVE BEEN MADE, FROM 204/1896 RODENTS OF ONLY 2 SPECIES I.E., Oryzomys capito goeldii...

1970-01-01

243

The taxonomy of vertebrate viruses  

Microsoft Academic Search

Viruses that infect vertebrates (i.e. humans and higher animals) exhibit great diversity. They also create a variety of diseases that arise from interaction with their vertebrate hosts. This review presents the diversity of the biological and molecular properties of vertebrate viruses that aid their transmission and survival using the currently accepted taxonomic system. The Universal System of Virus Taxonomy has

Craig R. Pringle

2006-01-01

244

Endosomes, exosomes and Trojan viruses  

Microsoft Academic Search

Retroviruses are enveloped viruses that are generally assumed to bud at the plasma membrane of infected cells. Recently it has become apparent that some of these viruses use the endocytic pathway to coordinate their assembly and release. In addition, these and some other enveloped viruses exploit the machinery that generates the internal membranes of multivesicular bodies (MVB). These observations and

Annegret Pelchen-Matthews; Graça Raposo; Mark Marsh

2004-01-01

245

Virus infection improves drought tolerance  

Microsoft Academic Search

Summary • Viruses are obligate intracellular symbionts. Plant viruses are often discovered and studied as pathogenic parasites that cause diseases in agricultural plants. However, here it is shown that viruses can extend survival of their hosts under conditions of abiotic stress that could benefit hosts if they subsequently recover and reproduce.  Various plant species were inoculated with four different

Ping Xu; Fang Chen; Jonathan P. Mannas; Tracy Feldman; Lloyd W. Sumner; Marilyn J. Roossinck

2008-01-01

246

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

2009-11-11

247

Ecology of prokaryotic viruses.  

PubMed

The finding that total viral abundance is higher than total prokaryotic abundance and that a significant fraction of the prokaryotic community is infected with phages in aquatic systems has stimulated research on the ecology of prokaryotic viruses and their role in ecosystems. This review treats the ecology of prokaryotic viruses ('phages') in marine, freshwater and soil systems from a 'virus point of view'. The abundance of viruses varies strongly in different environments and is related to bacterial abundance or activity suggesting that the majority of the viruses found in the environment are typically phages. Data on phage diversity are sparse but indicate that phages are extremely diverse in natural systems. Lytic phages are predators of prokaryotes, whereas lysogenic and chronic infections represent a parasitic interaction. Some forms of lysogeny might be described best as mutualism. The little existing ecological data on phage populations indicate a large variety of environmental niches and survival strategies. The host cell is the main resource for phages and the resource quality, i.e., the metabolic state of the host cell, is a critical factor in all steps of the phage life cycle. Virus-induced mortality of prokaryotes varies strongly on a temporal and spatial scale and shows that phages can be important predators of bacterioplankton. This mortality and the release of cell lysis products into the environment can strongly influence microbial food web processes and biogeochemical cycles. Phages can also affect host diversity, e.g., by 'killing the winner' and keeping in check competitively dominant species or populations. Moreover, they mediate gene transfer between prokaryotes, but this remains largely unknown in the environment. Genomics or proteomics are providing us now with powerful tools in phage ecology, but final testing will have to be performed in the environment. PMID:15109783

Weinbauer, Markus G

2004-05-01

248

Herpes Virus Amplicon Vectors  

PubMed Central

Since its emergence onto the gene therapy scene nearly 25 years ago, the replication-defective Herpes Simplex Virus Type-1 (HSV-1) amplicon has gained significance as a versatile gene transfer platform due to its extensive transgene capacity, widespread cellular tropism, minimal immunogenicity, and its amenability to genetic manipulation. Herein, we detail the recent advances made with respect to the design of the HSV amplicon, its numerous in vitro and in vivo applications, and the current impediments this virus-based gene transfer platform faces as it navigates a challenging path towards future clinical testing.

de Silva, Suresh; Bowers, William J.

2009-01-01

249

Rice Yellow Mottle Virus, an RNA Plant Virus, Evolves as Rapidly as Most RNA Animal Viruses  

Microsoft Academic Search

The rate of evolution of an RNA plant virus has never been estimated using temporally spaced sequence data, by contrast to the information available on an increasing range of animal viruses. Accordingly, the evolution rate of Rice yellow mottle virus (RYMV) was calculated from sequences of the coat protein gene of isolates collected from rice over a 40-year period in

D. Fargette; A. Pinel; M. Rakotomalala; E. Sangu; O. Traore ´; D. Sereme ´; F. Sorho; S. Issaka; E. Hebrard; Y. Sere; Z. Kanyeka; G. Konate

2008-01-01

250

Human immunodeficiency virus nephropathy  

Microsoft Academic Search

Varying components of the syndrome of human immunodeficiency virus nephropathy (HIVN) have been described, the most pertinent including proteinuria\\/nephrotic syndrome, progressive azotemia, normal blood pressure, enlarged and hyperechoic kidneys, rapid progression to end-stage renal disease (ESRD), and no response to treatment regimens. The diagnosis of HIVN requires identification of excessive proteinuria or albuminuria, determined by a total protein excretion on

Jose Strauss; Gaston Zilleruelo; Carolyn Abitbol; Brenda Montane; Victoriano Pardo

1993-01-01

251

From Shakespeare to Viruses  

ScienceCinema

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

252

Wineberry latent virus  

Technology Transfer Automated Retrieval System (TEKTRAN)

Wineberry latent virus (WLV) was discovered in a single symptomless plant of wineberry, Rubus phoenicolasius, which was growing in an experimental planting in Scotland. The plant originated in the United States, where wineberry is established in the wild in the Northeast. Experimentally, WLV can be ...

253

Yaba Virus Tumors.  

National Technical Information Service (NTIS)

The salient features of the Yaba tumor are that a DNA virus, probably a member of the pox group, produces characteristic subcutaneous growths on the face and distal portions of the limbs in some, but not all, species of nonhuman primates and in man. Tumor...

E. E. McConnell

1969-01-01

254

Blueberry shock virus  

Technology Transfer Automated Retrieval System (TEKTRAN)

Blueberry shock disease first observed in Washington state in 1987 and initially confused with blueberry scorch caused by Blueberry scorch virus (BlScV). However, shock affected plants produced a second flush of leaves after flowering and the plants appeared normal by late summer except for the lac...

255

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

256

Algal Virus: Isolation  

Microsoft Academic Search

Freshwater blue-green algae of the genera Lyngbya, Plectonema, and Phormidium are susceptible to a virus recently isolated from a waste-stabilization pond. Electron micrographs of a partially purified preparation show that the viral particle has an icosahedral structure about 66 mmu in diameter.

Robert S. Safferman; Mary-Ellen Morris

1963-01-01

257

VIRUS PERSISTENCE IN GROUNDWATER  

EPA Science Inventory

The purpose of the study was to determine whether measurable chemical and physical factors correlate with virus survival in groundwater. Groundwater samples were obtained from 11 sites throughout the United States. Water temperature was measured at the time of collection. Several...

258

Evolution of infectious salmon anaemia virus (ISA virus).  

PubMed

Infectious salmon anaemia virus, ISA virus (genus Isavirus, family Orthomyxoviridae), emerged in Norwegian salmon culture in the mid-80s. The genome consists of eight segments coding for at least 10 proteins. ISA viruses show many of similarities to influenza A viruses but differ in many important aspects such as the number of hosts, the host population structure and the route of transmission. The only known hosts and reservoirs for ISA viruses are salmonids found in countries surrounding the North Atlantic. In this study, four different segments of the genome of about 100 ISA viruses have been sequenced in an attempt to understand the evolution of ISA viruses and how these viruses are maintained in and transmitted between populations of farmed Atlantic salmon. The four gene segments code for the nucleoprotein (NP), the putative acid polymerase (PA), the fusion protein (F) and the haemagglutinin-esterase (HE). Analysis of these four genes showed that the substitution rates of the internal proteins (NP and PA) are lower than those of the two surface proteins (F and HE). All four segments are evolving at a lower rate than similar genes in influenza A viruses. The ISA virus populations consist of avirulent viruses and pathogenic strains with variable virulence in Atlantic salmon. Recombination resulting in inserts close to the proteolytic-cleavage site of the precursor F0 protein and deletions in the stalk region of the HE protein seem to be responsible for the transition from avirulent ISA viruses to pathogenic strains. It is also shown that reassortment is a frequent event among the dominating ISA viruses in farmed Atlantic salmon. The pattern that is obtained after phylogenetic analysis of the four gene segments from ISA viruses suggests that the variation is limited to a few distinct clades and that no major changes have occurred in the ISA virus population in Norway since the first viruses were isolated. Calculation of the time of most recent common ancestor (TMRCA) suggests that the Norwegian ISA viruses separated from the European subtype found in North America between 1932 and 1959. The TMRCA data also suggest that the ISA viruses in Chile were transmitted from Norway in the period from 1995 to 2007, depending on which of the four genes were used in the analysis. PMID:22886279

Plarre, Heidrun; Nylund, Are; Karlsen, Marius; Brevik, Øyvind; Sæther, Per Anton; Vike, Siri

2012-08-12

259

Molecular epidemiology of respiratory viruses in virus-induced asthma  

PubMed Central

Acute respiratory illness (ARI) due to various viruses is not only the most common cause of upper respiratory infection in humans but is also a major cause of morbidity and mortality, leading to diseases such as bronchiolitis and pneumonia. Previous studies have shown that respiratory syncytial virus (RSV), human rhinovirus (HRV), human metapneumovirus (HMPV), human parainfluenza virus (HPIV), and human enterovirus infections may be associated with virus-induced asthma. For example, it has been suggested that HRV infection is detected in the acute exacerbation of asthma and infection is prolonged. Thus it is believed that the main etiological cause of asthma is ARI viruses. Furthermore, the number of asthma patients in most industrial countries has greatly increased, resulting in a morbidity rate of around 10-15% of the population. However, the relationships between viral infections, host immune response, and host factors in the pathophysiology of asthma remain unclear. To gain a better understanding of the epidemiology of virus-induced asthma, it is important to assess both the characteristics of the viruses and the host defense mechanisms. Molecular epidemiology enables us to understand the pathogenesis of microorganisms by identifying specific pathways, molecules, and genes that influence the risk of developing a disease. However, the epidemiology of various respiratory viruses associated with virus-induced asthma is not fully understood. Therefore, in this article, we review molecular epidemiological studies of RSV, HRV, HPIV, and HMPV infection associated with virus-induced asthma.

Ishioka, Taisei; Noda, Masahiro; Kozawa, Kunihisa; Kimura, Hirokazu

2013-01-01

260

Structural basis for dsRNA recognition and interferon antagonism by Ebola VP35.  

PubMed

Ebola viral protein 35 (VP35), encoded by the highly pathogenic Ebola virus, facilitates host immune evasion by antagonizing antiviral signaling pathways, including those initiated by RIG-I-like receptors. Here we report the crystal structure of the Ebola VP35 interferon inhibitory domain (IID) bound to short double-stranded RNA (dsRNA), which together with in vivo results reveals how VP35-dsRNA interactions contribute to immune evasion. Conserved basic residues in VP35 IID recognize the dsRNA backbone, whereas the dsRNA blunt ends are 'end-capped' by a pocket of hydrophobic residues that mimic RIG-I-like receptor recognition of blunt-end dsRNA. Residues critical for RNA binding are also important for interferon inhibition in vivo but not for viral polymerase cofactor function of VP35. These results suggest that simultaneous recognition of dsRNA backbone and blunt ends provides a mechanism by which Ebola VP35 antagonizes host dsRNA sensors and immune responses. PMID:20081868

Leung, Daisy W; Prins, Kathleen C; Borek, Dominika M; Farahbakhsh, Mina; Tufariello, JoAnn M; Ramanan, Parameshwaran; Nix, Jay C; Helgeson, Luke A; Otwinowski, Zbyszek; Honzatko, Richard B; Basler, Christopher F; Amarasinghe, Gaya K

2010-01-17

261

Critical Role for the Cysteines Flanking the Internal Fusion Peptide of Avian Sarcoma/Leukosis Virus Envelope Glycoprotein  

PubMed Central

The transmembrane subunit (TM) of the envelope glycoprotein (Env) of the oncovirus avian sarcoma/leukosis virus (ASLV) contains an internal fusion peptide flanked by two cysteines (C9 and C45). These cysteines, as well as an analogous pair in the Ebola virus GP glycoprotein, are predicted to be joined by a disulfide bond. To examine the importance of these cysteines, we mutated C9 and C45 in the ASLV subtype A Env (EnvA), individually and together, to serine. All of the mutant EnvAs formed trimers that were composed of the proteolytically processed surface (SU) and TM subunits. All mutant EnvAs were incorporated into murine leukemia virus pseudotyped virions and bound receptor with wild-type affinity. Nonetheless, all mutant EnvAs were significantly impaired (?1,000-fold) in their ability to support infectivity. They were also significantly impaired in their ability to mediate cell-cell fusion. Our data are consistent with a model in which the internal fusion peptide of ASLV-A EnvA exists as a loop that is stabilized by a disulfide bond at its base and in which this stabilized loop serves an important function during virus-cell fusion. The fusion peptide of the Ebola virus GP glycoprotein may conform to a similar structure.

Delos, S. E.; White, J. M.

2000-01-01

262

Infectious Enveloped RNA Virus Antigenic Chimeras  

Microsoft Academic Search

Random insertion mutagenesis has been used to construct infectious Sindbis virus structural protein chimeras containing a neutralization epitope from a heterologous virus, Rift Valley fever virus. Insertion sites, permissive for recovery of chimeric viruses with growth properties similar to the parental virus, were found in the virion E2 glycoprotein and the secreted E3 glycoprotein. For the E2 chimeras, the epitope

Steven D. London; Alan L. Schmaljohn; Joel M. Dalrymple; Charles M. Rice

1992-01-01

263

Heparan Sulfate-Mediated Binding of Infectious Dengue Virus Type 2 and Yellow Fever Virus  

Microsoft Academic Search

Dengue virus type 2 and Yellow fever virus are arthropod-borne flaviviruses causing hemorrhagic fever in humans. Identification of virus receptors is important in understanding flavivirus pathogenesis. The aim of this work was to study the role of cellular heparan sulfate in the adsorption of infectious Yellow fever and Dengue type 2 viruses. Virus attachment was assessed by adsorbing virus to

Raphaële Germi; Jean-Marc Crance; Daniel Garin; Josette Guimet; Hugues Lortat-Jacob; Rob W. H. Ruigrok; Jean-Pierre Zarski; Emmanuel Drouet

2002-01-01

264

Hepatitis C Virus and other Flaviviridae Viruses Enter Cells via Low Density Lipoprotein Receptor  

Microsoft Academic Search

Endocytosis of the Flaviviridae viruses, hepatitis C virus, GB virus C\\/hepatitis G virus, and bovine viral diarrheal virus (BVDV) was shown to be mediated by low density lipoprotein (LDL) receptors on cultured cells by several lines of evidence: by the demonstration that endocytosis of these virus correlated with LDL receptor activity, by complete inhibition of detectable endocytosis by anti-LDL receptor

Vincent Agnello; Gyorgy Abel; Mutasim Elfahal; Glenn B. Knight; Qing-Xiu Zhang

1999-01-01

265

Single virus genomics: a new tool for virus discovery.  

PubMed

Whole genome amplification and sequencing of single microbial cells has significantly influenced genomics and microbial ecology by facilitating direct recovery of reference genome data. However, viral genomics continues to suffer due to difficulties related to the isolation and characterization of uncultivated viruses. We report here on a new approach called 'Single Virus Genomics', which enabled the isolation and complete genome sequencing of the first single virus particle. A mixed assemblage comprised of two known viruses; E. coli bacteriophages lambda and T4, were sorted using flow cytometric methods and subsequently immobilized in an agarose matrix. Genome amplification was then achieved in situ via multiple displacement amplification (MDA). The complete lambda phage genome was recovered with an average depth of coverage of approximately 437X. The isolation and genome sequencing of uncultivated viruses using Single Virus Genomics approaches will enable researchers to address questions about viral diversity, evolution, adaptation and ecology that were previously unattainable. PMID:21436882

Allen, Lisa Zeigler; Ishoey, Thomas; Novotny, Mark A; McLean, Jeffrey S; Lasken, Roger S; Williamson, Shannon J

2011-03-23

266

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

267

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

268

Computer viruses: ways of reproduction in MS-DOS  

Microsoft Academic Search

The methods used by computer viruses to reproduce themselves in IBM PC-compatibles operating under MS-DOS are studied. The results can be of use for classification of viruses and the creation of anti-virus tools. Viruses are examined under the following headings: irritating viruses, viruses that damage files, viruses that damage the file system and viruses that injure the hardware

S. I. Shoutkov; A. V. Spesivtsev

1991-01-01

269

Competitive virus assay method for titration of noncytopathogenic bovine viral diarrhea viruses (END? and END? viruses).  

PubMed

A new, reliable and secure virus assay method, named the competitive virus assay (CVA) method, has been established for the titration of bovine viral diarrhea viruses (BVDVs) that either show the exaltation of Newcastle disease virus (END) phenomenon or heterologous interference phenomenon (but not the END phenomenon). This method is based on the principle of (1) homologous interference between BVDVs, by using BVDV RK13/E(-) or BVDV RK13/E(+) strains as competitor virus, and (2) END phenomenon and heterologous interference, by using attenuated Newcastle disease virus (NDV) TCND strain as challenge virus. In titration of BVDV END(+) and BVDV END(-) viruses, no significant difference in estimated virus titer was observed between CVA and conventional methods. CVA method demonstrated comparable levels of sensitivity and accuracy as conventional END and interference methods, which require the use of a velogenic Miyadera strain of NDV and vesicular stomatitis virus (VSV), both of which are agents of high-risk diseases. As such, the CVA method is a safer alternative, with increased bio-safety and bio-containment, through avoidance of virulent strains that are commonly employed with conventional methods. PMID:23219806

Muhsen, Mahmod; Ohi, Kota; Aoki, Hiroshi; Ikeda, Hidetoshi; Fukusho, Akio

2012-12-05

270

Making Better Influenza Virus Vaccines?  

PubMed Central

Killed and live influenza virus vaccines are effective in preventing and curbing the spread of disease, but new technologies such as reverse genetics could be used to improve them and to shorten the lengthy process of preparing vaccine seed viruses. By taking advantage of these new technologies, we could develop live vaccines that would be safe, cross-protective against variant strains, and require less virus per dose than conventional vaccines. Furthermore, pandemic vaccines against highly virulent strains such as the H5N1 virus can only be generated by reverse genetics techniques. Other technologic breakthroughs should result in effective adjuvants for use with killed and live vaccines, increasing the number of available doses. Finally, universal influenza virus vaccines seem to be within reach. These new strategies will be successful if they are supported by regulatory agencies and if a robust market for influenza virus vaccines against interpandemic and pandemic threats is made and sustained.

2006-01-01

271

Principles of Virus Structural Organization  

PubMed Central

Viruses, the molecular nanomachines infecting hosts ranging from prokaryotes to eukaryotes, come in different sizes, shapes and symmetries. Questions such as what principles govern their structural organization, what factors guide their assembly, how these viruses integrate multifarious functions into one unique structure have enamored researchers for years. In the last five decades, following Caspar and Klug's elegant conceptualization of how viruses are constructed, high resolution structural studies using X-ray crystallography and more recently cryo-EM techniques have provided a wealth of information on structures of variety of viruses. These studies have significantly furthered our understanding of the principles that underlie structural organization in viruses. Such an understanding has practical impact in providing a rational basis for the design and development of antiviral strategies. In this chapter, we review principles underlying capsid formation in a variety of viruses, emphasizing the recent developments along with some historical perspective.

Prasad, B.V. Venkataram; Schmid, Michael F

2013-01-01

272

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

2012-10-04

273

Proteorhodopsin genes in giant viruses  

PubMed Central

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. This article was reviewed by Igor B. Zhulin and Laksminarayan M. Iyer. For the full reviews, see the Reviewers’ reports section.

2012-01-01

274

Acid Sensitivity of the Influenza Virus Hemagglutinin  

PubMed Central

Influenza virus hemagglutinin was shown to be acid resistant if precipitates which form during acidification are first removed. Adsorption of virus to precipitates formed during acidification may cause a virus to be described incorrectly as acid sensitive.

Henderson, Marilyn; Wallis, Craig; Melnick, Joseph L.

1973-01-01

275

West Nile Virus Infection and Pregnancy  

MedlinePLUS

... or visit us online at: www.OTISpregnancy.org . West Nile Virus Infection and Pregnancy This sheet talks about ... advice from your health care provider. What is West Nile Virus (WNV)? WNV is a virus that can ...

276

Advances in virus research. Volume 29  

SciTech Connect

This book contains nine chapters. Some of the titles are: Molecular Biology of Wound Tumor Virus; The Application of Monoclonal Antibodies in the Study of Viruses; Prions: Novel Infectious Pathogens; and Monoclonal Antibodies Against Plant Viruses.

Lauffer, M.A.; Maramorosch, K.

1984-01-01

277

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

278

Virus-encoded superantigens.  

PubMed Central

Superantigens are microbial agents that have a strong effect on the immune response of the host. Their initial target is the T lymphocyte, but a whole cascade of immunological reactions ensues. It is thought that the microbe engages the immune system of the host to its own advantage, to facilitate persistent infection and/or transmission. In this review, we discuss in detail the structure and function of the superantigen encoded by the murine mammary tumor virus, a B-type retrovirus which is the causative agent of mammary carcinoma. We will also outline what has more recently become known about superantigen activity associated with two human herpesviruses, cytomegalovirus and Epstein-Barr virus. It is likely that we have only uncovered the tip of the iceberg in our discovery of microbial superantigens, and we predict a flood of new information on this topic shortly.

Huber, B T; Hsu, P N; Sutkowski, N

1996-01-01

279

Immunopathogenesis of dengue virus infection  

Microsoft Academic Search

Dengue virus infection causes dengue fever (DF), dengue hemorrhagic fever (DHF), and dengue shock syndrome (DSS), whose pathogeneses are not clearly understood. Current hypotheses of antibody-dependent enhancement, virus virulence, and IFN-?\\/TNF?-mediated immunopathogenesis are insufficient to explain clinical manifestations of DHF\\/DSS such as thrombocytopenia and hemoconcentration. Dengue virus infection induces transient immune aberrant activation of CD4\\/CD8 ratio inversion and cytokine overproduction,

Huan-Yao Lei; Trai-Ming Yeh; Hsiao-Sheng Liu; Yee-Shin Lin; Shun-Hua Chen; Ching-Chuan Liu

2001-01-01

280

A DNA Virus of Drosophila  

Microsoft Academic Search

Little is known about the viruses infecting most species. Even in groups as well-studied as Drosophila, only a handful of viruses have been well-characterized. A viral metagenomic approach was used to explore viral diversity in 83 wild-caught Drosophila innubila, a mushroom feeding member of the quinaria group. A single fly that was injected with, and died from, Drosophila C Virus

Robert L. Unckless

2011-01-01

281

Epstein-Barr Virus  

Microsoft Academic Search

Epstein-Barr virus (EBV) is a ubiquitous human herpesvirus. Infection with EBV is common, worldwide in distribution, and largely\\u000a subclinical in early childhood. EBV has been established as the causative agent of heterophile-positive mononucleosis, which\\u000a occurs most frequently in late adolescence or early adulthood. In addition, seroepidemologic data have suggested that EBV\\u000a also plays an etiological role in African Burkitt’s lymphoma

Suresh B. Boppana

282

Genus Orthopoxvirus: Cowpox virus  

Microsoft Academic Search

\\u000a Cowpox virus (CPXV) is distinguished from other orthopoxvirus (OPV) species by producing cytoplasmic A-type inclusion bodies and flattened\\u000a pocks with a hemorrhagic center on the chorioallantoic membrane. CPXV is endemic to Western Eurasia and naturally infects\\u000a a broad range of host species including domestic animals, and zoo animals, as well as humans. Infections in humans seem to\\u000a increase in importance

Sandra Essbauer; Hermann Meyer

283

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

284

Genus Orthopoxvirus: Variola virus  

Microsoft Academic Search

Variola major virus caused the human disease smallpox; interpretations of the historic record indicate that the initial introduction\\u000a of disease in a naïve population had profound effects on its demographics. Smallpox was declared eradicated by the World Health\\u000a Organization (WHO) in 1980. This chapter reviews epidemiological, clinical and pathophysiological observations of disease,\\u000a and review some of the more recent observations

Inger K. Damon

285

Measles Virus Receptors  

Microsoft Academic Search

Measles virus (MV) has two envelope glycoproteins, the hemagglutinin (H) and fusion protein, which are responsible for attachment\\u000a and membrane fusion, respectively. Signaling lymphocyte activation molecule (SLAM, also called CD150), a membrane glycoprotein\\u000a expressed on immune cells, acts as the principal cellular receptor for MV, accounting for its lymphotropism and immunosuppressive\\u000a nature. MV also infects polarized epithelial cells via an

Y. Yanagi; M. Takeda; S. Ohno; T. Hashiguchi

286

9 CFR 113.311 - Bovine Virus Diarrhea Vaccine.  

Code of Federal Regulations, 2010 CFR

...Bovine Virus Diarrhea Vaccine. Bovine Virus Diarrhea Vaccine...follows: (1) Twenty-five bovine virus diarrhea susceptible...vaccinates and five controls). Blood samples shall be drawn from...be considered susceptible to bovine virus diarrhea virus...

2010-01-01

287

9 CFR 113.311 - Bovine Virus Diarrhea Vaccine.  

Code of Federal Regulations, 2010 CFR

...Bovine Virus Diarrhea Vaccine. Bovine Virus Diarrhea Vaccine...follows: (1) Twenty-five bovine virus diarrhea susceptible...vaccinates and five controls). Blood samples shall be drawn from...be considered susceptible to bovine virus diarrhea virus...

2009-01-01

288

Clinical, virologic, and immunologic follow-up of convalescent Ebola hemorrhagic fever patients and their household contacts, Kikwit, Democratic Republic of the Congo. Commission de Lutte contre les Epidémies à Kikwit.  

PubMed

A cohort of convalescent Ebola hemorrhagic fever (EHF) patients and their household contacts (HHCs) were studied prospectively to determine if convalescent body fluids contain Ebola virus and if secondary transmission occurs during convalescence. Twenty-nine EHF convalescents and 152 HHCs were monitored for up to 21 months. Blood specimens were obtained and symptom information was collected from convalescents and their HHCs; other body fluid specimens were also obtained from convalescents. Arthralgias and myalgia were reported significantly more often by convalescents than HHCs. Evidence of Ebola virus was detected by reverse transcription-polymerase chain reaction in semen specimens up to 91 days after disease onset; however, these and all other non-blood body fluids tested negative by virus isolation. Among 81 initially antibody negative HHCs, none became antibody positive. Blood specimens of 5 HHCs not identified as EHF patients were initially antibody positive. No direct evidence of convalescent-to-HHC transmission of EHF was found, although the semen of convalescents may be infectious. The existence of initially antibody-positive HHCs suggests that mild cases of Ebola virus infection occurred and that the full extent of the EHF epidemic was probably underestimated. PMID:9988162

Rowe, A K; Bertolli, J; Khan, A S; Mukunu, R; Muyembe-Tamfum, J J; Bressler, D; Williams, A J; Peters, C J; Rodriguez, L; Feldmann, H; Nichol, S T; Rollin, P E; Ksiazek, T G

1999-02-01

289

The temporal program of peripheral blood gene expression in the response of nonhuman primates to Ebola hemorrhagic fever  

Microsoft Academic Search

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. RESULTS: Using high-density cDNA microarrays, we analyzed genome-wide host expression patterns in sequential blood samples from nonhuman primates infected with EBOV. The temporal program

Kathleen H Rubins; Lisa E Hensley; Victoria Wahl-Jensen; Kathleen M Daddario DiCaprio; Howard A Young; Douglas S Reed; Peter B Jahrling; Patrick O Brown; David A Relman; Thomas W Geisbert

2007-01-01

290

Marek's disease virus morphogenesis.  

PubMed

Marek's disease virus (MDV) is a highly contagious virus that induces T-lymphoma in chicken. This viral infection still circulates in poultry flocks despite the use of vaccines. With the emergence of new virulent strains in the field over time, MDV remains a serious threat to the poultry industry. More than 40 yr after MDV identification as a herpesvirus, the visualization and purification of fully enveloped infectious particles remain a challenge for biologists. The various strategies used to detect such hidden particles by electron microscopy are reviewed herein. It is now generally accepted that the production of cell-free virions only occurs in the feather follicle epithelium and is associated with viral, cellular, or both molecular determinants expressed in this tissue. This tissue is considered the only source of efficient virus shedding into the environment and therefore the origin of successful transmission in birds. In other avian tissues or permissive cell cultures, MDV replication only leads to a very low number of intracellular enveloped virions. In the absence of detectable extracellular enveloped virions in cell culture, the nature of the transmitted infectious material and its mechanisms of spread from cell to cell remain to be deciphered. An attempt is made to bring together the current knowledge on MDV morphogenesis and spread, and new approaches that could help understand MDV morphogenesis are discussed. PMID:23901745

Denesvre, Caroline

2013-06-01

291

West Nile Virus Maps  

NSDL National Science Digital Library

One of the potential effects of global climate change is the spread of disease to new areas, as the vectors of those diseases (e.g., mosquitoes, birds) expand into new locations in response to shifting climate conditions. Although the direct cause of West Nile Virus (WNV) in the United States is not known, the National Atlas of the US Geological Survey (reviewed in the June 26, 1998 Scout Report) has recently launched this new resource on WNV distribution. First documented in the US during the summer of 1999 and previously limited to Africa, Eastern Europe, West Asia, and the Middle East, the West Nile Virus is of danger to humans as it interferes with "normal central nervous system functioning" and can cause encephalitis. This site describes WNV Surveillance Activity for the year 2000 and offers a series of maps highlighting the US distribution of WNV cases found in humans, wild birds, chickens, mosquitoes, and veterinary clinics. A series of links point to further information on the virus.

292

Nipah Virus Infection  

PubMed Central

In 1998, an outbreak of acute encephalitis with high mortality rates among pig handlers in Malaysia led to the discovery of a novel paramyxovirus named Nipah virus. A multidisciplinary investigation that included epidemiology, microbiology, molecular biology, and pathology was pivotal in the discovery of this new human infection. Clinical and autopsy findings were derived from a series of 32 fatal human cases of Nipah virus infection. Diagnosis was established in all cases by a combination of immunohistochemistry (IHC) and serology. Routine histological stains, IHC, and electron microscopy were used to examine autopsy tissues. The main histopathological findings included a systemic vasculitis with extensive thrombosis and parenchymal necrosis, particularly in the central nervous system. Endothelial cell damage, necrosis, and syncytial giant cell formation were seen in affected vessels. Characteristic viral inclusions were seen by light and electron microscopy. IHC analysis showed widespread presence of Nipah virus antigens in endothelial and smooth muscle cells of blood vessels. Abundant viral antigens were also seen in various parenchymal cells, particularly in neurons. Infection of endothelial cells and neurons as well as vasculitis and thrombosis seem to be critical to the pathogenesis of this new human disease.

Wong, Kum Thong; Shieh, Wun-Ju; Kumar, Shalini; Norain, Karim; Abdullah, Wahidah; Guarner, Jeannette; Goldsmith, Cynthia S.; Chua, Kaw Bing; Lam, Sai Kit; Tan, Chong Tin; Goh, Khean Jin; Chong, Heng Thay; Jusoh, Rani; Rollin, Pierre E.; Ksiazek, Thomas G.; Zaki, Sherif R.

2002-01-01

293

Rab9 GTPase Is Required for Replication of Human Immunodeficiency Virus Type 1, Filoviruses, and Measles Virus  

PubMed Central

Rab proteins and their effectors facilitate vesicular transport by tethering donor vesicles to their respective target membranes. By using gene trap insertional mutagenesis, we identified Rab9, which mediates late-endosome-to-trans-Golgi-network trafficking, among several candidate host genes whose disruption allowed the survival of Marburg virus-infected cells, suggesting that Rab9 is utilized in Marburg replication. Although Rab9 has not been implicated in human immunodeficiency virus (HIV) replication, previous reports suggested that the late endosome is an initiation site for HIV assembly and that TIP47-dependent trafficking out of the late endosome to the trans-Golgi network facilitates the sorting of HIV Env into virions budding at the plasma membrane. We examined the role of Rab9 in the life cycles of HIV and several unrelated viruses, using small interfering RNA (siRNA) to silence Rab9 expression before viral infection. Silencing Rab9 expression dramatically inhibited HIV replication, as did silencing the host genes encoding TIP47, p40, and PIKfyve, which also facilitate late-endosome-to-trans-Golgi vesicular transport. In addition, silencing studies revealed that HIV replication was dependent on the expression of Rab11A, which mediates trans-Golgi-to-plasma-membrane transport, and that increased HIV Gag was sequestered in a CD63+ endocytic compartment in a cell line stably expressing Rab9 siRNA. Replication of the enveloped Ebola, Marburg, and measles viruses was inhibited with Rab9 siRNA, although the nonenveloped reovirus was insensitive to Rab9 silencing. These results suggest that Rab9 is an important cellular target for inhibiting diverse viruses and help to define a late-endosome-to-plasma-membrane vesicular transport pathway important in viral assembly.

Murray, James L.; Mavrakis, Manos; McDonald, Natalie J.; Yilla, Mamadi; Sheng, Jinsong; Bellini, William J.; Zhao, Lijun; Le Doux, Joseph M.; Shaw, Michael W.; Luo, Chi-Cheng; Lippincott-Schwartz, Jennifer; Sanchez, Anthony; Rubin, Donald H.; Hodge, Thomas W.

2005-01-01

294

Development of human monoclonal antibodies against diseases caused by emerging and biodefense-related viruses.  

PubMed

Polyclonal antibodies have a century-old history of being effective against some viruses; recently, monoclonal antibodies (mAbs) have also shown success. The humanized mAb Synagis (palivizumab), which is still the only mAb against a viral disease approved by the US FDA, has been widely used as a prophylactic measure against respiratory syncytial virus infections in neonates and immunocompromised individuals. The first fully human mAbs against two other paramyxoviruses, Hendra and Nipah virus, which can cause high (up to 75%) mortality, were recently developed; one of them, m101, showed exceptional potency against infectious virus. In an amazing pace of research, several potent human mAbs targeting the severe acute respiratory syndrome coronavirus S glycoprotein that can affect infections in animal models have been developed months after the virus was identified in 2003. A potent humanized mAb with therapeutic potential was recently developed against the West Nile virus. The progress in developing neutralizing human mAbs against Ebola, Crimean-Congo hemorrhagic fever, vaccinia and other emerging and biodefense-related viruses is slow. A major problem in the development of effective therapeutic agents against viruses, including therapeutic antibodies, is the viruses' heterogeneity and mutability. A related problem is the low binding affinity of crossreactive antibodies able to neutralize a variety of primary isolates. Combinations of mAbs or mAbs with other drugs, and/or the identification of potent new mAbs and their derivatives that target highly conserved viral structures, which are critical for virus entry into cells, are some of the possible solutions to these problems, and will continue to be a major focus of antiviral research. PMID:16441209

Zhu, Zhongyu; Dimitrov, Antony S; Chakraborti, Samitabh; Dimitrova, Dimana; Xiao, Xiaodong; Broder, Christopher C; Dimitrov, Dimiter S

2006-02-01

295

Inhibition of RNA virus infections with peptide-conjugated morpholino oligomers.  

PubMed

RNA virus infections cause immense human disease burdens globally, and few effective antiviral drugs are available for their treatment. Peptide-conjugated phosphorodiamidate morpholino oligomers (PPMO) are nuclease resistant and water-soluble single-stranded-DNA-analogues that can enter cells readily and act as steric-blocking antisense agents through stable duplex formation with complementary RNA. Recently there have been a number of publications documenting sequence-specific and dose-dependent inhibition of non-retroviral RNA virus infections by PPMO in both cell culture and murine experimental systems. PPMO have suppressed viral titers by several orders of magnitude in cell cultures, and have reduced viral replication in and/or increased survivorship of mice experimentally infected with poliovirus, coxsackievirus B3, dengue virus, West Nile virus, Venezuelan Equine encephalitis virus, respiratory syncytial virus, Ebola virus and influenza A virus. Along with evaluating PPMO efficacy and toxicity, these studies also explored PPMO mechanism of action, pharmacologic properties and the generation and characterization of resistant virus. Effective PPMO target sites in viral RNA have included regions of highly conserved sequence thought to be important in the pre-initiation or initiation of translation, or in long-range RNA-RNA interactions involved in viral RNA synthesis. These studies provide guidance for the design of steric-blocking antisense agents against RNA viruses, insights into viral molecular biology and novel strategies for the development of antiviral therapeutics. The purpose of this review is to summarize notable findings from the reports documenting antiviral activity by PPMO, with a focus on the specific regions of viral RNA that provided the most effective targets for PPMO-based inhibition of viral replication. PMID:18991679

Stein, David A

2008-01-01

296

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

297

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

298

Structure of Flexible Filamentous Plant Viruses ?  

PubMed Central

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

2008-01-01

299

Physicochemical Properties of Tipula Iridescent Virus 1  

PubMed Central

The molecular weight of Tipula iridescent virus, based on sedimentation and diffusion coefficients, was 5.51 × 108, with hydration of 0.57 g of water per g of virus. Deoxyribonucleic acid content, based on total inorganic phosphorus liberated, was 19 ± 0.2%. At 260 m?, the virus gave an uncorrected absorbance of 18.2 cm2/mg of virus and a light-scattering corrected absorbance of 9.8 cm2/mg of virus. Amino acid analyses of the virus protein revealed a remarkable similarity to Sericesthis iridescent virus. The possibility is discussed that the four iridescent insect viruses reported to date bear a strain relationship. Images

Kalmakoff, J.; Tremaine, J. H.

1968-01-01

300

Genome of crocodilepox virus.  

PubMed

Here, we present the genome sequence, with analysis, of a poxvirus infecting Nile crocodiles (Crocodylus niloticus) (crocodilepox virus; CRV). The genome is 190,054 bp (62% G+C) and predicted to contain 173 genes encoding proteins of 53 to 1,941 amino acids. The central genomic region contains genes conserved and generally colinear with those of other chordopoxviruses (ChPVs). CRV is distinct, as the terminal 33-kbp (left) and 13-kbp (right) genomic regions are largely CRV specific, containing 48 unique genes which lack similarity to other poxvirus genes. Notably, CRV also contains 14 unique genes which disrupt ChPV gene colinearity within the central genomic region, including 7 genes encoding GyrB-like ATPase domains similar to those in cellular type IIA DNA topoisomerases, suggestive of novel ATP-dependent functions. The presence of 10 CRV proteins with similarity to components of cellular multisubunit E3 ubiquitin-protein ligase complexes, including 9 proteins containing F-box motifs and F-box-associated regions and a homologue of cellular anaphase-promoting complex subunit 11 (Apc11), suggests that modification of host ubiquitination pathways may be significant for CRV-host cell interaction. CRV encodes a novel complement of proteins potentially involved in DNA replication, including a NAD(+)-dependent DNA ligase and a protein with similarity to both vaccinia virus F16L and prokaryotic serine site-specific resolvase-invertases. CRV lacks genes encoding proteins for nucleotide metabolism. CRV shares notable genomic similarities with molluscum contagiosum virus, including genes found only in these two viruses. Phylogenetic analysis indicates that CRV is quite distinct from other ChPVs, representing a new genus within the subfamily Chordopoxvirinae, and it lacks recognizable homologues of most ChPV genes involved in virulence and host range, including those involving interferon response, intracellular signaling, and host immune response modulation. These data reveal the unique nature of CRV and suggest mechanisms of virus-reptile host interaction. PMID:16641289

Afonso, C L; Tulman, E R; Delhon, G; Lu, Z; Viljoen, G J; Wallace, D B; Kutish, G F; Rock, D L

2006-05-01

301

Magnetic Fluorescent Composite Nanoparticles for the Fluoroimmunoassays of Newcastle Disease Virus and Avian Virus Arthritis Virus  

Microsoft Academic Search

A new detection format for multiplexed analysis based on the use of magnetic fluorescent composite nanoparticles was presented\\u000a in this paper. Two different antigens, Newcastle disease virus (NDV) antigen and Avian virus arthritis virus (AVAV) antigen,\\u000a were conjugated to two kinds of magnetic fluorescent composite nanoparticles of different luminescent colors, while red-emitting\\u000a CdTe QDs were attached to the antibody of

Guannan Wang; Ping Xie; Chengrui Xiao; Pingfan Yuan; Xingguang Su

2010-01-01

302

DETECTION OF RETICULOENDOTHELIOSIS VIRUS IN LIVE VIRUS VACCINES OF POULTRY  

Technology Transfer Automated Retrieval System (TEKTRAN)

Reticuloendotheliosis virus (REV) is an avian oncornavirus that is structurally and antigenically unrelated to the leukosis-sarcoma group of viruses. All REV isolates are antigenically related to each other. However, using monoclonal antibodies, REV isolates can be classed into three different subty...

303

Peptide inhibitors of dengue virus and West Nile virus infectivity  

Microsoft Academic Search

Viral fusion proteins mediate cell entry by undergoing a series of conformational changes that result in virion-target cell membrane fusion. Class I viral fusion proteins, such as those encoded by influenza virus and human immunodeficiency virus (HIV), contain two prominent alpha helices. Peptides that mimic portions of these alpha helices inhibit structural rearrangements of the fusion proteins and prevent viral

Yancey M Hrobowski; Robert F Garry; Scott F Michael

2005-01-01

304

Electron microscopy of viruses and virus-cell interactions.  

PubMed

Electron microscopy is a powerful tool to visualize viruses in diagnostic as well as in research settings for investigating viral structure and virus-cell interactions. Here, a simple but efficient method is described for demonstrating viruses by negative staining, and its limit is discussed. A prerequisite to obtain reliable information on virus-cell interactions is excellent preservation of cellular and viral ultrastructure. The crux is that during fixation and embedding, by applying conventional protocols about 50% of the lipids are lost, which results in loss of integrity of cell membranes. To achieve good preservation of cellular architectures, good contrast, and both high spatial and temporal resolution, methods for freezing, freeze-substitution, and freeze-etching are described and their applicability discussed mostly taking complicated built herpes viruses as examples. PMID:18617049

Wild, Peter

2008-01-01

305

Prevalence and transmission of honeybee viruses.  

PubMed

Transmission mechanisms of six honeybee viruses, including acute bee paralysis virus (ABPV), black queen cell virus (BQCV), chronic bee paralysis virus (CBPV), deformed wing virus (DWV), Kashmir bee virus (KBV), and sacbrood bee virus (SBV), in honey bee colonies were investigated by reverse transcription-PCR (RT-PCR) methods. The virus status of individual queens was evaluated by examining the presence of viruses in the queens' feces and tissues, including hemolymph, gut, ovaries, spermatheca, head, and eviscerated body. Except for head tissue, all five tissues as well as queen feces were found to be positive for virus infections. When queens in bee colonies were identified as positive for BQCV, DWV, CBPV, KBV, and SBV, the same viruses were detected in their offspring, including eggs, larvae, and adult workers. On the other hand, when queens were found positive for only two viruses, BQCV and DWV, only these two viruses were detected in their offspring. The presence of viruses in the tissue of ovaries and the detection of the same viruses in queens' eggs and young larvae suggest vertical transmission of viruses from queens to offspring. To our knowledge, this is the first evidence of vertical transmission of viruses in honeybee colonies. PMID:16391097

Chen, Y P; Pettis, J S; Collins, A; Feldlaufer, M F

2006-01-01

306

INFECTIOUS DOSE OF NORWALK VIRUS  

EPA Science Inventory

The Norwalk virus and related viruses (caliciviruses) have been identified as a common cause of waterborne disease. Moreover, there are many outbreaks of waterborne disease every year where the causative agent was never identified, and it is thought that many of these are due to ...

307

Influenza Virus Assembly and Budding  

PubMed Central

Influenza A virus causes seasonal epidemics, sporadic pandemics and is a significant global heath 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, multistep 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.

Rossman, Jeremy S.; Lamb, Robert A.

2011-01-01

308

Preventing zoonotic influenza virus infection.  

PubMed

We evaluated 49 swine industry workers and 79 nonexposed controls for antibodies to swine influenza viruses. Multivariate modeling showed that workers who seldom used gloves (odds ratio [OR] 30.3) or who smoked (OR 18.7) most frequently had evidence of previous H1N1 swine virus. These findings may be valuable in planning for pandemic influenza. PMID:16707061

Ramirez, Alejandro; Capuano, Ana W; Wellman, Debbie A; Lesher, Kelly A; Setterquist, Sharon F; Gray, Gregory C

2006-06-01

309

VIRUS TRANSPORT IN THE SUBSURFACE  

EPA Science Inventory

The importance of virus transport in the subsurface is highlighted by implications to human health as well as drinking water regulations. The structure of virus particles is defined along with their colloidal physiochemical properties and a discussion of their more prominent sou...

310

Swine Influenza Virus: Emerging Understandings  

Technology Transfer Automated Retrieval System (TEKTRAN)

Introduction: In March-April 2009, a novel pandemic H1N1 emerged in the human population in North America [1]. The gene constellation of the emerging virus was demonstrated to be a combination of genes from swine influenza A viruses (SIV) of North American and Eurasian lineages that had never before...

311

West Nile Virus and Wildlife  

Microsoft Academic Search

West Nile virus (WNV) has spread rapidly across North America, resulting in human deaths and in the deaths of untold numbers of birds, mammals, and reptiles. The virus has reached Central America and the Caribbean and may spread to Hawaii and South America. Although tens of thousands of birds have died, and studies of some bird species show local declines,

Peter P. Marra; Sean Griffing; Carolee Caffrey; A. Marm Kilpatrick; Robert McLean; Christopher Brand; Emi Saito; Alan P. Dupuis; Laura Kramer; Robert Novak

2004-01-01

312

Cassava virus diseases in Africa  

Microsoft Academic Search

Cassava plays a key role in the food security of sub-Saharan Africa, but as a vegetatively propagated crop, it is particularly vulnerable to the effects of virus diseases and these therefore represent a major threat to the livelihoods of millions of Africans. Nine viruses have been isolated from African cassava, but only cassava mosaic geminiviruses (CMGs) and Cassava brown streak

J. M. Threshb

313

Cassava virus diseases in Africa  

Microsoft Academic Search

Abstract Cassava plays a key role in the food security of sub-Saharan Africa, but as a vegetatively propagated crop, it is particularly vulnerable to the effects of virus diseases and these therefore represent a major,threat to the livelihoods of millions of Africans. Nine viruses have been isolated from African cassava, but only cassava mosaic geminiviruses (CMGs) and Cassava brown streak

J. p. Legg; J. m. Thresh

314

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

315

Genetic Diversity of Toscana Virus  

PubMed Central

Distribution of Toscana virus (TOSV) is evolving with climate change, and pathogenicity may be higher in nonexposed populations outside areas of current prevalence (Mediterranean Basin). To characterize genetic diversity of TOSV, we determined the coding sequences of isolates from Spain and France. TOSV is more diverse than other well-studied phleboviruses (e.g.,Rift Valley fever virus).

Collao, Ximena; Palacios, Gustavo; Sanbonmatsu-Gamez, Sara; Perez-Ruiz, Mercedes; Negredo, Ana I.; Navarro-Mari, Jose-Maria; Grandadam, Marc; Aransay, Ana Maria; Lipkin, W. Ian; Tenorio, Antonio

2009-01-01

316

Virus-derived transgenes expressing hairpin RNA give immunity to Tobacco mosaic virus and Cucumber mosaic virus  

Microsoft Academic Search

BACKGROUND: An effective method for obtaining resistant transgenic plants is to induce RNA silencing by expressing virus-derived dsRNA in plants and this method has been successfully implemented for the generation of different plant lines resistant to many plant viruses. RESULTS: Inverted repeats of the partial Tobacco mosaic virus (TMV) movement protein (MP) gene and the partial Cucumber mosaic virus (CMV)

Qiong Hu; Yanbing Niu; Kai Zhang; Yong Liu; Xueping Zhou

2011-01-01

317

New aspects of influenza viruses.  

PubMed Central

Influenza virus infections continue to cause substantial morbidity and mortality with a worldwide social and economic impact. The past five years have seen dramatic advances in our understanding of viral replication, evolution, and antigenic variation. Genetic analyses have clarified relationships between human and animal influenza virus strains, demonstrating the potential for the appearance of new pandemic reassortants as hemagglutinin and neuraminidase genes are exchanged in an intermediate host. Clinical trials of candidate live attenuated influenza virus vaccines have shown the cold-adapted reassortants to be a promising alternative to the currently available inactivated virus preparations. Modern molecular techniques have allowed serious consideration of new approaches to the development of antiviral agents and vaccines as the functions of the viral genes and proteins are further elucidated. The development of techniques whereby the genes of influenza viruses can be specifically altered to investigate those functions will undoubtedly accelerate the pace at which our knowledge expands.

Shaw, M W; Arden, N H; Maassab, H F

1992-01-01

318

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

319

EPSTEIN-BARR VIRUS  

PubMed Central

Epstein-Barr virus (EBV)-transformed autologous lymphoblasts were repeatedly inoculated into three squirrel monkeys. Each animal developed the heterophile antibodies of infectious mononucleosis and EBV-specific antibodies. After serologic responses had disappeared or markedly declined, the animals were challenged with either whole cells, cell filtrate, or cell ghosts. Animals challenged with living cells and cell ghosts developed agglutinin responses; the recipient of filtrate did not. The results suggest that EBV induces the appearance of the infectious mononucleosis heterophile antigen on the transformed cell membrane.

Shope, Thomas; Miller, George

1973-01-01

320

Comparison of Immunohistochemistry and Virus Isolation for Diagnosis of West Nile Virus  

PubMed Central

Immunohistochemistry and virus isolation were performed on 1,057 birds. Immunohistochemistry, virus isolation, or both found 325 birds to be West Nile virus positive. Of these, 271 were positive by both methods. These results indicate that virus isolation and immunohistochemistry are approximately equal in their ability to detect West Nile virus.

Ellis, Angela E.; Mead, Daniel G.; Allison, Andrew B.; Gibbs, Samantha E. J.; Gottdenker, Nicole L.; Stallknecht, David E.; Howerth, Elizabeth W.

2005-01-01

321

Pathogenicity and immunogenicity of influenza viruses with genes from the 1918 pandemic virus  

Microsoft Academic Search

The 1918 influenza A H1N1 virus caused the worst pandemic of influenza ever recorded. To better understand the pathogenesis and immunity to the 1918 pandemic virus, we generated recombinant influenza viruses possessing two to five genes of the 1918 influenza virus. Recombinant influenza viruses possessing the hemagglutinin (HA), neuraminidase (NA), matrix (M), nonstructural (NS), and nucleoprotein (NP) genes or any

Terrence M. Tumpey; Adolfo García-Sastre; Jeffery K. Taubenberger; Peter Palese; David E. Swayne; Christopher F. Basler

2004-01-01

322

A Seven-Segmented Influenza A Virus Expressing the Influenza C Virus Glycoprotein HEF  

Microsoft Academic Search

Influenza viruses are classified into three types: A, B, and C. The genomes of A- and B-type influenza viruses consist of eight RNA segments, whereas influenza C viruses only have seven RNAs. Both A and B influenza viruses contain two major surface glycoproteins: the hemagglutinin (HA) and the neuraminidase (NA). Influenza C viruses have only one major surface glycoprotein, HEF

Qinshan Gao; Edward W. A. Brydon; Peter Palese

2008-01-01

323

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

324

STRAWBERRY NECROTIC SHOCK VIRUS: A NEW VIRUS PREVIOUSLY THOUGHT TO BE TOBACCO STREAK VIRUS  

Technology Transfer Automated Retrieval System (TEKTRAN)

Tobacco streak virus (TSV) has a wide host range that exceeds 80 species (Fulton, 1948). Most of the efforts carried out previously comparing TSV isolates was based on immunological relations between them. The isolates of the virus from Fragaria and Rubus have been considered very closely related, ...

325

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

2009-11-11

326

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

327

Pheasant Virus: New Class of Ribodeoxyvirus  

Microsoft Academic Search

Cocultivation of cells derived from embryos of golden pheasants or Amherst pheasants with chicken embryo cells infected with Bryan strain of Rous sarcoma virus resulted in the detection of viruses which appear to be endogenous in these pheasant cells. The pheasant viruses (PV) were similar to avian leukosis-sarcoma viruses (ALSV) in their gross morphology, in the size of their RNA,

T. Hanafusa; H. Hanafusa; C. E. Metroka; W. S. Hayward; C. W. Rettenmier; R. C. Sawyer; R. M. Dougherty; H. S. Distefano

1976-01-01

328

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

329

Polyoma Virus: Production in Bacillus subtilis  

Microsoft Academic Search

Particles of complete polyoma virus are produced in competent Bacillus subtilis incubated with DNA isolated from purified, conventionally grown polyoma virus. The virus grown in B. subtilis is biologically identical to polyoma virus produced by animal cells. Quantitative parameters of the system have been established, and fluctuation tests indicate that viral replication occurs within the infected bacteria.

K. E. Bayreuther; W. R. Romig

1964-01-01

330

Taxonomic Classification of Human Hepatitis B Virus  

Microsoft Academic Search

Summary Sufficient data have accumulated to permit the ICTV Study Group on the Nomenclature of Hepatitis Viruses to recognize human hepatitis B virus as a member of a unique group of viruses and to classify it, together with a number of related animal viruses, into a new family called the Hepadnaviridae. Over the past decade, the International Committee on Taxonomy

Ian D. Gust; Christopher J. Burrell; Anthony G. Coulepis; William S. Robinson; Arie J. Zuckerman

1986-01-01

331

Analysis of Complete Puumala Virus Genome, Finland  

PubMed Central

Puumala virus causes nephropathia epidemica, a rodent-borne zoonosis that is endemic to Europe. We sequenced the complete Puumala virus genome that was directly recovered from a person who died and compared it with those of viruses from local bank voles. The virus strain involved was neither a unique nor rare genetic variant.

Plyusnina, Angelina; Razzauti, Maria; Sironen, Tarja; Niemimaa, Jukka; Vapalahti, Olli; Vaheri, Antti; Henttonen, Heikki

2012-01-01

332

Analysis of complete Puumala virus genome, Finland.  

PubMed

Puumala virus causes nephropathia epidemica, a rodent-borne zoonosis that is endemic to Europe. We sequenced the complete Puumala virus genome that was directly recovered from a person who died and compared it with those of viruses from local bank voles. The virus strain involved was neither a unique nor rare genetic variant. PMID:23171600

Plyusnina, Angelina; Razzauti, Maria; Sironen, Tarja; Niemimaa, Jukka; Vapalahti, Olli; Vaheri, Antti; Henttonen, Heikki; Plyusnin, Alexander

2012-12-01

333

Interference Between the Vaccinal Virus and the Common Rabies Virus (Interference Entre le Virus Vaccinal et le Virus Rabique des Rues).  

National Technical Information Service (NTIS)

An interference between the vaccinal virus and the virus of rabies has been demonstrated using the rabbit. The method of inoculation for the vaccinal virus as well as for the rabies virus was the intradermal method and this method allowed the demonstratio...

J. Vieuchange M. A. Chabaud C. Vialat

1969-01-01

334

Structure of the Ebola VP35 interferon inhibitory domain  

PubMed Central

Ebola viruses (EBOVs) cause rare but highly fatal outbreaks of viral hemorrhagic fever in humans, and approved treatments for these infections are currently lacking. The Ebola VP35 protein is multifunctional, acting as a component of the viral RNA polymerase complex, a viral assembly factor, and an inhibitor of host interferon (IFN) production. Mutation of select basic residues within the C-terminal half of VP35 abrogates its dsRNA-binding activity, impairs VP35-mediated IFN antagonism, and attenuates EBOV growth in vitro and in vivo. Because VP35 contributes to viral escape from host innate immunity and is required for EBOV virulence, understanding the structural basis for VP35 dsRNA binding, which correlates with suppression of IFN activity, is of high importance. Here, we report the structure of the C-terminal VP35 IFN inhibitory domain (IID) solved to a resolution of 1.4 ? and show that VP35 IID forms a unique fold. In the structure, we identify 2 basic residue clusters, one of which is important for dsRNA binding. The dsRNA binding cluster is centered on Arg-312, a highly conserved residue required for IFN inhibition. Mutation of residues within this cluster significantly changes the surface electrostatic potential and diminishes dsRNA binding activity. The high-resolution structure and the identification of the conserved dsRNA binding residue cluster provide opportunities for antiviral therapeutic design. Our results suggest a structure-based model for dsRNA-mediated innate immune antagonism by Ebola VP35 and other similarly constructed viral antagonists.

Leung, Daisy W.; Ginder, Nathaniel D.; Fulton, D. Bruce; Nix, Jay; Basler, Christopher F.; Honzatko, Richard B.; Amarasinghe, Gaya K.

2009-01-01

335

Structure of the Ebola VP35 interferon inhibitory domain.  

PubMed

Ebola viruses (EBOVs) cause rare but highly fatal outbreaks of viral hemorrhagic fever in humans, and approved treatments for these infections are currently lacking. The Ebola VP35 protein is multifunctional, acting as a component of the viral RNA polymerase complex, a viral assembly factor, and an inhibitor of host interferon (IFN) production. Mutation of select basic residues within the C-terminal half of VP35 abrogates its dsRNA-binding activity, impairs VP35-mediated IFN antagonism, and attenuates EBOV growth in vitro and in vivo. Because VP35 contributes to viral escape from host innate immunity and is required for EBOV virulence, understanding the structural basis for VP35 dsRNA binding, which correlates with suppression of IFN activity, is of high importance. Here, we report the structure of the C-terminal VP35 IFN inhibitory domain (IID) solved to a resolution of 1.4 A and show that VP35 IID forms a unique fold. In the structure, we identify 2 basic residue clusters, one of which is important for dsRNA binding. The dsRNA binding cluster is centered on Arg-312, a highly conserved residue required for IFN inhibition. Mutation of residues within this cluster significantly changes the surface electrostatic potential and diminishes dsRNA binding activity. The high-resolution structure and the identification of the conserved dsRNA binding residue cluster provide opportunities for antiviral therapeutic design. Our results suggest a structure-based model for dsRNA-mediated innate immune antagonism by Ebola VP35 and other similarly constructed viral antagonists. PMID:19122151

Leung, Daisy W; Ginder, Nathaniel D; Fulton, D Bruce; Nix, Jay; Basler, Christopher F; Honzatko, Richard B; Amarasinghe, Gaya K

2009-01-02

336

African swine fever virus morphogenesis.  

PubMed

This review summarizes recent structural and molecular biology studies related to the morphogenesis of African swine fever virus (ASFV). ASFV possesses icosahedral morphology and is constituted by four concentric layers: the central nucleoid, the core shell, the inner envelope and the icosahedral capsid. The extracellular virus acquires an external envelope by budding through the plasma membrane. The genes coding for 19 of the 54 structural proteins of the ASFV particle are known and the localization within the virion of 18 of these components has been identified. ASFV morphogenesis occurs in specialized areas in the cytoplasm, named viral factories, which are proximal to the microtubule organization center near the nucleus. Investigations of the different steps of morphogenesis by immunocytochemical and electron microscopy techniques, as well as molecular biology and biochemical studies, have shed light on the formation of the different domains of the virus particle, including the recognition of endoplasmic reticulum membranes as the precursors of the virus inner envelope, the progressive formation of the capsid on the convex face of the inner envelope and the simultaneous assembly of the core shell on the concave side of the envelope, with the pivotal contribution of the virus polyproteins and their proteolytic processing by the virus protease for the development of this latter domain. The use of ASFV inducible recombinants as a tool for the study of the individual function of structural and nonstructural proteins has been determinant to understand their role in virus assembly and has provided new insights into the morphogenetic process. PMID:23059353

Salas, María L; Andrés, Germán

2012-10-08

337

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

338

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

339

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

Code of Federal Regulations, 2013 CFR

...2013-01-01 2013-01-01 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;...

2013-01-01

340

Primary Virus-Cell Interactions in the Immunofluorescence Assay of Venezuelan Equine Encephalomyelitis Virus.  

National Technical Information Service (NTIS)

The conditions under which Venezuelan equine encephalomyelitis (VEE) virus attached to host cells markedly influenced the assay of virus by the fluorescent cell-counting technique. When virus inoculum was centrifuged onto McCoy cell monolayers, approximat...

N. Hahon K. O. Cooke

1967-01-01

341

Morphology and morphogenesis of Soldado virus (Hughes group); similarities with viruses of the Bunyaviridae family  

Microsoft Academic Search

Summary Morphology and morphogenesis of Soldado virus were studied in the brain of infected suckling mice. The results suggest this virus and other viruses of Hughes group may be classified as members of Bunyaviridae family.

C. Chastel; G. Rogues; J.-C. Beaucournu

1979-01-01

342

Why do RNA viruses recombine?  

PubMed Central

Recombination occurs in many RNA viruses and can be of major evolutionary significance. However, rates of recombination vary dramatically among RNA viruses, which can range from clonal to highly recombinogenic. Here, we review the factors that might explain this variation in recombination frequency and show that there is little evidence that recombination is favoured by natural selection to create advantageous genotypes or purge deleterious mutations, as predicted if recombination functions as a form of sexual reproduction. Rather, recombination rates seemingly reflect larger-scale patterns of viral genome organization, such that recombination may be a mechanistic by-product of the evolutionary pressures acting on other aspects of virus biology.

Simon-Loriere, Etienne; Holmes, Edward C.

2012-01-01

343

NEUTRALIZATION OF EPIDEMIC INFLUENZA VIRUS  

PubMed Central

A linear relationship exists between the logarithm of the quantity of epidemic influenza virus neutralized and the logarithm of the quantity of antiserum which is capable of achieving this result. This relationship is the same for the serum of a ferret convalescent from experimental influenza as for the serum of a rabbit immunized with the virus. By means of the linear relationship between virus and antiserum it is possible to determine a fixed, rather than a relative, value for the neutralizing capacity of a serum.

Horsfall, Frank L.

1939-01-01

344

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

345

CROP VIRUSES AND VIRUS DISEASES: A GLOBAL PERSPECTIVE  

Microsoft Academic Search

Viruses were distinguished as a separate group of plant pathogens in the 1890s, as a consequence of pioneering studies in\\u000a Russia and the Netherlands (Bos, 2000). They have since received much attention from plant pathologists and more recently\\u000a from molecular biologists. Nevertheless, the information available on the distribution, prevalence, and importance of plant\\u000a viruses and the diseases they cause is

J. M. Thresh

346

Vesicular Stomatitis Virus and RNA Viruses as Gene Therapy Vectors  

Microsoft Academic Search

The ability of RNA viruses to efficiently reproduce in transformed cells was first recognized nearly 100 yr ago. However,\\u000a it wasn’t until the late 1990s that a resurrection of the interest in the ability of certain viruses to preferentially replicate\\u000a in malignant cells and less so in normal cells occurred, the curiosity being to evaluate whether these agents could be

Glen N. Barber

347

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

348

Simultaneous detection of cucumber mosaic virus, tomato mosaic virus and potato virus Y by flow cytometry.  

PubMed

The simultaneous detection is described of cucumber mosaic virus (CMV), potato virus Y (PVY) and tomato mosaic virus (ToMV) by flow cytometry. Extracts from leaves of healthy and CMV or PVY infected plants were incubated with latex particles, each with a diameter of 3 microm. Extracts from ToMV infected or uninfected plants, however, were incubated with particles, each with a diameter of 6 microm. Beads were washed and incubated in succession with primary and secondary antibodies, the latter labeled with phycoerythrin (PE) or fluorescein (FITC). CMV and PVY were distinguished on the basis of the fluorescence emitted by FITC and PE; ToMV was distinguished from CMV and PVY on the basis of the different diameter (6 microm) of the particles on which it was adsorbed. The three viruses were detected also by another approach. Latex particles with a diameter of 3, 6 and 10 microm were separately sensitized with antibodies specific for CMV, PVY and ToMV. An equal number of sensitized particles was mixed and incubated with the plant extracts containing the three viruses and then with anti-CMV, anti-PVY and anti-ToMV antibodies labeled with FITC. The study describes also a virus purification method based on the use of antibody coated latex particles. The method is simple technically and applicable to the purification of large as well as minute amounts of different viruses (CMV, PVY and ToMV). PMID:9504759

Iannelli, D; D'Apice, L; Cottone, C; Viscardi, M; Scala, F; Zoina, A; Del Sorbo, G; Spigno, P; Capparelli, R

1997-12-01

349

Toscana Virus in Spain  

PubMed Central

Toscana virus (TOSV, Phlebovirus, family Bunyaviridae) infection is one of the most prevalent arboviruses in Spain. Within the objectives of a multidisciplinary network, a study on the epidemiology of TOSV was conducted in Granada, in southern Spain. The overall seroprevalence rate was 24.9%, significantly increasing with age. TOSV was detected in 3 of 103 sandfly pools by viral culture or reverse transcription–polymerase chain reaction from a region of the L gene. Nucleotide sequence homology was 99%–100% in TOSV from vectors and patients and 80%–81% compared to the Italian strain ISS Phl.3. Sequencing of the N gene of TOSV isolates from patients and vectors indicated 87%–88% and 100% homology at the nucleotide and amino acid levels, respectively, compared to the Italian strain. These findings demonstrate the circulation of at least 2 different lineages of TOSV in the Mediterranean basin, the Italian lineage and the Spanish lineage.

Sanbonmatsu-Gamez, Sara; Perez-Ruiz, Mercedes; Collao, Ximena; Sanchez-Seco, Maria Paz; Morillas-Marquez, Francisco; de la Rosa-Fraile, Manuel; Navarro-Mari, Jose Maria; Tenorio, Antonio

2005-01-01

350

Feline immunodeficiency virus latency  

PubMed Central

Despite highly effective anti-retroviral therapy, HIV is thought to persist in patients within long-lived cellular reservoirs in the form of a transcriptionally inactive (latent) integrated provirus. Lentiviral latency has therefore come to the forefront of the discussion on the possibility of a cure for HIV infection in humans. Animal models of lentiviral latency provide an essential tool to study mechanisms of latency and therapeutic manipulation. Of the three animal models that have been described, the feline immunodeficiency virus (FIV)-infected cat is the most recent and least characterized. However, several aspects of this model make it attractive for latency research, and it may be complementary to other model systems. This article reviews what is known about FIV latency and chronic FIV infection and how it compares with that of other lentiviruses. It thereby offers a framework for the usefulness of this model in future research aimed at lentiviral eradication.

2013-01-01

351

Feline immunodeficiency virus latency.  

PubMed

Despite highly effective anti-retroviral therapy, HIV is thought to persist in patients within long-lived cellular reservoirs in the form of a transcriptionally inactive (latent) integrated provirus. Lentiviral latency has therefore come to the forefront of the discussion on the possibility of a cure for HIV infection in humans. Animal models of lentiviral latency provide an essential tool to study mechanisms of latency and therapeutic manipulation. Of the three animal models that have been described, the feline immunodeficiency virus (FIV)-infected cat is the most recent and least characterized. However, several aspects of this model make it attractive for latency research, and it may be complementary to other model systems. This article reviews what is known about FIV latency and chronic FIV infection and how it compares with that of other lentiviruses. It thereby offers a framework for the usefulness of this model in future research aimed at lentiviral eradication. PMID:23829177

McDonnel, Samantha J; Sparger, Ellen E; Murphy, Brian G

2013-07-06

352

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

353

Varicella-zoster virus.  

PubMed Central

Varicella-zoster virus (VZV) is a ubiquitous human alphaherpesvirus that causes varicella (chicken pox) and herpes zoster (shingles). Varicella is a common childhood illness, characterized by fever, viremia, and scattered vesicular lesions of the skin. As is characteristic of the alphaherpesviruses, VZV establishes latency in cells of the dorsal root ganglia. Herpes zoster, caused by VZV reactivation, is a localized, painful, vesicular rash involving one or adjacent dermatomes. The incidence of herpes zoster increases with age or immunosuppression. The VZV virion consists of a nucleocapsid surrounding a core that contains the linear, double-stranded DNA genome; a protein tegument separates the capsid from the lipid envelope, which incorporates the major viral glycoproteins. VZV is found in a worldwide geographic distribution but is more prevalent in temperate climates. Primary VZV infection elicits immunoglobulin G (IgG), IgM, and IgA antibodies, which bind to many classes of viral proteins. Virus-specific cellular immunity is critical for controlling viral replication in healthy and immunocompromised patients with primary or recurrent VZV infections. Rapid laboratory confirmation of the diagnosis of varicella or herpes zoster, which can be accomplished by detecting viral proteins or DNA, is important to determine the need for antiviral therapy. Acyclovir is licensed for treatment of varicella and herpes zoster, and acyclovir, valacyclovir, and famciclovir are approved for herpes zoster. Passive antibody prophylaxis with varicella-zoster immune globulin is indicated for susceptible high-risk patients exposed to varicella. A live attenuated varicella vaccine (Oka/Merck strain) is now recommended for routine childhood immunization.

Arvin, A M

1996-01-01

354

Varicella zoster virus vasculopathy  

PubMed Central

Objective: Varicella zoster virus (VZV) is an under-recognized yet treatable cause of stroke. No animal model exists for stroke caused by VZV infection of cerebral arteries. Thus, we analyzed cerebral and temporal arteries from 3 patients with VZV vasculopathy to identify features that will help in diagnosis and lead to a better understanding of VZV-induced vascular remodeling. Methods: Normal and VZV-infected cerebral and temporal arteries were examined histologically and by immunohistochemistry using antibodies directed against VZV, endothelium, and smooth muscle actin and myosin. Results: All VZV-infected arteries contained 1) a disrupted internal elastic lamina; 2) a hyperplastic intima composed of cells expressing ?-smooth muscle actin (?-SMA) and smooth muscle myosin heavy chain (SM-myosin) but not endothelial cells expressing CD31; and 3) decreased medial smooth muscle cells. The location of VZV antigen, degree of neointimal thickening, and disruption of the media were related to the duration of disease. Conclusions: The presence of VZV primarily in the adventitia early in infection and in the media and intima later supports the notion that after reactivation from ganglia, VZV spreads transaxonally to the arterial adventitia followed by transmural spread of virus. Disruption of the internal elastic lamina, progressive intimal thickening with cells expressing ?-SMA and SM-MHC, and decreased smooth muscle cells in the media are characteristic features of VZV vasculopathy. Stroke in VZV vasculopathy may result from changes in arterial caliber and contractility produced in part by abnormal accumulation of smooth muscle cells and myofibroblasts in thickened neointima and disruption of the media.

Nagel, M.A.; Traktinskiy, I.; Azarkh, Y.; Kleinschmidt- DeMasters, B.; Hedley-Whyte, T.; Russman, A.; VanEgmond, E.M.; Stenmark, K.; Frid, M.; Mahalingam, R.; Wellish, M.; Choe, A.; Cordery-Cotter, R.; Cohrs, R.J.

2011-01-01

355

Japanese Encephalitis Virus Vaccine Inactivated  

Center for Biologics Evaluation and Research (CBER)

... Complete List of Vaccines Licensed for Immunization and Distribution in the US. -. Japanese Encephalitis Virus Vaccine Inactivated. -. JE-Vax. -. -. -. ... More results from www.fda.gov/biologicsbloodvaccines/vaccines/approvedproducts

356

Viruses in Soil and Groundwater.  

National Technical Information Service (NTIS)

Human viruses usually gain access to soil systems through intentional or unintentional discharges of domestic wastewater. Intentional land treatment/disposal systems represent an attractive alternative to surface water discharges, providing both economic ...

J. M. Vaughn E. F. Landry

1981-01-01

357

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

358

Feasibility Study: Rubella Virus Vaccine.  

National Technical Information Service (NTIS)

The attenuated strain of rubella virus, was serially passed 14 times in AGMK cells and the markers of attenuation were verified. Rubella hemagglutinin and complement fixing antigen were produced in good titers in BHK-21 cells in sufficient quantities for ...

R. G. Brackett

1967-01-01

359

Virus Diseases of Small Fruits,  

National Technical Information Service (NTIS)

The illustrated handbook was compiled by international authorities on virus and viruslike diseases of small fruits. Crops covered are in the plant genera Fragaria (strawberry), Vaccinium (blueberry and cranberry), Ribes (currant and gooseberry), and Rubus...

R. H. Converse

1987-01-01

360

MEASLES VIRUS VACCINE LIVE (ATTENUVAX)  

Center for Biologics Evaluation and Research (CBER)

Text Version... Measles is a common childhood disease, caused by measles virus (paramyxovirus), that may be associated with serious complications and/or ... More results from www.fda.gov/downloads/biologicsbloodvaccines/vaccines

361

Bronchiolitis and Respiratory Syncytial Virus  

MedlinePLUS

ADVICE FOR PATIENTS Bronchiolitis and Respiratory Syncytial Virus B ronchiolitis is an infection that affects the lungs and breathing passages; the name “bronchiolitis” means inflammation of the small airways in the ...

362

Rapid Detection of Enveloped Viruses.  

National Technical Information Service (NTIS)

This report discusses the continuing effort to enhance the sensitivity of type A influenza virus detection systems utilizing the monoclonal antibodies to M-protein. Combinations of purified monoclonal antibodies to M-protein used as capture antibodies for...

D. J. Bucher

1986-01-01

363

Russian winter wheat mosaic virus  

Technology Transfer Automated Retrieval System (TEKTRAN)

The chapter contains a description of the Winter wheat (Russian) mosaic disease symptoms, transmission and occurrence. Characteristics of the disease agent, Winter wheat (Russian) mosaic virus are outlined, as are control measures....

364

Viroids and hepatitis delta virus.  

PubMed

There is a subviral world, whose most prominent representatives are viroids. Despite being solely composed by a circular, highly structured RNA of ~250 to 400 nucleotides without protein-coding ability (all viruses code for one or more proteins), viroids can infect and incite specific diseases in higher plants. The RNA of human hepatitis delta virus (HDV), the smallest genome of an animal virus, displays striking similarities with viroids: It is circular, folds into a rodlike secondary structure, and replicates through a rolling-circle mechanism catalyzed by host enzymes and cis-acting ribozymes. However, HDV RNA is larger (~1700 nucleotides), encodes a protein in its antigenomic polarity (the ? antigen), and depends for transmission on hepatitis B virus. The presence of ribozymes in some viroids and in HDV RNA, along with their structural simplicity, makes them candidates for being molecular fossils of the RNA world that presumably preceded our extant world based on DNA and proteins. PMID:22932968

Flores, Ricardo; Ruiz-Ruiz, Susana; Serra, Pedro

2012-08-29

365

Arthropod viruses and small RNAs.  

PubMed

The recently characterized small RNAs provide a new paradigm for physiological studies. These molecules have been shown to be integral players in processes as diverse as development and innate immunity against bacteria and viruses in eukaryotes. Several of the well-characterized small RNAs including small interfering RNAs, microRNAs and PIWI-interacting RNAs are emerging as important players in mediating arthropod host-virus interactions. Understanding the role of small RNAs in arthropod host-virus molecular interactions will facilitate manipulation of these pathways for both management of arthropod pests of agricultural and medical importance, and for protection of beneficial arthropods such as honey bees and shrimp. This review highlights recent research on the role of small RNAs in arthropod host-virus interactions with reference to other host-pathogen systems. PMID:23932976

Vijayendran, Diveena; Airs, Paul M; Dolezal, Kelly; Bonning, Bryony C

2013-08-08

366

Overview of hepatitis E virus  

Microsoft Academic Search

Hepatitis E virus (HEV) is an enterically transmitted virus usually presenting as an acute self-limiting disease. However,\\u000a mortality increases dramatically from around 1% to 20% in pregnant women. HEV has been the cause of very large outbreaks of\\u000a hepatitis in developing countries and is also responsible for a significant number of sporadic cases. It is clear that cases\\u000a occur outside

Susan Skidmore

2002-01-01

367

Measles virus antigen in panencephalitis  

Microsoft Academic Search

In a retrospective study of 42 cases with a histopathologic diagnosis of subacute sclerosing panencephalitis (SSPE) or similar panencephalitic processes, measles virus antigen was traced by means of indirect immunofluorescence (IF) and peroxidase-antiperoxidase (PAP) techniques on protease-pretreated histological sections from formol-fixed, paraffin-embedded brain biopsy or autopsy tissue, stored for up to 32 years. Measles virus antigen was detected in 28

H. Budka; H. Lassmann; Th. Popow-Kraupp

1982-01-01

368

Simian virus 40 in humans  

Microsoft Academic Search

Simian virus 40 (SV40) is a monkey virus that was administered to human populations by contaminated vaccines which were produced in SV40 naturally infected monkey cells. Recent molecular biology and epidemiological studies suggest that SV40 may be contagiously transmitted in humans by horizontal infection, independently from the earlier administration of SV40-contaminated vaccines. SV40 footprints in humans have been found associated

Fernanda Martini; Alfredo Corallini; Veronica Balatti; Silvia Sabbioni; Cecilia Pancaldi; Mauro Tognon

2007-01-01

369

Plant Viruses Transmitted by Whiteflies  

Microsoft Academic Search

One-hundred and fourteen virus species are transmitted by whiteflies (family Aleyrodidae). Bemisia tabaci transmits 111 of these species while Trialeurodes vaporariorum and T. abutilonia transmit three species each. B. tabaci and T. vaporariorum are present in the European–Mediterranean region, though the former is restricted in its distribution. Of the whitefly-transmitted virus species, 90% belong to the Begomovirus genus, 6% to

David R. Jones

2003-01-01

370

Transient inhibition of polyoma virus synthesis by sendai virus (parainfluenza I). II. Mechanism of the interference by inactivated virus.  

PubMed

The mechanism of the transient inhibition of polyoma virus synthesis by betapropiolactone-inactivated Sendai virus was studied. Polyoma virus early functions did not appear to be affected, although deoxyribonucleic acid (DNA) and structural protein synthesis were inhibited 60 and 35% respectively. The inhibition of macromolecular synthesis was not sufficient to account for the 90% inhibition of infectious progeny formation. Encapsidation of polyoma DNA into mature virions appears to be completely inhibited after superinfection by beta-propiolactone-inactivated Sendai virus. Ultraviolet irradiation of live or beta-propiolactone-inactivated Sendai virus preparations abolishes the interfering capacity, indicating that a functional Sendai virus ribonucleic acid molecule is the interfering component. PMID:4345489

Smith, G L; Consigli, R A

1972-12-01

371

Transient Inhibition of Polyoma Virus Synthesis by Sendai Virus (Parainfluenza I) II. Mechanism of the Interference by Inactivated Virus 1  

PubMed Central

The mechanism of the transient inhibition of polyoma virus synthesis by betapropiolactone-inactivated Sendai virus was studied. Polyoma virus early functions did not appear to be affected, although deoxyribonucleic acid (DNA) and structural protein synthesis were inhibited 60 and 35% respectively. The inhibition of macromolecular synthesis was not sufficient to account for the 90% inhibition of infectious progeny formation. Encapsidation of polyoma DNA into mature virions appears to be completely inhibited after superinfection by beta-propiolactone-inactivated Sendai virus. Ultraviolet irradiation of live or beta-propiolactone-inactivated Sendai virus preparations abolishes the interfering capacity, indicating that a functional Sendai virus ribonucleic acid molecule is the interfering component.

Smith, Gary L.; Consigli, Richard A.

1972-01-01

372

Virus detection using nanoelectromechanical devices  

NASA Astrophysics Data System (ADS)

We have used a resonating mechanical cantilever to detect immunospecific binding of viruses, captured from liquid. As a model virus, we used a nonpathogenic insect baculovirus to test the ability to specifically bind and detect small numbers of virus particles. Arrays of surface micromachined, antibody-coated polycrystalline silicon nanomechanical cantilever beams were used to detect binding from various concentrations of baculoviruses in a buffer solution. Because of their small mass, the 0.5 ?m×6 ?m cantilevers have mass sensitivities on the order of 10-19 g/Hz, enabling the detection of an immobilized AcV1 antibody monolayer corresponding to a mass of about 3×10-15 g. With these devices, we can detect the mass of single-virus particles bound to the cantilever. Resonant frequency shift resulting from the adsorbed mass of the virus particles distinguished solutions of virus concentrations varying between 105 and 107 pfu/ml. Control experiments using buffer solutions without baculovirus showed small amounts (<50 attograms) of nonspecific adsorption to the antibody layer.

Ilic, B.; Yang, Y.; Craighead, H. G.

2004-09-01

373

Virus-Like Particles, Methods of Preparation, and Immunogenic Compositions.  

National Technical Information Service (NTIS)

Briefly described, virus-like particles, methods of preparing virus-like particles, immunogenic compositions that include virus-like particles, and methods of liciting an immune response using immunogenic compositions that include virus-like particles are...

C. Yang Q. Yao R. W. Compans S. M. Kang

2003-01-01

374

9 CFR 113.203 - Feline Panleukopenia Vaccine, Killed Virus.  

Code of Federal Regulations, 2010 CFR

...2010-01-01 2010-01-01 false Feline Panleukopenia Vaccine, Killed Virus. 113.203...Killed Virus Vaccines § 113.203 Feline Panleukopenia Vaccine, Killed Virus. Feline Panleukopenia Vaccine, Killed Virus,...

2010-01-01

375

9 CFR 113.203 - Feline Panleukopenia Vaccine, Killed Virus.  

Code of Federal Regulations, 2010 CFR

...2009-01-01 2009-01-01 false Feline Panleukopenia Vaccine, Killed Virus. 113.203...Killed Virus Vaccines § 113.203 Feline Panleukopenia Vaccine, Killed Virus. Feline Panleukopenia Vaccine, Killed Virus,...

2009-01-01

376

Polynucleotide Ligase Activity in Cells Infected with Simian Virus 40, Polyoma Virus, or Vaccinia Virus  

PubMed Central

The conversion of simian virus 40 (SV40) component II deoxyribonucleic acid to component I has been used to assay polynucleotide ligase in extracts of tissue culture cells. All cell types examined, including chicken, hamster, mouse, monkey, and human cells, contained adenosine triphosphate-dependent ligase. After infection of mouse embryo, monkey kidney, and HeLa cells with polyoma virus, SV40, and vaccinia virus, respectively, the enzyme activity increased, but its cofactor requirement was unchanged. In vaccinia virus-infected cells, the increased activity was localized in the cytoplasm. Ligase induction occurred in the presence of cytosine arabinoside but was prevented by puromycin. Rifampicin blocked the production of infectious vaccinia particles but had little effect on the induction of ligase.

Sambrook, J.; Shatkin, A. J.

1969-01-01

377

Structural basis for dsRNA recognition and interferon antagonism by Ebola VP35  

PubMed Central

Summary The VP35 protein encoded by the highly pathogenic Ebola virus facilitates immune evasion by antagonizing antiviral signaling pathways, including those initiated by RIG-I like receptors. Here we report the crystal structure of Ebola VP35 interferon inhibitory domain (IID) bound to short double-stranded RNA (dsRNA), which reveals how VP35-dsRNA interactions contribute to immune evasion, and corresponding in vivo studies. Conserved basic residues in VP35 IID recognize the dsRNA backbone, whereas the dsRNA blunt ends are “end-capped” by a pocket of hydrophobic residues that mimics blunt end dsRNA recognition by RIG-I-like receptors. Residues that are critical for RNA binding are also important for interferon inhibition in vivo, but not for viral polymerase co-factor function of VP35. These results suggest that simultaneous recognition of dsRNA backbone and blunt ends provides a mechanism by which Ebola VP35 antagonizes host dsRNA sensors and immune responses.

Leung, Daisy W.; Prins, Kathleen C.; Borek, Dominika M.; Farahbakhsh, Mina; Tufariello, JoAnn M.; Ramanan, Parameshwaran; Nix, Jay C.; Helgeson, Luke; Otwinowski, Zbyszek; Honzatko, Richard B.; Basler, Christopher F.; Amarasinghe, Gaya K.

2010-01-01

378

Structure of viruses: a short history.  

PubMed

This review is a partially personal account of the discovery of virus structure and its implication for virus function. Although I have endeavored to cover all aspects of structural virology and to acknowledge relevant individuals, I know that I have favored taking examples from my own experience in telling this story. I am anxious to apologize to all those who I might have unintentionally offended by omitting their work. The first knowledge of virus structure was a result of Stanley's studies of tobacco mosaic virus (TMV) and the subsequent X-ray fiber diffraction analysis by Bernal and Fankuchen in the 1930s. At about the same time it became apparent that crystals of small RNA plant and animal viruses could diffract X-rays, demonstrating that viruses must have distinct and unique structures. More advances were made in the 1950s with the realization by Watson and Crick that viruses might have icosahedral symmetry. With the improvement of experimental and computational techniques in the 1970s, it became possible to determine the three-dimensional, near-atomic resolution structures of some small icosahedral plant and animal RNA viruses. It was a great surprise that the protecting capsids of the first virus structures to be determined had the same architecture. The capsid proteins of these viruses all had a 'jelly-roll' fold and, furthermore, the organization of the capsid protein in the virus were similar, suggesting a common ancestral virus from which many of today's viruses have evolved. By this time a more detailed structure of TMV had also been established, but both the architecture and capsid protein fold were quite different to that of the icosahedral viruses. The small icosahedral RNA virus structures were also informative of how and where cellular receptors, anti-viral compounds, and neutralizing antibodies bound to these viruses. However, larger lipid membrane enveloped viruses did not form sufficiently ordered crystals to obtain good X-ray diffraction. Starting in the 1990s, these enveloped viruses were studied by combining cryo-electron microscopy of the whole virus with X-ray crystallography of their protein components. These structures gave information on virus assembly, virus neutralization by antibodies, and virus fusion with and entry into the host cell. The same techniques were also employed in the study of complex bacteriophages that were too large to crystallize. Nevertheless, there still remained many pleomorphic, highly pathogenic viruses that lacked the icosahedral symmetry and homogeneity that had made the earlier structural investigations possible. Currently some of these viruses are starting to be studied by combining X-ray crystallography with cryo-electron tomography. PMID:23889891

Rossmann, Michael G

2013-05-01

379

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

380

Occurrence of Six Honeybee Viruses in Diseased Austrian Apiaries  

Microsoft Academic Search

The occurrence, prevalence, and distribution patterns of acute bee paralysis virus (ABPV), black queen cell virus (BQCV), chronic bee paralysis virus (CBPV), deformed wing virus (DWV), Kashmir bee virus (KBV), and sacbrood virus (SBV) were investigated in 90 Austrian honeybee colonies suffering from symptoms of depop- ulation, sudden collapse, paralysis, or dark coloring by employing reverse transcription-PCR. Infestation with parasites

Olga Berenyi; Tamas Bakonyi; Irmgard Derakhshifar; Hemma Koglberger; Norbert Nowotny

2006-01-01

381

Stochastic analysis of virus transport in aquifers  

USGS Publications Warehouse

A large-scale model of virus transport in aquifers is derived using spectral perturbation analysis. The effects of spatial variability in aquifer hydraulic conductivity and virus transport (attachment, detachment, and inactivation) parameters on large-scale virus transport are evaluated. A stochastic mean model of virus transport is developed by linking a simple system of local-scale free-virus transport and attached-virus conservation equations from the current literature with a random-field representation of aquifer and virus transport properties. The resultant mean equations for free and attached viruses are found to differ considerably from the local-scale equations on which they are based and include effects such as a free-virus effective velocity that is a function of aquifer heterogeneity as well as virus transport parameters. Stochastic mean free-virus breakthrough curves are compared with local model output in order to observe the effects of spatial variability on mean one-dimensional virus transport in three-dimensionally heterogeneous porous media. Significant findings from this theoretical analysis include the following: (1) Stochastic model breakthrough occurs earlier than local model breakthrough, and this effect is most pronounced for the least conductive aquifers studied. (2) A high degree of aquifer heterogeneity can lead to virus breakthrough actually preceding that of a conservative tracer. (3) As the mean hydraulic conductivity is increased, the mean model shows less sensitivity to the variance of the natural-logarithm hydraulic conductivity and mean virus diameter. (4) Incorporation of a heterogeneous colloid filtration term results in higher predicted concentrations than a simple first-order adsorption term for a given mean attachment rate. (5) Incorporation of aquifer heterogeneity leads to a greater range of virus diameters for which significant breakthrough occurs. (6) The mean model is more sensitive to the inactivation rate of viruses associated with solid surfaces than to the inactivation rate of viruses in solution.

Campbell, Rehmann, L. L.; Welty, C.; Harvey, R. W.

1999-01-01

382

Recombinant infectious bursal disease virus carrying hepatitis C virus epitopes.  

PubMed

The delivery of foreign epitopes by a replicating nonpathogenic avian infectious bursal disease virus (IBDV) was explored. The aim of the study was to identify regions in the IBDV genome that are amenable to the introduction of a sequence encoding a foreign peptide. By using a cDNA-based reverse genetics system, insertions or substitutions of sequences encoding epitope tags (FLAG, c-Myc, or hepatitis C virus epitopes) were engineered in the open reading frames of a nonstructural protein (VP5) and the capsid protein (VP2). Attempts were also made to generate recombinant IBDV that displayed foreign epitopes in the exposed loops (P(BC) and P(HI)) of the VP2 trimer. We successfully recovered recombinant IBDVs expressing c-Myc and two different virus-neutralizing epitopes of human hepatitis C virus (HCV) envelope glycoprotein E in the VP5 region. Western blot analyses with anti-c-Myc and anti-HCV antibodies provided positive identification of both the c-Myc and HCV epitopes that were fused to the N terminus of VP5. Genetic analysis showed that the recombinants carrying the c-Myc/HCV epitopes maintained the foreign gene sequences and were stable after several passages in Vero and 293T cells. This is the first report describing efficient expression of foreign peptides from a replication-competent IBDV and demonstrates the potential of this virus as a vector. PMID:21106739

Upadhyay, Chitra; Ammayappan, Arun; Patel, Deendayal; Kovesdi, Imre; Vakharia, Vikram N

2010-11-24

383

Emerging and Re-emerging Swine Viruses.  

PubMed

In the past two decades or so, a number of viruses have emerged in the global swine population. Some, such as porcine reproductive and respiratory syndrome virus (PRRSV) and porcine circovirus type 2 (PCV2), cause economically important diseases in pigs, whereas others such as porcine torque teno virus (TTV), now known as Torque teno sus virus (TTSuV), porcine bocavirus (PBoV) and related novel parvoviruses, porcine kobuvirus, porcine toroviruses (PToV) and porcine lymphotropic herpesviruses (PLHV), are mostly subclinical in swine herds. Although some emerging swine viruses such as swine hepatitis E virus (swine HEV), porcine endogenous retrovirus (PERV) and porcine sapovirus (porcine SaV) may have a limited clinical implication in swine health, they do pose a potential public health concern in humans due to zoonotic (swine HEV) or potential zoonotic (porcine SaV) and xenozoonotic (PERV, PLHV) risks. Other emerging viruses such as Nipah virus, Bungowannah virus and Menangle virus not only cause diseases in pigs but some also pose important zoonotic threat to humans. This article focuses on emerging and re-emerging swine viruses that have a limited or uncertain clinical and economic impact on pig health. The transmission, epidemiology and pathogenic potential of these viruses are discussed. In addition, the two economically important emerging viruses, PRRSV and PCV2, are also briefly discussed to identify important knowledge gaps. PMID:22225855

Meng, X J

2012-01-01

384

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

385

Phylogenetic Properties of RNA Viruses  

PubMed Central

A new word, phylodynamics, was coined to emphasize the interconnection between phylogenetic properties, as observed for instance in a phylogenetic tree, and the epidemic dynamics of viruses, where selection, mediated by the host immune response, and transmission play a crucial role. The challenges faced when investigating the evolution of RNA viruses call for a virtuous loop of data collection, data analysis and modeling. This already resulted both in the collection of massive sequences databases and in the formulation of hypotheses on the main mechanisms driving qualitative differences observed in the (reconstructed) evolutionary patterns of different RNA viruses. Qualitatively, it has been observed that selection driven by the host immune response induces an uneven survival ability among co-existing strains. As a consequence, the imbalance level of the phylogenetic tree is manifestly more pronounced if compared to the case when the interaction with the host immune system does not play a central role in the evolutive dynamics. While many imbalance metrics have been introduced, reliable methods to discriminate in a quantitative way different level of imbalance are still lacking. In our work, we reconstruct and analyze the phylogenetic trees of six RNA viruses, with a special emphasis on the human Influenza A virus, due to its relevance for vaccine preparation as well as for the theoretical challenges it poses due to its peculiar evolutionary dynamics. We focus in particular on topological properties. We point out the limitation featured by standard imbalance metrics, and we introduce a new methodology with which we assign the correct imbalance level of the phylogenetic trees, in agreement with the phylodynamics of the viruses. Our thorough quantitative analysis allows for a deeper understanding of the evolutionary dynamics of the considered RNA viruses, which is crucial in order to provide a valuable framework for a quantitative assessment of theoretical predictions.

Pompei, Simone; Loreto, Vittorio; Tria, Francesca

2012-01-01

386

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

387

Adeno-associated viruses.  

PubMed

Adeno-associated virus (AAV) vectors have evolved over the past decade as a particularly useful gene -vector for in vivo applications. In contrast to oncoretro- and lentiviral vectors, this vector stays essentially episomal after gene transfer, making it safer because of the absence of insertional mutagenesis. AAV's non-pathogenicity is a further advantage. For decades, this vector could only be produced at a small scale for research purposes and, eventually, used at very small doses for clinical studies, because only transfection methods were available, which have limited scalability. However, since the development of scalable production methods, this bottleneck is resolved and, from a technical point of view, large quantities of AAV vectors can be produced, opening the possibility of using AAV vectors for whole body treatments in gene therapy trials. This chapter presents the basic principles of small- and large-scale production procedures as well as detailed procedure of small-scale production, purification, and analytical protocols for AAV vectors. In Chapter 10, the reader will find a large-scale production method based on the use of the insect cell/baculovirus system. PMID:21590399

Mezzina, Mauro; Merten, Otto-Wilhelm

2011-01-01

388

Virus-Induced Neuronal Apoptosis Blocked by the Herpes Simplex Virus Latency-Associated Transcript  

Microsoft Academic Search

Latent infections with periodic reactivation are a common outcome after acute infection with many viruses. The latency-associated transcript (LAT) gene is required for wild-type reactivation of herpes simplex virus (HSV). However, the underlying mechanisms remain unclear. In rabbit trigeminal ganglia, extensive apoptosis occurred with LAT- virus but not with LAT+ viruses. In addition, a plasmid expressing LAT blocked apoptosis in

Guey-Chuen Perng; Clinton Jones; Janice Ciacci-Zanella; Melissa Stone; Gail Henderson; Ada Yukht; Susan M. Slanina; Florence M. Hofman; Homayon Ghiasi; Anthony B. Nesburn; Steven L. Wechsler

2000-01-01

389

Synthesis of Virus-Specific Proteins in Cells Infected with Venezuelan Equine Encephalomyelitis Virus.  

National Technical Information Service (NTIS)

The use of polyacrylamide jells has facilitated the investigation of virus-specific proteins both in the form of virions and in cells infected by the virus. This method has made possible the separation of virus-specific proteins of the polio-virus and the...

F. I. Ershov L. V. Uryvaev V. M. Zhdanov

1971-01-01

390

Mechanisms for enveloped virus budding: Can some viruses do without an ESCRT?  

Microsoft Academic Search

Many enveloped viruses complete their replication cycle by forming vesicles that bud from the plasma membrane. Some viruses encode “late” (L) domain motifs that are able to hijack host proteins involved in the vacuolar protein sorting (VPS) pathway, a cellular budding process that gives rise to multivesicular bodies and that is topologically equivalent to virus budding. Although many enveloped viruses

Benjamin J. Chen; Robert A. Lamb

2008-01-01

391

Protection against respiratory infection with bovine virus diarrhoea virus by passively acquired antibody  

Microsoft Academic Search

Howard, C. J., Clarke, M. C. and Brownlie, J., 1989. Protection against respiratory infection with bovine virus diarrhoea virus by passively acquired antibody. Vet. Microbiol., 19: 195-203. Susceptibility to infection with bovine virus diarrhoea virus (BVDV) was compared for calves with varying amounts of specific antibody in their sera passively acquired from the ingestion of colostrum. Challenge consisted of intranasal

C. J. HOWARD; M. C. CLARKE; J. BROWNLIE

1989-01-01

392

Sendai Virus and Herpes Virus Type 1 Induce Apoptosis in Human Peripheral Blood Mononuclear Cells  

Microsoft Academic Search

Recent reports suggest that several viruses, besides human immunodeficiency virus, induce apoptosis in infected cells. We report here that Sendai virus or Herpes simplex virus type 1 (HSV-1), two potent inducers of interferon-?, caused cell death in a consistent number of human peripheral blood mononuclear cells. A careful analysis of infected cells by different techniques, such as optical and electron

Franco Tropea; Leonarda Troiano; Daniela Monti; Elena Lovato; Walter Malorni; Gabriella Rainaldi; Paolo Mattana; Giuseppe Viscomi; Maria Cristina Ingletti; Marinella Portolani; Claudio Cermelli; Andrea Cossarizza; Claudio Franceschi

1995-01-01

393

Kupe Virus, a New Virus in the Family Bunyaviridae, Genus Nairovirus, Kenya  

Microsoft Academic Search

We have previously described isolation and preliminary identification of a virus related to Dugbe virus (DUGV), family Bunyaviridae, genus Nairovirus. Six isolates of the virus were obtained from pools of Amblyomma gemma and Rhipicephalus pulchellus ticks collected from hides of cattle in Nairobi, Kenya, in October 1999. We report results of further characterization of this virus, including growth kinetics in

Mary B. Crabtree; Rosemary Sang; Barry R. Miller

2009-01-01

394

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

395

Nyamanini and Midway Viruses Define a Novel Taxon of RNA Viruses in the Order Mononegavirales  

Microsoft Academic Search

Here, we report the sequencing and classification of Nyamanini virus (NYMV) and Midway virus (MIDWV), two antigenically related viruses that were first isolated in 1957 and 1966, respectively. Although these viruses have been cultured multiple times from cattle egrets, seabirds, and their ticks, efforts to classify them taxonomically using conventional serological and electron microscopic approaches have failed completely. We used

Kathie A. Mihindukulasuriya; Nang L. Nguyen; Guang Wu; Henry V. Huang; Vsevolod L. Popov; Robert B. Tesh; David Wang

2009-01-01

396

GENOMIC SEQUENCING OF DEER TICK VIRUS AND PHYLOGENY OF POWASSAN-RELATED VIRUSES OF NORTH AMERICA  

Microsoft Academic Search

Powassan (POW) virus is responsible for central nervous system infection in humans in North America and the eastern parts of Russia. Recently, a new flavivirus, deer tick (DT) virus, related to POW virus was isolated in the United States, but neither its pathogenic potential in human nor the taxonomic relationship with POW virus has been elucidated. In this study, we

G. KUNO; H. ARTSOB; N. KARABATSOS; K. R. TSUCHIYA; G. J. J. CHANG

2001-01-01

397

GB virus C\\/hepatitis G virus replicates in human haematopoietic cells and vascular endothelial cells  

Microsoft Academic Search

A novel flavivirus, GB virus C (GBV-C)\\/hepatitis G virus (HGV), has been detected in chronic liver disease patients. It is known that the viral RNA can be detected in C 5% of American blood donors. However, the implications for liver disease and the sites of virus replication remain unknown. Possible sites of virus replication were studied by using cell lines

Atsushi Handa; Kevin E. Brown

398

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

399

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

400

Realistic Approach to Virus Classification and Nomenclature  

Microsoft Academic Search

Prompted by Professor Lwoff's article ``Principles of Classification and Nomenclature of Viruses'' (Nature, 215, 13; 1967), Drs Gibbs and Harrison defend the idea of the cryptogram, and explain its advantage over a binomial system of nomenclature for viruses.

A. J. Gibbs

1968-01-01

401

Predicting "Airborne" Influenza Viruses: (Trans-) mission Impossible?  

PubMed Central

Repeated transmission of animal influenza viruses to humans has prompted investigation of the viral, host, and environmental factors responsible for transmission via aerosols or respiratory droplets. How do we determine – out of thousands of influenza virus isolates collected in animal surveillance studies each year – which viruses have the potential to become “airborne”, and hence pose a pandemic threat? Here, using knowledge from pandemic, zoonotic and epidemic viruses, we postulate that the minimal requirements for efficient transmission of an animal influenza virus between humans are: efficient virus attachment to (upper) respiratory tissues, replication to high titers in these tissues, and release and aerosolization of single virus particles. Investigating “airborne” transmission of influenza viruses is key to understand – and predict – influenza pandemics.

Sorrell, E.M.; Schrauwen, E.J.A.; Linster, M.; De Graaf, M.; Herfst, S.; Fouchier, R.A.M.

2011-01-01

402

Recombination and Transmission Studies with Influenza Virus.  

National Technical Information Service (NTIS)

Transmission of influenza virus infection in mice can be correlated with demonstrable airborne virus in the vicinity of infector mice during the period of their infectiousness; the critical difference that distinguishes transmissible and non-transmissible...

E. D. Kilbourne

1966-01-01

403

Predicting 'airborne' influenza viruses: (trans-) mission impossible?  

PubMed

Repeated transmission of animal influenza viruses to humans has prompted investigation of the viral, host, and environmental factors responsible for transmission via aerosols or respiratory droplets. How do we determine-out of thousands of influenza virus isolates collected in animal surveillance studies each year-which viruses have the potential to become 'airborne', and hence pose a pandemic threat? Here, using knowledge from pandemic, zoonotic and epidemic viruses, we postulate that the minimal requirements for efficient transmission of an animal influenza virus between humans are: efficient virus attachment to (upper) respiratory tissues, replication to high titers in these tissues, and release and aerosolization of single virus particles. Investigating 'airborne' transmission of influenza viruses is key to understand-and predict-influenza pandemics. PMID:22440921

Sorrell, E M; Schrauwen, E J A; Linster, M; De Graaf, M; Herfst, S; Fouchier, R A M

2011-09-03

404

West Nile Virus: Symptoms and Treatment  

MedlinePLUS

... message, please visit this page: About CDC.gov . West Nile Virus Share Compartir Add this to... Añadir en... ... Most people (70-80%) who become infected with West Nile virus do not develop any symptoms. Febrile illness ...

405

Adaptation of Newcastle Virus to Mammals.  

National Technical Information Service (NTIS)

Strain 'T' of the Newcastle virus was adapted to guinea pigs and other mammals. Following the intracerebral inoculation, the adapted virus caused an infection, clinically expressed by signs of central nervous system disease (irritability, anorexia, locomo...

V. N. Syurin

1966-01-01

406

FAQ: West Nile Virus and Dead Birds  

MedlinePLUS

... Digg Google Bookmarks FAQ: West Nile Virus & Dead Birds How do birds get infected with West Nile ... dead bird sightings to local authorities. How do birds get infected with West Nile virus? West Nile ...

407

Differentiation of porcine reproductive and respiratory syndrome virus N protein using a virus-based ELISA.  

PubMed

The bacterially expressed nucleocapsid (N) protein of porcine respiratory and reproductive syndrome virus (PRRSV) was used as immunogen to generate a rabbit-derived polyclonal antibody. The immunoreactivity of the protein to the antibody was confirmed by Western blot analysis. Using PRRSV, transmissible gastroenteritis virus, porcine epidemic diarrhea virus, pseudorabies virus, and avian infectious bronchitis virus as coating antigens, a virus-based ELISA was established. The polyclonal antibody against PRRSV N protein used as a diagnostic agent was capable of differentiating PRRSV from the other viruses. PMID:21529294

Li, Guangxing; Ren, Xiaofeng

2011-04-01

408

The dsRNA viruses.  

PubMed

The dsRNA viruses represent a large, diverse group of pathogens (affecting a very wide range of host species), several of which are of medical, veterinary or agricultural importance. Many of the icosahedral dsRNA viruses show striking structural and functional similarities that reflect the similar problems that they face replicating their dsRNA genomes while avoiding the dsRNA activated defence mechanisms of their host species. These similarities appear to indicate a common if distant ancestry that is not always evident simply by comparison of nucleotide or amino acid sequences. To facilitate the identification and comparisons of cognate proteins from different species, genera and families of dsRNA viruses, a series of tables were originally constructed for the 7th International Symposium of dsRNA viruses held in Aruba in 2000. These have now been updated and extended (for the 8th Symposium, held in Tuscany 2003) and are available from the dsRNA virus website at. PMID:15010213

Mertens, Peter

2004-04-01

409

Why genes overlap in viruses  

PubMed Central

The genomes of most virus species have overlapping genes—two or more proteins coded for by the same nucleotide sequence. Several explanations have been proposed for the evolution of this phenomenon, and we test these by comparing the amount of gene overlap in all known virus species. We conclude that gene overlap is unlikely to have evolved as a way of compressing the genome in response to the harmful effect of mutation because RNA viruses, despite having generally higher mutation rates, have less gene overlap on average than DNA viruses of comparable genome length. However, we do find a negative relationship between overlap proportion and genome length among viruses with icosahedral capsids, but not among those with other capsid types that we consider easier to enlarge in size. Our interpretation is that a physical constraint on genome length by the capsid has led to gene overlap evolving as a mechanism for producing more proteins from the same genome length. We consider that these patterns cannot be explained by other factors, namely the possible roles of overlap in transcription regulation, generating more divergent proteins and the relationship between gene length and genome length.

Chirico, Nicola; Vianelli, Alberto; Belshaw, Robert

2010-01-01

410

Fungal transmission of plant viruses.  

PubMed

Thirty soilborne viruses or virus-like agents are transmitted by five species of fungal vectors. Ten polyhedral viruses, of which nine are in the family Tombusviridae, are acquired in the in vitro manner and do not occur within the resting spores of their vectors, Olpidium brassicae and O. bornovanus. Fungal vectors for other viruses in the family should be sought even though tombusviruses are reputed to be soil transmitted without a vector. Eighteen rod-shaped viruses belonging to the furo- and bymovirus groups and to an unclassified group are acquired in the in vivo manner and survive within the resting spores of their vector, O. brassicae, Polymyxa graminis, P. betae, and Spongospora subterranea. The viral coat protein has an essential role in in vitro transmission. With in vivo transmission a site in the coat protein-read through protein (CP-RT) of beet necrotic yellow vein furovirus determines vector transmissibility as does a site in a similar 98-kDa polyprotein of barley mild mosaic bymovirus. The mechanisms by which virions move (or are moved) into and out of the protoplasm of zoospores or of thalli needs study. PMID:15012536

Campbell, R N

1996-01-01

411

Droplet Microfluidics for Virus Discovery  

NASA Astrophysics Data System (ADS)

The ability to detect, isolate, and characterize an infectious agent is important for diagnosing and curing infectious diseases. Detecting new viral diseases is a challenge because the number of virus particles is often low and/or localized to a small subset of cells. Even if a new virus is detected, it is difficult to isolate it from clinical or environmental samples where multiple viruses are present each with very different properties. Isolation is crucial for whole genome sequencing because reconstructing a genome from fragments of many different genomes is practically impossible. We present a Droplet Microfluidics platform that can detect, isolate and sequence single viral genomes from complex samples containing mixtures of many viruses. We use metagenomic information about the sample of mixed viruses to select a short genomic sequence whose genome we are interested in characterizing. We then encapsulate single virions from the same sample in picoliter volume droplets and screen for successful PCR amplification of the sequence of interest. The selected drops are pooled and their contents sequenced to reconstruct the genome of interest. This method provides a general tool for detecting, isolating and sequencing genetic elements in clinical and environmental samples.

Rotem, Assaf; Cockrell, Shelley; Guo, Mira; Pipas, James; Weitz, David

2012-02-01

412

Viruses and thyroiditis: an update  

PubMed Central

Viral infections are frequently cited as a major environmental factor involved in subacute thyroiditis and autoimmune thyroid diseases This review examines the data related to the role of viruses in the development of thyroiditis. Our research has been focused on human data. We have reviewed virological data for each type of thyroiditis at different levels of evidence; epidemiological data, serological data or research on circulating viruses, direct evidence of thyroid tissue infection. Interpretation of epidemiological and serological data must be cautious as they don't prove that this pathogen is responsible for the disease. However, direct evidence of the presence of viruses or their components in the organ are available for retroviruses (HFV) and mumps in subacute thyroiditis, for retroviruses (HTLV-1, HFV, HIV and SV40) in Graves's disease and for HTLV-1, enterovirus, rubella, mumps virus, HSV, EBV and parvovirus in Hashimoto's thyroiditis. However, it remains to determine whether they are responsible for thyroid diseases or whether they are just innocent bystanders. Further studies are needed to clarify the relationship between viruses and thyroid diseases, in order to develop new strategies for prevention and/or treatment.

Desailloud, Rachel; Hober, Didier

2009-01-01

413

Serological relationship of the Tacaribe complex of viruses to lymphocytic choriomeningitis virus.  

PubMed

By means of the indirect fluorescent-antibody test, cross serological reactivity was demonstrated between lymphocytic choriomeningitis (LCM) virus and the viruses of the Tacaribe complex. Antisera to all members of the Tacaribe complex reacted with LCM virus; LCM antisera gave significant staining of Amapari virus, but minimal or inconsistent reactions with Tacaribe virus, and no reaction with two other viruses of the Tacaribe complex. A low level cross-reaction was observed in complement fixation tests of Machupo and Pichinde antisera against LCM antigen. Immunization with Tacaribe and Amapari viruses did not protect mice against challenge with LCM virus. Because of the identical appearance of the virions, the sharing of antigens, and the many biological similarities between LCM and the Tacaribe complex viruses, it is proposed that they be considered as constituting a new taxonomic group of viruses. PMID:4985595

Rowe, W P; Pugh, W E; Webb, P A; Peters, C J

1970-03-01

414

Serological Relationship of the Tacaribe Complex of Viruses to Lymphocytic Choriomeningitis Virus  

PubMed Central

By means of the indirect fluorescent-antibody test, cross serological reactivity was demonstrated between lymphocytic choriomeningitis (LCM) virus and the viruses of the Tacaribe complex. Antisera to all members of the Tacaribe complex reacted with LCM virus; LCM antisera gave significant staining of Amapari virus, but minimal or inconsistent reactions with Tacaribe virus, and no reaction with two other viruses of the Tacaribe complex. A low level cross-reaction was observed in complement fixation tests of Machupo and Pichinde antisera against LCM antigen. Immunization with Tacaribe and Amapari viruses did not protect mice against challenge with LCM virus. Because of the identical appearance of the virions, the sharing of antigens, and the many biological similarities between LCM and the Tacaribe complex viruses, it is proposed that they be considered as constituting a new taxonomic group of viruses.

Rowe, Wallace P.; Pugh, Wendell E.; Webb, Patricia A.; Peters, Clarence J.

1970-01-01

415

Mutation of YMYL in the Nipah Virus Matrix Protein Abrogates Budding and Alters Subcellular Localization?  

PubMed Central

Matrix (M) proteins reportedly direct the budding of paramyxoviruses from infected cells. In order to begin to characterize the assembly process for the highly lethal, emerging paramyxovirus Nipah virus (NiV), we have examined the budding of NiV M. We demonstrated that expression of the NiV M protein is sufficient to produce budding virus-like particles (VLPs) that are physically and morphologically similar to NiV. We identified in NiV M a sequence, YMYL, with similarity to the YPDL late domain found in the equine infectious anemia virus Gag protein. When the YMYL within NiV M was mutated, VLP release was abolished and M was relocalized to the nucleus, but the mutant M proteins retained oligomerization activity. When YMYL was fused to a late-domain mutant of the Ebola virus VP40 matrix protein, VP40 budding was restored. These results suggest that the YMYL sequence may act as a trafficking signal and a late domain for NiV M.

Ciancanelli, Michael J.; Basler, Christopher F.

2006-01-01

416

Mass extinctions, biodiversity and mitochondrial function: are bats 'special' as reservoirs for emerging viruses?  

PubMed

For the past 10-15 years, bats have attracted growing attention as reservoirs of emerging zoonotic viruses. This has been due to a combination of factors including the emergence of highly virulent zoonotic pathogens, such as Hendra, Nipah, SARS and Ebola viruses, and the high rate of detection of a large number of previously unknown viral sequences in bat specimens. As bats have ancient evolutionary origins and are the only flying mammals, it has been hypothesized that some of their unique biological features may have made them especially suitable hosts for different viruses. So the question 'Are bats different, special or exceptional?' has become a focal point in the field of virology, bat biology and virus-host co-evolution. In this brief review, we examine the topic in a relatively unconventional way, that is, our discussion will be based on both scientific discoveries and theoretical predictions. This approach was chosen partially because the data in this field are so limited that it is impossible to conduct a useful review based on published results only and also because we believe it is important to provoke original, speculative or even controversial ideas or theories in this important field of research. PMID:22440923

Wang, Lin-Fa; Walker, Peter J; Poon, Leo L M

2011-11-09

417

The wonder world of microbial viruses  

PubMed Central

The first congress on Viruses of Microbes took place at the Institut Pasteur in Paris, France, on 21–25 June 2010. The advances in genomics and metagenomics reported at this meeting reveal striking and unexpected complexity of the virus world. Viruses, in particular viruses that infect prokaryotes and unicellular eukaryotes, are emerging as the most abundant class of biological entities on earth and a major evolutionary and geochemical force.

Koonin, Eugene V

2012-01-01

418

Reassortment of Thogoto Virus (a Tick-borne Influenza-like Virus) in a Vertebrate Host  

Microsoft Academic Search

SUMMARY Reassortment is an important factor in the evolution of segmented genome viruses. For arthropod-borne viruses it is important to determine whether the vertebrate host acts as a site of reassortant virus formation since vertebrates often act as amplifying hosts. Mutants of Thogoto virus, a tick-borne orthomyxo-like virus, were shown to produce wild-type progeny in a dually infected permissive host

LINDA D. JONES; CLIVE R. DAVIES; BERNADETTE M. GREEN; PATRICIA A. NUTTALL

1987-01-01

419

Reverse Genetics of Measles Virus and Resulting Multivalent Recombinant Vaccines: Applications of Recombinant Measles Viruses  

Microsoft Academic Search

An overview is given on the development of technologies to allow reverse genetics of RNA viruses, i.e., the rescue of viruses\\u000a from cDNA, with emphasis on nonsegmented negative-strand RNA viruses ( Mononegavirales ), as exemplified for measles virus\\u000a (MV). Primarily, these technologies allowed site-directed mutagenesis, enabling important insights into a variety of aspects\\u000a of the biology of these viruses. Concomitantly,

M. A. Billeter; H. Y. Naim; S. A. Udem

420

Lassa and Mopeia Virus Replication in Human Monocytes/Macrophages and in Endothelial Cells: Different Effects on IL-8 and TNF-? Gene Expression  

PubMed Central

Cells of the mononuclear and endothelial lineages are targets for viruses which cause hemorrhagic fevers (HF) such as the filoviruses Marburg and Ebola, and the arenaviruses Lassa and Junin. A recent model of Marburg HF pathogenesis proposes that virus directly causes endothelial cell damage and macrophage release of TNF-? which increases the permeability of endothelial monolayers [Feldmann et al., 1996]. We show that Lassa virus replicates in human monocytes/macrophages and endothelial cells without damaging them. Human endothelial cells (HUVEC) are highly susceptible to infection by both Lassa and Mopeia (a non-pathogenic Lassa-related arenavirus). Whereas monocytes must differentiate into macrophages before supporting even low level production of these viruses, the virus yields in the culture medium of infected HUVEC cells reach more than 7 log10 PFU/ml without cellular damage. In contrast to filovirus, Lassa virus replication in monocytes/ macrophages fails to stimulate TNF-? gene expression and even down-regulates LPS-stimulated TNF-? mRNA synthesis. The expression of IL-8, a prototypic proinflammatory CXC chemokine, was also suppressed in Lassa virus infected monocytes/macrophages and HUVEC on both the protein and mRNA levels. This contrasts with Mopeia virus infection of HUVEC in which neither IL-8 mRNA nor protein are reduced. The cumulative down-regulation of TNF-? and IL-8 expression could explain the absence of inflammatory and effective immune responses in severe cases of Lassa HF.

Lukashevich, Igor S.; Maryankova, Raisa; Vladyko, Alexander S.; Nashkevich, Natalia; Koleda, Svetlana; Djavani, Mahmoud; Horejsh, Douglas; Voitenok, Nikolai N.; Salvato, Maria S.

2008-01-01

421

Variation and evolution of plant virus populations  

Microsoft Academic Search

Over the last 15 years, interest in plant virus evolution has re-emerged, as shown by the increasing number of papers published on this subject. In recent times, research in plant virus evolution has been viewed from a molecular, rather than populational, standpoint, and there is a need for work aimed at understanding the processes involved in plant virus evolution. However, accumulated

Fernando García-Arenal; Aurora Fraile; José M. Malpica

2003-01-01

422

Studies with rinderpest virus in tissue culture  

Microsoft Academic Search

Summary The stability of cultured rinderpest virus, in maintenance medium containing 5% normal ox serum, was studied at 4°, 37°, and 56° C. The half-life at these temperatures was calculated and the results compared with figures available for other strains of rinderpest virus in cattle tissues and for measles virus in tissue culture fluids.

W. Plowright; R. D. Ferris

1962-01-01

423

Chimeric Measles Viruses with a Foreign Envelope  

Microsoft Academic Search

Measles virus (MV) and vesicular stomatitis virus (VSV) are both members of the Mononegavirales but are only distantly related. We generated two genetically stable chimeric viruses. In MGV, the reading frames of the MV envelope glycoproteins H and F were substituted by a single reading frame encoding the VSV G glyco- protein; MG\\/FV is similar but encodes a G\\/F hybrid

PIUS SPIELHOFER; THOMAS BACHI; THOMAS FEHR; GUDRUN CHRISTIANSEN; ROBERTO CATTANEO; KARIN KAELIN; MARTIN A. BILLETER; HUSSEIN Y. NAIM

1998-01-01

424

Signal Transduction in Resistance to Plant Viruses  

Microsoft Academic Search

Salicylic acid is part of a signal transduction pathway that induces resistance to viruses, bacteria and fungi. In tobacco and Arabidopsis the defensive signal transduction pathway branches downstream of salicylic acid. One branch induces PR-1 proteins and resistance to bacteria and fungi, while the other triggers induction of resistance to RNA and DNA viruses. This virus-specific branch can be activated

Alex M. Murphy; Androulla Gilliland; Chui Eng Wong; Joanne West; Davinder P. Singh; John P. Carr

2001-01-01

425

Further immunization studies with mammary tumor virus.  

PubMed

A single i.m. dose of formalin-inactivated murine mammary tumor virus greatly reduces viral expression and mammary tumorigenesis in Af (tumor incidence, 39%) and RIIIf (tumor incidence, 11%) mice, which carry only endogenous, gamete-transmitted virus. In C57BL mice, 1 mug of vaccine in Freund's complete adjuvant protects against later challenge with RIII virus. PMID:175938

Charney, J; Holben, J A; Cody, C M; Moore, D H

1976-02-01

426

Beet mosaic virus: epidemiology and damage  

Microsoft Academic Search

Overview:<\\/strong>The aim of the studies described in this thesis was to obtain a thorough understanding of the main factors determining the spread of a potyvirus in a high plant density crop. The factors studied included the relationships between virus, host and vector, the spread of the virus around an initial virus source consisting of one or more infected plants, the

A. N. Dusi

1999-01-01

427

Advances in virus research. Volume 32  

SciTech Connect

This book describes advances in the field of virus research. Topics covered include: Retroid virus genome replication; viral oncogenes, v-yes and kerbB, and their cellular counterparts; hepatitis A; and molecular studies of brome Mosaic virus using infectious transcripts from cloned cDNA.

Maramorosch, K.; Murphy, F.A.; Shatkin, A.J.

1987-01-01

428

Advances in virus research. Volume 31  

SciTech Connect

This book presents topics in virus research and advances made in this field. Topics covered include: ambisense RNA genomes of arenaviruses and phleboviruses; the molecular basis of antigenic variation in influenza virus; epitope mapping of flavivirus glycoproteins; regulation of adenovirus mRNA formation; regulation of protein synthesis in virus infected animal cells; and antibody-dependent enhancement of vira infectivity.

Maramorosch, K.; Murphy, F.A.; Shatkin, A.J.

1986-01-01

429

Plant virus taxonomy : some current issues  

Microsoft Academic Search

Summary Classification of viruses is regulated by the International Committee on the Taxonomy of Viruses (ICTV). This organisation provides not only the rules to be applied but has to approve all new names for virus species, genera or higher taxa. Anybody may make a taxonomic proposal but most frequently they are generated by specialist study groups that exist for most

M. J. ADAMS

430

Pathogenesis of Dengue Vaccine Viruses in Mosquitoes.  

National Technical Information Service (NTIS)

The dengue-2 vaccine virus (S-1) and its parent virus (PR-159) were compared for their ability to infect orally, to replicate in, and subsequently to be transmitted by Aedes aegypti mosquitoes. The vaccine virus was markedly less efficient in its ability ...

B. J. Beaty T. H. G. Aitken

1982-01-01

431

Ubiquitous Reassortments in influenza a viruses  

Microsoft Academic Search

Influenza A virus is a negative stranded RNA virus, composed of eight segmented RNA molecules, including polymerases (PB2, PB1, PA), haemaglutin (HA), nucleoprotein (NP), neuraminidase (NA), matrix protein (MP), and nonstructure gene (NS). The influenza A viruses are notorious for rapid mutations, frequent genomic reassortments, and possible recombinations. Among these evolutionary events, genetic reassortments refer to exchanges of internal fragments

Xiu-feng Wan; Mufit Ozden; Guohui Lin

2008-01-01

432

Arctic-like rabies virus, Bangladesh.  

PubMed

Arctic/Arctic-like rabies virus group 2 spread into Bangladesh ?32 years ago. Because rabies is endemic to and a major public health problem in this country, we characterized this virus group. Its glycoprotein has 3 potential N-glycosylation sites that affect viral pathogenesis. Diversity of rabies virus might have public health implications in Bangladesh. PMID:23171512

Jamil, Khondoker Mahbuba; Ahmed, Kamruddin; Hossain, Moazzem; Matsumoto, Takashi; Ali, Mohammad Azmat; Hossain, Sohrab; Hossain, Shakhawat; Islam, Aminul; Nasiruddin, Mohammad; Nishizono, Akira

2012-12-01

433

Role of viruses in human evolution  

Microsoft Academic Search

The study of viral molecular genetics has produced a considerable body of research into the se- quences and phylogenetic relationships of human and an- imal viruses. A review of this literature suggests that humans have been afflicted by viruses throughout their evolutionary history, although the number and types have changed. Some viruses show evidence of long-standing inti- mate relationship and

Linda M. Van Blerkom

2003-01-01

434

RNAi suppressors encoded by pathogenic human viruses  

Microsoft Academic Search

RNA silencing or RNAi interference (RNAi) serves as an innate antiviral mechanism in plants, fungi and animals. Human viruses, like plant viruses, encode suppressor proteins or RNAs that block or modulate the RNAi pathway. This review summarizes the mechanisms by which pathogenic human viruses affect the RNAi pathway. Furthermore, some applications of the viral RNAi suppressor functions and the consequences

Walter de Vries; Ben Berkhout

2008-01-01

435

GENETIC VARIABILITY IN MAIZE CHLOROTIC DWARF VIRUS  

Technology Transfer Automated Retrieval System (TEKTRAN)

Maize chlorotic dwarf virus (MCDV) (genus Waikavirus; family Sequiviridae) is a picorna-like virus transmitted by the black-faced leafhopper, Graminella nigrifrons, in a semi-persistent manner using a virus-encoded helper protein. The MCDV genome contains one large open reading frame encoding a poly...

436

Computer Viruses and Safe Educational Practices.  

ERIC Educational Resources Information Center

|This discussion of computer viruses explains how these viruses may be transmitted, describes their effects on data and/or computer application programs, and identifies three groups that propagate them. Ten major viruses are listed and described, and measures to deal with them are discussed. Nineteen antiviral programs are also listed and…

Azarmsa, Reza

1991-01-01

437

Some properties of feline panleukopenia virus  

Microsoft Academic Search

Summary Feline panleukopenia virus was isolated from a peracute, fatal disease in a 3-month-old Burmese kitten by inoculation of a 1 per cent spleen suspension onto freshly seeded cultures of a feline embryo (FEmb) cell line. The virus was assayed by the detection of intranuclear inclusion bodies in stained coverslips of FEmb cells. The virus was not inactivated by ether,

M. J. Studdert; J. E. Peterson

1973-01-01

438

A Classification of Viruses Through Recursion Theorems  

Microsoft Academic Search

We study computer virology from an abstract point of view. Viruses and worms are self-replicating programs, whose constructions are essen- tially based on Kleene's second recursion theorem. We show that we can classify viruses as solutions of fixed point equations which are obtained from dierent versions of Kleene's second recursion theorem. This lead us to consider four classes of viruses

Guillaume Bonfante; Matthieu Kaczmarek; Jean-yves Marion

2007-01-01

439

Virus entry: molecular mechanisms and biomedical applications  

Microsoft Academic Search

Viruses have evolved to enter cells from all three domains of life — Bacteria, Archaea and Eukaryotes. Of more than 3,600 known viruses, hundreds can infect human cells and most of those are associated with disease. To gain access to the cell interior, animal viruses attach to host-cell receptors. Advances in our understanding of how viral entry proteins interact with

Dimiter S. Dimitrov

2004-01-01

440

Persistent rubella virus infection in laboratory animals  

Microsoft Academic Search

Summary Several strains of rubella virus were able to establish a persistent or carrier-type infection in adult hamsters and suckling rabbits. No evidence of rubella virus persistence for prolonged periods was detected in suckling and adult ferrets or in adult rabbits, although serological studies suggested that these animals had been infected with rubella virus.

J. S. Oxford; C. W. Potter

1971-01-01

441

Inhibition of Interferons by Ectromelia Virus  

Microsoft Academic Search

Ectromelia virus (EV) is an orthopoxvirus (OPV) that causes mousepox, a severe disease of laboratory mice. Mousepox is a useful model of OPV infection because EV is likely to be a natural mouse pathogen, unlike its close relatives vaccinia virus (VV) and variola virus. Several studies have highlighted the importance of mouse interferons (IFNs) in resistance to and recovery from

Vincent P. Smith; Antonio Alcami

2002-01-01

442

An Epidemiological View of Worms and Viruses  

Microsoft Academic Search

The communal nature of the Internet exposes organizations and home computer users to a multitude of worms, viruses, and other malicious software (malware) threats such as spyware and Trojan horses. Viruses are program fragments attached to normal programs or files that hijack the execution control of the host program to reproduce copies of the virus. Worms are automated self-replicating programs

Thomas M. Chen

443

ENTOMOPATHOGENIC VIRUS FROM GLASSY-WINGED SHARPSHOOTER  

Technology Transfer Automated Retrieval System (TEKTRAN)

The glassy-winged sharpshooter, GWSS, has been shown to be susceptible to insect virus infections. A new virus was isolated from field caught GWSS and partially sequenced. Sequence identity showed that this was a new sharpshooter virus separate from those already reported by Hunter et. al. 2004, and...

444

Occult hepatitis B virus infection.  

PubMed

Many studies have shown that hepatitis B virus infection may also occur in hepatitis B surface antigen-negative patients. This occult infection has been identified both in patients with cryptogenic liver disease and in patients with hepatitis C virus-related chronic hepatitis, and much evidence suggests that it may be a risk factor of hepatocellular carcinoma development. However several aspects of this occult infection remain unclear such as its prevalence and the factor(s) involved in the lack of circulating hepatitis B surface antigen. Moreover, it is uncertain whether the occult hepatitis B virus infection may contribute to chronic liver damage, considering that it is usually associated with a suppressed viral replication. Evidence and hypotheses concerning this fascinating field of bio-medical research are reviewed. PMID:11215565

Raimondo, G; Balsano, C; Craxì, A; Farinati, F; Levrero, M; Mondelli, M; Pollicino, T; Squadrito, G; Tiribelli, C

2000-12-01

445

[Capping strategies in RNA viruses].  

PubMed

Most viruses use the mRNA-cap dependent cellular translation machinery to translate their mRNAs into proteins. The addition of a cap structure at the 5' end of mRNA is therefore an essential step for the replication of many virus families. Additionally, the cap protects the viral RNA from degradation by cellular nucleases and prevents viral RNA recognition by innate immunity mechanisms. Viral RNAs acquire their cap structure either by using cellular capping enzymes, by stealing the cap of cellular mRNA in a process named "cap snatching", or using virus-encoded capping enzymes. Many viral enzymes involved in this process have recently been structurally and functionally characterized. These studies have revealed original cap synthesis mechanisms and pave the way towards the development of specific inhibitors bearing antiviral drug potential. PMID:22549871

Bouvet, Mickaël; Ferron, François; Imbert, Isabelle; Gluais, Laure; Selisko, Barbara; Coutard, Bruno; Canard, Bruno; Decroly, Etienne

2012-04-25

446

Viruses & kidney disease: beyond HIV  

PubMed Central

HIV-infected patients may acquire new viral co-infections; they may also experience the reactivation or worsening of existing viral infections, including active, smoldering, or latent infections. HIV-infected patients may be predisposed to these viral infections due to immunodeficiency or to risk factors common to HIV and other viruses. A number of these affect the kidney, either by direct infection or by deposition of immune complexes. In this review we discuss the renal manifestations and treatment of hepatitis C virus, BK virus, adenovirus, cytomegalovirus, and parvovirus B19 in patients with HIV disease. We also discuss an approach to the identification of new viral renal pathogens, using a viral gene chip to identify viral DNA or RNA.

Waldman, Meryl; Marshall, Vickie; Whitby, Denise; Kopp, Jeffrey B.

2008-01-01

447

Treatment of gastrointestinal viruses.  

PubMed

The most common enteric viruses responsible for diarrhoea are rotavirus, enteric adenoviruses, caliciviruses including the Norwalk agent and astrovirus. These infections are usually mild to moderate in severity, self-limiting and of short duration and thus, specific antiviral therapy is not recommended. The standard management of these infections is restoration of fluid and electrolyte balance and then maintenance of hydration until the infection resolves. WHO oral rehydration therapy (ORT) was introduced about 30 years ago and has saved the lives of many infants and young children. During the last 10 years it has become evident that the efficacy of ORT can be increased by reducing the osmolality of the WHO oral rehydration solution (ORS) to produce a relatively hypotonic solution. Hypotonic ORS appears to be safe and effective in all forms of acute diarrhoea in childhood. Complex substrate ORS, which is also usually hypotonic, has been shown to have increased efficacy in cholera but not in other bacterial or viral diarrhoeas. Nevertheless, the scientific rationale for using rice or resistant starch as substrate in ORS is of physiological interest. Other treatments such as hyperimmune bovine colostrum, probiotics and antiviral agents are largely experimental and have not been introduced into routine clinical practice. Cytomegalovirus (CMV) infection of the gastrointestinal tract occurs mainly in the immunocompromised although it has been reported in immunocompetent individuals. CMV infects both the oesophagus and colon to produce oesophagitis, often with discrete ulcers, and colitis, respectively. Both conditions can be treated with ganciclovir or foscarnet. Failure to respond to monotherapy is an indication to use both agents concurrently. PMID:11444033

Farthing, M J

2001-01-01

448

Lagos Bat Virus in Kenya?  

PubMed Central

During lyssavirus surveillance, 1,221 bats of at least 30 species were collected from 25 locations in Kenya. One isolate of Lagos bat virus (LBV) was obtained from a dead Eidolon helvum fruit bat. The virus was most similar phylogenetically to LBV isolates from Senegal (1985) and from France (imported from Togo or Egypt; 1999), sharing with these viruses 100% nucleoprotein identity and 99.8 to 100% glycoprotein identity. This genome conservancy across space and time suggests that LBV is well adapted to its natural host species and that populations of reservoir hosts in eastern and western Africa have sufficient interactions to share pathogens. High virus concentrations, in addition to being detected in the brain, were detected in the salivary glands and tongue and in an oral swab, suggesting that LBV is transmitted in the saliva. In other extraneural organs, the virus was generally associated with innervations and ganglia. The presence of infectious virus in the reproductive tract and in a vaginal swab implies an alternative opportunity for transmission. The isolate was pathogenic for laboratory mice by the intracerebral and intramuscular routes. Serologic screening demonstrated the presence of LBV-neutralizing antibodies in E. helvum and Rousettus aegyptiacus fruit bats. In different colonies the seroprevalence ranged from 40 to 67% and 29 to 46% for E. helvum and R. aegyptiacus, respectively. Nested reverse transcription-PCR did not reveal the presence of viral RNA in oral swabs of bats in the absence of brain infection. Several large bat roosts were identified in areas of dense human populations, raising public health concerns for the potential of lyssavirus infection.

Kuzmin, Ivan V.; Niezgoda, Michael; Franka, Richard; Agwanda, Bernard; Markotter, Wanda; Beagley, Janet C.; Urazova, Olga Y.; Breiman, Robert F.; Rupprecht, Charles E.

2008-01-01

449

Preventing respiratory syncytial virus infections  

PubMed Central

Respiratory syncytial virus infection is the leading cause of lower respiratory tract infections in young children. Palivizumab, a respiratory syncytial virus-specific monoclonal antibody, reduces the hospitalization rate of high-risk children but it is very costly. This statement replaces three previous position statements from the Canadian Paediatric Society about this topic, and was updated primarily to discuss recent changes in the American Academy of Pediatrics guidelines in the Canadian context. It reviews the published literature and provides recommendations regarding palivizumab use in high-risk children.

Robinson, JL

2011-01-01

450

Neonatal herpes simplex virus infections.  

PubMed

Neonatal herpes simplex virus infections are uncommon, but because of the morbidity and mortality associated with the infection they are often considered in the differential diagnosis of ill neonates. The use of polymerase chain reaction for diagnosis of central nervous system infections and the development of safe and effective antiviral therapy has revolutionized the diagnosis and management of these infants. Initiation of long-term antiviral suppressive therapy in these infants has led to significant improvement in morbidity. This article summarizes the epidemiology of neonatal herpes simplex virus infections and discusses clinical presentation, diagnosis, management, and follow up of infants with neonatal herpes disease. PMID:23481105

Pinninti, Swetha G; Kimberlin, David W

2013-04-01

451

Charting the host adaptation of influenza viruses.  

PubMed

Four influenza pandemics have struck the human population during the last 100 years causing substantial morbidity and mortality. The pandemics were caused by the introduction of a new virus into the human population from an avian or swine host or through the mixing of virus segments from an animal host with a human virus to create a new reassortant subtype virus. Understanding which changes have contributed to the adaptation of the virus to the human host is essential in assessing the pandemic potential of current and future animal viruses. Here, we develop a measure of the level of adaptation of a given virus strain to a particular host. We show that adaptation to the human host has been gradual with a timescale of decades and that none of the virus proteins have yet achieved full adaptation to the selective constraints. When the measure is applied to historical data, our results indicate that the 1918 influenza virus had undergone a period of preadaptation prior to the 1918 pandemic. Yet, ancestral reconstruction of the avian virus that founded the classical swine and 1918 human influenza lineages shows no evidence that this virus was exceptionally preadapted to humans. These results indicate that adaptation to humans occurred following the initial host shift from birds to mammals, including a significant amount prior to 1918. The 2009 pandemic virus seems to have undergone preadaptation to human-like selective constraints during its period of circulation in swine. Ancestral reconstruction along the human virus tree indicates that mutations that have increased the adaptation of the virus have occurred preferentially along the trunk of the tree. The method should be helpful in assessing the potential of current viruses to found future epidemics or pandemics. PMID:21109586

dos Reis, Mario; Tamuri, Asif U; Hay, Alan J; Goldstein, Richard A

2010-11-25

452

Expression of rabies virus glycoprotein from a recombinant vaccinia virus  

Microsoft Academic Search

Rabies is one of the oldest diseases known to man, but its successful control has remained elusive. Although effective vaccines of tissue culture origin against rabies do exist1, such preparations are expensive. Live vaccinia virus (VV) recombinants expressing influenza or hepatitis B antigens have recently been used to immunize against these diseases2-4. We have now used this approach to produce

M. P. Kieny; R. Lathe; R. Drillien; D. Spehner; S. Skory; D. Schmitt; T. Wiktor; H. Koprowski; J. P. Lecocq

1984-01-01

453

Viruses and host evolution: virus-mediated self identity.  

PubMed

Virus evolution has become a topic that involves population based selection. Both quasispecies based populations and reticulated mosaic exchange of populations of genetic elements are now well established. This has led us to the understanding that a cooperative consortia can be a crucial aspect of virus driven evolution. Thus viruses exist in groups that can cooperate. However, consortial based evolution (group selection) has long been dismissed by evolutionary biologist. Recently, biocommunication theory has concluded that the evolution and editing of any code or language requires a consortial based process in order to adhere to pragmatic (context) requirements for meaning (in conflict with survival of the fittest concepts). This has led to the idea that viruses are the natural editors of biological codes or language. In this chapter, I present the view that the persistence of virus information in their host provides a natural process of host code editing that is inherently consortial. Since persistence requires mechanisms to attain stability and preclude competition, it also provided mechanisms that promote group identity. Accordingly, I review the viral origins of addiction modules and how these affect both persistence and group identity. The concepts emerging from addiction module based group identity are then generalized and applied to social identity systems as well. I then examine the prokaryotes and the involvement of viral elements in the emergence of their group identity systems (biofilms). Here, integrating dsDNA agents prevailed. In the eukaryotes, however, a large shift in virus-host evolution occurred in which the role of dsDNA agents was diminished but the role of retroviruses and retroposons was greatly enhanced. These agents provided greatly expanded and network based regulatory complexity that was controlled by sensory inputs. From this perspective, the role of virus in the origin of the adaptive immune system is then outlined. I then consider human evolution from the perspective of the great HERV colonization. The origin of a large social brain able to support the learning of language is presented from this viral perspective. The role of addiction modules in the origin of extended social bonding of humans is outlined and applied to the emergence of language as a system of group identity. PMID:22399381

Villarreal, Luis

2012-01-01

454

A cross-species view on viruses  

PubMed Central

We describe the creative ways that virologists are leveraging experimental cross-species infections to study the interactions between viruses and hosts. While viruses are usually well adapted to their hosts, cross-species approaches involve pairing viruses with species that they don’t naturally infect. These cross-species infections pit viruse