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https://www.readbyqxmd.com/read/29144446/structure-and-assembly-of-the-ebola-virus-nucleocapsid
#1
William Wan, Larissa Kolesnikova, Mairi Clarke, Alexander Koehler, Takeshi Noda, Stephan Becker, John A G Briggs
Ebola and Marburg viruses are filoviruses: filamentous, enveloped viruses that cause haemorrhagic fever. Filoviruses are within the order Mononegavirales, which also includes rabies virus, measles virus, and respiratory syncytial virus. Mononegaviruses have non-segmented, single-stranded negative-sense RNA genomes that are encapsidated by nucleoprotein and other viral proteins to form a helical nucleocapsid. The nucleocapsid acts as a scaffold for virus assembly and as a template for genome transcription and replication...
November 16, 2017: Nature
https://www.readbyqxmd.com/read/29142131/single-dose-trivalent-vesiculovax-vaccine-protects-macaques-from-lethal-ebolavirus-and-marburgvirus-challenge
#2
Demetrius Matassov, Chad E Mire, Theresa Latham, Joan B Geisbert, Rong Xu, Ayuko Ota-Setlik, Krystle N Agans, Dean J Kobs, Morgan Q S Wendling, Amanda Burnaugh, Thomas L Rudge, Carol L Sabourin, Michael A Egan, David K Clarke, Thomas W Geisbert, John H Eldridge
Previous studies demonstrated that a single intramuscular (IM) dose of an attenuated vesicular stomatitis virus vector (Vesiculovax™, rVSV-N4CT1) expressing the glycoprotein (GP) from the Mayinga strain of Zaire ebolavirus (EBOV) protected nonhuman primates (NHP) from lethal challenge with EBOV Kikwit and Makona strains. Here we studied the immunogenicity of an expanded range of attenuated rVSV vectors expressing filovirus GP in mice. Based on data from those studies an optimal attenuated tri-valent rVSV vector formulation was identified which included rVSV vectors expressing EBOV, Sudan ebolavirus (SUDV) or Angola strain of Marburg marburgvirus (MARV) GPs...
November 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29106386/sirna-rescues-nonhuman-primates-from-advanced-marburg-and-ravn-virus-disease
#3
Emily P Thi, Chad E Mire, Amy Ch Lee, Joan B Geisbert, Raul Ursic-Bedoya, Krystle N Agans, Marjorie Robbins, Daniel J Deer, Robert W Cross, Andrew S Kondratowicz, Karla A Fenton, Ian MacLachlan, Thomas W Geisbert
Ebolaviruses and marburgviruses belong to the family Filoviridae and cause high lethality in infected patients. There are currently no licensed filovirus vaccines or antiviral therapies. The development of broad-spectrum therapies against members of the Marburgvirus genus, including Marburg virus (MARV) and Ravn virus (RAVV), is difficult because of substantial sequence variability. RNAi therapeutics offer a potential solution, as identification of conserved target nucleotide sequences may confer activity across marburgvirus variants...
November 6, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29070075/marburg-virus-like-particles-by-co-expression-of-glycoprotein-and-matrix-protein-in-insect-cells-induces-immune-responses-in-mice
#4
Weiwei Gai, Xuexing Zheng, Chong Wang, Hualei Wang, Yongkun Zhao, Qi Wang, Gary Wong, Weijiao Zhang, Na Feng, Boning Qiu, Hang Chi, Nan Li, Tiecheng Wang, Yuwei Gao, Junjie Shan, Songtao Yang, Xianzhu Xia
BACKGROUND: Marburg virus (MARV) causes severe haemorrhagic fever in humans and nonhuman primates and has a high mortality rate. However, effective drugs or licensed vaccines are not currently available to control the outbreak and spread of this disease. METHODS: In this study, we generated MARV virus-like particles (VLPs) by co-expressing the glycoprotein (GP) and matrix protein (VP40) using the baculovirus expression system. MARV VLPs and three adjuvants, Poria cocos polysaccharide (PCP-II), poly(I:C) and aluminium hydroxide, were evaluated after intramuscular vaccination in mice...
October 25, 2017: Virology Journal
https://www.readbyqxmd.com/read/29038656/unveiling-a-drift-resistant-cryptotope-within-marburgvirus-nucleoprotein-recognized-by-llama-single-domain-antibodies
#5
John Anthony Garza, Alexander Bryan Taylor, Laura Jo Sherwood, Peter John Hart, Andrew Hayhurst
Marburg virus (MARV) is a highly lethal hemorrhagic fever virus that is increasingly re-emerging in Africa, has been imported to both Europe and the US, and is also a Tier 1 bioterror threat. As a negative sense RNA virus, MARV has error prone replication which can yield progeny capable of evading countermeasures. To evaluate this vulnerability, we sought to determine the epitopes of 4 llama single-domain antibodies (sdAbs or VHH) specific for nucleoprotein (NP), each capable of forming MARV monoclonal affinity reagent sandwich assays...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29034123/ecological-niche-modeling-for-filoviruses-a-risk-map-for-ebola-and-marburg-virus-disease-outbreaks-in-uganda
#6
Luke Nyakarahuka, Samuel Ayebare, Gladys Mosomtai, Clovice Kankya, Julius Lutwama, Frank Norbert Mwiine, Eystein Skjerve
INTRODUCTION: Uganda has reported eight outbreaks caused by filoviruses between 2000 to 2016, more than any other country in the world. We used species distribution modeling to predict where filovirus outbreaks are likely to occur in Uganda to help in epidemic preparedness and surveillance. METHODS: The MaxEnt software, a machine learning modeling approach that uses presence-only data was used to establish filovirus - environmental relationships. Presence-only data for filovirus outbreaks were collected from the field and online sources...
September 5, 2017: PLoS Currents
https://www.readbyqxmd.com/read/29031848/local-national-and-regional-viral-haemorrhagic-fever-pandemic-potential-in-africa-a-multistage-analysis
#7
David M Pigott, Aniruddha Deshpande, Ian Letourneau, Chloe Morozoff, Robert C Reiner, Moritz U G Kraemer, Shannon E Brent, Isaac I Bogoch, Kamran Khan, Molly H Biehl, Roy Burstein, Lucas Earl, Nancy Fullman, Jane P Messina, Adrian Q N Mylne, Catherine L Moyes, Freya M Shearer, Samir Bhatt, Oliver J Brady, Peter W Gething, Daniel J Weiss, Andrew J Tatem, Luke Caley, Tom De Groeve, Luca Vernaccini, Nick Golding, Peter Horby, Jens H Kuhn, Sandra J Laney, Edmond Ng, Peter Piot, Osman Sankoh, Christopher J L Murray, Simon I Hay
BACKGROUND: Predicting when and where pathogens will emerge is difficult, yet, as shown by the recent Ebola and Zika epidemics, effective and timely responses are key. It is therefore crucial to transition from reactive to proactive responses for these pathogens. To better identify priorities for outbreak mitigation and prevention, we developed a cohesive framework combining disparate methods and data sources, and assessed subnational pandemic potential for four viral haemorrhagic fevers in Africa, Crimean-Congo haemorrhagic fever, Ebola virus disease, Lassa fever, and Marburg virus disease...
October 11, 2017: Lancet
https://www.readbyqxmd.com/read/28945945/macromolecular-antiviral-agents-against-zika-ebola-sars-and-other-pathogenic-viruses
#8
Franziska Schandock, Camilla Frich Riber, Annika Röcker, Janis A Müller, Mirja Harms, Paulina Gajda, Kaja Zuwala, Anna H F Andersen, Kaja Borup Løvschall, Martin Tolstrup, Florian Kreppel, Jan Münch, Alexander N Zelikin
Viral pathogens continue to constitute a heavy burden on healthcare and socioeconomic systems. Efforts to create antiviral drugs repeatedly lag behind the advent of pathogens and growing understanding is that broad-spectrum antiviral agents will make strongest impact in future antiviral efforts. This work performs selection of synthetic polymers as novel broadly active agents and demonstrates activity of these polymers against Zika, Ebola, Lassa, Lyssa, Rabies, Marburg, Ebola, influenza, herpes simplex, and human immunodeficiency viruses...
September 25, 2017: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/28892520/knowledge-and-attitude-towards-ebola-and-marburg-virus-diseases-in-uganda-using-quantitative-and-participatory-epidemiology-techniques
#9
Luke Nyakarahuka, Eystein Skjerve, Daisy Nabadda, Doreen Chilolo Sitali, Chisoni Mumba, Frank N Mwiine, Julius J Lutwama, Stephen Balinandi, Trevor Shoemaker, Clovice Kankya
BACKGROUND: Uganda has reported five (5) Ebola virus disease outbreaks and three (3) Marburg virus disease outbreaks from 2000 to 2016. Peoples' knowledge and attitude towards Ebola and Marburg virus disease impact on control and prevention measures especially during outbreaks. We describe knowledge and attitude towards Ebola and Marburg virus outbreaks in two affected communities in Uganda to inform future outbreak responses and help in the design of health education and communication messages...
September 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28821722/egyptian-rousette-bats-maintain-long-term-protective-immunity-against-marburg-virus-infection-despite-diminished-antibody-levels
#10
Amy J Schuh, Brian R Amman, Tara K Sealy, Jessica R Spengler, Stuart T Nichol, Jonathan S Towner
Although bats are natural reservoir hosts for numerous zoonotic viruses, little is known about the long-term dynamics of the host immune response following infection and how these viruses are maintained in nature. The Egyptian rousette bat (ERB) is a known reservoir host for Marburg virus (MARV). Following infection of ERBs with MARV, virus-specific IgG antibodies are induced but rapidly wane and by 3 months post-infection the bats are seronegative. To determine whether reinfection of ERBs plays a role in MARV maintenance, we challenge groups of ERBs that were "naturally" or experimentally infected with MARV 17-24 months prior...
August 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28766193/filovirus-research-how-it-began
#11
Werner Slenczka
The first reported filovirus outbreak occurred in August 1967, when laboratory workers in Marburg and Frankfurt, Germany, and Belgrade, Yugoslavia (now Serbia) became infected with an unknown highly pathogenic agent. The disease was characterized by high fever, malaise, rash, hemorrhagic and tetanic manifestations, and high lethality, amounting to 25%. The disease was introduced to Europe by grivets (Chlorocebus aethiops), which were used for biomedical research and vaccine production. The causative agent, Marburg virus, was isolated and identified by scientists of the University of Marburg, Germany in cooperation with specialists for viral electron microscopy at the Bernhard Nocht Institute in Hamburg, Germany...
August 2, 2017: Current Topics in Microbiology and Immunology
https://www.readbyqxmd.com/read/28750668/from-hybridomas-to-a-robust-microalgal-based-production-platform-molecular-design-of-a-diatom-secreting-monoclonal-antibodies-directed-against-the-marburg-virus-nucleoprotein
#12
Franziska Hempel, Michael Maurer, Björn Brockmann, Christian Mayer, Nadine Biedenkopf, Anne Kelterbaum, Stephan Becker, Uwe G Maier
BACKGROUND: The ideal protein expression system should provide recombinant proteins in high quality and quantity involving low production costs only. However, especially for complex therapeutic proteins like monoclonal antibodies many challenges remain to meet this goal and up to now production of monoclonal antibodies is very costly and delicate. Particularly, emerging disease outbreaks like Ebola virus in Western Africa in 2014-2016 make it necessary to reevaluate existing production platforms and develop robust and cheap alternatives that are easy to handle...
July 27, 2017: Microbial Cell Factories
https://www.readbyqxmd.com/read/28724616/marburg-virus-survivor-immune-responses-are-th1-skewed-with-limited-neutralizing-antibody-responses
#13
Spencer W Stonier, Andrew S Herbert, Ana I Kuehne, Ariel Sobarzo, Polina Habibulin, Chen V Abramovitch Dahan, Rebekah M James, Moses Egesa, Stephen Cose, Julius Julian Lutwama, Leslie Lobel, John M Dye
Until recently, immune responses in filovirus survivors remained poorly understood. Early studies revealed IgM and IgG responses to infection with various filoviruses, but recent outbreaks have greatly expanded our understanding of filovirus immune responses. Immune responses in survivors of Ebola virus (EBOV) and Sudan virus (SUDV) infections have provided the most insight, with T cell responses as well as detailed antibody responses having been characterized. Immune responses to Marburg virus (MARV), however, remain almost entirely uncharacterized...
September 4, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28706276/kanyawara-virus-a-novel-rhabdovirus-infecting-newly-discovered-nycteribiid-bat-flies-infesting-previously-unknown-pteropodid-bats-in-uganda
#14
Tony L Goldberg, Andrew J Bennett, Robert Kityo, Jens H Kuhn, Colin A Chapman
Bats are natural reservoir hosts of highly virulent pathogens such as Marburg virus, Nipah virus, and SARS coronavirus. However, little is known about the role of bat ectoparasites in transmitting and maintaining such viruses. The intricate relationship between bats and their ectoparasites suggests that ectoparasites might serve as viral vectors, but evidence to date is scant. Bat flies, in particular, are highly specialized obligate hematophagous ectoparasites that incidentally bite humans. Using next-generation sequencing, we discovered a novel ledantevirus (mononegaviral family Rhabdoviridae, genus Ledantevirus) in nycteribiid bat flies infesting pteropodid bats in western Uganda...
July 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28659479/crystal-structure-of-the-marburg-virus-nucleoprotein-core-domain-chaperoned-by-a-vp35-peptide-reveals-a-conserved-drug-target-for-filovirus
#15
Tengfei Zhu, Hao Song, Ruchao Peng, Yi Shi, Jianxun Qi, George F Gao
Filovirus nucleoprotein (NP), viral protein 35 (VP35), and polymerase L are essential for viral replication and nucleocapsid formation. Here, we identify a 28-residue peptide (NP binding peptide [NPBP]) from Marburg virus (MARV) VP35 through sequence alignment with previously identified Ebola virus (EBOV) NPBP, which bound to the core region (residues 18 to 344) of the N-terminal portion of MARV NP with high affinity. The crystal structure of the MARV NP core/NPBP complex at a resolution of 2.6 Å revealed that NPBP binds to the C-terminal region of the NP core via electrostatic and nonpolar interactions...
September 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28653188/guide-to-the-correct-use-of-filoviral-nomenclature
#16
Jens H Kuhn
The International Committee on Taxonomy of Viruses (ICTV) currently recognizes three genera and seven species as part of the mononegaviral family Filoviridae. Eight distinct filoviruses (Bundibugyo virus, Ebola virus, Lloviu virus, Marburg virus, Ravn virus, Reston virus, Sudan virus, and Taï Forest virus) have been assigned to these seven species. This chapter briefly summarizes the status quo of filovirus classification and focuses on the importance of differentiating between filoviral species and filoviruses and the correct use of taxonomic and vernacular filovirus names and abbreviations in written and oral discourse...
June 27, 2017: Current Topics in Microbiology and Immunology
https://www.readbyqxmd.com/read/28645623/identification-of-a-coumarin-based-antihistamine-like-small-molecule-as-an-anti-filoviral-entry-inhibitor
#17
Han Cheng, Adam Schafer, Veronica Soloveva, Dima Gharaibeh, Tara Kenny, Cary Retterer, Rouzbeh Zamani, Sina Bavari, Norton P Peet, Lijun Rong
Filoviruses, consisting of Ebola virus, Marburg virus and Cuevavirus, cause severe hemorrhagic fevers in humans with high mortality rates up to 90%. Currently, there is no approved vaccine or therapy available for the prevention and treatment of filovirus infection in humans. The recent 2013-2015 West African Ebola epidemic underscores the urgency to develop antiviral therapeutics against these infectious diseases. Our previous study showed that GPCR antagonists, particularly histamine receptor antagonists (antihistamines) inhibit Ebola and Marburg virus entry...
September 2017: Antiviral Research
https://www.readbyqxmd.com/read/28636653/the-ebola-virus-vp35-protein-binds-viral-immunostimulatory-and-host-rnas-identified-through-deep-sequencing
#18
Kari A Dilley, Alexander A Voorhies, Priya Luthra, Vinita Puri, Timothy B Stockwell, Hernan Lorenzi, Christopher F Basler, Reed S Shabman
Ebola virus and Marburg virus are members of the Filovirdae family and causative agents of hemorrhagic fever with high fatality rates in humans. Filovirus virulence is partially attributed to the VP35 protein, a well-characterized inhibitor of the RIG-I-like receptor pathway that triggers the antiviral interferon (IFN) response. Prior work demonstrates the ability of VP35 to block potent RIG-I activators, such as Sendai virus (SeV), and this IFN-antagonist activity is directly correlated with its ability to bind RNA...
2017: PloS One
https://www.readbyqxmd.com/read/28622346/flavivirus-and-filovirus-evoprinters-new-alignment-tools-for-the-comparative-analysis-of-viral-evolution
#19
Thomas Brody, Amarendra S Yavatkar, Dong Sun Park, Alexander Kuzin, Jermaine Ross, Ward F Odenwald
BACKGROUND: Flavivirus and Filovirus infections are serious epidemic threats to human populations. Multi-genome comparative analysis of these evolving pathogens affords a view of their essential, conserved sequence elements as well as progressive evolutionary changes. While phylogenetic analysis has yielded important insights, the growing number of available genomic sequences makes comparisons between hundreds of viral strains challenging. We report here a new approach for the comparative analysis of these hemorrhagic fever viruses that can superimpose an unlimited number of one-on-one alignments to identify important features within genomes of interest...
June 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28611428/deep-sequencing-of-marburg-virus-genome-during-sequential-mouse-passaging-and-cell-culture-adaptation-reveals-extensive-changes-over-time
#20
Haiyan Wei, Jonathan Audet, Gary Wong, Shihua He, Xueyong Huang, Todd Cutts, Steven Theriault, Bianli Xu, Gary Kobinger, Xiangguo Qiu
Marburg virus (MARV) has caused outbreaks of filoviral hemorrhagic fever since its discovery in 1967. The largest and deadliest outbreak occurred in Angola in 2005, with 252 cases and 227 deaths. In 2014, we developed a mouse-adapted MARV, Angola variant through serial passaging in mice. The mouse-adapted MARV exhibits many of the hallmarks of MARV disease in humans. By applying deep-sequencing to every passage of the virus, we are able to study virus evolution in this host with surprising precision. We show that two regions go through substantial changes: the intergenic region between NP and VP35, as well as the first 100 amino acids of the VP40 protein...
June 13, 2017: Scientific Reports
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