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https://www.readbyqxmd.com/read/29040311/putative-endogenous-filovirus-vp35-like-protein-potentially-functions-as-an-ifn-antagonist-but-not-a-polymerase-cofactor
#1
Tatsunari Kondoh, Rashid Manzoor, Naganori Nao, Junki Maruyama, Wakako Furuyama, Hiroko Miyamoto, Asako Shigeno, Makoto Kuroda, Keita Matsuno, Daisuke Fujikura, Masahiro Kajihara, Reiko Yoshida, Manabu Igarashi, Ayato Takada
It has been proposed that some non-retroviral RNA virus genes are integrated into vertebrate genomes. Endogenous filovirus-like elements (EFLs) have been discovered in some mammalian genomes. However, their potential roles in ebolavirus infection are unclear. A filovirus VP35-like element (mlEFL35) is found in the little brown bat (Myotis lucifugus) genome. Putative mlEFL35-derived protein (mlEFL35p) contains nearly full-length amino acid sequences corresponding to ebolavirus VP35. Ebola virus VP35 has been shown to bind double-stranded RNA, leading to inhibition of type I interferon (IFN) production, and is also known as a viral polymerase cofactor that is essential for viral RNA transcription/replication...
2017: PloS One
https://www.readbyqxmd.com/read/29034123/ecological-niche-modeling-for-filoviruses-a-risk-map-for-ebola-and-marburg-virus-disease-outbreaks-in-uganda
#2
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/29031163/ebola-virus-requires-phosphatidylinositol-3-5-bisphosphate-production-for-efficient-viral-entry
#3
Shirley Qiu, Anders Leung, Yuxia Bo, Robert A Kozak, Sai Priya Anand, Corina Warkentin, Fabiola D R Salambanga, Jennifer Cui, Gary Kobinger, Darwyn Kobasa, Marceline Côté
For entry, Ebola virus (EBOV) requires the interaction of its viral glycoprotein with the cellular protein Niemann-Pick C1 (NPC1) which resides in late endosomes and lysosomes. How EBOV is trafficked and delivered to NPC1 and whether this is positively regulated during entry remain unclear. Here, we show that the PIKfyve-ArPIKfyve-Sac3 cellular complex, which is involved in the metabolism of phosphatidylinositol (3,5) bisphosphate (PtdIns(3,5)P2), is critical for EBOV infection. Although the expression of all subunits of the complex was required for efficient entry, PIKfyve kinase activity was specifically critical for entry by all pathogenic filoviruses...
October 11, 2017: Virology
https://www.readbyqxmd.com/read/29021793/intracellular-crosslinking-of-filoviral-nucleoproteins-with-xintrabodies-restricts-viral-packaging
#4
Tamarand Lee Darling, Laura Jo Sherwood, Andrew Hayhurst
Viruses assemble large macromolecular repeat structures that become part of the infectious particles or virions. Ribonucleocapsids (RNCs) of negative strand RNA viruses are a prime example where repetition of nucleoprotein (NP) along the genome creates a core polymeric helical scaffold that accommodates other nucleocapsid proteins including viral polymerase. The RNCs are transported through the cytosol for packaging into virions through association with viral matrix proteins at cell membranes. We hypothesized that RNC would be ideal targets for crosslinkers engineered to promote aberrant protein-protein interactions, thereby blocking their orderly transport and packaging...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28986842/testing-experimental-therapies-in-a-guinea-pig-model-for-hemorrhagic-fever
#5
Gary Wong, Yuhai Bi, Gary Kobinger, George F Gao, Xiangguo Qiu
Hemorrhagic fever viruses are among the deadliest pathogens known to humans, and often, licensed medical countermeasures are unavailable to prevent or treat infections. Guinea pigs are a commonly used animal for the preclinical development of any experimental candidates, typically to confirm data generated in mice and as a way to validate and support further testing in nonhuman primates. In this chapter, we use Sudan virus (SUDV), a lethal filovirus closely related to Ebola virus, as an example of the steps required for generating a guinea pig-adapted isolate that is used to test a monoclonal antibody-based therapy against viral hemorrhagic fevers...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28986839/minigenome-systems-for-filoviruses
#6
Thomas Hoenen
Filoviruses are among the most pathogenic viruses known to man, and work with live viruses is restricted to maximum containment laboratories. In order to study individual aspects of the virus life cycle outside of maximum containment laboratories, life cycle modeling systems have been established, which use reporter-encoding miniature versions of the viral genome called minigenomes. With basic minigenome systems viral genome replication and transcription can be studied, whereas more advanced systems also allow us to model other aspects of the virus life cycle outside of a maximum containment laboratory...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28986836/hemorrhagic-fever-virus-budding-studies
#7
Ronald N Harty
Independent expression of the VP40 or Z matrix proteins of filoviruses (marburgviruses and ebolaviruses) and arenaviruses (Lassa fever and Junín), respectively, gives rise to the production and release of virus-like particles (VLPs) that are morphologically identical to infectious virions. We can detect and quantify VLP production and egress in mammalian cells by transient transfection, SDS-PAGE, Western blotting, and live cell imaging techniques such as total internal reflection fluorescence (TIRF) microscopy...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28978704/human-metapneumovirus-induces-formation-of-inclusion-bodies-for-efficient-genome-replication-and-transcription
#8
Nicolás Cifuentes-Muñoz, Jean Branttie, Kerri Beth Slaughter, Rebecca Ellis Dutch
Human metapneumovirus (HMPV) causes significant upper and lower respiratory disease to all age groups worldwide. The virus possesses a negative-sense single-stranded RNA genome of approximately 13.3 Kb encapsidated by multiple copies of the nucleoprotein (N), giving rise to helical nucleocapsids. In addition, copies of the phosphoprotein (P) and the large RNA polymerase (L) decorate the viral nucleocapsids. After viral attachment, endocytosis, and fusion mediated by the viral glycoproteins, HMPV nucleocapsids are released into the cell cytoplasm...
October 4, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28959255/immunological-control-of-viral-infections-in-bats-and-the-emergence-of-viruses-highly-pathogenic-to-humans
#9
Tony Schountz, Michelle L Baker, John Butler, Vincent Munster
Bats are reservoir hosts of many important viruses that cause substantial disease in humans, including coronaviruses, filoviruses, lyssaviruses, and henipaviruses. Other than the lyssaviruses, they do not appear to cause disease in the reservoir bats, thus an explanation for the dichotomous outcomes of infections of humans and bat reservoirs remains to be determined. Bats appear to have a few unusual features that may account for these differences, including evidence of constitutive interferon (IFN) activation and greater combinatorial diversity in immunoglobulin genes that do not undergo substantial affinity maturation...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28931675/comparative-transcriptomics-highlights-the-role-of-the-ap1-transcription-factor-in-the-host-response-to-ebolavirus
#10
James W Wynne, Shawn Todd, Victoria Boyd, Mary Tachedjian, Reuben Klein, Brian Shiell, Megan Dearnley, Alexander J McAuley, Amanda P Woon, Anthony W Purcell, Glenn A Marsh, Michelle L Baker
Ebolavirus and Marburgvirus comprise two genera of negative-sense single-stranded RNA viruses that cause severe hemorrhagic fevers in humans. Despite considerable research efforts, the molecular events following Ebola virus (EBOV) infection are poorly understood. With the view of identifying host factors that underpin EBOV pathogenesis, we compared the transcriptomes of EBOV-infected human, pig and bat kidney cells using an RNAseq approach. Despite a significant difference in viral transcription/replication between the cell lines, all cells responded to EBOV infection through a robust induction of extracellular growth factors...
September 20, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28922082/combinatorial-peptide-based-epitope-mapping-from-ebola-virus-dna-vaccines-and-infections-reveals-residue-level-determinants-of-antibody-binding
#11
Daniel R Ripoll, Daniel A J Mitchell, Lesley C Dupuy, Anders Wallqvist, Connie Schmaljohn, Sidhartha Chaudhury
Ebola virus (EBOV) infection is highly lethal and results in severe febrile bleeding disorders that affect humans and non-human primates. One of the therapeutic approaches for treating EBOV infection focus largely on cocktails of monoclonal antibodies (mAbs) that bind to specific regions of the EBOV glycoprotein (GP) and neutralize the virus. Recent structural studies using cryo-electron microscopy have identified key epitopes for several EBOV mAbs. While such information has yielded deep insights into antibody binding, limitations on resolution of these structures often preclude a residue-level analysis of EBOV epitopes...
September 18, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/28918537/reverse-genetics-of-filoviruses
#12
Thomas Hoenen, Janine Brandt, Yíngyún Caì, Jens H Kuhn, Courtney Finch
Reverse genetics systems are used for the generation of recombinant viruses. For filoviruses, this technology has been available for more than 15 years and has been used to investigate questions regarding the molecular biology, pathogenicity, and host adaptation determinants of these viruses. Further, reporter-expressing, recombinant viruses are increasingly used as tools for screening for and characterization of candidate medical countermeasures. Thus, reverse genetics systems represent powerful research tools...
September 17, 2017: Current Topics in Microbiology and Immunology
https://www.readbyqxmd.com/read/28892520/knowledge-and-attitude-towards-ebola-and-marburg-virus-diseases-in-uganda-using-quantitative-and-participatory-epidemiology-techniques
#13
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/28795188/filovirus-structural-biology-the-molecules-in-the-machine
#14
Robert N Kirchdoerfer, Hal Wasserman, Gaya K Amarasinghe, Erica Ollmann Saphire
In this chapter, we describe what is known thus far about the structures and functions of the handful of proteins encoded by filovirus genomes. Amongst the fascinating findings of the last decade is the plurality of functions and structures that these polypeptides can adopt. Many of the encoded proteins can play multiple, distinct roles in the virus life cycle, although the mechanisms by which these functions are determined and controlled remain mostly veiled. Further, some filovirus proteins are multistructural: adopting different oligomeric assemblies and sometimes, different tertiary structures to achieve their separate, and equally essential functions...
August 10, 2017: Current Topics in Microbiology and Immunology
https://www.readbyqxmd.com/read/28769016/favipiravir-t-705-a-broad-spectrum-inhibitor-of-viral-rna-polymerase
#15
Yousuke Furuta, Takashi Komeno, Takaaki Nakamura
Favipiravir (T-705; 6-fluoro-3-hydroxy-2-pyrazinecarboxamide) is an anti-viral agent that selectively and potently inhibits the RNA-dependent RNA polymerase (RdRp) of RNA viruses. Favipiravir was discovered through screening chemical library for anti-viral activity against the influenza virus by Toyama Chemical Co., Ltd. Favipiravir undergoes an intracellular phosphoribosylation to be an active form, favipiravir-RTP (favipiravir ribofuranosyl-5'-triphosphate), which is recognized as a substrate by RdRp, and inhibits the RNA polymerase activity...
2017: Proceedings of the Japan Academy. Series B, Physical and Biological Sciences
https://www.readbyqxmd.com/read/28766193/filovirus-research-how-it-began
#16
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/28724616/marburg-virus-survivor-immune-responses-are-th1-skewed-with-limited-neutralizing-antibody-responses
#17
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/28710694/ecology-of-filoviruses
#18
Brian R Amman, Robert Swanepoel, Stuart T Nichol, Jonathan S Towner
Filoviruses can cause severe and often fatal disease in humans. To date, there have been 47 outbreaks resulting in more than 31,500 cases of human illness and over 13,200 reported deaths. Since their discovery, researchers from many scientific disciplines have worked to better understand the natural history of these deadly viruses. Citing original research wherever possible, this chapter reviews laboratory and field-based studies on filovirus ecology and summarizes efforts to identify where filoviruses persist in nature, how virus is transmitted to other animals and ultimately, what drivers cause spillover to human beings...
July 15, 2017: Current Topics in Microbiology and Immunology
https://www.readbyqxmd.com/read/28685291/filovirus-strategies-to-escape-antiviral-responses
#19
Judith Olejnik, Adam J Hume, Daisy W Leung, Gaya K Amarasinghe, Christopher F Basler, Elke Mühlberger
This chapter describes the various strategies filoviruses use to escape host immune responses with a focus on innate immune and cell death pathways. Since filovirus replication can be efficiently blocked by interferon (IFN), filoviruses have evolved mechanisms to counteract both type I IFN induction and IFN response signaling pathways. Intriguingly, marburg- and ebolaviruses use different strategies to inhibit IFN signaling. This chapter also summarizes what is known about the role of IFN-stimulated genes (ISGs) in filovirus infection...
July 8, 2017: Current Topics in Microbiology and Immunology
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
#20
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
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