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Marburg virus

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https://www.readbyqxmd.com/read/28197304/ester-prodrugs-of-ihvr-19029-with-enhanced-oral-exposure-and-prevention-of-gastrointestinal-glucosidase-interaction
#1
Julia Ma, Shuo Wu, Xuexiang Zhang, Fang Guo, Katherine Yang, Jia Guo, Qing Su, Huagang Lu, Patrick Lam, Yuhuan Li, Zhengyin Yan, William Kinney, Ju-Tao Guo, Timothy M Block, Jinhong Chang, Yanming Du
IHVR-19029 (6) is a lead endoplasmic reticulum α-glucosidases I and II inhibitor, which efficiently protected mice from lethal Ebola and Marburg virus infections via injection route, but suffered from low bioavailability and off-target interactions with gut glucosidases when administered orally. In an effort to improve efficacious exposure levels and avoid side effects, we designed and synthesized ester prodrugs. Not only were the prodrugs stable in simulated gastric and intestinal fluids and were inactive against glucosidases but they also exhibited antiviral activities against dengue virus infection in a cell based assay...
February 9, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28194016/modelling-filovirus-maintenance-in-nature-by-experimental-transmission-of-marburg-virus-between-egyptian-rousette-bats
#2
Amy J Schuh, Brian R Amman, Megan E B Jones, Tara K Sealy, Luke S Uebelhoer, Jessica R Spengler, Brock E Martin, Jo Ann D Coleman-McCray, Stuart T Nichol, Jonathan S Towner
The Egyptian rousette bat (ERB) is a natural reservoir host for Marburg virus (MARV); however, the mechanisms by which MARV is transmitted bat-to-bat and to other animals are unclear. Here we co-house MARV-inoculated donor ERBs with naive contact ERBs. MARV shedding is detected in oral, rectal and urine specimens from inoculated bats from 5-19 days post infection. Simultaneously, MARV is detected in oral specimens from contact bats, indicating oral exposure to the virus. In the late study phase, we provide evidence that MARV can be horizontally transmitted from inoculated to contact ERBs by finding MARV RNA in blood and oral specimens from contact bats, followed by MARV IgG antibodies in these same bats...
February 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/28167534/detection-of-lipid-induced-structural-changes-of-the-marburg-virus-matrix-protein-vp40-using-hydrogen-deuterium-exchange-mass-spectrometry
#3
Kaveesha J Wijesinghe, Sarah Urata, Nisha Bhattarai, Edgar E Kooijman, Bernard S Gerstman, Prem P Chapagain, Sheng Li, Robert V Stahelin
Marburg virus (MARV) is a lipid-enveloped virus from the Filoviridae family containing a negative sense RNA genome. One of the seven MARV genes encodes the matrix protein VP40, which forms a matrix layer beneath the plasma membrane inner leaflet to facilitate budding from the host cell. MARV VP40 (mVP40) has been shown to be a dimeric peripheral protein with a broad and flat basic surface that can associate with anionic phospholipids such as phosphatidylserine. While a number of mVP40 cationic residues have been shown to facilitate binding to membranes containing anionic lipids, much less is known on how mVP40 assembles to form the matrix layer following membrane binding...
February 6, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28135118/ebola-virus-and-marburg-virus-in-human-milk-are-inactivated-by-holder-pasteurization
#4
Erin Hamilton Spence, Monica Huff, Karen Shattuck, Amy Vickers, Nadezda Yun, Slobodan Paessler
BACKGROUND: Potential donors of human milk are screened for Ebola virus (EBOV) using standard questions, but testing for EBOV and Marburg virus (MARV) is not part of routine serological testing performed by milk banks. Research aim: This study tested the hypothesis that EBOV would be inactivated in donor human milk (DHM) by standard pasteurization techniques (Holder) used in all North American nonprofit milk banks. METHODS: Milk samples were obtained from a nonprofit milk bank...
January 1, 2017: Journal of Human Lactation: Official Journal of International Lactation Consultant Association
https://www.readbyqxmd.com/read/28130780/membrane-insertion-of-fusion-peptides-from-ebola-and-marburg-viruses-studied-by-replica-exchange-molecular-dynamics-simulations
#5
Mark A Olson, Michael S Lee, In-Chul Yeh
This work presents replica-exchange molecular dynamics simulations of inserting a 16-residue Ebola virus fusion peptide into a membrane bilayer. A computational approach is applied for modeling the peptide at the explicit all-atom level and the membrane-aqueous bilayer by a generalized Born continuum model with a smoothed switching function (GBSW). We provide an assessment of the model calculations in terms of three metrics: (1) the ability to reproduce the NMR structure of the peptide determined in the presence of SDS micelles and comparable structural data on other fusion peptides; (2) determination of the effects of the mutation Trp-8 to Ala and sequence discrimination of the homologous Marburg virus; and (3) calculation of potentials of mean force for estimating the partitioning free energy and their comparison to predictions from the Wimley-White interfacial hydrophobicity scale...
January 28, 2017: Journal of Computational Chemistry
https://www.readbyqxmd.com/read/28122983/innate-immune-response-of-bat-and-human-cells-to-filoviruses-commonalities-and-distinctions
#6
Ivan V Kuzmin, Toni M Schwarz, Philipp A Ilinykh, Ingo Jordan, Thomas G Ksiazek, Ravi Sachidanandam, Christopher F Basler, Alexander Bukreyev
: Marburg (MARV) and Ebola (EBOV) viruses are zoonotic pathogens that cause severe hemorrhagic fever in humans. The natural reservoir of MARV is the Egyptian rousette bat (Rousettus aegyptiacus); that of EBOV is unknown but believed to be another bat species. The Egyptian rousette develops subclinical productive infection with MARV but is refractory to EBOV. Interaction of filoviruses with hosts is greatly affected by the viral interferon (IFN)-inhibiting domains (IID). Our study was aimed at characterization of innate immune responses to filoviruses and the role of filovirus IID in bat and human cells...
January 25, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28109709/the-effect-of-gamma-irradiation-conditions-on-the-immunogenicity-of-whole-inactivated-influenza-a-virus-vaccine
#7
Shannon C David, Josyane Lau, Eve V Singleton, Rachelle Babb, Justin Davies, Timothy R Hirst, Shaun R McColl, James C Paton, Mohammed Alsharifi
Gamma-irradiation, particularly an irradiation dose of 50kGy, has been utilised widely to sterilise highly pathogenic agents such as Ebola, Marburg Virus, and Avian Influenza H5N1. We have reported previously that intranasal vaccination with a gamma-irradiated Influenza A virus vaccine (γ-Flu) results in cross-protective immunity. Considering the possible inclusion of highly pathogenic Influenza strains in future clinical development of γ-Flu, an irradiation dose of 50kGy may be used to enhance vaccine safety beyond the internationally accepted Sterility Assurance Level (SAL)...
January 18, 2017: Vaccine
https://www.readbyqxmd.com/read/28076420/chaperone-mediated-autophagy-protein-bag3-negatively-regulates-ebola-and-marburg-vp40-mediated-egress
#8
Jingjing Liang, Cari A Sagum, Mark T Bedford, Sachdev S Sidhu, Marius Sudol, Ziying Han, Ronald N Harty
Ebola (EBOV) and Marburg (MARV) viruses are members of the Filoviridae family which cause outbreaks of hemorrhagic fever. The filovirus VP40 matrix protein is essential for virus assembly and budding, and its PPxY L-domain motif interacts with WW-domains of specific host proteins, such as Nedd4 and ITCH, to facilitate the late stage of virus-cell separation. To identify additional WW-domain-bearing host proteins that interact with VP40, we used an EBOV PPxY-containing peptide to screen an array of 115 mammalian WW-domain-bearing proteins...
January 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28074834/corrigendum-differential-transcriptional-responses-to-ebola-and-marburg-virus-infection-in-bat-and-human-cells
#9
Martin Hölzer, Verena Krähling, Fabian Amman, Emanuel Barth, Stephan H Bernhart, Victor A O Carmelo, Maximilian Collatz, Gero Doose, Florian Eggenhofer, Jan Ewald, Jörg Fallmann, Lasse M Feldhahn, Markus Fricke, Juliane Gebauer, Andreas J Gruber, Franziska Hufsky, Henrike Indrischek, Sabina Kanton, Jörg Linde, Nelly Mostajo, Roman Ochsenreiter, Konstantin Riege, Lorena Rivarola-Duarte, Abdullah H Sahyoun, Sita J Saunders, Stefan E Seemann, Andrea Tanzer, Bertram Vogel, Stefanie Wehner, Michael T Wolfinger, Rolf Backofen, Jan Gorodkin, Ivo Grosse, Ivo Hofacker, Steve Hoffmann, Christoph Kaleta, Peter F Stadler, Stephan Becker, Manja Marz
No abstract text is available yet for this article.
January 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28012899/corning-hyperflask-%C3%A2-for-viral-amplification-and-production-of-diagnostic-reagents
#10
Brian J Kearney, Matthew A Voorhees, Priscilla L Williams, Scott P Olschner, Cynthia A Rossi, Randal J Schoepp
Viral preparations are essential components in diagnostic research and development. The production of large quantities of virus traditionally is done by infecting numerous tissue culture flasks or roller bottles, which require large incubators and/or roller bottle racks. The Corning HYPERFlask(®) is a multilayer flask that uses a gas permeable film to provide gas exchange between the cells and culture medium and the atmospheric environment. This study evaluated the suitability of the HYPERFlask for production of Lassa, Ebola, Bundibugyo, Reston, and Marburg viruses and compared it to more traditional methods using tissue culture flasks and roller bottles...
December 21, 2016: Journal of Virological Methods
https://www.readbyqxmd.com/read/27979676/ebola-virus-derived-g-quadruplexes-thiazole-orange-interaction
#11
Petra Krafčíková, Erika Demkovičová, Viktor Víglaský
The Ebola and Marburg viruses are some of the deadliest viruses in the world. In this study a series of G-rich DNA sequences derived from these types of viruses which possess the potential to form G-quadruplex structures are analyzed. A set of DNA oligonucleotides derived from original viral isolates was used as a representative modeling sequence with which to demonstrate the influence of thiazole orange on circular dichroism (CD) spectral profiles. The results show the unique profile of the induced CD (ICD) signal in the visible region caused by interactions between the ligand and G-quadruplexes...
December 13, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27976688/a-hamster-model-for-marburg-virus-infection-accurately-recapitulates-marburg-hemorrhagic-fever
#12
Andrea Marzi, Logan Banadyga, Elaine Haddock, Tina Thomas, Kui Shen, Eva J Horne, Dana P Scott, Heinz Feldmann, Hideki Ebihara
Marburg virus (MARV), a close relative of Ebola virus, is the causative agent of a severe human disease known as Marburg hemorrhagic fever (MHF). No licensed vaccine or therapeutic exists to treat MHF, and MARV is therefore classified as a Tier 1 select agent and a category A bioterrorism agent. In order to develop countermeasures against this severe disease, animal models that accurately recapitulate human disease are required. Here we describe the development of a novel, uniformly lethal Syrian golden hamster model of MHF using a hamster-adapted MARV variant Angola...
December 15, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27930961/novel-activities-by-ebolavirus-and-marburgvirus-interferon-antagonists-revealed-using-a-standardized-in-vitro-reporter-system
#13
Jonathan C Guito, César G Albariño, Ayan K Chakrabarti, Jonathan S Towner
Filoviruses are highly lethal in humans and nonhuman primates, likely due to potent antagonism of host interferon (IFN) responses early in infection. Filoviral protein VP35 is implicated as the major IFN induction antagonist, while Ebola virus (EBOV) VP24 or Marburg virus (MARV) VP40 are known to block downstream IFN signaling. Despite progress elucidating EBOV and MARV antagonist function, those for most other filoviruses, including Reston (RESTV), Sudan (SUDV), Taï Forest (TAFV), Bundibugyo (BDBV) and Ravn (RAVV) viruses, remain largely neglected...
January 15, 2017: Virology
https://www.readbyqxmd.com/read/27918527/induction-and-suppression-of-antiviral-rna-interference-by-influenza-a-virus-in-mammalian-cells
#14
Yang Li, Megha Basavappa, Jinfeng Lu, Shuwei Dong, D Alexander Cronkite, John T Prior, Hans-Christian Reinecker, Paul Hertzog, Yanhong Han, Wan-Xiang Li, Sihem Cheloufi, Fedor V Karginov, Shou-Wei Ding, Kate L Jeffrey
Influenza A virus (IAV) causes annual epidemics and occasional pandemics, and is one of the best-characterized human RNA viral pathogens(1). However, a physiologically relevant role for the RNA interference (RNAi) suppressor activity of the IAV non-structural protein 1 (NS1), reported over a decade ago(2), remains unknown(3). Plant and insect viruses have evolved diverse virulence proteins to suppress RNAi as their hosts produce virus-derived small interfering RNAs (siRNAs) that direct specific antiviral defence(4-7) by an RNAi mechanism dependent on the slicing activity of Argonaute proteins (AGOs)(8,9)...
December 5, 2016: Nature Microbiology
https://www.readbyqxmd.com/read/27909582/ebola-research-funding-a-systematic-analysis-1997-2015
#15
Joseph Ra Fitchett, Amos Lichtman, Damilola T Soyode, Ariel Low, Jimena Villar de Onis, Michael G Head, Rifat Atun
BACKGROUND: The latest outbreak of Ebola in West Africa overwhelmed the affected countries, with the impact on health extending far beyond Ebola-related deaths that have exceeded 11 000. The need to promptly mobilise resources to control emerging infections is widely recognized. Yet, data on research funding for emerging infections remains inadequately documented. METHODS: We defined research investment as all funding flows for Ebola and/or Marburg virus from 1997 to April 2015 whose primary purpose was to advance knowledge and new technologies to prevent or cure disease...
December 2016: Journal of Global Health
https://www.readbyqxmd.com/read/27908828/assessment-of-the-potential-for-host-targeted-iminosugars-uv-4-and-uv-5-activity-against-filovirus-infections-in%C3%A2-vitro-and-in%C3%A2-vivo
#16
Kelly L Warfield, Travis K Warren, Xiangguo Qiu, Jay Wells, Chad E Mire, Joan B Geisbert, Kelly S Stuthman, Nicole L Garza, Sean A Van Tongeren, Amy C Shurtleff, Krystle N Agans, Gary Wong, Michael V Callahan, Thomas W Geisbert, Brennan Klose, Urban Ramstedt, Anthony M Treston
Iminosugars are host-directed antivirals with broad-spectrum activity. The iminosugar, N-butyl-deoxynojirimycin (NB-DNJ or Miglustat(®)), is used in humans for treatment of Gaucher's disease and has mild antiviral properties. More potent analogs of NB-DNJ have been generated and have demonstrated activity against a variety of viruses including flaviviruses, influenza, herpesviruses and filoviruses. In the current study, a panel of analogs based on NB-DNJ was analyzed for activity against Ebola (EBOV) and Marburg viruses (MARV)...
February 2017: Antiviral Research
https://www.readbyqxmd.com/read/27887599/how-severe-and-prevalent-are-ebola-and-marburg-viruses-a-systematic-review-and-meta-analysis-of-the-case-fatality-rates-and-seroprevalence
#17
Luke Nyakarahuka, Clovice Kankya, Randi Krontveit, Benjamin Mayer, Frank N Mwiine, Julius Lutwama, Eystein Skjerve
BACKGROUND: Ebola and Marburg virus diseases are said to occur at a low prevalence, but are very severe diseases with high lethalities. The fatality rates reported in different outbreaks ranged from 24-100%. In addition, sero-surveys conducted have shown different seropositivity for both Ebola and Marburg viruses. We aimed to use a meta-analysis approach to estimate the case fatality and seroprevalence rates of these filoviruses, providing vital information for epidemic response and preparedness in countries affected by these diseases...
November 25, 2016: BMC Infectious Diseases
https://www.readbyqxmd.com/read/27847355/crystal-structure-of-the-marburg-virus-vp35-oligomerization-domain
#18
Jessica F Bruhn, Robert N Kirchdoerfer, Sarah M Urata, Sheng Li, Ian J Tickle, Gérard Bricogne, Erica Ollmann Saphire
: Marburg virus (MARV) is a highly pathogenic filovirus that is classified in a genus distinct from that of Ebola virus (EBOV) (genera Marburgvirus and Ebolavirus, respectively). Both viruses produce a multifunctional protein termed VP35, which acts as a polymerase cofactor, a viral protein chaperone, and an antagonist of the innate immune response. VP35 contains a central oligomerization domain with a predicted coiled-coil motif. This domain has been shown to be essential for RNA polymerase function...
January 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/27811840/notes-from-the-field-rift-valley-fever-response-kabale-district-uganda-march-2016
#19
Annabelle de St Maurice, Luke Nyakarahuka, Lawrence Purpura, Elizabeth Ervin, Alex Tumusiime, Stephen Balinandi, Jackson Kayondo, Sophia Mulei, Anne Marion Namutebi, Patrick Tusiime, Steven Wiersma, Stuart Nichol, Pierre Rollin, John Klena, Barbara Knust, Trevor Shoemaker
On March 9, 2016, a male butcher from Kabale District, Uganda, aged 45 years, reported to the Kabale Regional Referral Hospital with fever, fatigue, and headache associated with black tarry stools and bleeding from the nose. One day later, a student aged 16 years from a different sub-county in Kabale District developed similar symptoms and was admitted to the same hospital. The student also had a history of contact with livestock. Blood specimens collected from both patients were sent for testing for Marburg virus disease, Ebola virus disease, Rift Valley fever (RVF), and Crimean Congo Hemorrhagic fever at the Uganda Virus Research Institute, as part of the viral hemorrhagic fevers surveillance program...
November 4, 2016: MMWR. Morbidity and Mortality Weekly Report
https://www.readbyqxmd.com/read/27807228/tim-1-promotes-hepatitis-c-virus-cell-attachment-and-infection
#20
Jing Wang, Luhua Qiao, Zhouhua Hou, Guangxiang Luo
: Human TIM and TAM family proteins were recently found to serve as phosphatidylserine (PS) receptors which promote infections by many different viruses, including dengue virus, West Nile virus, Ebola virus, Marburg virus, and Zika virus. In the present study, we provide substantial evidence demonstrating that TIM-1 is important for efficient infection by hepatitis C virus (HCV). The knockdown of TIM-1 expression significantly reduced HCV infection but not HCV RNA replication. Likewise, TIM-1 knockout in Huh-7...
January 15, 2017: Journal of Virology
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