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https://www.readbyqxmd.com/read/29045192/a-dna-vaccine-delivered-by-dermal-electroporation-fully-protects-cynomolgus-macaques-against-lassa-fever
#1
Kathleen A Cashman, Eric R Wilkinson, Carl I Shaia, Paul R Facemire, Todd M Bell, Jeremy J Bearss, Joshua D Shamblin, Suzanne E Wollen, Kate E Broderick, Niranjan Y Sardesai, Connie S Schmaljohn
Lassa virus (LASV) is an ambisense RNA virus in the Arenaviridae family and is the etiological agent of Lassa fever, a severe hemorrhagic disease endemic to West and Central Africa (1,2) . There are no U.S. Food and Drug Administration (FDA)-licensed vaccines available to prevent Lassa fever (1,2) . in our previous studies, we developed a gene-optimized DNA vaccine that encodes the glycoprotein precursor gene of LASV (Josiah strain) and demonstrated that three vaccinations accompanied by dermal electroporation protected guinea pigs from LASV-associated illness and death...
October 18, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/29031848/local-national-and-regional-viral-haemorrhagic-fever-pandemic-potential-in-africa-a-multistage-analysis
#2
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/29019310/lessons-learnt-from-imported-cases-and-onward-transmission-of-lassa-fever-in-europe-support-broader-management-of-viral-haemorrhagic-fevers
#3
Roger Hewson
No abstract text is available yet for this article.
September 2017: Euro Surveillance: Bulletin Européen sur les Maladies Transmissibles, European Communicable Disease Bulletin
https://www.readbyqxmd.com/read/29019309/management-of-a-lassa-fever-outbreak-rhineland-palatinate-germany-2016
#4
Lutz Ehlkes, Maja George, Gerhard Samosny, Florian Burckhardt, Manfred Vogt, Stefan Bent, Klaus Jahn, Philipp Zanger
Due to rapid diagnosis and isolation of imported cases, community outbreaks of viral haemorrhagic fevers (VHF) are considered unlikely in industrialised countries. In March 2016, the first documented locally acquired case of Lassa fever (LF) outside Africa occurred, demonstrating the disease's potential as a cross-border health threat. We describe the management surrounding this case of LF in Rhineland-Palatinate - the German federal state where secondary transmission occurred. Twelve days after having been exposed to the corpse of a LF case imported from Togo, a symptomatic undertaker tested positive for Lassa virus RNA...
September 2017: Euro Surveillance: Bulletin Européen sur les Maladies Transmissibles, European Communicable Disease Bulletin
https://www.readbyqxmd.com/read/29019307/control-measures-following-a-case-of-imported-lassa-fever-from-togo-north-rhine-westphalia-germany-2016
#5
Clara Lehmann, Matthias Kochanek, Diana Abdulla, Stephan Becker, Boris Böll, Anne Bunte, Daniel Cadar, Arno Dormann, Markus Eickmann, Petra Emmerich, Torsten Feldt, Christina Frank, Jochen Fries, Martin Gabriel, Udo Goetsch, René Gottschalk, Stephan Günther, Michael Hallek, Dieter Häussinger, Christian Herzog, Björn Jensen, Felix Kolibay, Michael Krakau, Georg Langebartels, Toni Rieger, Lars Schaade, Jonas Schmidt-Chanasit, Edgar Schömig, Gundolf Schüttfort, Alexander Shimabukuro-Vornhagen, Michael von Bergwelt-Baildon, Ulrike Wieland, Gerhard Wiesmüller, Timo Wolf, Gerd Fätkenheuer
In a patient transferred from Togo to Cologne, Germany, Lassa fever was diagnosed 12 days post mortem. Sixty-two contacts in Cologne were categorised according to the level of exposure, and gradual infection control measures were applied. No clinical signs of Lassa virus infection or Lassa specific antibodies were observed in the 62 contacts. Thirty-three individuals had direct contact to blood, other body fluids or tissue of the patients. Notably, with standard precautions, no transmission occurred between the index patient and healthcare workers...
September 2017: Euro Surveillance: Bulletin Européen sur les Maladies Transmissibles, European Communicable Disease Bulletin
https://www.readbyqxmd.com/read/29017278/favipiravir-and-ribavirin-treatment-of-epidemiologically-linked-cases-of-lassa-fever
#6
Vanessa N Raabe, Gerrit Kann, Bruce S Ribner, Andres Morales, Jay B Varkey, Aneesh K Mehta, G Marshall Lyon, Sharon Vanairsdale, Kelly Faber, Stephan Becker, Markus Eickmann, Thomas Strecker, Shelley Brown, Ketan Patel, Philipp De Leuw, Gundolf Schuettfort, Christoph Stephan, Holger Rabenau, John D Klena, Pierre E Rollin, Anita McElroy, Ute Ströher, Stuart Nichol, Colleen S Kraft, Timo Wolf
Two patients with Lassa fever are described who are the first human cases treated with a combination of ribavirin and favipiravir. Both patients survived but developed transaminitis and had prolonged detectable virus RNA in blood and semen, suggesting that the possibility of sexual transmission of Lassa virus should be considered.
September 1, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/28986849/determining-the-virus-life-cycle-stage-blocked-by-an-antiviral
#7
Claudia S Sepúlveda, Cybele C García, Elsa B Damonte
Among the members of the Arenaviridae family, Junín virus and Lassa virus represent important human health threats generating annual outbreaks of severe human hemorrhagic fever (HF) in endemic areas of Argentina and Western Africa, respectively. Given the lack of a specific and safe chemotherapy, the search for effective antiviral compounds is a continuous demanding effort. During the last two decades, academic research studies originated important results identifying novel molecules to be considered for further in vivo characterization...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28986843/a-primate-model-for-viral-hemorrhagic-fever
#8
Maria S Salvato, Igor S Lukashevich, Yida Yang, Sandra Medina-Moreno, Mahmoud Djavani, Joseph Bryant, Juan David Rodas, Juan Carlos Zapata
Lymphocytic choriomeningitis virus strain WE (LCMV-WE), a Risk Group 3 virus, causes a disease in rhesus monkeys that closely resembles human infection with Lassa fever virus, a Risk Group 4 agent. Three stages of disease progression have been defined and profiled in this model: pre-viremic, viremic, and terminal. The earliest or pre-viremic stage reveals changes in the blood profile predictive of the later stages of disease. In order to identify whether specific changes are pathognomonic, it was necessary to perform a parallel infection with an attenuated virus (LCMV-Armstrong)...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28986841/murine-models-for-viral-hemorrhagic-fever
#9
Rosana Gonzalez-Quintial, Roberto Baccala
Hemorrhagic fever (HF) viruses, such as Lassa, Ebola, and dengue viruses, represent major human health risks due to their highly contagious nature, the severity of the clinical manifestations induced, the lack of vaccines, and the very limited therapeutic options currently available. Appropriate animal models are obviously critical to study disease pathogenesis and develop efficient therapies. We recently reported that the clone 13 (Cl13) variant of the lymphocytic choriomeningitis virus (LCMV-Cl13), a prototype arenavirus closely related to Lassa virus, causes in some mouse strains endothelial damage, vascular leakage, platelet loss, and death, mimicking pathological aspects typically observed in Lassa and other HF syndromes...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28986836/hemorrhagic-fever-virus-budding-studies
#10
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/28986834/assays-to-demonstrate-the-roles-of-arenaviral-nucleoproteins-nps-in-viral-rna-synthesis-and-in-suppressing-type-i-interferon
#11
Qinfeng Huang, Junjie Shao, Yuying Liang, Hinh Ly
Arenaviruses, such as Lassa virus (LASV) and Pichindé virus (PICV), are enveloped viruses with a bi-segmented ambisense RNA genome. The large (L) genomic segment encodes the Z matrix protein and the L RNA-dependent RNA polymerase, whereas the small (S) genomic segment encodes the nucleoprotein (NP) and the glycoprotein (GPC). The NP encapsidates viral genome, is required for viral transcription and replication, and acts as a type I interferon (IFN) antagonist. This article describes assays to demonstrate that NP contains 3'-5' exoribonuclease (RNase) activity to degrade modeled RNA of the pathogen-associated molecular pattern type and suppresses the IFNβ promoter-driven luciferase reporter gene...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28986833/expression-and-x-ray-structural-determination-of-the-nucleoprotein-of-lassa-fever-virus
#12
Xiaoxuan Qi, Wenjian Wang, Haohao Dong, Yuying Liang, Changjiang Dong, Hinh Ly
We describe methods to express the nucleoprotein (NP) of Lassa fever virus (LASV) in E. coli, to purify and crystallize it using the sitting-drop vapor diffusion method. The crystals were screened using Rigaku micro-007 X-ray generator and a dataset was collected at a resolution of 2.36 Å. The crystals belong to space group P3, with the unit cell parameters a = b = 176.35 Å, c = 56.40 Å, α = β = 90°, and γ = 120°. Using the X-ray diffraction method, we constructed a three-dimensional structure of the LASV NP that should aid in the development of novel therapeutic strategies against this virus, for which vaccine and effective treatment modalities are currently unavailable...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28986832/assays-to-assess-arenaviral-glycoprotein-function
#13
Junjie Shao, Xiaoying Liu, Yuying Liang, Hinh Ly
Arenaviruses, such as Lassa virus (LASV) and Pichindé virus (PICV), are enveloped viruses with a bi-segmented ambisense RNA genome. The large (L) genomic segment encodes the Z matrix protein and the L RNA-dependent RNA polymerase, whereas the small (S) genomic segment encodes the nucleoprotein (NP) and the glycoprotein precursor complex (GPC). GPC is processed by signal peptidase in the endoplasmic reticulum into the stable signal peptide (SSP) and GP1/GP2, which is further cleaved by the Golgi-resident subtilisin kexin isozyme-1 (SKI-1)/site-1 protease (S1P) into the cellular receptor-recognition subunit GP1 and the transmembrane subunit GP2, which helps promote the membrane fusion reaction to allow virus entry into the cell...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28986830/studies-of-lassa-virus-cell-entry
#14
Antonella Pasquato, Antonio Herrador Fernandez, Stefan Kunz
Host cell entry is the first and most fundamental step of every virus infection and represents a major barrier for zoonotic transmission and viral emergence. Targeting viral entry appears further as a promising strategy for therapeutic intervention. Several cellular receptors have been identified for Lassa virus, including dystroglycan, TAM receptor tyrosine kinases, and C-type lectins. Upon receptor binding, LASV enters the host cell via a largely unknown clathrin- and dynamin-independent endocytotic pathway that delivers the virus to late endosomes, where fusion occurs after engagement of a second, intracellular receptor, the late endosomal/lysosomal resident protein LAMP1...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28986826/diagnostics-for-lassa-fever-detecting-host-antibody-responses
#15
Maria S Salvato, Igor S Lukashevich, Sandra Medina-Moreno, Juan Carlos Zapata
There are two types of viral diagnostics: (1) those that detect components of the pathogen (like viral RNA or proteins) and (2) those that detect host molecules that rise or fall as a consequence of pathogen infection (like anti-viral antibodies or virus-induced inflammatory cytokines). Quantitative PCR to detect Lassa RNA, and clinical chemistry to detect high liver enzymes (AST/ALT) are commonly used to diagnose Lassa fever. Here, we discuss the various types of diagnostics for Lassa fever and the urgent need for early diagnosis...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28977439/the-genomic-landscape-of-african-populations-in-health-and-disease
#16
Charles N Rotimi, Amy R Bentley, Ayo P Doumatey, Guanjie Chen, Daniel Shriner, Adebowale Adeyemo
A deeper appreciation of the complex architecture of African genomes is critical to the global effort to understand human history, biology and differential distribution of disease by geography and ancestry. Here, we report on how the growing engagement of African populations in genome science is providing new insights into the forces that shaped human genomes before and after the Out-of-Africa migrations. As a result of this human evolutionary history, African ancestry populations have the greatest genomic diversity in the world, and this diversity has important ramifications for genomic research...
October 1, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28967498/comparative-non-metric-and-morphometric-analyses-of-rats-at-residential-halls-of-the-university-of-benin-campus-nigeria
#17
E A Odigie, O K Ekeolu, O D Asemota, E A Uwagie-Ero, I T Aighewi, S U Ighedosa, S F Usifoh, B O Olugasa, O Asemota, T N E Fagboya
BACKGROUND: In mammals and across rat species, the variation in conformation is markedly observed in the head and the variation in the shape of the head is mostly determined by the shape of the skull. Hence comparative topographic analysis and morphometry is a veritable tool in precise categorization of peri-domestic rats and species identification. METHODS: Killed rodents around residential dwellings of students on campus were collected and measurements taken of external morphology...
September 26, 2017: Journal of Infection and Public Health
https://www.readbyqxmd.com/read/28963882/oxidation-sensitive-polymersomes-as-vaccine-nanocarriers-enhance-humoral-responses-against-lassa-virus-envelope-glycoprotein
#18
Clara Galan-Navarro, Marcela Rincon-Restrepo, Gert Zimmer, Erica Ollmann Saphire, Jeffrey A Hubbell, Sachiko Hirosue, Melody A Swartz, Stefan Kunz
Lassa virus (LASV) causes severe hemorrhagic fever with high mortality, yet no vaccine currently exists. Antibodies targeting viral attachment proteins are crucial for protection against many viral infections. However, the envelope glycoprotein (GP)-1 of LASV elicits weak antibody responses due to extensive glycan shielding. Here, we explored a novel vaccine strategy to enhance humoral immunity against LASV GP1. Using structural information, we designed a recombinant GP1 immunogen, and then encapsulated it into oxidation-sensitive polymersomes (PS) as nanocarriers that promote intracellular MHCII loading...
September 27, 2017: Virology
https://www.readbyqxmd.com/read/28945945/macromolecular-antiviral-agents-against-zika-ebola-sars-and-other-pathogenic-viruses
#19
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/28937957/whole-blood-based-multiplex-immunoassays-for-the-evaluation-of-human-biomarker-responses-to-emerging-viruses-in-resource-limited-regions
#20
Jessica R Harmon, Stuart T Nichol, Christina F Spiropoulou, Anita K McElroy
Many emerging viruses such as Ebola and Lassa occur in resource-limited areas of the world. The advent of multiplex immunoassays has facilitated the study of biomarkers of disease since only small amounts of clinical material are required; however, such assays are designed and validated for only plasma or serum. This is a significant impediment when studying infectious diseases in the context of an outbreak in a developing nation. Plasma or serum can be difficult to obtain in the field due to the need for additional processing of infectious materials...
September 22, 2017: Viral Immunology
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