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A Multicenter, Multi-Outbreak, Randomized, Controlled Safety And
2018 Ebola MCM RCT Protocol Page 1 of 92 IND#: 125530 CONFIDENTIAL 4 October 2019, version 7.0 A Multicenter, Multi-Outbreak, Randomized, Controlled Safety and Efficacy Study of Investigational Therapeutics for the Treatment of Patients with Ebola Virus Disease Short Title: 2018 Ebola MCM RCT Protocol Sponsored by: Office of Clinical Research Policy and Regulatory Operations (OCRPRO) National Institute of Allergy and Infectious Diseases 5601 Fishers Lane Bethesda, MD 20892 NIH Protocol Number: 19-I-0003 Protocol IND #: 125530 ClinicalTrials.gov Number: NCT03719586 Date: 4 October 2019 Version: 7.0 CONFIDENTIAL This document is confidential. No part of it may be transmitted, reproduced, published, or used by other persons without prior written authorization from the study sponsor and principal investigator. 2018 Ebola MCM RCT Protocol Page 2 of 92 IND#: 125530 CONFIDENTIAL 4 October 2019, version 7.0 KEY ROLES DRC Principal Investigator: Jean-Jacques Muyembe-Tamfum, MD, PhD Director-General, DRC National Institute for Biomedical Research Professor of Microbiology, Kinshasa University Medical School Kinshasa Gombe Democratic Republic of the Congo Phone: +243 898949289 Email: [email protected] Other International Investigators: see Appendix E Statistical Lead: Lori Dodd, PhD Biostatistics Research Branch, DCR, NIAID 5601 Fishers Lane, Room 4C31 Rockville, MD 20852 Phone: 240-669-5247 Email: [email protected] U.S. Principal Investigator: Richard T. Davey, Jr., MD Clinical Research Section, LIR, NIAID, NIH Building 10, Room 4-1479, Bethesda, -
Grapevine Virus Diseases: Economic Impact and Current Advances in Viral Prospection and Management1
1/22 ISSN 0100-2945 http://dx.doi.org/10.1590/0100-29452017411 GRAPEVINE VIRUS DISEASES: ECONOMIC IMPACT AND CURRENT ADVANCES IN VIRAL PROSPECTION AND MANAGEMENT1 MARCOS FERNANDO BASSO2, THOR VINÍCIUS MArtins FAJARDO3, PASQUALE SALDARELLI4 ABSTRACT-Grapevine (Vitis spp.) is a major vegetative propagated fruit crop with high socioeconomic importance worldwide. It is susceptible to several graft-transmitted agents that cause several diseases and substantial crop losses, reducing fruit quality and plant vigor, and shorten the longevity of vines. The vegetative propagation and frequent exchanges of propagative material among countries contribute to spread these pathogens, favoring the emergence of complex diseases. Its perennial life cycle further accelerates the mixing and introduction of several viral agents into a single plant. Currently, approximately 65 viruses belonging to different families have been reported infecting grapevines, but not all cause economically relevant diseases. The grapevine leafroll, rugose wood complex, leaf degeneration and fleck diseases are the four main disorders having worldwide economic importance. In addition, new viral species and strains have been identified and associated with economically important constraints to grape production. In Brazilian vineyards, eighteen viruses, three viroids and two virus-like diseases had already their occurrence reported and were molecularly characterized. Here, we review the current knowledge of these viruses, report advances in their diagnosis and prospection of new species, and give indications about the management of the associated grapevine diseases. Index terms: Vegetative propagation, plant viruses, crop losses, berry quality, next-generation sequencing. VIROSES EM VIDEIRAS: IMPACTO ECONÔMICO E RECENTES AVANÇOS NA PROSPECÇÃO DE VÍRUS E MANEJO DAS DOENÇAS DE ORIGEM VIRAL RESUMO-A videira (Vitis spp.) é propagada vegetativamente e considerada uma das principais culturas frutíferas por sua importância socioeconômica mundial. -
Imaging, Tracking and Computational Analyses of Virus Entry and Egress
1 Review 2 Imaging, Tracking and Computational Analyses of 3 Virus Entry and Egress with the Cytoskeleton 4 I-Hsuan Wang 1,†, Christoph J. Burckhardt 2,†, A. Yakimovich 3 and Urs F. Greber 4,* 5 1 Division of Virology, Institute of Medical Science, tHe University of ToKyo, ToKyo 108-8639, Japan 6 2 UT SoutHwestern Medical Center, Lyda Hill Department of Bioinformatics, Dallas TX 75390, USA 7 3 MRC Laboratory for Molecular Cell Biology, University College London, London, United Kingdom 8 4 Department of Molecular Life Sciences, University of ZuricH, WintertHurerstrasse 190, CH-8057 ZuricH, 9 Switzerland 10 * Correspondence: [email protected], Telephone: +41 44 635 4841, Fax: +41 44 635 6817 11 † These autHors contributed equally to tHis work. 12 Received: date; Accepted: date; PublisHed: date 13 Abstract: Viruses Have a dual nature - particles are ‘passive substances’ lacKing chemical energy 14 transformation, wHereas infected cells are ‘active substances’ turning-over energy. How passive 15 viral substances convert to active substances, comprising viral replication and assembly 16 compartments Has been of intense interest to virologists, cell and molecular biologists and 17 immunologists. Infection starts witH virus entry into a susceptible cell and delivers tHe viral 18 genome to the replication site. THis is a multi-step process, and involves tHe cytosKeleton and 19 associated motor proteins. LiKewise, the egress of progeny virus particles from the replication site 20 to the extracellular space is enHanced by tHe cytosKeleton and associated motor proteins. THis 21 overcomes tHe limitation of tHermal diffusion, and transports virions and virion components, 22 often in association witH cellular organelles. -
Changes to Virus Taxonomy 2004
Arch Virol (2005) 150: 189–198 DOI 10.1007/s00705-004-0429-1 Changes to virus taxonomy 2004 M. A. Mayo (ICTV Secretary) Scottish Crop Research Institute, Invergowrie, Dundee, U.K. Received July 30, 2004; accepted September 25, 2004 Published online November 10, 2004 c Springer-Verlag 2004 This note presents a compilation of recent changes to virus taxonomy decided by voting by the ICTV membership following recommendations from the ICTV Executive Committee. The changes are presented in the Table as decisions promoted by the Subcommittees of the EC and are grouped according to the major hosts of the viruses involved. These new taxa will be presented in more detail in the 8th ICTV Report scheduled to be published near the end of 2004 (Fauquet et al., 2004). Fauquet, C.M., Mayo, M.A., Maniloff, J., Desselberger, U., and Ball, L.A. (eds) (2004). Virus Taxonomy, VIIIth Report of the ICTV. Elsevier/Academic Press, London, pp. 1258. Recent changes to virus taxonomy Viruses of vertebrates Family Arenaviridae • Designate Cupixi virus as a species in the genus Arenavirus • Designate Bear Canyon virus as a species in the genus Arenavirus • Designate Allpahuayo virus as a species in the genus Arenavirus Family Birnaviridae • Assign Blotched snakehead virus as an unassigned species in family Birnaviridae Family Circoviridae • Create a new genus (Anellovirus) with Torque teno virus as type species Family Coronaviridae • Recognize a new species Severe acute respiratory syndrome coronavirus in the genus Coro- navirus, family Coronaviridae, order Nidovirales -
Serological Detection of Cardamom Mosaic Virus Infecting Small Cardamom, Elettaria Cardamomum L
Int. J. Life. Sci. Scienti. Res., 2(4): 333-338 (ISSN: 2455-1716) Impact Factor 2.4 JULY-2016 Research Article (Open access) Serological Detection of Cardamom Mosaic Virus Infecting Small Cardamom, Elettaria cardamomum L. Snigdha Tiwari 1*, Anitha Peter2, Shamprasad Phadnis3 1Ph. D Scholar, Department of Molecular Biology and Genetic Engineering, G. B. Pant University of Agriculture and Technology, Pantnagar, Uttarkhand, India 2Associate Professor, Department of Plant Biotechnology, UAS (B), GKVK, Bangalore, India 3Ph.D. Scholar, Department of Plant Biotechnology, UAS (B), GKVK, Bangalore, India *Address for Correspondence: Snigdha Tiwari, Ph. D Scholar, Department of Molecular Biology and Genetic Engineering, G. B. Pant University of Agriculture and Technology, Pantnagar, Uttarkhand, India Received: 20 April 2016/Revised: 19 May 2016/Accepted: 16 June 2016 ABSTRACT- Small Cardamom (Elettariacardamomum L. Maton) is one of the major spice crops of India, which were the world’s largest producer and exporter of cardamom till 1980. There has however been a reduction in production, mainly because of Katte disease, caused by cardamom mosaic virus (CdMV) a potyvirus. Viral diseases can be managed effectively by early diagnosis using serological methods. In the present investigation, CdMV isolates were sampled from Mudigere, Karnataka, ultra purified, and electron micro graphed for confirmation. Polyclonal antibodies were raised against the virus and a direct antigen coating plate Enzyme linked immunosorbent Assay (DAC-ELISA) and Dot-ELISA (DIBA) standardized to detect the virus in diseased and tissue cultured plants. Early diagnosis in planting material will aid in using disease free material for better yields and hence increased profit to the farmer. -
Molecular Analysis of Carnivore Protoparvovirus Detected in White Blood Cells of Naturally Infected Cats
Balboni et al. BMC Veterinary Research (2018) 14:41 DOI 10.1186/s12917-018-1356-9 RESEARCHARTICLE Open Access Molecular analysis of carnivore Protoparvovirus detected in white blood cells of naturally infected cats Andrea Balboni1, Francesca Bassi1, Stefano De Arcangeli1, Rosanna Zobba2, Carla Dedola2, Alberto Alberti2 and Mara Battilani1* Abstract Background: Cats are susceptible to feline panleukopenia virus (FPV) and canine parvovirus (CPV) variants 2a, 2b and 2c. Detection of FPV and CPV variants in apparently healthy cats and their persistence in white blood cells (WBC) and other tissues when neutralising antibodies are simultaneously present, suggest that parvovirus may persist long-term in the tissues of cats post-infection without causing clinical signs. The aim of this study was to screen a population of 54 cats from Sardinia (Italy) for the presence of both FPV and CPV DNA within buffy coat samples using polymerase chain reaction (PCR). The DNA viral load, genetic diversity, phylogeny and antibody titres against parvoviruses were investigated in the positive cats. Results: Carnivore protoparvovirus 1 DNA was detected in nine cats (16.7%). Viral DNA was reassembled to FPV in four cats and to CPV (CPV-2b and 2c) in four cats; one subject showed an unusually high genetic complexity with mixed infection involving FPV and CPV-2c. Antibodies against parvovirus were detected in all subjects which tested positive to DNA parvoviruses. Conclusions: The identification of FPV and CPV DNA in the WBC of asymptomatic cats, despite the presence of specific antibodies against parvoviruses, and the high genetic heterogeneity detected in one sample, confirmed the relevant epidemiological role of cats in parvovirus infection. -
Advances in the Study of Transmissible Respiratory Tumours in Small Ruminants Veterinary Microbiology
Veterinary Microbiology 181 (2015) 170–177 Contents lists available at ScienceDirect Veterinary Microbiology journa l homepage: www.elsevier.com/locate/vetmic Advances in the study of transmissible respiratory tumours in small ruminants a a a a,b a, M. Monot , F. Archer , M. Gomes , J.-F. Mornex , C. Leroux * a INRA UMR754-Université Lyon 1, Retrovirus and Comparative Pathology, France; Université de Lyon, France b Hospices Civils de Lyon, France A R T I C L E I N F O A B S T R A C T Sheep and goats are widely infected by oncogenic retroviruses, namely Jaagsiekte Sheep RetroVirus (JSRV) Keywords: and Enzootic Nasal Tumour Virus (ENTV). Under field conditions, these viruses induce transformation of Cancer differentiated epithelial cells in the lungs for Jaagsiekte Sheep RetroVirus or the nasal cavities for Enzootic ENTV Nasal Tumour Virus. As in other vertebrates, a family of endogenous retroviruses named endogenous Goat JSRV Jaagsiekte Sheep RetroVirus (enJSRV) and closely related to exogenous Jaagsiekte Sheep RetroVirus is present Lepidic in domestic and wild small ruminants. Interestingly, Jaagsiekte Sheep RetroVirus and Enzootic Nasal Respiratory infection Tumour Virus are able to promote cell transformation, leading to cancer through their envelope Retrovirus glycoproteins. In vitro, it has been demonstrated that the envelope is able to deregulate some of the Sheep important signaling pathways that control cell proliferation. The role of the retroviral envelope in cell transformation has attracted considerable attention in the past years, but it appears to be highly dependent of the nature and origin of the cells used. Aside from its health impact in animals, it has been reported for many years that the Jaagsiekte Sheep RetroVirus-induced lung cancer is analogous to a rare, peculiar form of lung adenocarcinoma in humans, namely lepidic pulmonary adenocarcinoma. -
An Expanded View of Viruses
An Expanded View of Viruses Urs F. Greber 1) & Ralf Bartenschlager 2) 1) Department of Molecular Life Sciences, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland 2) Department of Infectious Diseases, Molecular Virology, Heidelberg University, Im Neuenheimer Feld 345, 69198 Heidelberg, Germany Correspondence to: [email protected] [email protected] 1 figure Keywords: Zoonosis; Pandemics; Dengue, Ebola; Influenza; Entry; Endocytosis; Uncoating; Transport; Filovirus; Comparative genomics; Computational analyses; Virus-host interactions; Filamentous virus; Bacterial biofilm; Phage; Bacteriophage; Glycan; Immunity; Infection; Disease; Evolution; Variability; Giant virus; Ferret; Guinea pig; Emerging disease; Pandemic; Host range; Enveloped virus; 1 Viruses are ubiquitous, and are important in medicine, biology, biotechnology and ecology. All kinds of cells can be infected with viruses, and sometimes, a particular cell is infected with different viruses at the same time. The virus particle, ‘virion’ is composed of the viral coat proteins sheltering the viral genome, and is often surrounded by a lipid “envelope”. A virion is small compared to cells, and when it enters cells gives rise to infection distinct from an intracellular bacterial pathogen (Lwoff, 1957). A virus-infected cell has a profoundly altered homeostasis due to numerous interactions between cellular and viral components. This leads to evolutionary pressure on both virus and host, and argues that viruses are a part of life (Ludmir & Enquist, 2009). Our cells can be infected by viruses causing acute disease, such as respiratory disease by Influenza virus or rhinoviruses, or chronic disease, such as hepatitis or immune deficiency. However, most viral attacks on cells are fend off, or the spread of viruses in an infected organism is restricted, and infection abrogated. -
A Field Guide to Eukaryotic Transposable Elements
GE54CH23_Feschotte ARjats.cls September 12, 2020 7:34 Annual Review of Genetics A Field Guide to Eukaryotic Transposable Elements Jonathan N. Wells and Cédric Feschotte Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York 14850; email: [email protected], [email protected] Annu. Rev. Genet. 2020. 54:23.1–23.23 Keywords The Annual Review of Genetics is online at transposons, retrotransposons, transposition mechanisms, transposable genet.annualreviews.org element origins, genome evolution https://doi.org/10.1146/annurev-genet-040620- 022145 Abstract Annu. Rev. Genet. 2020.54. Downloaded from www.annualreviews.org Access provided by Cornell University on 09/26/20. For personal use only. Copyright © 2020 by Annual Reviews. Transposable elements (TEs) are mobile DNA sequences that propagate All rights reserved within genomes. Through diverse invasion strategies, TEs have come to oc- cupy a substantial fraction of nearly all eukaryotic genomes, and they rep- resent a major source of genetic variation and novelty. Here we review the defining features of each major group of eukaryotic TEs and explore their evolutionary origins and relationships. We discuss how the unique biology of different TEs influences their propagation and distribution within and across genomes. Environmental and genetic factors acting at the level of the host species further modulate the activity, diversification, and fate of TEs, producing the dramatic variation in TE content observed across eukaryotes. We argue that cataloging TE diversity and dissecting the idiosyncratic be- havior of individual elements are crucial to expanding our comprehension of their impact on the biology of genomes and the evolution of species. 23.1 Review in Advance first posted on , September 21, 2020. -
Toll-Like Receptor and Cytokine Responses to Infection with Endogenous and Exogenous Koala Retrovirus, and Vaccination As a Control Strategy
Review Toll-Like Receptor and Cytokine Responses to Infection with Endogenous and Exogenous Koala Retrovirus, and Vaccination as a Control Strategy Mohammad Enamul Hoque Kayesh 1,2 , Md Abul Hashem 1,3,4 and Kyoko Tsukiyama-Kohara 1,4,* 1 Transboundary Animal Diseases Centre, Joint Faculty of Veterinary Medicine, Kagoshima University, Kagoshima 890-0065, Japan; [email protected] (M.E.H.K.); [email protected] (M.A.H.) 2 Department of Microbiology and Public Health, Faculty of Animal Science and Veterinary Medicine, Patuakhali Science and Technology University, Barishal 8210, Bangladesh 3 Department of Health, Chattogram City Corporation, Chattogram 4000, Bangladesh 4 Laboratory of Animal Hygiene, Joint Faculty of Veterinary Medicine, Kagoshima University, Kagoshima 890-0065, Japan * Correspondence: [email protected]; Tel.: +81-99-285-3589 Abstract: Koala populations are currently declining and under threat from koala retrovirus (KoRV) infection both in the wild and in captivity. KoRV is assumed to cause immunosuppression and neoplastic diseases, favoring chlamydiosis in koalas. Currently, 10 KoRV subtypes have been identified, including an endogenous subtype (KoRV-A) and nine exogenous subtypes (KoRV-B to KoRV-J). The host’s immune response acts as a safeguard against pathogens. Therefore, a proper understanding of the immune response mechanisms against infection is of great importance for Citation: Kayesh, M.E.H.; Hashem, the host’s survival, as well as for the development of therapeutic and prophylactic interventions. M.A.; Tsukiyama-Kohara, K. Toll-Like A vaccine is an important protective as well as being a therapeutic tool against infectious disease, Receptor and Cytokine Responses to Infection with Endogenous and and several studies have shown promise for the development of an effective vaccine against KoRV. -
Rabbit Anti-Marburgvirus (MARV) VLP Pab ELISA Data
4 Research Court, Suite 300 Rockville, MD 20850 877-411-2041 [email protected] Rabbit anti-Marburgvirus (MARV) VLP pAb ELISA Data: Catalog #: 04-0005 IgG IgG + IgG + Lot #: MMIG201001IBT Dilution MMARV ZEBOV 1:X Antigen Antigen Immunogen: MARV (Musoke strain) Virus-like Particles (VLPs) containing glycoprotein (GP) 1000 3.30 2.66 Nucleoprotein (NP), and viral protein (VP40). 3162 3.07 1.80 10000 2.68 0.89 Description: Protein A purified rabbit polyclonal 31623 1.87 0.37 antibody reactive to MARV VLP raised in New 100000 0.99 0.14 Zealand white rabbits. 316228 0.43 0.05 1000000 0.17 0.02 Supplied: 0.5 mg of antibody is supplied in PBS at a concentration of 5.75 mg/mL. 0.01% Sodium azide has been added. -Antigen is coated on ELISA plates overnight. -Add 200µl blocking buffer then wash wells with Clonality: Polyclonal PBST. -Antiserum is diluted semi-log. Relevance: the filovirus Marburgvirus is a -Incubate antibody for 2 hour. Category A (NIAID) and HHS select agent. -Wash unbound antibodies and add HRP- Recommended Dilutions: conjugated anti-rabbit IgG. -Wash plates and add substrate to develop color for ELISA: Assay-dependent dilution. 20 minutes. WB: Assay-dependent dilution -Read absorbance at 650nm. Amount of color is directly proportional to amount of antibodies. Storage: 2-3 weeks +4oC, -20◦C long term Western Blot Cross Reactivity: Historical data showed some cross-reactivity with Ebola Virus (EBOV) and -Antiserum recognizes Marburg musoke Sudan Virus (SUDV) VLP’s, most likely due to glycoprotein, nucleoprotein, and VP40 antibodies against Baculovirus proteins since the VLP’s were expressed in SF9-Baculovirus system. -
Porcine Parvovirus VP1/VP2 on a Time Series Epitope Mapping: Exploring the Effects of High Hydrostatic Pressure on the Immune Recognition of Antigens
bioRxiv preprint doi: https://doi.org/10.1101/330589; this version posted May 25, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Porcine Parvovirus VP1/VP2 on a Time Series Epitope Mapping: exploring the effects of high hydrostatic pressure on the immune recognition of antigens. Ancelmo Rabelo de Souzaa, Marriam Yamina, Danielle Gavac, Janice Reis Ciacci Zanellac, Maria Sílvia Viccari Gattia, Carlos Francisco Sampaio Bonafea, Daniel Ferreira de Lima Netoa,b* aDepartamento de Bioquímica e Biologia Tecidual e bDepartamento de Genética, Evolução e Bioagentes, Instituto de Biologia, Universidade Estadual de Campinas (UNICAMP), Rua Monteiro Lobato, 255, Cidade Universitária Zeferino Vaz, 13083- 862, Campinas, SP, Brazil. cEmbrapa Suínos e Aves, Laboratório de Virologia de Suínos, 89715-899, Concórdia, SC, Brazil. *Corresponding author: Tel.: +55 19 3521-6229; E-mail: [email protected] bioRxiv preprint doi: https://doi.org/10.1101/330589; this version posted May 25, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. ABSTRACT Porcine parvovirus (PPV) is a DNA virus that causes reproductive failure in gilts and sows, resulting in embryonic and fetal losses worldwide. Epitope mapping of PPV is important for developing new vaccines. In this study, we used spot synthesis analysis for epitope mapping of the capsid proteins of PPV (NADL-2 strain) and correlated the findings with predictive data from immunoinformatics. The virus was exposed to three conditions prior to inoculation in pigs: native (untreated), high hydrostatic pressure (350 MPa for 1 h) at room temperature and high hydrostatic pressure (350 MPa for 1 h) at -18 °C, compared with a commercial vaccine produced using inactivated PPV.