Recent #advances in #marburgvirus #research (F1000Res., abstract)

[Source: F1000 Research, full page: (LINK). Abstract, edited.]

Recent advances in marburgvirus research [version 1; peer review: 3 approved]

Judith Olejnik 1,2, Elke Mühlberger 1,2, Adam J. Hume 1,2

Author details: 1 Department of Microbiology, Boston University School of Medicine, Boston, Massachusetts, 02118, USA; 2 National Emerging Infectious Diseases Laboratories, Boston University, Boston, Massachusetts, 02118, USA

 

Abstract

Marburgviruses are closely related to ebolaviruses and cause a devastating disease in humans. In 2012, we published a comprehensive review of the first 45 years of research on marburgviruses and the disease they cause, ranging from molecular biology to ecology. Spurred in part by the deadly Ebola virus outbreak in West Africa in 2013–2016, research on all filoviruses has intensified. Not meant as an introduction to marburgviruses, this article instead provides a synopsis of recent progress in marburgvirus research with a particular focus on molecular biology, advances in animal modeling, and the use of Egyptian fruit bats in infection experiments.

Keywords: Marburg virus, marburgviruses, filovirus, filoviruses, Egyptian rousette, viral proteins

Corresponding author: Adam J. Hume

Competing interests: No competing interests were disclosed.

Grant information: This work was supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under award numbers R01-AI133486 and R21-AI135912.

The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Copyright:  © 2019 Olejnik J et al. This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

How to cite: Olejnik J, Mühlberger E and Hume AJ. Recent advances in marburgvirus research [version 1; peer review: 3 approved]. F1000Research 2019, 8(F1000 Faculty Rev):704 (https://doi.org/10.12688/f1000research.17573.1)

First published: 21 May 2019, 8(F1000 Faculty Rev):704 (https://doi.org/10.12688/f1000research.17573.1)

Latest published: 21 May 2019, 8(F1000 Faculty Rev):704 (https://doi.org/10.12688/f1000research.17573.1)

Keywords: Filovirus; Marburg virus.

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Generation and Selection of a #Panel of Pan- #Filovirus Single-Chain #Antibodies using Cell-Free Ribosome Display (Am J Trop Med Hyg., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Am J Trop Med Hyg. 2019 May 6. doi: 10.4269/ajtmh.18-0658. [Epub ahead of print]

Generation and Selection of a Panel of Pan-Filovirus Single-Chain Antibodies using Cell-Free Ribosome Display.

Kunamneni A1,2, Clarke EC2, Ye C2, Bradfute SB2, Durvasula R2,1.

Author information: 1 Department of Medicine, Loyola University Medical Center, Chicago, Illinois. 2 Department of Internal Medicine, Center for Global Health, University of New Mexico, Albuquerque, New Mexico.

 

Abstract

Filoviruses, which include ebolaviruses and marburgvirus, can cause outbreaks of highly lethal hemorrhagic fever. This disease causes significant morbidity and mortality in humans and non-human primates, with human fatality rates reaching 90% during some outbreaks. Currently, there are a lack of licensed vaccines or antivirals for these viruses. Since early symptoms of filovirus infection mimic more common diseases, there is a strong unmet public health and biodefense need for broad-spectrum filovirus rapid diagnostics. We have generated a panel of mouse single-chain Fv-antibodies (scFvs) to filovirus glycoproteins (GPs) using cell-free ribosome display and determined their cross-reactivity profiles to all known filovirus species. Two scFvs (4-2 and 22-1) were able to detect all known Ebolavirus and Marburgvirusspecies. This is the first report on ribosome display scFvs that can detect a broad set of filovirus GPs, which demonstrates the potential for use in diagnostics.

PMID: 31074409 DOI: 10.4269/ajtmh.18-0658

Keywords: Filovirus; Ebola; Marburg; Diagnostic tests.

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Comparative analysis of #serologic cross-reactivity using #convalescent sera from #filovirus-experimentally infected fruit #bats (Sci Rep., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Sci Rep. 2019 Apr 30;9(1):6707. doi: 10.1038/s41598-019-43156-z.

Comparative analysis of serologic cross-reactivity using convalescent sera from filovirus-experimentally infected fruit bats.

Schuh AJ1,2, Amman BR1, Sealy TS1, Flietstra TD1, Guito JC1, Nichol ST1, Towner JS3,4.

Author information: 1 Viral Special Pathogens Branch, Division of High-Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, Atlanta, GA, 30329, USA. 2 Commissioned Corps, United States Public Health Service, Rockville, MD, 20852, USA. 3 Viral Special Pathogens Branch, Division of High-Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, Atlanta, GA, 30329, USA. jit8@cdc.gov. 4 Department of Pathology, College of Veterinary Medicine, University of Georgia, Athens, GA, 30602, USA. jit8@cdc.gov.

 

Abstract

With the exception of Reston and Bombali viruses, the marburgviruses and ebolaviruses (family Filoviridae) cause outbreaks of viral hemorrhagic fever in sub-Saharan Africa. The Egyptian rousette bat (ERB) is a natural reservoir host for the marburgviruses and evidence suggests that bats are also natural reservoirs for the ebolaviruses. Although the search for the natural reservoirs of the ebolaviruses has largely involved serosurveillance of the bat population, there are no validated serological assays to screen bat sera for ebolavirus-specific IgG antibodies. Here, we generate filovirus-specific antisera by prime-boost immunization of groups of captive ERBs with all seven known culturable filoviruses. After validating a system of filovirus-specific indirect ELISAs utilizing infectious-based virus antigens for detection of virus-specific IgG antibodies from bat sera, we assess the level of serological cross-reactivity between the virus-specific antisera and heterologous filovirus antigens. This data is then used to generate a filovirus antibody fingerprint that can predict which of the filovirus species in the system is most antigenically similar to the species responsible for past infection. Our filovirus IgG indirect ELISA system will be a critical tool for identifying bat species with high ebolavirus seroprevalence rates to target for longitudinal studies aimed at establishing natural reservoir host-ebolavirus relationships.

PMID: 31040343 DOI: 10.1038/s41598-019-43156-z

Keywords: Serology; Ebola; Marburg; Filovirus; Bats.

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#ICTV Virus #Taxonomy #Profile: #Filoviridae (J Gen Virol., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

J Gen Virol. 2019 Apr 25. doi: 10.1099/jgv.0.001252. [Epub ahead of print]

ICTV Virus Taxonomy Profile: Filoviridae.

Kuhn JH1, Amarasinghe GK2, Basler CF3, Bavari S4, Bukreyev A5, Chandran K6, Crozier I7, Dolnik O8, Dye JM4, Formenty PBH9, Griffiths A10, Hewson R11, Kobinger GP12, Leroy EM13, Mühlberger E10, Netesov Нетёсов Сергей Викторович SV14, Palacios G4, Pályi B15, Pawęska JT16, Smither SJ17, Takada 高田礼人 A18, Towner JS19, Wahl V20, Ictv Report Consortium.

Author information: 1 ​NIH/NIAID Integrated Research Facility at Fort Detrick, (IRF-Frederick), Frederick, MD 21702, USA. 2 ​Washington University School of Medicine, St. Louis, MO 63110, USA. 3 ​Center for Microbial Pathogenesis, Georgia State University, Atlanta GA 30303, USA. 4 ​United States Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702, USA. 5 ​The University of Texas Medical Branch, Galveston, TX 77555, USA. 6 ​Albert Einstein College of Medicine, Bronx, NY 10461, USA. 7 ​Integrated Research Facility at Fort Detrick, Clinical Monitoring Research Program Directorate, Frederick National Laboratory for Cancer Research supported by the National Cancer Institute, Frederick, MD 21702, USA. 8 ​Institute of Virology, Philipps University Marburg, 35043 Marburg, Germany. 9 ​World Health Organization, CH-1211 Geneva, Switzerland. 10 ​Department of Microbiology and National Emerging Infectious Diseases Laboratories, Boston University School of Medicine, Boston, MA 02118, USA. 11​ Public Health England, Porton Down, Wiltshire, SP4 0JG Salisbury, UK. 12 ​Université Laval, Québec City, QC G1V 0A6, Canada. 13 ​Infectious Diseases and Vectors Unit, Institut de Recherche pour le Développement, 911 Av Agropolis, 34394 Montpellier, France. 14 ​Novosibirsk State University, Novosibirsk, Novosibirsk Oblast, 630090, Russia. 15 ​National Biosafety Laboratory, National Public Health Center, Budapest, Hungary. 16​ National Institute for Communicable Diseases of the National Health Laboratory Service, 2131 Sandringham-Johannesburg, Gauteng, South Africa. 17 ​Defence Science and Technology Laboratory, Porton Down, Salisbury, Wiltshire SP4 0JQ, UK. 18 ​Division of Global Epidemiology, Hokkaido University Research Center for Zoonosis Control, 001-0020 Sapporo, Japan. 19 ​Viral Special Pathogens Branch, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA. 20 ​National Biodefense Analysis and Countermeasures Center, Frederick, MD 21702, USA.

 

Abstract

Members of the family Filoviridae produce variously shaped, often filamentous, enveloped virions containing linear non-segmented, negative-sense RNA genomes of 15-19 kb. Several filoviruses (e.g., Ebola virus) are pathogenic for humans and are highly virulent. Several filoviruses infect bats (e.g., Marburg virus), whereas the hosts of most other filoviruses are unknown. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on Filoviridae, which is available at http://www.ictv.global/report/filoviridae.

PMID: 31021739 DOI: 10.1099/jgv.0.001252

Keywords: Filovirus.

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#Assessment of the #function and intergenus-compatibility of #Ebola and #Lloviu virus #proteins (J Gen Virol., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

J Gen Virol. 2019 Apr 24. doi: 10.1099/jgv.0.001261. [Epub ahead of print]

Assessment of the function and intergenus-compatibility of Ebola and Lloviu virus proteins.

Kämper L1, Zierke L1, Schmidt ML1, Müller A1, Wendt L1, Brandt J1, Hartmann E1, Braun S1, Holzerland J2, Groseth A2, Hoenen T1.

Author information: 1 Institute for Molecular Virology and Cell Biology, Friedrich-Loeffler-Institut, Greifswald – Insel Riems, Germany. 2 Junior Research Group Arenavirus Biology, Friedrich-Loeffler-Institut, Greifswald – Insel Riems, Germany.

 

Abstract

Sequences for Lloviu virus (LLOV), a putative novel filovirus, were first identified in Miniopterus schreibersii bats in Spain following a massive bat die-off in 2002, and also recently found in bats in Hungary. However, until now it is unclear if these sequences correspond to a fully functional, infectious virus, and whether it will show a pathogenic phenotype like African filoviruses, such as ebola- and marburgviruses, or be apathogenic for humans, like the Asian filovirus Reston virus. Since no infectious virus has been recovered, the only opportunity to study infectious LLOV is to use a reverse genetics-based full-length clone system to de novo generate LLOV. As a first step in this process, and to investigate whether the identified sequences indeed correspond to functional viral proteins, we have developed life cycle modelling systems for LLOV, which allow us to study genome replication and transcription as well as entry of this virus. We show that all LLOV proteins fulfill their canonical role in the virus life cycle as expected based on the well-studied related filovirus Ebola virus. Further, we have analysed the intergenus-compatibility of proteins that have to act in concert to facilitate the virus life cycle. We show that some but not all proteins from LLOV and Ebola virus are compatible with each other, emphasizing the close relationship of these viruses, and informing future studies of filovirus biology with respect to the generation of genus-chimeric proteins in order to probe virus protein-protein interactions on a functional level.

PMID: 31017565 DOI: 10.1099/jgv.0.001261

Keywords: Filovirus; Bats; Lloviu virus; Spain; Hungary; Ebola.

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#Diagnostics for #filovirus #detection: impact of recent #outbreaks on the diagnostic landscape (BMJ Glob Health, abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

BMJ Glob Health. 2019 Feb 7;4(Suppl 2):e001112. doi: 10.1136/bmjgh-2018-001112. eCollection 2019.

Diagnostics for filovirus detection: impact of recent outbreaks on the diagnostic landscape.

Emperador DM1, Mazzola LT1, Wonderly Trainor B2, Chua A3, Kelly-Cirino C1.

Author information: 1 FIND, Emerging Threats Programme, Geneva, Switzerland. 2 FIND, Geneva, Switzerland. 3 Médecins Sans Frontières (MSF), Geneva, Switzerland.

 

Abstract

Ebolaviruses and Marburg virus (MARV) both belong to the family Filoviridae and cause severe haemorrhagic fever in humans. Due to high mortality rates and potential for spread from rural to urban regions, they are listed on the WHO R&D blueprint of high-priority pathogens. Recent ebolavirus outbreaks in Western and Central Africa have highlighted the importance of diagnostic testing in epidemic preparedness for these pathogens and led to the rapid development of a number of commercially available benchtop and point-of-care nucleic acid amplification tests as well as serological assays and rapid diagnostic tests. Despite these advancements, challenges still remain. While products approved under emergency use licenses during outbreak periods may continue to be used post-outbreak, a lack of clarity and incentive surrounding the regulatory approval pathway during non-outbreak periods has deterred many manufacturers from seeking full approvals. Waning of funding and poor access to samples after the 2014-2016 outbreak also contributed to cessation of development once the outbreak was declared over. There is a need for tests with improved sensitivity and specificity, and assays that can use alternative sample types could reduce the need for invasive procedures and expensive equipment, making testing in field conditions more feasible. For MARV, availability of diagnostic tests is still limited, restricted to a single ELISA test and assay panels designed to differentiate between multiple pathogens. It may be helpful to extend the target product profile for ebolavirus diagnostics to include MARV, as the viruses have many overlapping characteristics.

KEYWORDS: ebolavirus; in vitro diagnostics; marburgvirus; outbreak

PMID: 30899573 PMCID: PMC6407532 DOI: 10.1136/bmjgh-2018-001112

Keywords: Filovirus; Ebola; Marburg; Diagnostic tests.

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Achieving cross-reactivity with #panebolavirus #antibodies (Curr Opin Virol., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Curr Opin Virol. 2019 Mar 15;34:140-148. doi: 10.1016/j.coviro.2019.01.003. [Epub ahead of print]

Achieving cross-reactivity with pan-ebolavirus antibodies.

King LB1, Milligan JC1, West BR1, Schendel SL1, Ollmann Saphire E2.

Author information: 1 Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA. 2 Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA; Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA. Electronic address: erica@scripps.edu.

 

Abstract

Filoviruses are the causative agents of highly lethal outbreaks in sub-Saharan Africa. Although an experimental vaccine and several therapeutics are being deployed in the Democratic Republic of Congo to combat the ongoing Ebola virus outbreak, these therapies are specific for only one filovirus species. There is currently significant interest in developing broadly reactive monoclonal antibodies (mAbs) with utility against the variety of ebolaviruses that may emerge. Thus far, the primary target of these mAbs has been the viral spike glycoprotein (GP). Here we present an overview of GP-targeted antibodies that exhibit broad reactivity and the structural characteristics that could confer this cross-reactivity. We also discuss how these structural features could be leveraged to design vaccine antigens that elicit cross-reactive antibodies.

Copyright © 2019 Elsevier B.V. All rights reserved.

PMID: 30884329 DOI: 10.1016/j.coviro.2019.01.003

Keywords: Ebola; Filovirus; Monoclonal antibodies.

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