Special Issue "Advances in Filovirus Research 2013"
Deadline for manuscript submissions: 31 July 2013
Dr. Jens H. Kuhn
Integrated Research Facility at Fort Detrick (IRF-Frederick), Office 3A110, NIH/NIAID/DCR, B-8200 Research Plaza, Fort Detrick, Frederick, MD 21702, USA
Phone: +1 301 631 7245
Fax: +1 301 619 5029
Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. Papers will be published continuously (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.
Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are refereed through a peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Viruses is an international peer-reviewed Open Access monthly journal published by MDPI.
Type of Paper: Communication
Title: Dose Considerations for Non-Human Primate Filovirus Challenge Studies
Authors: Michael Bailey 1‡, Elizabeth Glaze 2,*‡
Affiliations: 1 Transformational Medical Technologies JPEO-Chemical and Biological Defense, Fort Belvoir, VA, USA; Michael.Bailey@DTRA.MIL; 2 Division of Microbiology and Infectious Diseases, National Institutes of Allergy and Infectious Diseases, Bethesda, MD, USA; email@example.com
* Author to whom correspondence should be addressed; firstname.lastname@example.org; Tel.: 1-301-435-7612; Fax: 1-301-402-0804.
‡ Co facilitators for the FANG Animal Model Subgroup
Abstract: Design considerations for animal model studies intended to demonstrate efficacy of medical countermeasures using FDA’s “Animal Rule” (21 CRF 314.600 for drugs: 21 CRF 601.90 for biological products) should ideally include the following, (1) a challenge agent that is as close as possible to the etiologic agent that causes the human disease, (2) the pathogenic determinants of the disease induced by the challenge agent in the animal model should be similar to those understood in humans, (3) the route of exposure to the challenge agent should be the same as the anticipated human exposure route, and (4) there should be reliable and reproducible methods to quantify the challenge dose. In this paper, we discussed the basis for selection of an infectious dose for filovirus challenge studies in nonhuman primates. Key to the discussion, were the implications of the challenge route on the dose selection, and the current limitations of using a lethal dose-based approach when designing filovirus challenge studies for nonhuman primates. We identify research gaps that, when filled, will enhance the reliability of the nonhuman primate models of filovirus infection.
Keywords: Filovirus; Ebolavirus, Marburgvirus, Animal Model Development; Animal Rule
Type of Paper: Review
Title: Immune Evasion in Ebolavirus Infections
Authors: Jonathan Audet 1 and Gary P. Kobinger 1,2,3,4*
Affiliations: 1 Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba, Canada. E-Mail: email@example.com;
2 National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, Canada, R3E 3R2;
3 Department of Immunology, University of Manitoba, Winnipeg, Manitoba, Canada;
4 Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medi-cine, Philadelphia, PA, USA; * Author to whom correspondence should be addressed; E-Mail: Gary_Kobinger@phac-aspc.gc.ca (F.L.); Tel.: +1-204-784-5923; Fax: +1-204-789-2140.
Abstract: Ebolavirus infects humans as well as several animal species. It can lead to a highly lethal disease, with mortality rates approaching 90% in primates. Recent advances have deepened our understanding of how this virus is able to prevent the development of protective immune responses. The Ebolavirus genome encodes 8 proteins, four of which were shown to interact with the host in ways that counteract the immune response. The VP35 is capable of capping dsRNA and prevents detection of the virus by immune cells. The main role of sGP is still unclear, but it is capable of subverting the anti-GP1,2 antibody response. The GP1,2 protein has shown anti-tetherin activity. Finally, VP24 interferes with the production of interferons and interferon signalling in infected cells. Taken together, these data point to extensive adaptation of Ebolavirus to evade the immune system of dead end hosts. Acquiring a better understanding of these interactions may help develop treat-ments that will not be restricted to a single Ebolavirus species.
Keywords: Ebolavirus; host-pathogen interactions; immune evasion.
The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.
Type of Paper: Article
Title: Clinical Pathology Parameters for Objective Euthanasia Assessment in Ebola Virus Infected Nonhuman Primates
Authors: Travis K. Warren 1,*, Jay Wells 1, Anna Honko 1, Joshua C. Johnson 1, Eric Mucker 1, Sarah W. Norris 1, Mark Chappell 1,2, John M. Dye 1, and William D. Pratt 2
Affiliations: 1 US Army Medical Research Institute for Infectious Diseases, 1425 Porter St., Fort Detrick, Maryland, 21702; E-Mails: Travis.Warren@amedd.army.mil; Jay.B.Wells@us.army.mil; Anna.Honko@us.army.mil; Joshua.C.Johnson@us.army.mil; Eric.Mucker@amedd.army.mil; Sarah.W.Norris@us.army.mil; Mark.Chappell@usuhs.edu; John.M.Dye1@us.army.mil; Willamd.Pratt@us.army.mil; 2 Current Affiliation, Armed Forces Radiobiology Research Institute, 8901 Wisconsin Avenue, Building 42, Bethesda, MD 20889; * Author to whom correspondence should be addressed; E-Mail: Travis.Warren@amedd.army.mil; Tel.: +1-301-619-3414; Fax: +1-301-619-0350
Abstract: Although no vaccine and therapeutic products have yet been licensed for use against filovirus infections, multiple products – including both vaccine and therapeutic candidates – are currently being developed. In the US, demonstrations of efficacy for these products will likely occur using any or a number of nonhuman primate models of filovirus infection, to satisfy requirements for licensure under the Animal Rule. In most instances, the critical endpoint for efficacy assessment will be survival following experimental infection; however, as yet there exists no standardized approach for assessing the health status or euthanasia criteria for filovirus-exposed nonhuman primates. Consideration of objective criteria during these assessment processes is important to a) ensure that unprotected or infection-control subjects are humanely euthanized without unnecessary suffering, b) enhance the likelihood that animals exhibiting mild or moderate signs of disease, but which may ultimately clear the infection and survive, are not prematurely euthanized, c) minimize the occurrence of spontaneous deaths, for which acquisition of important end-stage samples may be foregone, d) enhance the reproducibility of experimental results conducted by different research teams, and e) provide a defensible rationale for euthanasia decisions that withstands scrutiny by regulatory agencies. To determine whether clinical pathology parameters routinely monitored during nonhuman primate efficacy studies were predictive of survival status, historic records were compiled for 58 surviving and nonsurviving rhesus monkeys infected by the intramuscular or aerosol routes with Ebola virus at the US Army Medical Research Institute for Infectious Diseases. These parameters were statistically analyzed and those exhibiting predicative value for survival outcome are reported. These findings may be useful for standardization of objective animal-health and euthanasia assessments for the rhesus-monkey Ebola-virus infection model and may serve as a useful approach to guide similar standardization strategies for other test systems or viral hemorrhagic fever disease models.
Keywords: filovirus; nonhuman primate; viral hemorrhagic fever; euthanasia; clinical pathology; Ebola virus
Type of Paper: Communication
Title: Sequence and Identity of Ebola Virus Variant E718
Author: Jens H. Kuhn, Loreen Lofts, and Gustavo Palacios
Affiliation: USAMRIID, 1425 Porter St, Fort Detrick, Frederick, MD 21702; E-Mail: firstname.lastname@example.org
Abstract: Several isolates of Ebola virus were obtained during the first recognized Ebola virus disease outbreak in 1976 around Yambuku, Zaire. Here we present the complete genome sequence of isolate E718, and review the history of research that has been performed with this isolate in the past.
Type of Paper: Review
Title: Current Views of Filovirus Transcription and Replication
Authors: Kristina Brauburger and Elke Mühlberger
Affiliation: Department of Microbiology, School of Medicine and National Emerging Infectious Diseases Laboratories Institute, Boston University, 72 East Concord Street, Boston, MA 02118, USA
Abstract: Filoviruses, comprising members of the genera Ebolavirus and Marburgvirus, have a nonsegmented single-stranded (NNS) RNA genome of negative polarity. Along with the paramyxo-, rhabdo-, and bornaviruses they belong to the order Mononegavirales. This review focuses on advances in understanding the complex molecular, structural and cellular aspects of gene expression and genome replication of the highly pathogenic filoviruses. It summarizes the current knowledge about the viral proteins involved in mediating and regulating replication and transcription and the role of regulatory regions on the genome in RNA synthesis. Unique features that have evolved among the filoviruses and differ from other NNS RNA viruses are discussed. In addition, we highlight important structural and mechanistic differences of transcription and replication between marburg- and ebolaviruses.
Last update: 29 April 2013