Special Issue "Advances in Filovirus Research 2013"

Guest Editor
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
E-Mail: kuhnjens@mail.nih.gov
Phone: +1 301 631 7245
Fax: +1 301 619 5029

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ID: viruses-20033
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; glazee@mail.nih.gov
* Author to whom correspondence should be addressed; glazee@mail.nih.gov; 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: umaudet7@cc.umanitoba.ca;
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.