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Clinical, Histopathologic, and Immunohistochemical Characterization of Experimental Marburg Virus Infection in A Natural Reservoir Host, the Egyptian Rousette Bat (Rousettus aegyptiacus).

Abstract
Egyptian rousette bats (Rousettus aegyptiacus) are natural reservoir hosts of Marburg virus (MARV), and Ravn virus (RAVV; collectively called marburgviruses) and have been linked to human cases of Marburg virus disease (MVD). We investigated the clinical and pathologic effects of experimental MARV infection in Egyptian rousettes through a serial euthanasia study and found clear evidence of mild but transient disease. Three groups of nine, captive-born, juvenile male bats were inoculated subcutaneously with 10,000 TCID50 of Marburg virus strain Uganda 371Bat2007, a minimally passaged virus originally isolated from a wild Egyptian rousette. Control bats (n = 3) were mock-inoculated. Three animals per day were euthanized at 3, 5⁻10, 12 and 28 days post-inoculation (DPI); controls were euthanized at 28 DPI. Blood chemistry analyses showed a mild, statistically significant elevation in alanine aminotransferase (ALT) at 3, 6 and 7 DPI. Lymphocyte and monocyte counts were mildly elevated in inoculated bats after 9 DPI. Liver histology revealed small foci of inflammatory infiltrate in infected bats, similar to lesions previously described in wild, naturally-infected bats. Liver lesion severity scores peaked at 7 DPI, and were correlated with both ALT and hepatic viral RNA levels. Immunohistochemical staining detected infrequent viral antigen in liver (3⁻8 DPI, n = 8), spleen (3⁻7 DPI, n = 8), skin (inoculation site; 3⁻12 DPI, n = 20), lymph nodes (3⁻10 DPI, n = 6), and oral submucosa (8⁻9 DPI, n = 2). Viral antigen was present in histiocytes, hepatocytes and mesenchymal cells, and in the liver, antigen staining co-localized with inflammatory foci. These results show the first clear evidence of very mild disease caused by a filovirus in a reservoir bat host and provide support for our experimental model of this virus-reservoir host system.
AuthorsMegan E B Jones, Brian R Amman, Tara K Sealy, Luke S Uebelhoer, Amy J Schuh, Timothy Flietstra, Brian H Bird, JoAnn D Coleman-McCray, Sherif R Zaki, Stuart T Nichol, Jonathan S Towner
JournalViruses (Viruses) Vol. 11 Issue 3 (03 02 2019) ISSN: 1999-4915 [Electronic] Switzerland
PMID30832364 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
Chemical References
  • Antibodies, Viral
  • Immunoglobulin G
  • RNA, Viral
  • Alanine Transaminase
Topics
  • Alanine Transaminase (blood)
  • Animals
  • Antibodies, Viral (blood)
  • Chiroptera (virology)
  • Disease Reservoirs (virology)
  • Immunoglobulin G (blood)
  • Immunohistochemistry
  • Liver (pathology, virology)
  • Lymphocyte Count
  • Male
  • Marburg Virus Disease (immunology, pathology)
  • Marburgvirus
  • RNA, Viral (genetics)
  • Subcutaneous Absorption

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