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

Viruses. 2019 Mar 2;11(3):214. doi: 10.3390/v11030214.

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.

Keywords: Egyptian rousette bat; Marburg virus; Rousettus aegyptiacus; filovirus; histopathologic; immunohistochemical; natural reservoir.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Alanine Transaminase / blood
  • Animals
  • Antibodies, Viral / blood
  • Chiroptera / virology*
  • Disease Reservoirs / virology*
  • Immunoglobulin G / blood
  • Immunohistochemistry
  • Liver / pathology
  • Liver / virology*
  • Lymphocyte Count
  • Male
  • Marburg Virus Disease / immunology*
  • Marburg Virus Disease / pathology
  • Marburgvirus
  • RNA, Viral / genetics
  • Subcutaneous Absorption

Substances

  • Antibodies, Viral
  • Immunoglobulin G
  • RNA, Viral
  • Alanine Transaminase