Pathogenesis of Kasokero virus in experimentally infected Egyptian rousette bats (Rousettus aegyptiacus)

Egyptian rousette bats (ERBs; Rousettus aegyptiacus; family Pteropodidae) are associated with a growing number of bunyaviruses of public health importance, including Kasokero virus (KASV), which was first identified as a zoonosis in Uganda in 1977. In this study, formalin-fixed paraffin-embedded tissues from a previous experiment in which KASV infection was confirmed in 18 experimentally infected ERBs were used for an in-depth analysis using histopathology, in situ hybridization (ISH) for detection of viral RNA, immunohistochemistry (IHC) to assess the mononuclear phagocyte system response, and quantitative digital image analysis to investigate virus clearance from the liver and spleen within a spatial context. Significant gross and histological lesions were limited to the liver, where KASV-infected bats developed mild to moderate, acute viral hepatitis, which was first observed at 3 days postinfection (DPI), peaked at 6 DPI, and was resolved by 20 DPI. A subset of bats had glycogen depletion (n = 10) and hepatic necrosis (n = 3), rarely with intralesional bacteria (n = 1). Virus replication was confirmed by ISH in the liver, spleen, lymph nodes, and tongue. In the liver, KASV replicated in the cytoplasm of hepatocytes, to a lesser extent in mononuclear phagocytes, and rarely in presumptive endothelial cells. Most KASV RNA, as detected by ISH, was cleared from the spleen and liver by 6 DPI. It is concluded that ERBs have effective mechanisms to respond to this virus, clearing it without evidence of clinical disease.

[1]  A. Schuh,et al.  Natural reservoir Rousettus aegyptiacus bat host model of orthonairovirus infection identifies potential zoonotic spillover mechanisms , 2022, Scientific Reports.

[2]  M. Groschup,et al.  Diagnosis and Pathogenesis of Nairobi Sheep Disease Orthonairovirus Infections in Sheep and Cattle , 2021, Viruses.

[3]  A. Davis,et al.  Insights into the Pathogenesis of Viral Haemorrhagic Fever Based on Virus Tropism and Tissue Lesions of Natural Rift Valley Fever , 2021, Viruses.

[4]  M. Meyer-Hermann,et al.  Rate of Immune Complex Cycling in Follicular Dendritic Cells Determines the Extent of Protecting Antigen Integrity and Availability to Germinal Center B Cells , 2020, The Journal of Immunology.

[5]  A. Schuh,et al.  Asymptomatic Infection of Marburg Virus Reservoir Bats Is Explained by a Strategy of Immunoprotective Disease Tolerance , 2020, Current Biology.

[6]  A. Nitsche,et al.  First detection of bat-borne Issyk-Kul virus in Europe , 2020, Scientific Reports.

[7]  A. Schuh,et al.  Human-Pathogenic Kasokero Virus in Field-Collected Ticks , 2020, Emerging infectious diseases.

[8]  A. Schuh,et al.  Experimental infection of Egyptian rousette bats (Rousettus aegyptiacus) with Sosuga virus demonstrates potential transmission routes for a bat-borne human pathogenic paramyxovirus , 2020, PLoS neglected tropical diseases.

[9]  A. Schuh,et al.  Isolation of Angola-like Marburg virus from Egyptian rousette bats from West Africa , 2020, Nature Communications.

[10]  Darci R Smith,et al.  Animal Models for Crimean-Congo Hemorrhagic Fever Human Disease , 2019, Viruses.

[11]  A. Satyaningtijas,et al.  The spleen morphophysiology of fruit bats , 2019, Anatomia, histologia, embryologia.

[12]  Timothy D. Flietstra,et al.  Clinical, Histopathologic, and Immunohistochemical Characterization of Experimental Marburg Virus Infection in A Natural Reservoir Host, the Egyptian Rousette Bat (Rousettus aegyptiacus) , 2019, Viruses.

[13]  R. Kading,et al.  Can Bats Serve as Reservoirs for Arboviruses? , 2019, Viruses.

[14]  J. Mccarville,et al.  Disease tolerance: concept and mechanisms. , 2018, Current opinion in immunology.

[15]  Peter Bankhead,et al.  QuPath: Open source software for digital pathology image analysis , 2017, Scientific Reports.

[16]  J. Kranich,et al.  How Follicular Dendritic Cells Shape the B-Cell Antigenome , 2016, Front. Immunol..

[17]  H. Guzmán,et al.  Genomic Characterization of Yogue, Kasokero, Issyk-Kul, Keterah, Gossas, and Thiafora Viruses: Nairoviruses Naturally Infecting Bats, Shrews, and Ticks. , 2015, The American journal of tropical medicine and hygiene.

[18]  A. Schuh,et al.  A Recently Discovered Pathogenic Paramyxovirus, Sosuga Virus, is Present in Rousettus aegyptiacus Fruit Bats at Multiple Locations in Uganda , 2015, Journal of wildlife diseases.

[19]  A. Schuh,et al.  Experimental Inoculation of Egyptian Rousette Bats (Rousettus aegyptiacus) with Viruses of the Ebolavirus and Marburgvirus Genera , 2015, Viruses.

[20]  A. Schuh,et al.  ORAL SHEDDING OF MARBURG VIRUS IN EXPERIMENTALLY INFECTED EGYPTIAN FRUIT BATS (ROUSETTUS AEGYPTIACUS) , 2015, Journal of wildlife diseases.

[21]  Kimihito Ito,et al.  A nairovirus isolated from African bats causes haemorrhagic gastroenteritis and severe hepatic disease in mice , 2014, Nature Communications.

[22]  Mathias Vandenbogaert,et al.  A Preliminary Study of Viral Metagenomics of French Bat Species in Contact with Humans: Identification of New Mammalian Viruses , 2014, PloS one.

[23]  Ruslan Medzhitov,et al.  Disease Tolerance as a Defense Strategy , 2012, Science.

[24]  J. Flanagan,et al.  RNAscope: a novel in situ RNA analysis platform for formalin-fixed, paraffin-embedded tissues. , 2012, The Journal of molecular diagnostics : JMD.

[25]  J. Cyster,et al.  Follicular dendritic cells help establish follicle identity and promote B cell retention in germinal centers , 2011, The Journal of experimental medicine.

[26]  J. Guarner,et al.  Pathologic studies on suspect animal and human cases of Rift Valley fever from an outbreak in Eastern Africa, 2006-2007. , 2010, The American journal of tropical medicine and hygiene.

[27]  Alan Kemp,et al.  Isolation of Genetically Diverse Marburg Viruses from Egyptian Fruit Bats , 2009, PLoS pathogens.

[28]  G. Grard,et al.  Marburg Virus Infection Detected in a Common African Bat , 2007, PloS one.

[29]  R. Lunt,et al.  Pathogenesis studies with Australian bat lyssavirus in grey-headed flying foxes (Pteropus poliocephalus). , 2002, Australian veterinary journal.

[30]  L. Mukwaya,et al.  Kasokero virus: a new human pathogen from bats (Rousettus aegyptiacus) in Uganda. , 1986, The American journal of tropical medicine and hygiene.

[31]  M. Varma,et al.  Keterah virus infections in four species of Argas ticks (Ixodoidea: Argasidae). , 1976, Journal of medical entomology.