Histopathologic and Immunohistochemical Evaluation of Induced Lesions, Tissue Tropism and Host Responses following Experimental Infection of Egyptian Rousette Bats (Rousettus aegyptiacus) with the Zoonotic Paramyxovirus, Sosuga Virus
Abstract
:1. Introduction
2. Materials and Methods
2.1. Tissue Samples
2.2. Histology
2.3. Immunohistochemistry (IHC)
2.4. Histopathological Lesion Scoring
2.5. SOSV Immunohistochemical Scoring
2.6. Whole-Slide Digital Image Analysis (CD3 and Iba1 Staining Quantifications)
2.7. Statistical Analyses
3. Results
3.1. Histopathology
3.1.1. Small Intestines
3.1.2. Salivary Glands
3.1.3. Histopathological Lesion Scores
3.2. Immunohistochemistry
3.2.1. SOSV Tissue Tropism
3.2.2. Quantification and Spatial Analyses of Iba1- and CD3-Immunopositive Cell Populations
Small Intestines
Salivary Glands
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Acknowledgments
Conflicts of Interest
References
- Constantine, D.G. Bat Rabies and Other Lyssavirus Infections; U.S. Geological Survey: Reston, VA, USA, 2009; p. 68.
- McColl, K.A.; Chamberlain, T.; Lunt, R.A.; Newberry, K.M.; Middleton, D.; Westbury, H.A. Pathogenesis studies with Australian bat lyssavirus in grey-headed flying foxes (Pteropus poliocephalus). Aust. Vet. J. 2002, 80, 636–641. [Google Scholar] [CrossRef] [PubMed]
- Middleton, D.J.; Morrissy, C.J.; van der Heide, B.M.; Russell, G.M.; Braun, M.A.; Westbury, H.A.; Halpin, K.; Daniels, P.W. Experimental Nipah virus infection in pteropid bats (Pteropus poliocephalus). J. Comp. Pathol. 2007, 136, 266–272. [Google Scholar] [CrossRef] [PubMed]
- Mahalingam, S.; Herrero, L.J.; Playford, E.G.; Spann, K.; Herring, B.; Rolph, M.S.; Middleton, D.; McCall, B.; Field, H.; Wang, L.F. Hendra virus: An emerging paramyxovirus in Australia. Lancet Infect. Dis. 2012, 12, 799–807. [Google Scholar] [CrossRef]
- Amman, B.R.; Albarino, C.G.; Bird, B.H.; Nyakarahuka, L.; Sealy, T.K.; Balinandi, S.; Schuh, A.J.; Campbell, S.M.; Stroher, U.; Jones, M.E.; et al. A Recently Discovered Pathogenic Paramyxovirus, Sosuga Virus, is Present in Rousettus aegyptiacus Fruit Bats at Multiple Locations in Uganda. J. Wildl. Dis. 2015, 51, 774–779. [Google Scholar] [CrossRef]
- Amman, B.R.; Carroll, S.A.; Reed, Z.D.; Sealy, T.K.; Balinandi, S.; Swanepoel, R.; Kemp, A.; Erickson, B.R.; Comer, J.A.; Campbell, S.; et al. Seasonal pulses of Marburg virus circulation in juvenile Rousettus aegyptiacus bats coincide with periods of increased risk of human infection. PLoS Pathog. 2012, 8, e1002877. [Google Scholar] [CrossRef]
- Amman, B.R.; Jones, M.E.; Sealy, T.K.; Uebelhoer, L.S.; Schuh, A.J.; Bird, B.H.; Coleman-McCray, J.D.; Martin, B.E.; Nichol, S.T.; Towner, J.S. Oral shedding of Marburg virus in experimentally infected Egyptian fruit bats (Rousettus aegyptiacus). J. Wildl. Dis. 2015, 51, 113–124. [Google Scholar] [CrossRef]
- Jones, M.E.; Schuh, A.J.; Amman, B.R.; Sealy, T.K.; Zaki, S.R.; Nichol, S.T.; Towner, J.S. Experimental Inoculation of Egyptian Rousette Bats (Rousettus aegyptiacus) with Viruses of the Ebolavirus and Marburgvirus Genera. Viruses 2015, 7, 3420–3442. [Google Scholar] [CrossRef]
- Jones, M.E.; Amman, B.R.; Sealy, T.K.; Uebelhoer, L.S.; Schuh, A.J.; Flietstra, T.; Bird, B.H.; Coleman-McCray, J.D.; Zaki, S.R.; Nichol, S.T.; et al. Clinical, Histopathologic, and Immunohistochemical Characterization of Experimental Marburg Virus Infection in A Natural Reservoir Host, the Egyptian Rousette Bat (Rousettus aegyptiacus). Viruses 2019, 11, 214. [Google Scholar] [CrossRef]
- Towner, J.S.; Amman, B.R.; Sealy, T.K.; Carroll, S.A.R.; Comer, J.A.; Kemp, A.; Swanepoel, R.; Paddock, C.D.; Balinandi, S.; Khristova, M.L.; et al. Isolation of genetically diverse Marburg viruses from Egyptian fruit bats. PLoS Pathog. 2009, 5, e1000536. [Google Scholar] [CrossRef]
- Towner, J.S.; Pourrut, X.; Albariño, C.G.; Nkogue, C.N.; Bird, B.H.; Grard, G.; Ksiazek, T.G.; Gonzalez, J.-P.; Nichol, S.T.; Leroy, E.M. Marburg virus infection detected in a common African bat. PLoS ONE 2007, 2, e764. [Google Scholar] [CrossRef]
- Drexler, J.F.; Corman, V.M.; Müller, M.A.; Maganga, G.D.; Vallo, P.; Binger, T.; Gloza-Rausch, F.; Cottontail, V.M.; Rasche, A.; Yordanov, S.; et al. Bats host major mammalian paramyxoviruses. Nat. Commun. 2012, 3, 796. [Google Scholar] [CrossRef] [PubMed]
- Latinne, A.; Hu, B.; Olival, K.J.; Zhu, G.; Zhang, L.; Li, H.; Chmura, A.A.; Field, H.E.; Zambrana-Torrelio, C.; Epstein, J.H.; et al. Origin and cross-species transmission of bat coronaviruses in China. Nat. Commun. 2020, 11, 4235. [Google Scholar] [CrossRef] [PubMed]
- Banerjee, A.; Kulcsar, K.; Misra, V.; Frieman, M.; Mossman, K. Bats and Coronaviruses. Viruses 2019, 11, 41. [Google Scholar] [CrossRef]
- Cui, J.; Li, F.; Shi, Z.L. Origin and evolution of pathogenic coronaviruses. Nat. Rev. Microbiol. 2019, 17, 181–192. [Google Scholar] [CrossRef] [PubMed]
- Letko, M.; Seifert, S.N.; Olival, K.J.; Plowright, R.K.; Munster, V.J. Bat-borne virus diversity, spillover and emergence. Nat. Rev. Genet. 2020, 18, 461–471. [Google Scholar] [CrossRef]
- Database of Bat-Associated Viruses. Available online: http://www.mgc.ac.cn/DBatVir/ (accessed on 17 March 2022).
- Albariño, C.A.; Foltzer, M.; Towner, J.S.; Rowe, L.A.; Campbell, S.; Jaramillo, C.M.; Bird, B.H.; Reeder, D.M.; Vodzak, M.E.; Rota, P.; et al. Novel Paramyxovirus Associated with Severe Acute Febrile Disease, South Sudan and Uganda, 2012. Emerg. Infect. Dis. J. 2014, 20, 211. [Google Scholar] [CrossRef]
- Towner, J.S.; Khristova, M.L.; Sealy, T.K.; Vincent, M.J.; Erickson, B.R.; Bawiec, D.A.; Hartman, A.L.; Comer, J.A.; Zaki, S.R.; Stroher, U.; et al. Marburgvirus genomics and association with a large hemorrhagic fever outbreak in Angola. J. Virol. 2006, 80, 6497–6516. [Google Scholar] [CrossRef]
- Pawęska, J.T.; Storm, N.; Markotter, W.; Di Paola, N.; Wiley, M.R.; Palacios, G.; Van Vuren, P.J. Shedding of Marburg Virus in Naturally Infected Egyptian Rousette Bats, South Africa, 2017. Emerg Infect Dis 2020, 26, 3051–3055. [Google Scholar] [CrossRef]
- Amman, B.R.; Nyakarahuka, L.; McElroy, A.K.; Dodd, K.A.; Sealy, T.K.; Schuh, A.J.; Shoemaker, T.R.; Balinandi, S.; Atimnedi, P.; Kaboyo, W.; et al. Marburgvirus resurgence in Kitaka Mine bat population after extermination attempts, Uganda. Emerg. Infect. Dis. 2014, 20, 1761–1764. [Google Scholar] [CrossRef]
- Kalunda, M.; Mukwaya, L.G.; Mukuye, A.; Lule, M.; Sekyalo, E.; Wright, J.; Casals, J. Kasokero virus: A new human pathogen from bats (Rousettus aegyptiacus) in Uganda. Am. J. Trop. Med. Hyg. 1986, 35, 387–392. [Google Scholar] [CrossRef]
- Schuh, A.J.; Amman, B.R.; Patel, K.; Sealy, T.K.; Swanepoel, R.; Towner, J.S. Human-Pathogenic Kasokero Virus in Field-Collected Ticks. Emerg. Infect. Dis. 2020, 26, 2944–2950. [Google Scholar] [CrossRef]
- Fagre, A.C.; Lee, J.S.; Kityo, R.M.; Bergren, N.A.; Mossel, E.C.; Nakayiki, T.; Nalikka, B.; Nyakarahuka, L.; Gilbert, A.T.; Peterhans, J.K.; et al. Discovery and Characterization of Bukakata orbivirus (Reoviridae:Orbivirus), a Novel Virus from a Ugandan Bat. Viruses 2019, 11, 209. [Google Scholar] [CrossRef] [PubMed]
- Mortlock, M.; Dietrich, M.; Weyer, J.; Paweska, J.T.; Markotter, W. Co-Circulation and Excretion Dynamics of Diverse Rubula- and Related Viruses in Egyptian Rousette Bats from South Africa. Viruses 2019, 11, 37. [Google Scholar] [CrossRef] [PubMed]
- Mortlock, M.; Kuzmin, I.V.; Weyer, J.; Gilbert, A.T.; Agwanda, B.; Rupprecht, C.E.; Nel, L.H.; Kearney, T.; Malekani, J.M.; Markotter, W. Novel Paramyxoviruses in Bats from Sub-Saharan Africa, 2007–2012. Emerg. Infect. Dis. 2015, 21, 1840–1843. [Google Scholar] [CrossRef] [PubMed]
- Amman, B.R.; Schuh, A.J.; Sealy, T.K.; Spengler, J.R.; Welch, S.R.; Kirejczyk, S.G.M.; Albariño, C.G.; Nichol, S.T.; Towner, J.S. Experimental infection of Egyptian rousette bats (Rousettus aegyptiacus) with Sosuga virus demonstrates potential transmission routes for a bat-borne human pathogenic paramyxovirus. PLoS Negl. Trop. Dis. 2020, 14, e0008092. [Google Scholar] [CrossRef]
- Gibson-Corley, K.N.; Olivier, A.K.; Meyerholz, D.K. Principles for valid histopathologic scoring in research. Vet. Pathol. 2013, 50, 1007–1015. [Google Scholar] [CrossRef]
- Bankhead, P.; Loughrey, M.B.; Fernández, J.A.; Dombrowski, Y.; McArt, D.G.; Dunne, P.D.; McQuaid, S.; Gray, R.T.; Murray, L.J.; Coleman, H.G.; et al. QuPath: Open source software for digital pathology image analysis. Sci. Rep. 2017, 7, 16878. [Google Scholar] [CrossRef]
- Mandl, J.N.; Schneider, C.; Schneider, D.S.; Baker, M.L. Going to Bat(s) for Studies of Disease Tolerance. Front. Immunol. 2018, 9, 2112. [Google Scholar] [CrossRef]
- Guito, J.C.; Prescott, J.B.; Arnold, C.E.; Amman, B.R.; Schuh, A.J.; Spengler, J.R.; Sealy, T.K.; Harmon, J.R.; Coleman-McCray, J.D.; Kulcsar, K.A.; et al. Asymptomatic Infection of Marburg Virus Reservoir Bats Is Explained by a Strategy of Immunoprotective Disease Tolerance. Curr. Biol. 2021, 31, 257–270.e5. [Google Scholar] [CrossRef]
- McCarville, J.L.; Ayres, J.S. Disease tolerance: Concept and mechanisms. Curr. Opin. Immunol. 2018, 50, 88–93. [Google Scholar] [CrossRef]
- Pavlovich, S.S.; Lovett, S.P.; Koroleva, G.; Guito, J.C.; Arnold, C.; Nagle, E.R.; Kulcsar, K.; Lee, A.; Thibaud-Nissen, F.; Hume, A.; et al. The Egyptian Rousette Genome Reveals Unexpected Features of Bat Antiviral Immunity. Cell 2018, 173, 1098–1110.e18. [Google Scholar] [CrossRef] [PubMed]
- Soares, M.P.; Gozzelino, R.; Weis, S. Tissue damage control in disease tolerance. Trends Immunol. 2014, 35, 483–494. [Google Scholar] [CrossRef] [PubMed]
- Martins, R.; Carlos, A.R.; Braza, F.; Thompson, J.A.; Bastos-Amador, P.; Ramos, S.; Soares, M.P. Disease Tolerance as an Inherent Component of Immunity. Annu. Rev. Immunol. 2019, 37, 405–437. [Google Scholar] [CrossRef] [PubMed]
- Medzhitov, R.; Schneider, D.S.; Soares, M.P. Disease tolerance as a defense strategy. Science 2012, 335, 936–941. [Google Scholar] [CrossRef] [PubMed]
- Desalegn, G.; Pabst, O. Inflammation triggers immediate rather than progressive changes in monocyte differentiation in the small intestine. Nat. Commun. 2019, 10, 3229. [Google Scholar] [CrossRef]
- Smith, P.D.; Smythies, L.E.; Shen, R.; Greenwell-Wild, T.; Gliozzi, M.; Wahl, S.M. Intestinal macrophages and response to microbial encroachment. Mucosal Immunol. 2011, 4, 31–42. [Google Scholar] [CrossRef]
- Bain, C.C.; Schridde, A. Origin, Differentiation, and Function of Intestinal Macrophages. Front. Immunol. 2018, 9, 2733. [Google Scholar] [CrossRef]
- De Schepper, S.; Verheijden, S.; Aguilera-Lizarraga, J.; Viola, M.F.; Boesmans, W.; Stakenborg, N.; Voytyuk, I.; Schmidt, I.; Boeckx, B.; de Casterlé, I.D.; et al. Self-Maintaining Gut Macrophages Are Essential for Intestinal Homeostasis. Cell 2018, 175, 400–415.e13. [Google Scholar] [CrossRef]
- Čermák, V.; Gandalovičová, A.; Merta, L.; Fučíková, J.; Špíšek, R.; Rösel, D.; Brábek, J. RNA-seq of macrophages of amoeboid or mesenchymal migratory phenotype due to specific structure of environment. Sci. Data 2018, 5, 180198. [Google Scholar] [CrossRef]
- Young, D.F.; Wignall-Fleming, E.B.; Busse, D.C.; Pickin, M.J.; Hankinson, J.; Randall, E.M.; Tavendale, A.; Davison, A.J.; Lamont, D.; Tregoning, J.S.; et al. The switch between acute and persistent paramyxovirus infection caused by single amino acid substitutions in the RNA polymerase P subunit. PLoS Pathog. 2019, 15, e1007561. [Google Scholar] [CrossRef]
- Sohayati, A.R.; Hassan, L.; Sharifah, S.H.; Lazarus, K.; Zaini, C.M.; Epstein, J.H.; Naim, N.S.; Field, H.E.; Arshad, S.S.; Aziz, J.A.; et al. Evidence for Nipah virus recrudescence and serological patterns of captive Pteropus vampyrus. Epidemiol. Infect. 2011, 139, 1570–1579. [Google Scholar] [CrossRef] [PubMed]
- Jelley-Gibbs, D.M.; Brown, D.M.; Dibble, J.P.; Haynes, L.; Eaton, S.M.; Swain, S.L. Unexpected prolonged presentation of influenza antigens promotes CD4 T cell memory generation. J. Exp. Med. 2005, 202, 697–706. [Google Scholar] [CrossRef] [PubMed]
- Schuh, A.J.; Amman, B.R.; Sealy, T.K.; Kainulainen, M.H.; Chakrabarti, A.K.; Guerrero, L.W.; Nichol, S.T.; Albarino, C.G.; Towner, J.S. Antibody-Mediated Virus Neutralization Is Not a Universal Mechanism of Marburg, Ebola, or Sosuga Virus Clearance in Egyptian Rousette Bats. J. Infect. Dis. 2019, 219, 1716–1721. [Google Scholar] [CrossRef] [PubMed]
DPI | Bat ID | Small Intestines | Salivary Gland | AxLN | Spleen | Large Intestinal GALT |
---|---|---|---|---|---|---|
3 | 283936 | NP | - | + | - | NP |
284049 | - | - | + | - | - | |
284459 | - | - | - | - | - | |
6 | 284509 | - | - | ++ | - | - |
284899 | + | + | + | ++ | - | |
285146 | - | - | - | - | - | |
9 | 287014 | - | - | - | - | - |
287253 | - | - | - | + | - | |
287756 | + | - | + | + | + | |
21 | 289338 | - | + | - | - | - |
289953 * | + | - | + | + | + | |
290040 | - | - | + | - | - | |
Control | 290195 | - | - | NP | NP | - |
290494 | - | - | - | - | - | |
290631 | - | - | - | - | - |
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Kirejczyk, S.G.M.; Amman, B.R.; Schuh, A.J.; Sealy, T.K.; Albariño, C.G.; Zhang, J.; Brown, C.C.; Towner, J.S. Histopathologic and Immunohistochemical Evaluation of Induced Lesions, Tissue Tropism and Host Responses following Experimental Infection of Egyptian Rousette Bats (Rousettus aegyptiacus) with the Zoonotic Paramyxovirus, Sosuga Virus. Viruses 2022, 14, 1278. https://doi.org/10.3390/v14061278
Kirejczyk SGM, Amman BR, Schuh AJ, Sealy TK, Albariño CG, Zhang J, Brown CC, Towner JS. Histopathologic and Immunohistochemical Evaluation of Induced Lesions, Tissue Tropism and Host Responses following Experimental Infection of Egyptian Rousette Bats (Rousettus aegyptiacus) with the Zoonotic Paramyxovirus, Sosuga Virus. Viruses. 2022; 14(6):1278. https://doi.org/10.3390/v14061278
Chicago/Turabian StyleKirejczyk, Shannon G. M., Brian R. Amman, Amy J. Schuh, Tara K. Sealy, César G. Albariño, Jian Zhang, Corrie C. Brown, and Jonathan S. Towner. 2022. "Histopathologic and Immunohistochemical Evaluation of Induced Lesions, Tissue Tropism and Host Responses following Experimental Infection of Egyptian Rousette Bats (Rousettus aegyptiacus) with the Zoonotic Paramyxovirus, Sosuga Virus" Viruses 14, no. 6: 1278. https://doi.org/10.3390/v14061278
APA StyleKirejczyk, S. G. M., Amman, B. R., Schuh, A. J., Sealy, T. K., Albariño, C. G., Zhang, J., Brown, C. C., & Towner, J. S. (2022). Histopathologic and Immunohistochemical Evaluation of Induced Lesions, Tissue Tropism and Host Responses following Experimental Infection of Egyptian Rousette Bats (Rousettus aegyptiacus) with the Zoonotic Paramyxovirus, Sosuga Virus. Viruses, 14(6), 1278. https://doi.org/10.3390/v14061278