Theoretical aspects of the immunopathogenesis of coronavirus infection in cats
Abstract
Feline Infectious Peritonitis (FIP) is a severe and specific coronavirus infection caused by a mutated feline coronavirus (Feline Infectious Peritonitis Virus (FIPV)). FIP is frequently associated with high mortality rates and a complex multisystem immuno p a thogenesis. This article provides a comprehensive review of contemporary theoretical knowledge on the pathogenesis of FIP, i n cluding the molecular and cellular mechanisms of the immune response underlying disease development. Special attention is given to the analysis of factors determining the virulence of FCoV, mechanisms of viral (FIPV) interaction with macrophages, the role of pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) in the progression of the infectious process, and the potential connection of the Arthus reaction to the intricate immunopathological mechanisms involved in FIP. The article discusses the significance of ant i body-dependent enhancement (ADE) in stimulating viral replication in target cells and the role of class G immunoglobulins in disease pathogenesis. The article summarises key aspects of FIP pathogenesis, including the immunological mechanisms respons i ble for the clinical manifestations of the disease. It details the pathogenesis of primary clinical forms of FIP, with an analysis of specific changes occurring in various systems of the body (digestive, respiratory, renal, nervous, and cardiovascular). Additionally, it addresses microcirculatory disturbances and increased vascular wall permeability contributing to systemic inflammation. The text also delves into the cytokine storm induced by hyperactivity of virus-infected immune-competent cells, primarily macrophages. The interplay between pathogen virulence and its ability to modulate the host's immune response by suppressing adaptive immunity is explored. This review synthesises current research, focusing on theoretical insights into the immunopathogenesis of FIP and emphasising the significance of a pathogenetic approach to its diagnosis and prevention.References
Barker, E. N., Tasker, S., Gruffydd-Jones, T. J., Tuplin, C. K., Burton, K., Porter, E., Day, M. J., Harley, R., Fews, D., Helps, C. R., & Siddell, S. G. (2013). Phylogenetic analysis of feline coronavirus strains in an outbreak of feline infectious peritonitis. Journal of Veterinary Internal Medicine, 27(2), 445–450.
Barker, E., & Tasker, S. (2020). Update on feline infectious peritonitis. In Practice, 42(7), 372–383.
Baş, T. M., Sevinç, M., & Ok, M. (2020). Coronavirus infection in cats. Eurasian Journal of Veterinary Sciences, 36, 106–117.
Baydar, E., Eröksüz, Y., Mö, T., & Eröksüz, H. (2014). Feline infectious peritonitis with distinct ocular involvement in a cat in Turkey. Kafkas Üniversitesi Veteriner Fakültesi Dergisi, 20(6), 961–965.
Borisevich, B., Dzimira, S., Lisova, V., & Kotlyarov, E. (2023). Morphological changes in the small intestine mesentery of cats with infectious peritonitis. Ukrainian Journal of Veterinary Sciences, 14(4), 23–39.
Černá, P., Lobová, D., Bubeníková, J., Vrábelová, J., Molínková, D., & Hořín, P. (2022). Shedding persistency and intensity patterns of feline coronavirus (FCoV) in feces of cats living in breeding catteries in the Czech Republic. Research in Veterinary Science, 152, 524–529.
Chang, H. W., de Groot, R. J., Egberink, H. F., & Rottier, P. J. (2010). Feline infectious peritonitis: Insights into feline coronavirus pathobiogenesis and epidemiology based on genetic analysis of the viral 3c gene. Journal of General Virology, 91(2), 415–420.
Chang, H. W., Egberink, H. F., Halpin, R., Spiro, D. J., & Rottier, P. J. (2012). Spike protein fusion peptide and feline coronavirus virulence. Emerging infectious diseases, 18(7), 1089.
Chen, C. H., Chang, C. C., Chen, W. C., & Lee, Y. J. (2024). Evaluation of chronic stress status and quality of life in cats suffering from chronic kidney disease and suspected feline infectious peritonitis based on hair cortisol concentration analysis and a questionnaire. Veterinary Quarterly, 44(1), 1–9.
Chen, D., López-Pérez, A. M., Vernau, K. M., Maggs, D. J., Kim, S., & Foley, J. (2023). Prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and feline enteric coronavirus (FECV) in shelter-housed cats in the Central Valley of California, USA. Veterinary Record Open, 10(2), e73.
Chen, Y., Zhang, Y., Wang, X., Zhou, J., Ma, L., Li, J., Yang, L., Ouyang, H., Yuan, H., & Pang, D. (2023). Transmissible gastroenteritis virus: An update review and perspective. Viruses, 15(2), 359.
Cony, F. G., Pereira, V. C., Slaviero, M., Lima, R. P., de Castro, L. T., de Moraes, J. T., Aliardi, J. M. G., Driemeier, D., Sonne, L., Panziera, W., & Pavarini, S. P. (2024). Anatomopathological characterization of hepatic lesions of feline infectious peritonitis in cats. Journal of Comparative Pathology, 215, 59–65.
Decaro, N., Mari, V., Lanave, G., Lorusso, E., Lucente, M. S., Desario, C., Colaianni, M. L., Elia, G., Ferringo, F., Alfano F., & Buonavoglia, C. (2021). Mutation analysis of the spike protein in Italian feline infectious peritonitis virus and feline enteric coronavirus sequences. Research in Veterinary Science, 135, 15–19.
Delaplace, M., Huet, H., Gambino, A., & Le Poder, S. (2021). Feline coronavirus antivirals: A review. Pathogens, 10(9), 1150.
Dewerchin, H. L., Cornelissen, E., & Nauwynck, H. J. (2005). Replication of feline coronaviruses in peripheral blood monocytes. Archives of Virology, 150, 2483–2500.
Dong, B., Zhang, X., Song, Y., Li, C., Zhang, G., & Lin, W. (2022). Genomic and phylogenetic analysis of the ORF7b gene from a Chinese feline infectious peritonitis virus isolate. The Thai Journal of Veterinary Medicine, 52(2), 303–309.
Drechsler, Y., Alcaraz, A., Bossong, F. J., Collisson, E. W., & Diniz, P. P. V. (2011). Feline coronavirus in multicat environments. Veterinary Clinics of North America: Small Animal Practice, 41(6), 1133–1169.
Drechsler, Y., Vasconcelos, E. J., Griggs, L. M., Diniz, P. P., & Collisson, E. (2020). Host gene expression of macrophages in response to feline coronavirus infection. Cells, 9(6), 1431.
Ehmann, R., Kristen-Burmann, C., Bank-Wolf, B., König, M., Herden, C., Hain, T., Thiel, H., Ziebuhr, J., & Tekes, G. (2018). Reverse genetics for type I feline coronavirus field isolate to study the molecular pathogenesis of feline infectious peritonitis. MBio, 9(4), 01422-18.
Ergin, İ. R. E. M., Sainkaplan, S., Sayim, A. A., & Şenel, O. O. (2024). Suspicion of feline infectious peritonitis in cats with uveitis: Diagnostic value of coronavirus antibodies and blood parameters. Kafkas Üniversitesi Veteriner Fakültesi Dergisi, 30(6), 769–777.
Falchieri, M., Coward, V. J., Reid, S. M., Lewis, T., & Banyard, A. C. (2024). Infectious bronchitis virus: An overview of the “chicken coronavirus”. Journal of Medical Microbiology, 73(5), 001828.
Felten, S., & Hartmann, K. (2019). Diagnosis of feline infectious peritonitis: A review of the current literature. Viruses, 11(11), 1068.
Felten, S., Klein-Richers, U., Unterer, S., Bergmann, M., Zablotski, Y., Hofmann-Lehmann, R., & Hartmann, K. (2023). Patterns of feline coronavirus shedding and associated factors in cats from breeding catteries. Viruses, 15(6), 1279.
Gu, G., Fung, T. S., Hung, W. T., Osterrieder, N., & Go, Y. Y. (2024). Development and characterization of reverse genetics systems of feline infectious peritonitis virus for antiviral research. Veterinary Research, 55, 124.
Guarnieri, C., Bertola, L., Ferrari, L., Quintavalla, C., Corradi, A., & Di Lecce, R. (2024). Myocarditis in an FIP-diseased cat with FCoV M1058L mutation: Clinical and pathological changes. Animals, 14(11), 1673.
Gülersoy, E., Balıkçı, C., Kısmet, E., Günal, İ., Şahan, A., Güçlü, M. A., & Ok, M. (2023). Renal ultrasonography findings in cats with feline infectious peritonitis. Van Veterinary Journal, 34(1), 63–69.
Gülersoy, E., Ok, M., Üney, K., Durgut, M. K., Parlak, T. M., & Ekici, Y. E. (2023). Intestinal injury and vasculitis biomarkers in cats with feline enteric coronavirus and effusive feline infectious peritonitis. Veterinary Medicine and Science, 9(6), 2420–2429.
Hartmann, K. (2005). Feline infectious peritonitis. Veterinary Clinics of North America: Small Animal Practice, 35(1), 39–79.
Hohdatsu, T., Yamada, M., Tominaga, R., Makino, K., Kida, K., & Koyama, H. (1998). Antibody-dependent enhancement of feline infectious peritonitis virus infection in feline alveolar macrophages and human monocyte cell line U937 by serum of cats experimentally or naturally infected with feline coronavirus. Journal of Veterinary Medical Science, 60(1), 49–55.
Holzworth J. E. (1963). Some important disorders of cats. Cornell Veterinarian, 53, 157–160.
Hu, T., Zhang, H., Zhang, X., Hong, X., & Zhang, T. (2024). Prevalence and risk factors associated with feline infectious peritonitis (FIP) in Mainland China between 2008 and 2023: A systematic review and meta-analysis. Animals, 14(8), 1220.
Jähne, S., Felten, S., Bergmann, M., Erber, K., Matiasek, K., Meli, M. L., Hofmann-Lehmann, R., & Hartmann, K. (2022). Detection of feline coronavirus variants in cats without feline infectious peritonitis. Viruses, 14(8), 1671.
Jaimes, J. A., & Whittaker, G. R. (2018). Feline coronavirus: Insights into viral pathogenesis based on the spike protein structure and function. Virology, 517, 108–121.
Jaimes, J. A., Millet, J. K., Stout, A. E., André, N. M., & Whittaker, G. R. (2020). A tale of two viruses: The distinct spike glycoproteins of feline coronaviruses. Viruses, 12(1), 83.
Jiao, Z., Wang, P., Hu, X., Chen, Y., Xu, J., Zhang, J., Benyuan, W., Ruxu, L., Yuejun, S., & Peng, G. (2024). Feline infectious peritonitis virus ORF7a is a virulence factor involved in inflammatory pathology in cats. Antiviral Research, 222, 105794.
Kennedy, M. A. (2020). Feline infectious peritonitis: Update on pathogenesis, diagnostics, and treatment. Veterinary Clinics of North America: Small Animal Practice, 50(5), 1001–1011.
Kennedy, M. A., Abd-Eldaim, M., Zika, S. E., Mankin, J. M., & Kania, S. A. (2008). Evaluation of antibodies against feline coronavirus 7b protein for diagnosis of feline infectious peritonitis in cats. American Journal of Veterinary Research, 69(9), 1179–1182.
Kennedy, U., Paterson, M. B. A., Magalhaes, R. S., Callaghan, T., & Clark, N. (2024). A scoping review of the evidence on prevalence of feline upper respiratory tract infections and associated risk factors. Veterinary Sciences, 11(6), 232.
Kipar, A., & Meli, M. L. (2014). Feline infectious peritonitis: still an enigma? Veterinary Pathology, 51(2), 505–526.
Klein-Richers, U., Hartmann, K., Hofmann-Lehmann, R., Unterer, S., Bergmann, M., Rieger, A., Leutenegger, C., Pantchev, N., Balzer, J., & Felten, S. (2020). Prevalence of feline coronavirus shedding in German catteries and associated risk factors. Viruses, 12(9), 1000.
Lin, L., Yao, D., Wu, L., Fan, R., Liu, Y., & Zhou, Z. (2022). Molecular epidemiology of type I and II feline coronavirus from cats with suspected feline infectious peritonitis in China between 2019 and 2021. Archives of Virology, 167(1), 189–194.
Lisova, V., & Kotliarov, E. (2022). Microscopic changes in the spleen due to feline infectious peritonitis. Ukrainian Journal of Veterinary Sciences, 13(4), 35–41.
Lombardi, A. F., Afsahi, A. M., Gupta, A., & Gholamrezanezhad, A. (2021). Severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), influenza, and COVID-19, beyond the lungs: A review article. La Radiologia Medica, 126, 561–569.
Malbon, A. J., Fonfara, S., Meli, M. L., Hahn, S., Egberink, H., & Kipar, A. (2019). Feline infectious peritonitis as a systemic inflammatory disease: Contribution of liver and heart to the pathogenesis.Viruses, 11(12), 1144.
Mangiaterra, S., Gavazza, A., Biagini, L., & Rossi, G. (2024). Study of macrophage activity in cats with FIP and naturally FCoV-shedding healthy cats. Pathogens, 13(6), 437.
Melnyk, V., Martyniuk, O., Bodnar, A., & Bodnar, M. (2022). Epizootological features of coronavirus infection in cats. Ukrainian Journal of Veterinary Sciences, 13(1), 52–60.
Melnyk, V., Mickiewicz, M., Martyniuk, O., Bodnar, A., & Bodnar, M. (2022). Morphological and biochemical changes in blood parameters in cats with infectious peritonitis. Ukrainian Journal of Veterinary Sciences, 13(3), 42–49.
Moyadee, W., Sunpongsri, S., Choowongkomon, K., Roytrakul, S., Rattanasrisomporn, A., Tansakul, N., & Rattanasrisomporn, J. (2024). Feline infectious peritonitis: A comprehensive evaluation of clinical manifestations, laboratory diagnosis, and therapeutic approaches. Journal of Advanced Veterinary and Animal Research, 11(1), 19–26.
Müller, T. R., Penninck, D. G., Webster, C. R., & Conrado, F. O. (2023). Abdominal ultrasonographic findings of cats with feline infectious peritonitis: An update. Journal of Feline Medicine and Surgery, 25(12), 1098612X231216000.
Murphy, B. G., Castillo, D., Neely, N. E., Kol, A., Brostoff, T., Grant, C. K., & Reagan, K. L. (2024). Serologic, virologic and pathologic features of cats with naturally occurring feline infectious peritonitis enrolled in antiviral clinical trials. Viruses, 16(3), 462.
Myrrha, L. W., Silva, F. M. F., Vidigal, P. M. P., Resende, M., Bressan, G. C., Fietto, J. L. R., Santos, M. R., Silva, L. M. N, Assao, V. S., Silva Junior, A., & de Almeida, M. R. (2019). Feline coronavirus isolates from a part of Brazil: Insights into molecular epidemiology and phylogeny inferred from the 7b gene. Journal of Veterinary Medical Science, 81(10), 1455–1460.
Ouyang, H., Liu, J., Yin, Y., Cao, S., Yan, R., Ren, Y., Zhou, D., Li, Q., Li, J., Liao, X., Ji, W., Du, B., Si, Y., & Hu, C. (2022). Epidemiology and comparative analyses of the S gene on feline coronavirus in Central China. Pathogens, 11(4), 460.
Paltrinieri, S., Giordano, A., Stranieri, A., & Lauzi, S. (2021). Feline infectious peritonitis (FIP) and coronavirus disease 19 (COVID‐19): Are they similar? Transboundary and Emerging Diseases, 68(4), 1786–1799.
Pedersen, N. C. (2014). An update on feline infectious peritonitis: Virology and immunopathogenesis. The Veterinary Journal, 201(2), 123–132.
Pedersen, N. C., Liu, H., Scarlett, J., Leutenegger, C. M., Golovko, L., Kennedy, H., & Kamal, F. M. (2012). Feline infectious peritonitis: Role of the feline coronavirus 3c gene in intestinal tropism and pathogenicity based upon isolates from resident and adopted shelter cats. Virus Research, 165(1), 17–28.
Pedersen, N. C., Perron, M., Bannasch, M., Montgomery, E., Murakami, E., Liepnieks, M., & Liu, H. (2019). Efficacy and safety of the nucleoside analog GS-441524 for treatment of cats with naturally occurring feline infectious peritonitis. Journal of Feline Medicine and Surgery, 21(4), 271–281.
Pineda, A. M., Lavergne, E., Brauge, C., Laveran, E., Bertagnoli, S., Boucraut-Baralon, C., & Bessière, P. (2024). Feline coronavirus-associated uveitis: The eye as a gateway to systemic spread and feline infectious peritonitis? Veterinary Microbiology, 301, 110355.
Prince, T., Smith, S. L., Radford, A. D., Solomon, T., Hughes, G. L., Patterson, E. I. (2021). SARS-CoV-2 infections in animals: Reservoirs for reverse zoonosis and models for study. Viruses, 13, 494.
Ramezanpour Eshkevari, S., Sasani, F., Shokrpoor, S., Mardjanmehr, S. H., Akbarein, H., & Ashrafi, I. (2024). A histopathological study on the changes in the central nervous system of dead cats with neurological symptoms. Iranian Journal of Veterinary Medicine, 18(4), 545–554.
Regan, A. D., Ousterout, D. G., & Whittaker, G. R. (2010). Feline lectin activity is critical for the cellular entry of feline infectious peritonitis virus. Journal of Virology, 84(15), 7917–7921.
Riemer, F., Kuehner, K. A., Ritz, S., Sauter-Louis, C., & Hartmann, K. (2016). Clinical and laboratory features of cats with feline infectious peritonitis – a retrospective study of 231 confirmed cases (2000–2010). Journal of Feline Medicine and Surgery, 18(4), 348–356.
Rossi, G. (2023). Acute phase proteins in cats: Diagnostic and prognostic role, future directions, and analytical challenges. Veterinary Clinical Pathology, 52, 37–49.
Rottier, P. J., Nakamura, K., Schellen, P., Volders, H., & Haijema, B. J. (2005). Acquisition of macrophage tropism during the pathogenesis of feline infectious peritonitis is determined by mutations in the feline coronavirus spike protein. Journal of Virology, 79(22), 14122–14130.
Shi, J., Wen, Z., Zhong, G., Yang, H., Wang, C., Liu, R., He, X,. Shuai, L., Sun, Z., Zhao, Y., Liang, L., Cui, P., Wang, J., Zhang, X., Guan, Y., Chen, H., Bu, Z., & Chen, H. (2020). Susceptibility of ferrets, cats, dogs, and different domestic animals to SARS-coronavirus-2. Science, 368(6469), 1016–1020.
Slaviero, M., Cony, F. G., da Silva, R. C., De Lorenzo, C., de Almeida, B. A., Bertolini, M., Driemeier, D., Pavarini, S., & Sonne, L. (2024). Pathological findings and patterns of feline infectious peritonitis in the respiratory tract of cats. Journal of Comparative Pathology, 210, 15–24.
Solikhah, T. I., Dwi Agustin, Q. A., Damaratri, R. A., Fika Siwi, D. A., Rafi’uttaqi, G. N., Hartadi, V. A., & Solikhah, G. P. (2024). A review of feline infectious peritonitis virus infection. Veterinary World, 17(11), 2417–2432.
Sweet, A. N., André, N. M., Stout, A. E., Licitra, B. N., & Whittaker, G. R. (2022). Clinical and molecular relationships between COVID-19 and feline infectious peritonitis (FIP). Viruses, 14(3), 481.
Takano, T., Nakaguchi, M., Doki, T., & Hohdatsu, T. (2017). Antibody-dependent enhancement of serotype II feline enteric coronavirus infection in primary feline monocytes. Archives of Virology, 162, 3339–3345.
Takano, T., Wakayama, Y., & Doki, T. (2019). Endocytic pathway of feline coronavirus for cell entry: Differences in serotype-dependent viral entry pathway. Pathogens, 8(4), 300.
Takano, T., Yamada, S., Doki, T., & Hohdatsu, T. (2019). Pathogenesis of oral type I feline infectious peritonitis virus (FIPV) infection: Antibody-dependent enhancement infection of cats with type I FIPV via the oral route. Journal of Veterinary Medical Science, 81(6), 911–915.
Tekes, G., & Thiel, H. J. (2016). Feline coronaviruses: Pathogenesis of feline infectious peritonitis. Advances in Virus Research, 96, 193–218.
Terada, Y., Kuroda, Y., Morikawa, S., Matsuura, Y., Maeda, K., & Kamitani, W. (2019). Establishment of a virulent full-length cDNA clone for type I feline coronavirus strain C3663. Journal of Virology, 93(21), 01208-19.
Thayer, V., Gogolski, S., Felten, S., Hartmann, K., Kennedy, M., & Olah, G. A. (2022). 2022 AAFP/EveryCat feline infectious peritonitis diagnosis guidelines. Journal of Feline Medicine and Surgery, 24(9), 905–933.
Vlasova, A. N., & Saif, L. J. (2021). Bovine coronavirus and the associated diseases. Frontiers in Veterinary Science, 8, 643220.
Wronski, J. G., de Cecco, B. S., Raiter, J., Henker, L. C., de Lorenzo, C., Bandinelli, M. B., Driemeier, D., Pavarini, S., & Sonne, L. (2023). Ophthalmic and immunopathological characterization of systemic infectious diseases in cats. Veterinary Pathology, 60(3), 352–359.
Xing, N., Wang, Z., Wang, J., Nascimento, M., Jongkaewwattana, A., Trimpert, J., Osterrieder, N., & Kunec, D. (2022). Engineering and characterization of avian coronavirus mutants expressing fluorescent reporter proteins from the replicase gene. Journal of Virology, 96(14), e00653-22.
Yang, H., Peng, Q., Lang, Y., Du, S., Cao, S., Wu, R., Zhao, Q., Huang, X., Wen, Y., Lin., J., Zhao, S., & Yan, Q. (2022). Phylogeny, evolution, and transmission dynamics of canine and feline coronaviruses: A retro-prospective study. Frontiers in Microbiology, 13, 850516.
Zhao, Y., Yang, Y., Gao, J., Huang, K., Hu, C., Hui, X., & Jin, M. (2022). A serological survey of severe acute respiratory syndrome coronavirus 2 in dogs in Wuhan. Transboundary and Emerging Diseases, 69(2), 591–597.
Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons «Attribution» 4.0 License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
