Immune Responses and Pathogenesis following Experimental SARS-CoV-2 Infection in Domestic Cats

Sandra Vreman; Elisabeth M D L van der Heijden; Lars Ravesloot; Irene S Ludwig; Judith M A van den Brand; Frank Harders; Andries A Kampfraath; Herman F Egberink; Jose L Gonzales; Nadia Oreshkova; Femke Broere; Wim H M van der Poel; Nora M Gerhards

doi:10.3390/v15051052

Immune Responses and Pathogenesis following Experimental SARS-CoV-2 Infection in Domestic Cats

Sandra Vreman^*, Elisabeth M D L van der Heijden, Lars Ravesloot, Irene S Ludwig, Judith M A van den Brand, Frank Harders, Andries A Kampfraath, Herman F Egberink, Jose L Gonzales, Nadia Oreshkova, Femke Broere, Wim H M van der Poel, Nora M Gerhards^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Several reports demonstrated the susceptibility of domestic cats to SARS-CoV-2 infection. Here, we describe a thorough investigation of the immune responses in cats after experimental SARS-CoV-2 inoculation, along with the characterization of infection kinetics and pathological lesions. Specific pathogen-free domestic cats ( n = 12) were intranasally inoculated with SARS-CoV-2 and subsequently sacrificed on DPI (days post-inoculation) 2, 4, 7 and 14. None of the infected cats developed clinical signs. Only mild histopathologic lung changes associated with virus antigen expression were observed mainly on DPI 4 and 7. Viral RNA was present until DPI 7, predominantly in nasal and throat swabs. The infectious virus could be isolated from the nose, trachea and lungs until DPI 7. In the swab samples, no biologically relevant SARS-CoV-2 mutations were observed over time. From DPI 7 onwards, all cats developed a humoral immune response. The cellular immune responses were limited to DPI 7. Cats showed an increase in CD8+ cells, and the subsequent RNA sequence analysis of CD4+ and CD8+ subsets revealed a prominent upregulation of antiviral and inflammatory genes on DPI 2. In conclusion, infected domestic cats developed a strong antiviral response and cleared the virus within the first week after infection without overt clinical signs and relevant virus mutations.

Original language	English
Article number	1052
Pages (from-to)	1-18
Number of pages	18
Journal	Viruses
Volume	15
Issue number	5
DOIs	https://doi.org/10.3390/v15051052
Publication status	Published - May 2023

Bibliographical note

Funding Information:
This research was funded by the Dutch Ministry of Agriculture and Food under the ARVODI-2018 agreement concerning policy supporting research on COVID-19 in cats and dogs.

Publisher Copyright:
© 2023 by the authors.

Keywords

CD4 and CD8
COVID-19
SARS-CoV-2
cats
immunology
intranasal inoculation
pathology
viral shedding

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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viruses-15-01052-v2Final published version, 35.5 MBLicence: CC BY

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Vreman, S., van der Heijden, E. M. D. L., Ravesloot, L., Ludwig, I. S., van den Brand, J. M. A., Harders, F., Kampfraath, A. A., Egberink, H. F., Gonzales, J. L., Oreshkova, N., Broere, F., van der Poel, W. H. M., & Gerhards, N. M. (2023). Immune Responses and Pathogenesis following Experimental SARS-CoV-2 Infection in Domestic Cats. Viruses, 15(5), 1-18. Article 1052. https://doi.org/10.3390/v15051052

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title = "Immune Responses and Pathogenesis following Experimental SARS-CoV-2 Infection in Domestic Cats",

abstract = "Several reports demonstrated the susceptibility of domestic cats to SARS-CoV-2 infection. Here, we describe a thorough investigation of the immune responses in cats after experimental SARS-CoV-2 inoculation, along with the characterization of infection kinetics and pathological lesions. Specific pathogen-free domestic cats ( n = 12) were intranasally inoculated with SARS-CoV-2 and subsequently sacrificed on DPI (days post-inoculation) 2, 4, 7 and 14. None of the infected cats developed clinical signs. Only mild histopathologic lung changes associated with virus antigen expression were observed mainly on DPI 4 and 7. Viral RNA was present until DPI 7, predominantly in nasal and throat swabs. The infectious virus could be isolated from the nose, trachea and lungs until DPI 7. In the swab samples, no biologically relevant SARS-CoV-2 mutations were observed over time. From DPI 7 onwards, all cats developed a humoral immune response. The cellular immune responses were limited to DPI 7. Cats showed an increase in CD8+ cells, and the subsequent RNA sequence analysis of CD4+ and CD8+ subsets revealed a prominent upregulation of antiviral and inflammatory genes on DPI 2. In conclusion, infected domestic cats developed a strong antiviral response and cleared the virus within the first week after infection without overt clinical signs and relevant virus mutations. ",

keywords = "CD4 and CD8, COVID-19, SARS-CoV-2, cats, immunology, intranasal inoculation, pathology, viral shedding",

author = "Sandra Vreman and {van der Heijden}, {Elisabeth M D L} and Lars Ravesloot and Ludwig, {Irene S} and {van den Brand}, {Judith M A} and Frank Harders and Kampfraath, {Andries A} and Egberink, {Herman F} and Gonzales, {Jose L} and Nadia Oreshkova and Femke Broere and {van der Poel}, {Wim H M} and Gerhards, {Nora M}",

note = "Funding Information: This research was funded by the Dutch Ministry of Agriculture and Food under the ARVODI-2018 agreement concerning policy supporting research on COVID-19 in cats and dogs. Publisher Copyright: {\textcopyright} 2023 by the authors.",

year = "2023",

month = may,

doi = "10.3390/v15051052",

language = "English",

volume = "15",

pages = "1--18",

journal = "Viruses",

issn = "1999-4915",

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Vreman, S, van der Heijden, EMDL, Ravesloot, L, Ludwig, IS , van den Brand, JMA, Harders, F, Kampfraath, AA, Egberink, HF, Gonzales, JL, Oreshkova, N, Broere, F, van der Poel, WHM & Gerhards, NM 2023, 'Immune Responses and Pathogenesis following Experimental SARS-CoV-2 Infection in Domestic Cats', Viruses, vol. 15, no. 5, 1052, pp. 1-18. https://doi.org/10.3390/v15051052

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T1 - Immune Responses and Pathogenesis following Experimental SARS-CoV-2 Infection in Domestic Cats

AU - Vreman, Sandra

AU - van der Heijden, Elisabeth M D L

AU - Ravesloot, Lars

AU - Ludwig, Irene S

AU - van den Brand, Judith M A

AU - Harders, Frank

AU - Kampfraath, Andries A

AU - Egberink, Herman F

AU - Gonzales, Jose L

AU - Oreshkova, Nadia

AU - Broere, Femke

AU - van der Poel, Wim H M

AU - Gerhards, Nora M

N1 - Funding Information: This research was funded by the Dutch Ministry of Agriculture and Food under the ARVODI-2018 agreement concerning policy supporting research on COVID-19 in cats and dogs. Publisher Copyright: © 2023 by the authors.

PY - 2023/5

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N2 - Several reports demonstrated the susceptibility of domestic cats to SARS-CoV-2 infection. Here, we describe a thorough investigation of the immune responses in cats after experimental SARS-CoV-2 inoculation, along with the characterization of infection kinetics and pathological lesions. Specific pathogen-free domestic cats ( n = 12) were intranasally inoculated with SARS-CoV-2 and subsequently sacrificed on DPI (days post-inoculation) 2, 4, 7 and 14. None of the infected cats developed clinical signs. Only mild histopathologic lung changes associated with virus antigen expression were observed mainly on DPI 4 and 7. Viral RNA was present until DPI 7, predominantly in nasal and throat swabs. The infectious virus could be isolated from the nose, trachea and lungs until DPI 7. In the swab samples, no biologically relevant SARS-CoV-2 mutations were observed over time. From DPI 7 onwards, all cats developed a humoral immune response. The cellular immune responses were limited to DPI 7. Cats showed an increase in CD8+ cells, and the subsequent RNA sequence analysis of CD4+ and CD8+ subsets revealed a prominent upregulation of antiviral and inflammatory genes on DPI 2. In conclusion, infected domestic cats developed a strong antiviral response and cleared the virus within the first week after infection without overt clinical signs and relevant virus mutations.

AB - Several reports demonstrated the susceptibility of domestic cats to SARS-CoV-2 infection. Here, we describe a thorough investigation of the immune responses in cats after experimental SARS-CoV-2 inoculation, along with the characterization of infection kinetics and pathological lesions. Specific pathogen-free domestic cats ( n = 12) were intranasally inoculated with SARS-CoV-2 and subsequently sacrificed on DPI (days post-inoculation) 2, 4, 7 and 14. None of the infected cats developed clinical signs. Only mild histopathologic lung changes associated with virus antigen expression were observed mainly on DPI 4 and 7. Viral RNA was present until DPI 7, predominantly in nasal and throat swabs. The infectious virus could be isolated from the nose, trachea and lungs until DPI 7. In the swab samples, no biologically relevant SARS-CoV-2 mutations were observed over time. From DPI 7 onwards, all cats developed a humoral immune response. The cellular immune responses were limited to DPI 7. Cats showed an increase in CD8+ cells, and the subsequent RNA sequence analysis of CD4+ and CD8+ subsets revealed a prominent upregulation of antiviral and inflammatory genes on DPI 2. In conclusion, infected domestic cats developed a strong antiviral response and cleared the virus within the first week after infection without overt clinical signs and relevant virus mutations.

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KW - SARS-CoV-2

KW - cats

KW - immunology

KW - intranasal inoculation

KW - pathology

KW - viral shedding

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DO - 10.3390/v15051052

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C2 - 37243138

SN - 1999-4915

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SP - 1

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JO - Viruses

JF - Viruses

IS - 5

M1 - 1052

ER -

Immune Responses and Pathogenesis following Experimental SARS-CoV-2 Infection in Domestic Cats

Abstract

Bibliographical note

Keywords

UN SDGs

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