Serologic, Virologic and Pathologic Features of Cats with Naturally Occurring Feline Infectious Peritonitis Enrolled in Antiviral Clinical Trials
Feline infectious peritonitis (FIP) is a multisystemic, generally lethal immuno-inflammatory disease of domestic cats caused by an infection with a genetic variant of feline coronavirus, referred to as the FIP virus (FIPV). We leveraged data from four different antiviral clinical trials performed at...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2024-03-01
|
| Series: | Viruses |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1999-4915/16/3/462 |
| _version_ | 1797239052016025600 |
|---|---|
| author | Brian G. Murphy Diego Castillo N E Neely Amir Kol Terza Brostoff Chris K. Grant Krystle L. Reagan |
| author_facet | Brian G. Murphy Diego Castillo N E Neely Amir Kol Terza Brostoff Chris K. Grant Krystle L. Reagan |
| author_sort | Brian G. Murphy |
| collection | DOAJ |
| description | Feline infectious peritonitis (FIP) is a multisystemic, generally lethal immuno-inflammatory disease of domestic cats caused by an infection with a genetic variant of feline coronavirus, referred to as the FIP virus (FIPV). We leveraged data from four different antiviral clinical trials performed at the University of California, Davis. Collectively, a total of 60 client-owned domestic cats, each with a confirmed diagnosis of naturally occurring FIP, were treated with a variety of antiviral compounds. The tested therapies included the antiviral compounds GS-441524, remdesivir, molnupiravir and allogeneic feline mesenchymal stem/stroma cell transfusions. Four client-owned cats with FIP did not meet the inclusion criteria for the trials and were not treated with antiviral therapies; these cats were included in the data set as untreated FIP control cats. ELISA and Western blot assays were performed using feline serum/plasma or ascites effusions obtained from a subset of the FIP cats. Normalized tissue/effusion viral loads were determined in 34 cats by a quantitative RT-PCR of nucleic acids isolated from either effusions or abdominal lymph node tissue. Twenty-one cats were PCR “serotyped” (genotyped) and had the S1/S2 region of the coronaviral <i>spike</i> gene amplified, cloned and sequenced from effusions or abdominal lymph node tissue. In total, 3 untreated control cats and 14 (23.3%) of the 60 antiviral-treated cats died or were euthanized during (13) or after the completion of (1) antiviral treatment. Of these 17 cats, 13 had complete necropsies performed (10 cats treated with antivirals and 3 untreated control cats). We found that anticoronaviral serologic responses were persistent and robust throughout the treatment period, primarily the IgG isotype, and focused on the viral structural Nucleocapsid and Membrane proteins. Coronavirus serologic patterns were similar for the effusions and serum/plasma of cats with FIP and in cats entering remission or that died. Viral RNA was readily detectable in the majority of the cats in either abdominal lymph node tissue or ascites effusions, and all of the viral isolates were determined to be serotype I FIPV. Viral nucleic acids in cats treated with antiviral compounds became undetectable in ascites or abdominal lymph node tissue by 11 days post-treatment using a sensitive quantitative RT-PCR assay. The most common pathologic lesions identified in the necropsied cats were hepatitis, abdominal effusion (ascites), serositis, pancreatitis, lymphadenitis, icterus and perivasculitis. In cats treated with antiviral compounds, gross and histological lesions characteristic of FIP persisted for several weeks, while the viral antigen became progressively less detectable. |
| first_indexed | 2024-04-24T17:45:24Z |
| format | Article |
| id | doaj.art-bb02d15788dd49f1a7821efe0ada804d |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-04-24T17:45:24Z |
| publishDate | 2024-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-bb02d15788dd49f1a7821efe0ada804d2024-03-27T14:07:58ZengMDPI AGViruses1999-49152024-03-0116346210.3390/v16030462Serologic, Virologic and Pathologic Features of Cats with Naturally Occurring Feline Infectious Peritonitis Enrolled in Antiviral Clinical TrialsBrian G. Murphy0Diego Castillo1N E Neely2Amir Kol3Terza Brostoff4Chris K. Grant5Krystle L. Reagan6Department of Pathology, Microbiology and Immunology, School of Veterinary Medicine, University of California, Davis, CA 95616, USADepartment of Pathology, Microbiology and Immunology, School of Veterinary Medicine, University of California, Davis, CA 95616, USASchool of Veterinary Medicine, University of California, Davis, CA 95616, USADepartment of Pathology, Microbiology and Immunology, School of Veterinary Medicine, University of California, Davis, CA 95616, USADepartment of Pathology, Microbiology and Immunology, School of Veterinary Medicine, University of California, Davis, CA 95616, USACustom Monoclonals International, 813 Harbor Boulevard, West Sacramento, CA 95691, USADepartment of Medicine and Epidemiology, School of Veterinary Medicine, University of California, Davis, CA 95616, USAFeline infectious peritonitis (FIP) is a multisystemic, generally lethal immuno-inflammatory disease of domestic cats caused by an infection with a genetic variant of feline coronavirus, referred to as the FIP virus (FIPV). We leveraged data from four different antiviral clinical trials performed at the University of California, Davis. Collectively, a total of 60 client-owned domestic cats, each with a confirmed diagnosis of naturally occurring FIP, were treated with a variety of antiviral compounds. The tested therapies included the antiviral compounds GS-441524, remdesivir, molnupiravir and allogeneic feline mesenchymal stem/stroma cell transfusions. Four client-owned cats with FIP did not meet the inclusion criteria for the trials and were not treated with antiviral therapies; these cats were included in the data set as untreated FIP control cats. ELISA and Western blot assays were performed using feline serum/plasma or ascites effusions obtained from a subset of the FIP cats. Normalized tissue/effusion viral loads were determined in 34 cats by a quantitative RT-PCR of nucleic acids isolated from either effusions or abdominal lymph node tissue. Twenty-one cats were PCR “serotyped” (genotyped) and had the S1/S2 region of the coronaviral <i>spike</i> gene amplified, cloned and sequenced from effusions or abdominal lymph node tissue. In total, 3 untreated control cats and 14 (23.3%) of the 60 antiviral-treated cats died or were euthanized during (13) or after the completion of (1) antiviral treatment. Of these 17 cats, 13 had complete necropsies performed (10 cats treated with antivirals and 3 untreated control cats). We found that anticoronaviral serologic responses were persistent and robust throughout the treatment period, primarily the IgG isotype, and focused on the viral structural Nucleocapsid and Membrane proteins. Coronavirus serologic patterns were similar for the effusions and serum/plasma of cats with FIP and in cats entering remission or that died. Viral RNA was readily detectable in the majority of the cats in either abdominal lymph node tissue or ascites effusions, and all of the viral isolates were determined to be serotype I FIPV. Viral nucleic acids in cats treated with antiviral compounds became undetectable in ascites or abdominal lymph node tissue by 11 days post-treatment using a sensitive quantitative RT-PCR assay. The most common pathologic lesions identified in the necropsied cats were hepatitis, abdominal effusion (ascites), serositis, pancreatitis, lymphadenitis, icterus and perivasculitis. In cats treated with antiviral compounds, gross and histological lesions characteristic of FIP persisted for several weeks, while the viral antigen became progressively less detectable.https://www.mdpi.com/1999-4915/16/3/462catFIPfeline coronavirusantiviral compoundserology |
| spellingShingle | Brian G. Murphy Diego Castillo N E Neely Amir Kol Terza Brostoff Chris K. Grant Krystle L. Reagan Serologic, Virologic and Pathologic Features of Cats with Naturally Occurring Feline Infectious Peritonitis Enrolled in Antiviral Clinical Trials Viruses cat FIP feline coronavirus antiviral compound serology |
| title | Serologic, Virologic and Pathologic Features of Cats with Naturally Occurring Feline Infectious Peritonitis Enrolled in Antiviral Clinical Trials |
| title_full | Serologic, Virologic and Pathologic Features of Cats with Naturally Occurring Feline Infectious Peritonitis Enrolled in Antiviral Clinical Trials |
| title_fullStr | Serologic, Virologic and Pathologic Features of Cats with Naturally Occurring Feline Infectious Peritonitis Enrolled in Antiviral Clinical Trials |
| title_full_unstemmed | Serologic, Virologic and Pathologic Features of Cats with Naturally Occurring Feline Infectious Peritonitis Enrolled in Antiviral Clinical Trials |
| title_short | Serologic, Virologic and Pathologic Features of Cats with Naturally Occurring Feline Infectious Peritonitis Enrolled in Antiviral Clinical Trials |
| title_sort | serologic virologic and pathologic features of cats with naturally occurring feline infectious peritonitis enrolled in antiviral clinical trials |
| topic | cat FIP feline coronavirus antiviral compound serology |
| url | https://www.mdpi.com/1999-4915/16/3/462 |
| work_keys_str_mv | AT briangmurphy serologicvirologicandpathologicfeaturesofcatswithnaturallyoccurringfelineinfectiousperitonitisenrolledinantiviralclinicaltrials AT diegocastillo serologicvirologicandpathologicfeaturesofcatswithnaturallyoccurringfelineinfectiousperitonitisenrolledinantiviralclinicaltrials AT neneely serologicvirologicandpathologicfeaturesofcatswithnaturallyoccurringfelineinfectiousperitonitisenrolledinantiviralclinicaltrials AT amirkol serologicvirologicandpathologicfeaturesofcatswithnaturallyoccurringfelineinfectiousperitonitisenrolledinantiviralclinicaltrials AT terzabrostoff serologicvirologicandpathologicfeaturesofcatswithnaturallyoccurringfelineinfectiousperitonitisenrolledinantiviralclinicaltrials AT chriskgrant serologicvirologicandpathologicfeaturesofcatswithnaturallyoccurringfelineinfectiousperitonitisenrolledinantiviralclinicaltrials AT krystlelreagan serologicvirologicandpathologicfeaturesofcatswithnaturallyoccurringfelineinfectiousperitonitisenrolledinantiviralclinicaltrials |