Pharmacokinetic and Efficacy Study of Acyclovir Against Cyprinid Herpesvirus 3 in Cyprinus carpio
Cyprinid Herpesvirus 3 (CyHV-3), more commonly known as Koi Herpesvirus (KHV), is a re-emergent virus causing acute systemic infection with high mortality rates in koi fish (Cyprinus carpio). Survivors from outbreaks can become latent carriers, with viral reactivation under stressful conditions and...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-10-01
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| Series: | Frontiers in Veterinary Science |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fvets.2020.587952/full |
| _version_ | 1818400288336248832 |
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| author | Eva Marie Quijano Cardé Zeinab Yazdi Susan Yun Ruixue Hu Heather Knych Denise M. Imai Esteban Soto |
| author_facet | Eva Marie Quijano Cardé Zeinab Yazdi Susan Yun Ruixue Hu Heather Knych Denise M. Imai Esteban Soto |
| author_sort | Eva Marie Quijano Cardé |
| collection | DOAJ |
| description | Cyprinid Herpesvirus 3 (CyHV-3), more commonly known as Koi Herpesvirus (KHV), is a re-emergent virus causing acute systemic infection with high mortality rates in koi fish (Cyprinus carpio). Survivors from outbreaks can become latent carriers, with viral reactivation under stressful conditions and permissible temperatures. No vaccines or treatments are currently available in the United States. Acyclovir has been shown effective in vitro against KHV. This study aimed to evaluate the cytotoxicity of acyclovir and cidofovir to koi fin (KF1) cells, the efficacy of a single antiviral intracoelomic dose in a koi fingerling cohabitation challenge, and the pharmacokinetics of the effective antiviral. Initially, a lactate dehydrogenase release-based assay revealed no significant acyclovir or cidofovir cytotoxicity to KF1 cells for 24 h at up to 1,500 μM. In laboratory-controlled challenges, KHV associated mortalities occurred 2 weeks post-infection. At this point, fish were treated with an antiviral (10 mg/kg acyclovir or 5 mg/kg cidofovir) or sterile phosphate-buffered solution. Morbidity and mortality were monitored for 30 days. A significant cumulative mortality reduction (p ≤ 0.05), and a 3-day mortality delay were detected in the acyclovir-treated group. Similar viral loads were detected in gills recovered from mortalities throughout the challenge and surviving fish at the end of the challenge regardless of treatment. For pharmacokinetic analysis, blood was collected at various timepoints after acyclovir administration. Liquid chromatography tandem mass spectrometry plasma analysis indicated a 141 μM peak plasma concentration at 0.75 h, a 14 h half-life, and a 0.05/h elimination rate constant. Histopathology of target tissues detected no evidence of acyclovir toxicity. Results suggest that a single 10 mg/kg dose of acyclovir administered intracoelomically to koi fingerlings is safe and reduces cumulative mortality during a KHV mortality event. However, multiple doses are probably required for effective treatment of pet fish. |
| first_indexed | 2024-12-14T07:34:11Z |
| format | Article |
| id | doaj.art-5c160b5a457b44aea5b351f32943d24d |
| institution | Directory Open Access Journal |
| issn | 2297-1769 |
| language | English |
| last_indexed | 2024-12-14T07:34:11Z |
| publishDate | 2020-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Veterinary Science |
| spelling | doaj.art-5c160b5a457b44aea5b351f32943d24d2022-12-21T23:11:15ZengFrontiers Media S.A.Frontiers in Veterinary Science2297-17692020-10-01710.3389/fvets.2020.587952587952Pharmacokinetic and Efficacy Study of Acyclovir Against Cyprinid Herpesvirus 3 in Cyprinus carpioEva Marie Quijano Cardé0Zeinab Yazdi1Susan Yun2Ruixue Hu3Heather Knych4Denise M. Imai5Esteban Soto6Department of Medicine and Epidemiology, School of Veterinary Medicine, University of California, Davis, Davis, CA, United StatesDepartment of Medicine and Epidemiology, School of Veterinary Medicine, University of California, Davis, Davis, CA, United StatesDepartment of Medicine and Epidemiology, School of Veterinary Medicine, University of California, Davis, Davis, CA, United StatesDepartment of Medicine and Epidemiology, School of Veterinary Medicine, University of California, Davis, Davis, CA, United StatesK. L. Maddy Equine Analytical Pharmacology Laboratory, School of Veterinary Medicine, University of California, Davis, Davis, CA, United StatesComparative Pathology Laboratory, University of California, Davis, Davis, CA, United StatesDepartment of Medicine and Epidemiology, School of Veterinary Medicine, University of California, Davis, Davis, CA, United StatesCyprinid Herpesvirus 3 (CyHV-3), more commonly known as Koi Herpesvirus (KHV), is a re-emergent virus causing acute systemic infection with high mortality rates in koi fish (Cyprinus carpio). Survivors from outbreaks can become latent carriers, with viral reactivation under stressful conditions and permissible temperatures. No vaccines or treatments are currently available in the United States. Acyclovir has been shown effective in vitro against KHV. This study aimed to evaluate the cytotoxicity of acyclovir and cidofovir to koi fin (KF1) cells, the efficacy of a single antiviral intracoelomic dose in a koi fingerling cohabitation challenge, and the pharmacokinetics of the effective antiviral. Initially, a lactate dehydrogenase release-based assay revealed no significant acyclovir or cidofovir cytotoxicity to KF1 cells for 24 h at up to 1,500 μM. In laboratory-controlled challenges, KHV associated mortalities occurred 2 weeks post-infection. At this point, fish were treated with an antiviral (10 mg/kg acyclovir or 5 mg/kg cidofovir) or sterile phosphate-buffered solution. Morbidity and mortality were monitored for 30 days. A significant cumulative mortality reduction (p ≤ 0.05), and a 3-day mortality delay were detected in the acyclovir-treated group. Similar viral loads were detected in gills recovered from mortalities throughout the challenge and surviving fish at the end of the challenge regardless of treatment. For pharmacokinetic analysis, blood was collected at various timepoints after acyclovir administration. Liquid chromatography tandem mass spectrometry plasma analysis indicated a 141 μM peak plasma concentration at 0.75 h, a 14 h half-life, and a 0.05/h elimination rate constant. Histopathology of target tissues detected no evidence of acyclovir toxicity. Results suggest that a single 10 mg/kg dose of acyclovir administered intracoelomically to koi fingerlings is safe and reduces cumulative mortality during a KHV mortality event. However, multiple doses are probably required for effective treatment of pet fish.https://www.frontiersin.org/articles/10.3389/fvets.2020.587952/fullantiviral therapycidofovirfish medicineKHVkoi Acyclovir |
| spellingShingle | Eva Marie Quijano Cardé Zeinab Yazdi Susan Yun Ruixue Hu Heather Knych Denise M. Imai Esteban Soto Pharmacokinetic and Efficacy Study of Acyclovir Against Cyprinid Herpesvirus 3 in Cyprinus carpio Frontiers in Veterinary Science antiviral therapy cidofovir fish medicine KHV koi Acyclovir |
| title | Pharmacokinetic and Efficacy Study of Acyclovir Against Cyprinid Herpesvirus 3 in Cyprinus carpio |
| title_full | Pharmacokinetic and Efficacy Study of Acyclovir Against Cyprinid Herpesvirus 3 in Cyprinus carpio |
| title_fullStr | Pharmacokinetic and Efficacy Study of Acyclovir Against Cyprinid Herpesvirus 3 in Cyprinus carpio |
| title_full_unstemmed | Pharmacokinetic and Efficacy Study of Acyclovir Against Cyprinid Herpesvirus 3 in Cyprinus carpio |
| title_short | Pharmacokinetic and Efficacy Study of Acyclovir Against Cyprinid Herpesvirus 3 in Cyprinus carpio |
| title_sort | pharmacokinetic and efficacy study of acyclovir against cyprinid herpesvirus 3 in cyprinus carpio |
| topic | antiviral therapy cidofovir fish medicine KHV koi Acyclovir |
| url | https://www.frontiersin.org/articles/10.3389/fvets.2020.587952/full |
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