Respiratory and neurological disease in rabbits experimentally infected with equid herpesvirus 1

Kanitz, Fábio Adriano; Cargnelutti, Juliana Felipetto; Anziliero, Deniz; Gonçalves, Kelley V.; Masuda, Eduardo Kenji; Weiblen, Rudi; Flores, Eduardo Furtado

doi:10.1016/j.micpath.2015.07.007

Cited by 6 publications

(7 citation statements)

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“…The use of animal models is an attractive alternative for in vivo studies of antiviral drugs, mainly to determine doses, administration routes, time of treatment, toxicity and drug efficacy. Experimental infection of rabbits with EHV-1 (KANITZ et al, 2015) resulted in infection and development of respiratory and neurological signs. In this sense, the initial evaluation in vivo of the antiviral activity of drugs such as GCV, may be performed in this animal model, as they developed respiratory disease similar to naturally infected horses.…”

Section: Resultsmentioning

confidence: 99%

In vitro activity of six antiviral drugs against equid alphaherpesvirus type 1 indicates ganciclovir as promising drug for in vivo studies

et al. 2018

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Equid alphaherpesvirus type 1 (EHV-1) is distributed worldwide and is a major agent of abortion, respiratory and neurological disease in horses. No specific treatment is available for EHV-1 infection, yet the potential of antiviral therapy has been explored. In this study we investigated the in vitro activity of Acyclovir, Ganciclovir, Foscarnet, Famciclovir, Vidarabina and Cidofovir against EHV-1. For this, the MTT test was performed, in which all the tested drugs showed no toxicity up to 200μg/mL. Subsequently, different drug concentrations were submitted to viral plaque reduction assays in cell culture. The selectivity index (SI) of the compounds was determined using the cytotoxic concentration for 50% of cells (CC50), obtained by MTT, and effective drug concentration to inhibit by 50% the number of viral plaques (EC50). Ganciclovir (SI: 490; EC50: 1.9 μg/mL) was the most efficient and safest drug against EHV-1, followed by Cidofovir (SI: 150, EC50: 5.7μg/mL), Acyclovir (SI: 37.4, EC50: 22.2μg/mL), Famciclovir (SI: 25.1, EC50: 24.5μg/mL), Vidarabine (SI: 12.2, EC50: 40.9μg/mL) and Foscarnet (SI: 6.9, EC50: 49.5 μg/mL), respectively. These results indicated that Ganciclovir (followed by Cidofovir), is a promising candidate for use in in vivo experiments.

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Section: Resultsmentioning

confidence: 99%

In vitro activity of six antiviral drugs against equid alphaherpesvirus type 1 indicates ganciclovir as promising drug for in vivo studies

et al. 2018

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“…Regardless, the activity of GCV in the respiratory disease by EHV-1 remained unexploited. In this study we investigated its activity in vivo, using a rabbit model for EHV-1 respiratory disease established previously (Kanitz et al 2015).…”

Section: Discussionmentioning

confidence: 99%

“…Eighteen New Zealand rabbits (approximately 30-days-old) were allocated in three groups of six animals each according to the respective treatments: G1 (uninfected controls, inoculated IN with RPMI medium); G2 (inoculated with EHV-1); G3 (inoculated with EHV-1 and treated with GCV). Animals from G2 and G3 were inoculated into the paranasal sinuses (Kanitz et al 2015) with 1mL of culture supernatant containing 10 7 mean tissue culture infectious doses (TCID 50 ) of EHV-1 after sedation with ketamine (50mg/kg) and xylazine (5mg/kg). Starting at the day of virus inoculation, animals of G3 received GCV intravenously (5mg/kg/day) during seven days.…”

Section: Methodsmentioning

confidence: 99%

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Ganciclovir attenuates the respiratory disease induced by Equid alphaherpesvirus 1 in rabbits

et al. 2019

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Equid alphaherpesvirus 1 (EHV-1) is an important pathogen of horses, associated with respiratory, neurological disease and abortions. As vaccination is not always effective, anti-herpetic therapy may represent an alternative to prevent the losses caused by the infection. We herein investigated the activity of ganciclovir (GCV), an anti-herpetic human drug, in rabbits experimentally infected with EHV-1. Thirty-days-old New Zealand rabbits were allocated in three groups (6 animals each) and submitted to different treatments: G1 (non-infected controls), G2 (inoculated with EHV-1) - 107 TCID50 intranasally - IN) and G3 (inoculated IN with EHV-1 and treated with GCV - 5mg/kg/day for 7 days) and monitored thereafter. All animals of G2 developed systemic signs (moderate to severe apathy, anorexia), ocular discharge and respiratory signs (serous to mucopurulent nasal discharge), including mild to severe respiratory distress. Viremia was detected in all rabbits of G2 for up to 11 days (mean duration = 6.5 days). One animal died after severe respiratory distress and neurological signs (bruxism, opistotonus). In addition, these animals gained less weight than the control (G1) and GCV-treated rabbits (G3) from days 4 to 14pi (p<0.05). The clinical score of rabbits of G2 was statistically higher than the other groups from days 3 to 6pi (p<0.05), demonstrating a more severe disease. In contrast, G3 rabbits did not present systemic signs, presented only a mild and transient nasal secretion and gained more weight than G2 animals (p<0.05). In addition, viremia was detected in only 3 rabbits and was transient (average of 2.3 days). Thus, administration of GCV to rabbits inoculated IN with EHV-1 resulted in an important attenuation of the clinical disease as demonstrated by full prevention of systemic signs, maintenance of weight gain and by drastic reduction in viremia and in the magnitude of respiratory signs. These results are promising towards further testing of GCV as a potential drug for anti-herpetic therapy in horses.

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“…Recentemente, Kanitz et al (2015) (IFN-γ, TNF-α, IL-6) e da quimiocina MCP-1 (CCL2), pelo método de citometria de fluxo, em camundongos das linhagens isogênicas BALB/c (H2 d ) e C57BL/6 (H2 b ) e C3H/HeJ (H2 k ), infectados pelo EHV-1.…”

Section: Sinais Clínicosunclassified

<b>Avaliação da resposta inflamatória no sistema nervoso central causada pelo herpesvírus equino tipo 1 utilizando um modelo murino de neuroinfecção</b>

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Ao meu noivo Lucas Garcia Rios À querida Rebeca (in memoriam) À querida Pérola EPÍGRAFE "Há uma força motriz mais poderosa que o vapor, a eletricidade e a energia atômica: a vontade." Albert Einstein AGRADECIMENTOS A Deus, por iluminar meus caminhos e sempre me fortalecer em todos os momentos de minha vida. Aos meus queridos pais, Amauri Tonietti e Roseli de Oliveira Tonietti, pela amizade, apoio, carinho em todas as fases da minha vida e principalmente pelo exemplo de dignidade e respeito. Ao meu noivo Lucas Garcia Rios, pela paciência, carinho e atenção em todos os momentos. Ao Prof. Dr. Paulo César Maiorka, pela orientação, oportunidade de crescimento, confiança, amizade, conselhos, e grandes ensinamentos, proporcionando a execução deste trabalho.

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Respiratory and neurological disease in rabbits experimentally infected with equid herpesvirus 1

Cited by 6 publications

References 25 publications

In vitro activity of six antiviral drugs against equid alphaherpesvirus type 1 indicates ganciclovir as promising drug for in vivo studies

In vitro activity of six antiviral drugs against equid alphaherpesvirus type 1 indicates ganciclovir as promising drug for in vivo studies

Ganciclovir attenuates the respiratory disease induced by Equid alphaherpesvirus 1 in rabbits

<b>Avaliação da resposta inflamatória no sistema nervoso central causada pelo herpesvírus equino tipo 1 utilizando um modelo murino de neuroinfecção</b>

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