Acute and latent infection by bovine herpesvirus type 2 in a guinea pig model

Torres, Fabrício Dias; Cargnelutti, Juliana Felipetto; Masuda, Eduardo Kenji; Weiblen, Rudi; Flores, Eduardo Furtado

doi:10.1016/j.micpath.2009.11.003

Cited by 3 publications

(5 citation statements)

References 27 publications

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“…Provavelmente, isso se deve ao custo elevado do tratamento, principalmente para grandes animais. Neste sentido, coelhos têm sido utilizados como modelo para estudos de patogenia do BoHV-1 e BoHV-5 ) e cobaias para estudos com o BoHV-2 (Torres et al 2009). Para estas espécies, existe a possibilidade de se realizar estudos com antivirais, associados ou não a outros fárma-cos. Assim, o conhecimento acerca da atividade in vitro de antivirais contra esses agentes pode permitir a realização de estudos de patogenia e terapêutica adicionais frente ao BoHV-1, BoHV-2 e BoHV-5, bem como, em situações especiais, para o tratamento de animais de alto valor zootécnico (Dezengrini et al 2009).…”

Section: Introductionunclassified

Atividade de três drogas antivirais sobre os herpesvírus bovino tipos 1, 2 e 5 em cultivo celular

et al. 2010

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The activity of three anti-herpetic drugs (Acyclovir [ACV], Gancyclovir [GCV] and Foscarnet [PFA]) was tested against bovine herpesvirus 1 (BoHV-1), 2 (BoHV-2) and 5 (BoHV-5) in vitro using the plaque reduction assay. Different drug concentrations were tested against one hundred 50% tissue culture infectious dose (TCID 50 ) of the respective viruses. Drug concentrations lower than 200μg/mL resulted in viability rates of more than 80% for MDBK and Hep2 cells in the MTT test (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide). The selectivity index (IS) of the drugs was calculated dividing the concentration of the drug that is cytotoxic for 50% of the cells (CC 50 ) by the concentration of the drug that was effective in reducing by 50% the number of viral plaques (EC 50 ) for the three herpesviruses. Thus, ACV was shown to be moderately active against BoHV-1 (EC 50 : 112.9μg/mL; IS: 4.5), BoHV-2 (EC 50 : 114.2μg/mL; IS: 4.5) and BoHV-5 (EC 50 : 96.9μg/mL; IS: 5.3). GCV was effective against BoHV-2 (EC 50 : 33.5μg/mL; IS: 16.6), moderately effective against BoHV-5 (EC 50 : 123.2μg/mL; IS: 4.5) and poorly active against BoHV-1 (EC 50 : 335.8μg/mL; IS: 1.7). PFA exhibited the highest antiviral activity, being the only drug that, at concentration of 100μg/mL, completely inhibited plaque formation by all three viruses. PFA was the most effective in vitro against BoHV-1 (EC 50 : 29.5μg/mL; IS: 42.2), BoHV-2 (EC 50 : 45.2μg/mL; IS: 27.6) and BoHV-5 (EC 50 : 7.8μg/mL; IS: 160.6). Thus, the results indicate that PFA is a promising candidate for experimental therapeutic testing in vivo against bovine herpesviruses.INDEX TERMS: Antivirals, BoHV-1, BoHV-2, BoHV-5, Foscarnet, Gancyclovir, Acyclovir. INTRODUÇÃOOs herpesvírus bovino tipos 1 (BoHV-1), 2 (BoHV-2) e 5 (BoHV-5) são vírus DNA de cadeia dupla linear, que possuem um capsídeo de simetria icosaédrica e envelope lipoprotéico, classificados na família Herpesviridae, subfamília Alphaherpesvirinae. Esses vírus estabelecem e reativam infecções latentes em seus hospedeiros, propriedade que permite a sua manutenção na natureza (Rock et al. 1992, Roizman 1992. O BoHV-1 e 5 pertencem ao gênero Varicellovirus, e o BoHV-2 é classificado no gêne-ro Simplexvirus (Roizman 1992). O BoHV-1 é associado com doença respiratória (rinotraqueíte infecciosa bovina, IBR), conjuntivite, vulvovaginite/balanopostite pustular infecciosa (IPV/IBP), infertilidade transitória e abortos (Roizman 1992, Kahrs 2001. O BoHV-2 é associado à mamilite herpética bovina (BHM), doença vesicular e erosiva do úbere e tetos, que acomete principalmente vacas leiteiras de primeira cria (Kahrs 2001). O BoHV-5 é o agente da meningoencefalite herpética, doença geralmente fatal em bovinos jovens, e que ocorre com frequência na Argentina e no Brasil (Carrillo et al. 1983, Rissi et al. 2006.Historicamente, os herpesvírus humanos têm sido alvo para o desenvolvimento e teste de fármacos antivirais. O Aciclovir (ACV) e o Ganciclovir (GCV) são análogos de nucleosídeos, cujas moléculas consistem de uma guanina ass...

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Section: Introductionunclassified

Atividade de três drogas antivirais sobre os herpesvírus bovino tipos 1, 2 e 5 em cultivo celular

et al. 2010

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“…The scarce knowledge about its biology, molecular biology and pathogenesis has somehow hampered its use as a model for human simplex viruses and as a vector for vaccine delivery, among others. Our group has long been interested in BoHV-2 epidemiology and pathogenesis (Almeida et al 2008, Torres et al 2010. More recently, we have focused our interest in the use of BoHV-2 for anti-viral drug testing and for development of vaccine platforms for antigen delivery.…”

Section: Discussionmentioning

confidence: 99%

“…Second, the biological and genetic similarity of BoHV-2 with human simplex viruses may be exploited for the research and development of pharmaceuticals and vaccines as well. In this sense, BoHV-2 has been proposed as a potential target/model for the development of anti-herpetic drugs (Field et al 2006, Dezengrini et al 2010, Torres et al 2010). Third, animal herpesviruses have been long proposed as potential platforms for vaccine delivery and a number of current animal vaccines are based on herpesvirus vectors (Verma & Weitzman 2005, Kanekiyo et al 2019.…”

Section: Discussionmentioning

confidence: 99%

Pathogenesis of Bovine alphaherpesvirus 2 in calves following different routes of inoculation

et al. 2020

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Bovine alphaherpesvirus 2 (BoHV-2) is the agent of herpetic mammilitis (BHM), a cutaneous and self-limiting disease affecting the udder and teats of cows. The pathogenesis of BoHV-2 is pourly understood, hampering the development of therapeutic drugs, vaccines and other control measures. This study investigated the pathogenesis of BoHV-2 in calves after inoculation through different routes. Three- to four-months seronegative calves were inoculated with BoHV-2 (107TCID50.mL-1) intramuscular (IM, n=4), intravenous (IV, n=4) or transdermal (TD) after mild scarification (n=4) and submitted to virological, clinical and serological monitoring. Calves inoculated by the IV route presented as light increase in body temperature between days 6 to 9 post-inoculation (pi). Virus inoculation by the TD route resulted in mild inflammatory lesions at the sites of inoculation, characterized by hyperemia, small vesicles, mild exudation and scab formation, between days 2 and 8pi. Virus or viral DNA was detected by PCR in the crusts/swabs collected from lesions of 3 out of 4 animals inoculated TD from day 2 to 8pi. Viremia was detected in 3/4 animals of the IM group (from day 4 to 8pi); in 2/4 animals of the IV group (days 6 and 8pi) but not in the TD group. Calves from all inoculated groups seroconverted to BoHV-2 in titers from 4 to 64, as indicated by virus-neutralizing (VN) assays performed in sera collected at day 15pi. Administration of dexamethasone (Dex) to the inoculated calves at day 48pi, did not result in virus reactivation as indicated by lack of virus detection in the blood and/or in inoculation sites and no increase in VN antibody titers. These results demonstrated that BoHV-2 was able to replicate efficiently in calves following different routes of exposure, produced viremia after IM and IV inoculation and was not reactivated by Dex treatment.

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“…It is assumed that, after seroconversion, clinical signs tend to disappear, but there would be latent virus in the skin, nervous system, and lymph nodes. 4,17,18 Potential differential diagnoses should include ringworm (Trichophyton verrucosum), contact dermatitis, photosensitization, poxvirus and parapoxvirus (e.g., bovine papular stomatitis virus and cowpox virus) skin diseases, and BVDV dermatitis. In the present case, ringworm was not detected.…”

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confidence: 99%

“…It is assumed that, after seroconversion, clinical signs tend to disappear, but there would be latent virus in the skin, nervous system, and lymph nodes. 4,17,18…”

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confidence: 99%

Outbreaks of bovine herpesvirus 2 infections in calves causing ear and facial skin lesions

et al. 2017

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We describe 3 outbreaks of superficial dermatitis caused by bovine herpesvirus 2 (BoHV-2) in dairy breed calves. Clinically, all of the affected calves were 12-26 d of age, had alopecia and crusts on the face and ears, and were non-pruritic and afebrile. Affected animals recovered spontaneously without any treatment within 2-4 wk after onset of clinical signs based on 1 herd with follow up. Histologic examination of all skin crust or tissue samples identified neutrophilic inflammation, mild hyperkeratosis, multinucleate syncytial cells, and intranuclear inclusion bodies in the syncytial cells. Real-time PCR testing on affected surface crusts or tissue provided evidence of BoHV-2, and testing, where performed, was negative for parapoxvirus including bovine papular stomatitis virus and the ovine form of malignant catarrhal fever tested in EDTA blood samples. Bovine viral diarrhea virus also was negative by ELISA, as well as bovine herpesvirus 1 by immunohistochemistry. Direct electron microscopy of infected tissues in the first outbreak revealed herpesvirus-like particles.

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Acute and latent infection by bovine herpesvirus type 2 in a guinea pig model

Cited by 3 publications

References 27 publications

Atividade de três drogas antivirais sobre os herpesvírus bovino tipos 1, 2 e 5 em cultivo celular

Atividade de três drogas antivirais sobre os herpesvírus bovino tipos 1, 2 e 5 em cultivo celular

Pathogenesis of Bovine alphaherpesvirus 2 in calves following different routes of inoculation

Outbreaks of bovine herpesvirus 2 infections in calves causing ear and facial skin lesions

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