Patogênese e terapia experimental da infecção pelo alfaherpesvírus bovino 2
Autor(a) principal: | |
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Data de Publicação: | 2020 |
Tipo de documento: | Tese |
Idioma: | por |
Título da fonte: | Repositório Institucional Manancial UFSM |
Texto Completo: | http://repositorio.ufsm.br/handle/1/21588 |
Resumo: | Bovine alphaherpesvirus 2 (BoHV-2) - the agent of bovine herpetic mamillitis (BHM) – is related to Human alphaherpesviruses 1 and 2 (HHV-1, HHV-2) and has been proposed as a model for vaccine and drug testing. In addition, very little is known about the pathogenesis of BoHV-2 infection. Herein we studied the pathogenesis of BoHV-2 in calves after inoculation through different routes and investigated the activity of candidate anti-viral drugs in vitro and in vivo against BoHV-2. In the first study, 3 to 4-months-old calves were inoculated with BoHV-2 (107TCID50.mL-1) intramuscularly (IM, n=4), intravenously (IV, n=4) or transdermally (TD) after mild scarification (n=4) and monitored thereafter. 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. Administration of dexamethasone (Dex) to the inoculated calves at day 48pi, did not result in virus reactivation. In the second study, we investigated the anti-viral activity in vitro against BoHV-2 of three anti-herpetic drugs: Cidofovir (CDV), Fanciclovir (FAM), Foscarnet (PFA), and diphenyl disselenide (PhSe)2 by plaque reduction assays (PRA). A significant reduction in the number of viral plaques was observed by treating the monolayers with (PhSe)2 (79.7% reduction, p<0.05) or CDV (62.8%, p<0.05). FAM treatment resulted in a slight decrease in plaque number (22.9%, p<0.05) and PFA showed no anti-viral activity. Next, we investigated the effects of (PhSe)2 and CDV, alone or in combination, in the infection and disease produced by BoHV-2 in ewes inoculated transdermally and submitted to topic treatment with a vehicle gel containing (PhSe)2, CDV, and combined (PhSe)2 + CDV. Thirteen out of 14 (92.8%) inoculated ewes developed local lesions that typically progressed through the stages of hyperemia (days 2 – 6pi), large papules or depressed/flat dark areas (day 4 to 12pi), accompanied/followed by scab/crust formation that lasted beyond day 15pi in untreated ewes. Treatment with (PhSe)2 resulted in an important reduction in clinical score from day 8 pi onwards (p<0.05), shortening of clinical course and reduction in duration of virus shedding (p<0.05) compared to untreated controls. Combined ((PhSe)2+CDV) treatment and CDV alone, also led to clinical improvement (p<0.05), yet less pronounced and delayed (after day 11 pi and 13 pi, respectively), but no significant reduction in virus shedding. Taken together, these findings contribute to the knowledge of BoHV-2 pathogenesis and are promising towards the use of diphenyl disselenide (PhSe)2, alone or in combination with anti-herpetic drugs, in the treatment of lesions induced by BoHV-2 in the udder and teats of dairy cows. |
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2021-07-23T14:37:57Z2021-07-23T14:37:57Z2020-08-25http://repositorio.ufsm.br/handle/1/21588Bovine alphaherpesvirus 2 (BoHV-2) - the agent of bovine herpetic mamillitis (BHM) – is related to Human alphaherpesviruses 1 and 2 (HHV-1, HHV-2) and has been proposed as a model for vaccine and drug testing. In addition, very little is known about the pathogenesis of BoHV-2 infection. Herein we studied the pathogenesis of BoHV-2 in calves after inoculation through different routes and investigated the activity of candidate anti-viral drugs in vitro and in vivo against BoHV-2. In the first study, 3 to 4-months-old calves were inoculated with BoHV-2 (107TCID50.mL-1) intramuscularly (IM, n=4), intravenously (IV, n=4) or transdermally (TD) after mild scarification (n=4) and monitored thereafter. 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. Administration of dexamethasone (Dex) to the inoculated calves at day 48pi, did not result in virus reactivation. In the second study, we investigated the anti-viral activity in vitro against BoHV-2 of three anti-herpetic drugs: Cidofovir (CDV), Fanciclovir (FAM), Foscarnet (PFA), and diphenyl disselenide (PhSe)2 by plaque reduction assays (PRA). A significant reduction in the number of viral plaques was observed by treating the monolayers with (PhSe)2 (79.7% reduction, p<0.05) or CDV (62.8%, p<0.05). FAM treatment resulted in a slight decrease in plaque number (22.9%, p<0.05) and PFA showed no anti-viral activity. Next, we investigated the effects of (PhSe)2 and CDV, alone or in combination, in the infection and disease produced by BoHV-2 in ewes inoculated transdermally and submitted to topic treatment with a vehicle gel containing (PhSe)2, CDV, and combined (PhSe)2 + CDV. Thirteen out of 14 (92.8%) inoculated ewes developed local lesions that typically progressed through the stages of hyperemia (days 2 – 6pi), large papules or depressed/flat dark areas (day 4 to 12pi), accompanied/followed by scab/crust formation that lasted beyond day 15pi in untreated ewes. Treatment with (PhSe)2 resulted in an important reduction in clinical score from day 8 pi onwards (p<0.05), shortening of clinical course and reduction in duration of virus shedding (p<0.05) compared to untreated controls. Combined ((PhSe)2+CDV) treatment and CDV alone, also led to clinical improvement (p<0.05), yet less pronounced and delayed (after day 11 pi and 13 pi, respectively), but no significant reduction in virus shedding. Taken together, these findings contribute to the knowledge of BoHV-2 pathogenesis and are promising towards the use of diphenyl disselenide (PhSe)2, alone or in combination with anti-herpetic drugs, in the treatment of lesions induced by BoHV-2 in the udder and teats of dairy cows.O Alfaherpesvírus bovino 2 – agente da mamilite herpética bovina (BHM) – é relacionado aos Alfaherpesvírus humanos 1 e 2 (HHV-1, HHV-2) e, como tal, tem sido sugerido como modelo para testes de vacinas e drogas antivirais. Além disso, pouco é conhecido sobre a patogenia do BoHV-2. Neste trabalho foi estudada a patogenia da infecção pelo BoHV-2 em bezerros, após diferentes rotas de inoculação e investigada a atividade de diferentes fármacos antivirais in vitro e in vivo contra o BoHV-2. No primeiro estudo, bezerros soronegativos de três a quatro meses foram inoculados com BoHV-2 (107TCID50.mL-1) por via intramuscular (IM, n=4), por via intravenosa (IV, n=4) ou transdérmica (TD, n=4) após escarificação leve e submetidos a monitoramento. Os bezerros inoculados pela via IV apresentaram aumento leve da temperatura corporal entre os dias 6 a 9 pós-inoculação (pi). A inoculação do vírus pela via TD resultou em lesões inflamatórias leves nos locais de inoculação, caracterizadas por hiperemia, pequenas vesículas, exsudação leve e formação de crostas, entre os dias 2 e 8pi. O vírus ou DNA viral foi detectado por PCR nas crostas/swabs coletados de lesões de 3 de 4 animais inoculados TD do dia 2 ao 8pi. Viremia foi detectada em 3/4 dos animais do grupo IM (do dia 4 ao 8pi); em 2/4 animais do grupo IV (dias 6 e 8pi), mas não no grupo TD. Administração de dexametasona (Dex) nos bezerros inoculados no dia 48pi, não resultou em reativação do vírus. No segundo estudo, investigou-se a atividade anti-viral in vitro contra o BoHV-2 de três drogas anti-herpéticas: Cidofovir (CDV), Famciclovir (FAM), Foscarnet (PFA), e do disseleneto de difenila (PhSe)2 pelo teste de redução de placas (PRA). Redução significativa do número de placas virais foi observada pelo tratamento dos tapetes celulares com (PhSe)2 (redução de 79.7%, p<0.05) ou com CDV (62.8%, p<0.05). Tratamento com FAM resultou em redução menor (22.9%, p<0.05) e o PFA não demonstrou atividade antiviral. A seguir, investigou-se o efeito do (PhSe)2 e CDV, isoladamente ou combinados, sobre a infecção e doença produzida pelo BoHV-2 em ovelhas inoculadas pela via transdérmica e submetidas a tratamento tópico com um veículo cremoso contendo (PhSe)2, CDV, e (PhSe)2 + CDV associados. Treze de 14 ovelhas (92.8%) inoculadas desenvolveram lesões locais que progrediram pelas fases de hiperemia (dias 2 – 6pi), grandes pápulas ou áreas planas achatadas/escuras (dias 4 a 12pi), acompanhadas pela formação de crostas que duraram além do dia 15pi nos animais não-tratados. Tratamento com (PhSe)2 resultou em redução importante no escore clínico a partir do dia 8 pi (p<0.05), em redução do período clínico e na duração da excreção viral (p<0.05) comparado aos controles. Tratamento combinado ((PhSe)2+CDV) e CDV sozinho, também resultaram em melhoria clínica (p<0.05), mas menos pronunciada e mais tardia (após dias 11 pi e 13 pi, respectivamente), mas não reduziram significativamente o tempo de excreção viral. Em conjunto, esses resultados contribuem para o conhecimento da patogenia da infecção pelo BoHV-2 e são promissores no sentido do uso disseleneto de difenila (PhSe)2, isolado ou em combinação com drogas anti-herpéticas, no tratamento de lesões ocasionadas pelo BoHV-2 no úbere de vacas leiteiras.Conselho Nacional de Pesquisa e Desenvolvimento Científico e Tecnológico - CNPqCoordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESporUniversidade Federal de Santa MariaCentro de Ciências RuraisPrograma de Pós-Graduação em Medicina VeterináriaUFSMBrasilMedicina VeterináriaAn error occurred on the license name.An error occurred getting the license - uri.info:eu-repo/semantics/openAccessAlfaherpesvírus bovino 2BovinosPatogêneseMamiliteTratamentoOvelhasBovine alphaherpesvirus 2CattlePathogenesisMammillitisTherapyEwesCNPQ::CIENCIAS AGRARIAS::MEDICINA VETERINARIAPatogênese e terapia experimental da infecção pelo alfaherpesvírus bovino 2Experimental pathogenesis and therapy of bovine alphaherpesvirus 2 infectioninfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisFlores, Eduardo Furtadohttp://lattes.cnpq.br/0446078331070694Anziliero, DenizCargnelutti, Juliana FelipettoSlhessarenko, Renata DezengriniWeiblen, Rudihttp://lattes.cnpq.br/5119613885179185Amaral, Bruna Portolan5005000000076006006006006006006001cd49172-b6b6-4db1-b27e-daf2b145ba82622f2301-481a-44dd-ae67-ca258836b5151cb1f07d-1da6-4e65-9857-ecca628adad69a82a3b4-b1a0-4cbc-a69f-1b4d58dd0cb38f21ccb1-0362-49be-98b8-764b815338f531cd7453-8e16-4d9b-a7c9-50aebad0ba0ereponame:Repositório Institucional Manancial UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSMLICENSElicense.txtlicense.txttext/plain; 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dc.title.por.fl_str_mv |
Patogênese e terapia experimental da infecção pelo alfaherpesvírus bovino 2 |
dc.title.alternative.eng.fl_str_mv |
Experimental pathogenesis and therapy of bovine alphaherpesvirus 2 infection |
title |
Patogênese e terapia experimental da infecção pelo alfaherpesvírus bovino 2 |
spellingShingle |
Patogênese e terapia experimental da infecção pelo alfaherpesvírus bovino 2 Amaral, Bruna Portolan Alfaherpesvírus bovino 2 Bovinos Patogênese Mamilite Tratamento Ovelhas Bovine alphaherpesvirus 2 Cattle Pathogenesis Mammillitis Therapy Ewes CNPQ::CIENCIAS AGRARIAS::MEDICINA VETERINARIA |
title_short |
Patogênese e terapia experimental da infecção pelo alfaherpesvírus bovino 2 |
title_full |
Patogênese e terapia experimental da infecção pelo alfaherpesvírus bovino 2 |
title_fullStr |
Patogênese e terapia experimental da infecção pelo alfaherpesvírus bovino 2 |
title_full_unstemmed |
Patogênese e terapia experimental da infecção pelo alfaherpesvírus bovino 2 |
title_sort |
Patogênese e terapia experimental da infecção pelo alfaherpesvírus bovino 2 |
author |
Amaral, Bruna Portolan |
author_facet |
Amaral, Bruna Portolan |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Flores, Eduardo Furtado |
dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/0446078331070694 |
dc.contributor.referee1.fl_str_mv |
Anziliero, Deniz |
dc.contributor.referee2.fl_str_mv |
Cargnelutti, Juliana Felipetto |
dc.contributor.referee3.fl_str_mv |
Slhessarenko, Renata Dezengrini |
dc.contributor.referee4.fl_str_mv |
Weiblen, Rudi |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/5119613885179185 |
dc.contributor.author.fl_str_mv |
Amaral, Bruna Portolan |
contributor_str_mv |
Flores, Eduardo Furtado Anziliero, Deniz Cargnelutti, Juliana Felipetto Slhessarenko, Renata Dezengrini Weiblen, Rudi |
dc.subject.por.fl_str_mv |
Alfaherpesvírus bovino 2 Bovinos Patogênese Mamilite Tratamento Ovelhas |
topic |
Alfaherpesvírus bovino 2 Bovinos Patogênese Mamilite Tratamento Ovelhas Bovine alphaherpesvirus 2 Cattle Pathogenesis Mammillitis Therapy Ewes CNPQ::CIENCIAS AGRARIAS::MEDICINA VETERINARIA |
dc.subject.eng.fl_str_mv |
Bovine alphaherpesvirus 2 Cattle Pathogenesis Mammillitis Therapy Ewes |
dc.subject.cnpq.fl_str_mv |
CNPQ::CIENCIAS AGRARIAS::MEDICINA VETERINARIA |
description |
Bovine alphaherpesvirus 2 (BoHV-2) - the agent of bovine herpetic mamillitis (BHM) – is related to Human alphaherpesviruses 1 and 2 (HHV-1, HHV-2) and has been proposed as a model for vaccine and drug testing. In addition, very little is known about the pathogenesis of BoHV-2 infection. Herein we studied the pathogenesis of BoHV-2 in calves after inoculation through different routes and investigated the activity of candidate anti-viral drugs in vitro and in vivo against BoHV-2. In the first study, 3 to 4-months-old calves were inoculated with BoHV-2 (107TCID50.mL-1) intramuscularly (IM, n=4), intravenously (IV, n=4) or transdermally (TD) after mild scarification (n=4) and monitored thereafter. 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. Administration of dexamethasone (Dex) to the inoculated calves at day 48pi, did not result in virus reactivation. In the second study, we investigated the anti-viral activity in vitro against BoHV-2 of three anti-herpetic drugs: Cidofovir (CDV), Fanciclovir (FAM), Foscarnet (PFA), and diphenyl disselenide (PhSe)2 by plaque reduction assays (PRA). A significant reduction in the number of viral plaques was observed by treating the monolayers with (PhSe)2 (79.7% reduction, p<0.05) or CDV (62.8%, p<0.05). FAM treatment resulted in a slight decrease in plaque number (22.9%, p<0.05) and PFA showed no anti-viral activity. Next, we investigated the effects of (PhSe)2 and CDV, alone or in combination, in the infection and disease produced by BoHV-2 in ewes inoculated transdermally and submitted to topic treatment with a vehicle gel containing (PhSe)2, CDV, and combined (PhSe)2 + CDV. Thirteen out of 14 (92.8%) inoculated ewes developed local lesions that typically progressed through the stages of hyperemia (days 2 – 6pi), large papules or depressed/flat dark areas (day 4 to 12pi), accompanied/followed by scab/crust formation that lasted beyond day 15pi in untreated ewes. Treatment with (PhSe)2 resulted in an important reduction in clinical score from day 8 pi onwards (p<0.05), shortening of clinical course and reduction in duration of virus shedding (p<0.05) compared to untreated controls. Combined ((PhSe)2+CDV) treatment and CDV alone, also led to clinical improvement (p<0.05), yet less pronounced and delayed (after day 11 pi and 13 pi, respectively), but no significant reduction in virus shedding. Taken together, these findings contribute to the knowledge of BoHV-2 pathogenesis and are promising towards the use of diphenyl disselenide (PhSe)2, alone or in combination with anti-herpetic drugs, in the treatment of lesions induced by BoHV-2 in the udder and teats of dairy cows. |
publishDate |
2020 |
dc.date.issued.fl_str_mv |
2020-08-25 |
dc.date.accessioned.fl_str_mv |
2021-07-23T14:37:57Z |
dc.date.available.fl_str_mv |
2021-07-23T14:37:57Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/doctoralThesis |
format |
doctoralThesis |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://repositorio.ufsm.br/handle/1/21588 |
url |
http://repositorio.ufsm.br/handle/1/21588 |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.relation.cnpq.fl_str_mv |
500500000007 |
dc.relation.confidence.fl_str_mv |
600 600 600 600 600 600 600 |
dc.relation.authority.fl_str_mv |
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dc.rights.driver.fl_str_mv |
An error occurred on the license name. An error occurred getting the license - uri. info:eu-repo/semantics/openAccess |
rights_invalid_str_mv |
An error occurred on the license name. An error occurred getting the license - uri. |
eu_rights_str_mv |
openAccess |
dc.publisher.none.fl_str_mv |
Universidade Federal de Santa Maria Centro de Ciências Rurais |
dc.publisher.program.fl_str_mv |
Programa de Pós-Graduação em Medicina Veterinária |
dc.publisher.initials.fl_str_mv |
UFSM |
dc.publisher.country.fl_str_mv |
Brasil |
dc.publisher.department.fl_str_mv |
Medicina Veterinária |
publisher.none.fl_str_mv |
Universidade Federal de Santa Maria Centro de Ciências Rurais |
dc.source.none.fl_str_mv |
reponame:Repositório Institucional Manancial UFSM instname:Universidade Federal de Santa Maria (UFSM) instacron:UFSM |
instname_str |
Universidade Federal de Santa Maria (UFSM) |
instacron_str |
UFSM |
institution |
UFSM |
reponame_str |
Repositório Institucional Manancial UFSM |
collection |
Repositório Institucional Manancial UFSM |
bitstream.url.fl_str_mv |
http://repositorio.ufsm.br/bitstream/1/21588/3/license.txt http://repositorio.ufsm.br/bitstream/1/21588/1/TES_PPGMV_2020_AMARAL_BRUNA.pdf http://repositorio.ufsm.br/bitstream/1/21588/2/license_rdf http://repositorio.ufsm.br/bitstream/1/21588/4/TES_PPGMV_2020_AMARAL_BRUNA.pdf.txt http://repositorio.ufsm.br/bitstream/1/21588/5/TES_PPGMV_2020_AMARAL_BRUNA.pdf.jpg |
bitstream.checksum.fl_str_mv |
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bitstream.checksumAlgorithm.fl_str_mv |
MD5 MD5 MD5 MD5 MD5 |
repository.name.fl_str_mv |
Repositório Institucional Manancial UFSM - Universidade Federal de Santa Maria (UFSM) |
repository.mail.fl_str_mv |
ouvidoria@ufsm.br |
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1808854700175392768 |