Data/hora: 01/06/2024 00:55:25

Provedor de dados: | 58
País: | Brazil
Título: | Selection and characterization of brivudin resistant bovine herpesvirus type 5
Autores: | Brum,Mário Celso Sperotto; Santos,Cyndia Mara Bezerra dos; Weiblen,Rudi; Flores,Eduardo Furtado.
Data: | 2010-03-01
Ano: | 2010
Palavras-chave: | BoHV-5; Thymidine kinase; Drug resistant; Brivudin.
Resumo: | Bovine herpesvirus type 5 (BoHV-5) is the agent of meningoencephalitis, an important disease of cattle in South America. The neuropathogenesis of BoHV-5 infection is poorly understood and most previous research focused on the role of envelope glicoproteins in neurovirulence. Thymidine kinase (TK) is a viral enzyme necessary for virus replication in neurons and, therefore, represents a potential target for virus attenuation. The selection and characterization of BoHV-5 variants resistant to the nucleoside analog brivudin (BVDU), which selects TK-defective viruses is here described. Several BVDU-resistant clones were obtained after multiple passages in tissue culture in the presence of BVDU and one clone (BoHV-5/R-27) was further characterized. The selected clone replicated to similar titers and produced plaques with similar size and morphology to those of wild-type virus (SV507/99). The genetic stability of the resistant virus was demonstrated after ten passages in cell culture in the absence of the drug. Moreover, the drug-resistant virus showed reduced virulence in a rabbit model: virus inoculation in four rabbits did not result in disease, in contrast with 75% morbidity (3/4) and 50% mortality (2/2) among rabbits inoculated with the parental virus. These results demonstrate that BoHV-5 is sensitive to BVDU and that drug-resistant mutants can be readily selected upon BVDU treatment. BVDU-resistant mutants, likely defective in TK, retained their ability to replicate in tissue culture yet were attenuated for rabbits. This strategy to obtain TK-defective BoHV-5 may be useful to study the role of TK in BoHV-5 neuropathogenesis and for vaccine development.
Tipo: | Info:eu-repo/semantics/article
Idioma: | Inglês
Identificador: | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1517-83822010000100019
Editor: | Sociedade Brasileira de Microbiologia
Relação: | 10.1590/S1517-83822010000100019
Formato: | text/html
Fonte: | Brazilian Journal of Microbiology  v.41 n.1 2010
Fonte: | info:eu-repo/semantics/openAccess