Selection and characterization of brivudin resistant bovine herpesvirus type 5
Braz. j. microbiol
;
41(1): 124-132, Jan.-Mar. 2010. graf
Article
in English
| LILACS
| ID: lil-531743
ABSTRACT
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 percent morbidity (3/4) and 50 percent 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.
Full text:
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Index:
LILACS (Americas)
Main subject:
Thymidine Kinase
/
Drug Resistance, Microbial
/
Vaccines
/
Homeopathic Pathogenesy
/
Meningoencephalitis
/
Nucleosides
Type of study:
Diagnostic study
/
Prognostic study
Limits:
Animals
Language:
English
Journal:
Braz. j. microbiol
Journal subject:
Microbiology
Year:
2010
Type:
Article
Affiliation country:
Brazil
Institution/Affiliation country:
Universidade Federal de Santa Maria/BR
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