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Trans R Soc Trop Med Hyg ; 101(3): 289-98, 2007 Mar.
Article in English | MEDLINE | ID: mdl-17169387

ABSTRACT

Dengue virus, a mosquito-borne flavivirus, is one of the most formidable public health threats in tropical and subtropical regions. As yet, there is no licensed vaccine to protect against the disease. A chimeric yellow fever (YF) 17D/dengue (DEN) type 1 virus was constructed by replacing the pre-membrane and envelope genes of YF 17D virus with those from DEN 1 VeMir95 virus, a Venezuelan isolate. The chimeric YF 17D/DEN 1 VeMir95 virus was regenerated from full-length infectious clones stably propagated in Escherichia coli by transfection of Vero cells with in vitro transcribed RNA. The chimeric virus proliferated efficiently in Vero cells ( approximately 6.6 log(10) plaque-forming units/ml). The chimeric virus was not neurovirulent to 3-week-old Swiss Webster mice inoculated by the intracerebral route, in contrast to the YF 17DD vaccine strain that was lethal for 90% of the mice. The YF 17D/DEN 1 virus at Passage 6 was more attenuated for rhesus monkeys than the YF 17DD commercial vaccine after intracerebral inoculation according to the standard neurovirulence test. This virus is a potential candidate to be included in a tetravalent DEN vaccine formulation. The availability of the cloned cDNA allows further structure/function studies on the viral envelope.


Subject(s)
Dengue Virus/genetics , Reassortant Viruses/genetics , Yellow fever virus/genetics , Amino Acid Sequence , Animals , Base Sequence , Chlorocebus aethiops , Dengue Vaccines , Dengue Virus/growth & development , Dengue Virus/pathogenicity , Genes, Viral , Mice , Molecular Sequence Data , Reassortant Viruses/growth & development , Reassortant Viruses/pathogenicity , Recombination, Genetic , Transfection , Vaccines, Attenuated , Vero Cells , Viral Envelope Proteins/genetics , Virulence , Yellow fever virus/growth & development , Yellow fever virus/pathogenicity
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