Construction and biological properties of yellow fever 17D/dengue type 1 recombinant virus.
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.
Mateu
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Fundacão Oswaldo Cruz, Departamento de Bioquimica e Biología Molecular, Avenida Brasil 4365, Manguinhos, 21045-900 Rio de Janeiro, RJ, Brazil.
Marchevsky
R S
RS
Liprandi
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F
Bonaldo
M C
MC
Coutinho
E S F
ES
Dieudonné
M
M
Caride
E
E
Jabor
A V
AV
Freire
M S
MS
Galler
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R
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002522:Chlorocebus aethiops; D053059:Dengue Vaccines; D003716:Dengue Virus / Q000235:genetics* / Q000254:growth & development / Q000472:pathogenicity; D005814:Genes, Viral; D051379:Mice; D008969:Molecular Sequence Data; D016865:Reassortant Viruses / Q000235:genetics* / Q000254:growth & development / Q000472:pathogenicity; D011995:Recombination, Genetic; D014162:Transfection; D014613:Vaccines, Attenuated; D014709:Vero Cells; D014759:Viral Envelope Proteins / Q000235:genetics; D014774:Virulence; D015005:Yellow fever virus / Q000235:genetics* / Q000254:growth & development / Q000472:pathogenicity
D053059:Dengue Vaccines; D014613:Vaccines, Attenuated; D014759:Viral Envelope Proteins