Linked Life Data

10891421

Source:http://linkedlifedata.com/resource/pubmed/id/10891421

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2000-8-11
pubmed:abstractText
Rubella virus (RUB), a small plus-strand RNA virus, is a significant human pathogen. The RA27/3 vaccine strain of RUB is one of the most successful live attenuated vaccines developed. In this article, we report the construction of an RA27/3 infectious clone, a complete cDNA copy of the RA27/3 genome that can be transcribed in vitro to generate infectious RNA molecules. Virus generated from such in vitro transcripts was phenotypically similar to RA27/3 virus. To investigate the attenuation of the RA27/3 strain, a series of chimeras was made by the insertion of different fragments of the RA27/3 genome into an infectious clone based on the Therien wild-type strain of RUB. Analysis of the resulting chimeric viruses revealed that the pattern of RA27/3 attenuation in cell culture is complex: attenuating elements in the RA27/3 genome were found in the 5' untranslated region (UTR), a region of the nonstructural proteins containing the protease motif and the capsid gene. Within the 5' UTR, the attenuation determinant was mapped to nt 7. Surprisingly, these analyses also revealed a potentiating mutation at nt 164 of the RA27/3 genome. Although this determinant was within the coding sequences of the nonstructural proteins, the encoded amino acid had no effect on cell culture phenotype and thus the determinant may operate at the level of RNA structure. In addition to investigation of the mechanisms of RA27/3 attenuation, the availability of the RA27/3 infectious clone offers the opportunity for strict genetic control over RUB vaccine manufacturing, for development of novel DNA-based vaccines against RUB, and for development of recombinant RUB vaccines that also target other diseases.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0042-6822
pubmed:author
pubmed:copyrightInfo
Copyright 2000 Academic Press.
pubmed:issnType
Print
pubmed:day
20
pubmed:volume
273
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
189-97
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:10891421-5' Untranslated Regions, pubmed-meshheading:10891421-Animals, pubmed-meshheading:10891421-Cercopithecus aethiops, pubmed-meshheading:10891421-Cloning, Molecular, pubmed-meshheading:10891421-DNA, Complementary, pubmed-meshheading:10891421-DNA, Recombinant, pubmed-meshheading:10891421-DNA, Viral, pubmed-meshheading:10891421-Genes, Viral, pubmed-meshheading:10891421-Genome, Viral, pubmed-meshheading:10891421-Point Mutation, pubmed-meshheading:10891421-RNA, Viral, pubmed-meshheading:10891421-Rubella Vaccine, pubmed-meshheading:10891421-Rubella virus, pubmed-meshheading:10891421-Transfection, pubmed-meshheading:10891421-Vaccines, Attenuated, pubmed-meshheading:10891421-Vaccines, Synthetic, pubmed-meshheading:10891421-Vero Cells, pubmed-meshheading:10891421-Viral Proteins, pubmed-meshheading:10891421-Virus Replication
pubmed:year
2000
pubmed:articleTitle
Infectious cDNA clone of the RA27/3 vaccine strain of Rubella virus.
pubmed:affiliation
Department of Biology, Georgia State University, Atlanta, Georgia, 30303, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't