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Virology. 2014 Mar;452-453:202-11. doi: 10.1016/j.virol.2014.01.017. Epub 2014 Feb 8.

Improved genetic stability of recombinant yellow fever 17D virus expressing a lentiviral Gag gene fragment.

Author information

  • 1Laboratório de Biologia Molecular de Flavivírus, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, Brazil; Department of Pathology, University of Miami, Miller School of Medicine, United States of America.
  • 2Laboratório de Biologia Molecular de Flavivírus, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, Brazil.
  • 3Department of Pathology, University of Miami, Miller School of Medicine, United States of America.
  • 4Instituto de Tecnologia em Imunobiológicos, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil.
  • 5Laboratório de Biologia Molecular de Flavivírus, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, Brazil. Electronic address: mbonaldo@ioc.fiocruz.br.

Abstract

We have previously designed a method to construct viable recombinant Yellow Fever (YF) 17D viruses expressing heterologous polypeptides including part of the Simian Immunodeficiency Virus (SIV) Gag protein. However, the expressed region, encompassing amino acid residues from 45 to 269, was genetically unstable. In this study, we improved the genetic stability of this recombinant YF 17D virus by introducing mutations in the IRES element localized at the 5' end of the SIV gag gene. The new stable recombinant virus elicited adaptive immune responses similar to those induced by the original recombinant virus. It is, therefore, possible to increase recombinant stability by removing functional motifs from the insert that may have deleterious effects on recombinant YF viral fitness.

Copyright © 2014 Elsevier Inc. All rights reserved.

KEYWORDS:

Genetic stability; Recombinant virus; SIV Gag; SIV gag IRES; Viral vector; Yellow Fever 17D virus

PMID:
24606697
[PubMed - indexed for MEDLINE]
PMCID:
PMC3955954
[Available on 2015/3/1]
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