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

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

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.

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

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • AIDS Vaccines / chemistry
  • AIDS Vaccines / genetics*
  • AIDS Vaccines / immunology
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Cytokines / immunology
  • Female
  • Gene Products, gag / genetics*
  • Gene Products, gag / immunology
  • Genetic Vectors / genetics
  • Genetic Vectors / immunology
  • HIV Infections / immunology
  • HIV Infections / virology*
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Molecular Sequence Data
  • Nucleic Acid Conformation
  • Simian Immunodeficiency Virus / chemistry
  • Simian Immunodeficiency Virus / genetics*
  • Simian Immunodeficiency Virus / immunology
  • Yellow fever virus / genetics*
  • Yellow fever virus / immunology

Substances

  • AIDS Vaccines
  • Cytokines
  • Gene Products, gag