Skip to main content

Targeted entry via somatostatin receptors using a novel modified retrovirus glycoprotein that delivers genes at levels comparable to those of wild-type viral glycoproteins.

Publication ,  Journal Article
Li, F; Ryu, BY; Krueger, RL; Heldt, SA; Albritton, LM
Published in: J Virol
January 2012

Here we report a novel viral glycoprotein created by replacing a natural receptor-binding sequence of the ecotropic Moloney murine leukemia virus envelope glycoprotein with the peptide ligand somatostatin. This new chimeric glycoprotein, which has been named the Sst receptor binding site (Sst-RBS), gives targeted transduction based on three criteria: (i) a gain of the use of a new entry receptor not used by any known virus; (ii) targeted entry at levels comparable to gene delivery by wild-type ecotropic Moloney murine leukemia virus and vesicular stomatitis virus (VSV) G glycoproteins; and (iii) a loss of the use of the natural ecotropic virus receptor. Retroviral vectors coated with Sst-RBS gained the ability to bind and transduce human 293 cells expressing somatostatin receptors. Their infection was specific to target somatostatin receptors, since a synthetic somatostatin peptide inhibited infection in a dose-dependent manner and the ability to transduce mouse cells bearing the natural ecotropic receptor was effectively lost. Importantly, vectors coated with the Sst-RBS glycoprotein gave targeted entry of up to 1 × 10(6) transducing U/ml, a level comparable to that seen with infection of vectors coated with the parental wild-type ecotropic Moloney murine leukemia virus glycoprotein through the ecotropic receptor and approaching that of infection of VSV G-coated vectors through the VSV receptor. To our knowledge, this is the first example of a glycoprotein that gives targeted entry of retroviral vectors at levels comparable to the natural capacity of viral envelope glycoproteins.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

J Virol

DOI

EISSN

1098-5514

Publication Date

January 2012

Volume

86

Issue

1

Start / End Page

373 / 381

Location

United States

Related Subject Headings

  • Virus Internalization
  • Virology
  • Viral Envelope Proteins
  • Somatostatin
  • Receptors, Virus
  • Receptors, Somatostatin
  • Protein Engineering
  • Protein Binding
  • Moloney murine leukemia virus
  • Molecular Sequence Data
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Li, F., Ryu, B. Y., Krueger, R. L., Heldt, S. A., & Albritton, L. M. (2012). Targeted entry via somatostatin receptors using a novel modified retrovirus glycoprotein that delivers genes at levels comparable to those of wild-type viral glycoproteins. J Virol, 86(1), 373–381. https://doi.org/10.1128/JVI.05411-11
Li, Fang, Byoung Y. Ryu, Robin L. Krueger, Scott A. Heldt, and Lorraine M. Albritton. “Targeted entry via somatostatin receptors using a novel modified retrovirus glycoprotein that delivers genes at levels comparable to those of wild-type viral glycoproteins.J Virol 86, no. 1 (January 2012): 373–81. https://doi.org/10.1128/JVI.05411-11.

Published In

J Virol

DOI

EISSN

1098-5514

Publication Date

January 2012

Volume

86

Issue

1

Start / End Page

373 / 381

Location

United States

Related Subject Headings

  • Virus Internalization
  • Virology
  • Viral Envelope Proteins
  • Somatostatin
  • Receptors, Virus
  • Receptors, Somatostatin
  • Protein Engineering
  • Protein Binding
  • Moloney murine leukemia virus
  • Molecular Sequence Data