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Updated: May 15, 2026

MicroRNA-based Regulation of Picornavirus Tropism
09:05

MicroRNA-based Regulation of Picornavirus Tropism

Published on: February 6, 2017

Neuroattenuation of vesicular stomatitis virus through picornaviral internal ribosome entry sites

Arun Ammayappan1, Rebecca Nace, Kah-Whye Peng

  • 1Department of Molecular Medicine, Mayo Clinic, Rochester, MN, USA.

Journal of Virology
|January 4, 2013
PubMed

Insights

Engineered vesicular stomatitis virus (VSV) using picornavirus IRES elements significantly reduced neurotoxicity. This modification maintained VSV

Area of Science:

  • Oncolytic virotherapy
  • Viral gene therapy
  • Neurovirology

Background:

  • Vesicular stomatitis virus (VSV) shows promise for cancer treatment.
  • VSV's clinical application is limited by neurotoxicity.
  • Picornaviral internal ribosome entry site (IRES) elements can restrict neuronal activity.

Purpose of the Study:

  • To engineer VSV with picornavirus IRES elements to reduce neuropathogenicity.
  • To assess the impact of IRES elements on VSV neurovirulence and oncolytic potency.

Main Methods:

  • Incorporated IRES elements from human rhinovirus type 2 (HRV2) and foot-and-mouth disease virus (FMDV) into VSV.
  • Controlled the translation of the VSV matrix (M) gene using IRES elements.
  • Evaluated IRES-controlled VSV growth kinetics in vitro and neurovirulence/oncolytic potency in vivo.

Main Results:

  • In vitro studies showed slower growth kinetics for IRES-controlled VSVs in most cell lines.
  • In vivo studies demonstrated severe attenuation of VSV neurovirulence by HRV2 and FMDV IRES elements.
  • Oncolytic potency of VSV was not perturbed by the IRES modifications.

Conclusions:

  • Picornavirus IRES elements can be effectively engineered into VSV to attenuate neurotoxicity.
  • This strategy offers a promising approach to enhance the safety of VSV-based oncolytic virotherapy.
  • Engineered VSV maintains its efficacy against cancer while exhibiting reduced neuropathogenicity.

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