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Isolation of Fidelity Variants of RNA Viruses and Characterization of Virus Mutation Frequency
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Single Amino Acid Differences between Closely Related Reovirus T3D Lab Strains Alter Oncolytic Potency In Vitro and

Adil Mohamed1, Derek R Clements2, Shashi A Gujar2,3

  • 1Department of Medical Microbiology and Immunology, Li Ka Shing Institute of Virology, University of Alberta, Edmonton, Alberta, Canada.

Journal of Virology
|November 22, 2019
PubMed

Insights

Genetic variations in Mammalian orthoreovirus (T3D) strains significantly impact oncolytic therapy effectiveness. Laboratory-acquired genetic changes in T3D influence viral replication and therapeutic potency in cancer treatment.

Area of Science:

  • Virology
  • Oncolytic Virotherapy
  • Molecular Biology

Background:

  • Mammalian orthoreovirus (T3D) is under investigation as an oncolytic virotherapy for cancer.
  • Studies on T3D efficacy often use virus stocks from different laboratories, raising questions about strain consistency.

Purpose of the Study:

  • To investigate how genetic variations among different T3D laboratory strains affect their oncolytic activity.
  • To identify specific genetic changes responsible for differences in viral potency.

Main Methods:

  • Assessed in vitro replication and cytolytic properties by measuring virus plaque size on tumor cells.
  • Utilized reassortant and reverse genetics analyses to pinpoint key genes and polymorphisms.
  • Evaluated in vivo oncolytic activity in a murine melanoma model.

Main Results:

  • Significant differences in oncolytic activity were observed between T3D strains from different laboratories (e.g., T3DPL vs. T3DTD).
  • In vitro plaque size correlated with in vivo oncolytic potency.
  • Five single amino acid changes in S4, M1, and L3 genome segments were identified as key contributors to differences in plaque size and potency.

Conclusions:

  • Genetic diversification of T3D strains during laboratory propagation can substantially alter their therapeutic efficacy.
  • Attention to genomic divergence among virus strains is crucial for consistent research and optimization of reovirus-based cancer therapies.
Keywords:
divergenceoncolyticreovirusstrains

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