Single Amino Acid Differences between Closely Related Reovirus T3D Lab Strains Alter Oncolytic Potency In Vitro and In Vivo

Author:

Mohamed Adil1,Clements Derek R.2,Gujar Shashi A.23,Lee Patrick W.2,Smiley James R.1,Shmulevitz Maya1

Affiliation:

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

2. Department of Pathology and Department of Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia, Canada

3. Centre for Innovative and Collaborative Health Systems Research, IWK Health Centre, Halifax, Nova Scotia, Canada

Abstract

The reovirus serotype 3 Dearing (T3D) strain is in clinical trials for cancer therapy. We find that closely related laboratory strains of T3D exhibit large differences in their abilities to replicate in cancer cells in vitro , which correlates with oncolytic activity in a in a murine model of melanoma. The study reveals that five single amino acid changes among three reovirus genes strongly impact reovirus therapeutic potency. In general, the findings suggest that attention should be given to genomic divergence of virus strains during research and optimization for cancer therapy.

Funder

Canada Research Chairs

Gouvernement du Canada | Canadian Institutes of Health Research

Canada Foundation for Innovation

Publisher

American Society for Microbiology

Subject

Virology,Insect Science,Immunology,Microbiology

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