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Nadishka Jayawardena,1 John T Poirier,2 Laura N Burga,1 Mihnea Bostina1,3 1Department of Microbiology and Immunology, University of Otago, Dunedin, New Zealand; 2Department of Medicine and Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA; 3Otago Micro and Nano Imaging, University of Otago, Dunedin, New ZealandCorrespondence: Laura N Burga; Mihnea Bostina Tel +64 2 244 5583Email laura.burga@otago.ac.nz; mihnea.bostina@otago.ac.nzAbstract: Oncolytic viruses (OVs) are replication competent agents that selectively target cancer cells. After penetrating the tumor cell, viruses replicate and eventually trigger cell lysis, releasing the new viral progeny, which at their turn will attack and kill neighbouring cells. The ability of OVs to self-amplify within the tumor while sparing normal cells can provide several advantages including the capacity to encode and locally produce therapeutic protein payloads, and to prime the host immune system. OVs targeting of cancer cells is mediated by host factors that are differentially expressed between normal tissue and tumors, including viral receptors and internalization factors. In this review article, we will discuss the evolution of oncolytic viruses that have reached the stage of clinical trials, their mechanisms of oncolysis, cellular receptors, strategies for targeting cancers, viral neutralization and developments to bypass virus neutralization.Keywords: oncolytic viruses, virus-receptor interaction, virus neutralization

Nadishka Jayawardena,1 Laura N Burga,1 John T Poirier,2 Mihnea Bostina1,3 1Department of Microbiology and Immunology, University of Otago, Dunedin, New Zealand; 2Perlmutter Cancer Center, NYU Langone Health, New York, NY, USA; 3Otago Micro and Nano Imaging, University of Otago, Dunedin, New ZealandCorrespondence: Mihnea BostinaDepartment of Microbiology and Immunology, University of Otago, Dunedin, New ZealandTel +64 22 44 5583 Email mihnea.bostina@otago.ac.nzAbstract: Recent advancements in oncolytic virotherapy commend a special attention to developing new strategies for targeting cancer cells with oncolytic viruses (OVs). Modifications of the viral envelope or coat proteins serve as a logical mean of repurposing viruses for cancer treatment. In this review, we discuss how detailed structural knowledge of the interactions between OVs and their natural receptors provide valuable insights into tumor specificity of some viruses and re-targeting of alternate receptors for broad tumor tropism or improved tumor selectivity.Keywords: oncolytic viruses, virus–receptor interaction, virus entry