Oncolytic viruses (OVs) form a group of novel anticancer therapeutic agents which selectively infect and lyse cancer cells. Members of several viral families, including Picornaviridae, have been shown to have anticancer activity. Picornaviruses are small icosahedral non-enveloped, positive-sense, single-stranded RNA viruses infecting a wide range of hosts. They possess several advantages for development for cancer therapy: Their genomes do not integrate into host chromosomes, do not encode oncogenes, and are easily manipulated as cDNA. This review focuses on the picornaviruses investigated for anticancer potential and the mechanisms that underpin this specificity.

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.

Seneca Valley Virus, like some other members of the picornaviridae, forms naturally occurring empty capsids, known as procapsids. The procapsid has the same antigenicity as the full virion, so they present an interesting possibility for the formation of stable virus-like particles. Interestingly, although SVV is a livestock pathogen, it has also been found to preferentially infect tumour cells, and is being explored for use as a therapeutic agent in the treatment of small cell lung cancers. Here we used cryo-electron microscopy to investigate the procapsid structure and describe the transition of capsid protein VP0 to the cleaved forms of VP4 and VP2. We show that the SVV receptor binds the procapsid, as evidence of its native antigenicity. In comparing the procapsid structure to that of the full virion, we also show that a cage of RNA serves to stabilize the inside surface of the virus, thereby making it more acid-stable.Viruses are extensively studied to help us understand infection and disease. One of the by-products of some virus infections are the naturally occurring empty virus capsids (containing no genome), termed procapsids, whose function remains unclear. Here we investigate the structure and formation of the procapsids of Seneca Valley Virus, to better understand how they form, what causes them to form, how they behave, and how we can make use of them. One potential benefit of this work is the modification of the procapsid to develop it for targeted delivery of therapeutics or to make a stable vaccine against SVV, which could be of great interest to the agricultural industry.

SignificanceAnthrax toxin receptor 1 (ANTXR1), also known as Tumor Endothelial Marker 8, is overexpressed on the surface of tumor cells in over 60% of human cancers. A serious drawback for developing specific ligands for targeted therapy against ANTXR1 is the cross-reactivity with ANTXR2. Recently, ANTXR1 was identified as the high-affinity cellular receptor for Seneca Valley Virus (SVV). SVV has shown promising results as an oncolytic agent in clinical trials, and this discovery offers a powerful biomarker for selecting patient response to treatment. The identification of specific interaction sites between SVV and ANTXR1 lays the foundation to construct potent virus mutants with specific cancer tropism that can escape host antibody response and to expand the development of both antiangiogenic and anticancer antibody therapy.

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.