Introduction of Poliovirus as Oncolytic Virus
Introduction to Poliovirus
Poliovirus, a member of the Picornaviridae family, is a single-stranded RNA virus and the main cause of many infectious diseases. In general, poliovirus consists of an RNA genome, a coat protein, and a capsid protein. Meanwhile, four types of virion proteins, including VP1, VP2, VP3, as well as VP4, have been identified to play an important role in producing different protomers for coat and capsid synthesis. Moreover, pilot studies have shown that all virion proteins can be arranged in icosahedral symmetry based on β sheet arrays. Recent reports have also revealed that a ring structure of poliovirus has been confirmed and used as an antigenic site to bind specific antibodies.
Due to the differences in capsid proteins, poliovirus has been divided into three subtypes, such as types 1, type 2, and type 3. Among them, type 1 is the most common virus in nature, but all three are highly infectious. Poliovirus is capable of entering and infecting several tissues of the human body to cause respiratory tract infection diseases in humans. For instance, previous studies have indicated that poliovirus is the etiologic agent of polio disease. In polio infection, poliovirus can enter the blood and attack nerve cells to paralyze the patient.
The Poliovirus as Oncolytic Virus in Disease Treatment
Poliovirus is a positive nonenveloped RNA virus that has become a serious threat to human health. In the past few years, many attempts have been made to study the structure of poliovirus and develop its vaccines for preventing polio diseases in different populations. Nowadays, many researchers have illustrated that poliovirus can be considered as an oncolytic virus and broadly used for treating various cancers, such as glioma and neuroblastoma. Poliovirus can be genetically modified to reduce potential toxicity for the host and to target different kinds of cancer cells.
For example, a novel recombinant oncolytic poliovirus has been generated by replacing the internal ribosomal entry site (IRES) element of natural poliovirus with the corresponding component of human rhinovirus type 2 (HRV2). The data have suggested that this recombinant oncolytic poliovirus can trigger enough innate immune response and present antitumor activity against prostate and breast cancer.
Fig.1 Structural features of poliovirus. (Levy, 2010)
The Poliovirus as Oncolytic Virus in Clinical Trials
Engineered oncolytic poliovirus has been regarded as an attractive tool for cancer immunotherapy. The result derived from many preclinical studies has proved that these polioviruses have become a key factor for activating tumor-specific antitumor immunity with oncolytic virotherapy approaches. Recently, a wide spectrum of clinical trials has been carried both on healthy volunteers and polio patients to prove the safety and efficacy of new recombinant oncolytic poliovirus. For instance, 67 health adult individuals have been recruited to receive single or multiple doses of poliovirus-based oncolytic virotherapy in a large scale of phase I trial. The new findings have shown that long-term survival has been found in patients with glioblastoma who experience durable responses to viral oncolytic therapies based on poliovirus.
Reference
- Levy, H. C.; et al. Catching a Virus in the Act of RNA Release: a Novel Poliovirus Uncoating Intermediate Characterized by Cryo-Electron Microscopy. J Virol. 2010, 84(9): 4426-41.