Expanding Opportunities in Viral Oncolysis

Oncolytic Viruses (OVs) preferentially infect and lyse cancer cells either naturally, or through modifications that improve its efficiency and reduce its virulence. In addition, nonreplicating viral vectors can be used to carry therapeutic genes that are able to target tumor cells inducing cell death and antitumoral immunity. Oncolysis has been grown as a response to the radio- and drug-resistance phenomena, where malignant tumors stop responding to conventional and target-directed therapies, immunotherapy, and its combinations.

For this DNA and Cell Biology Special Focus on viral oncolysis, the selected authors bring us an innovative and integrated vision on the subject and provide state-of-the-art information on some of the challenges of the field, so as the discussion on the potential to expand this therapeutic approach to include new viral alternatives and new targets that have not yet been considered, as pathogenic unicellular parasites.

Mendonça and colleagues bring new data regarding the use of nonreplicating adenoviral vectors used for p14ARF and interferon-b (hIFNb) gene transfer in human melanoma cell lines. In this study, p14ARF (alternative reading frame of CDKN2a, p14ARF in humans, p19Arf in mice) and interferon-b (IFNb) genes were shown to induced oncolysis accompanied by immunogenic cell death markers and upregulation of genes involved in immune regulation. These data reflect an improvement of the viral vector approach for melanoma.

In a review, Zhou and colleagues discussed the potential of Zika virus (ZIKV) as OVs. ZIKV, a mosquito-borne flavivirus, was shown to preferentially target neural cells, which is particularly harmful to embryo development, leading to microcephaly and severe neurological disease. In contrast, Zika infection in adults is usually symptomless or cause only mild symptoms. ZIKV's natural tropism toward glioma cells and the promising therapeutic effects in treating glioblastoma multiforme (GBM) in preclinical models are discussed in this review. Also, the authors discuss the candidate surface receptors responsible for the ZIKV tropism toward GBM, and the combinatory therapy involving immunotherapy and checkpoint inhibitors.

Siew and colleagues explored the potential of zoonotic viruses of the Reoviridae family as OVs. Despite the tropism of some viruses toward tumor cells, the use of wild-type viruses raises concerns regarding cross-species viral transmission risk and autoimmune response to the therapy. Thus, genetic modifications were introduced to reduce the pathogenicity of OV and improve its anticancer efficacy. In this review, is presented a historical perspective of the use of reovirus as an oncolytic virus. And it is also highlighted some family members of interest and their mode of action. Avian and pteropine reoviruses potential are updated. Concerns and challenges over these zoonotic reoviruses are discussed so as clinical and preclinical studies of oncolytic reoviruses.

The work of Fernandes brings a discussion of the possible expansion of viral-mediated lysis to biological entities other than tumors. The review focuses on other virus-eukaryotic cell interactions that may provide important insights on the possibility to transpose viral oncolysis to Leishmaniasis and other neglected diseases. The article explores the natural interaction between viruses and Leishmania species, as well as the similarities among the outcomes of viral infections of amoeba and yeast with tumors, highlighting the importance of viral-like particles as well as the vesicular system's features and its potential to allow viral-induced lysis of intracellular parasites, or at least reduce its virulence.

This series of articles contemplates the need to discuss perspectives on the application of viral oncolysis in the near future, pushing some boundaries of this exciting field of knowledge.

We hope the readers enjoy these engaging discussions.