Can a mosquito-borne virus become a cancer therapy? rethinking Getah virus through the lens of oncolytic virotherapy.

Getah virus (GetV) is an arthropod-borne alphavirus historically recognized as an emerging zoonotic pathogen of veterinary significance, particularly in livestock and equine populations across Asia and parts of the Western Pacific. Over the past several decades, its expanding ecological range, broad mosquito vector competence, and increasing frequency of animal outbreaks have positioned GetV as a growing concern for animal health surveillance, diagnostics, and vaccine development. However, beyond its established role in veterinary virology, a critical and underexplored dimension of GetV biology is its emerging potential in oncolytic virotherapy. Recent discoveries, particularly involving the M1 strain, reveal a striking capacity for tumor-selective replication driven by defects in antiviral innate immune signaling within malignant cells. This property positions GetV-derived platforms as promising candidates for next-generation oncolytic virus development, capable of direct tumor lysis and secondary activation of antitumor immunity. These findings signal a paradigm shift in how traditionally zoonotic alphaviruses may be repurposed for precision oncology. We therefore hypothesize that whilst broad cellular tropism enables Getah virus entry into different kinds of cells, the oncolytic efficacy requires another layer of intracellular permissiveness characterized by tumor-specific innate immune defects. This Perspective synthesizes the current state of knowledge on GetV from both veterinary and translational oncology viewpoints and outlines the dual-use trajectory of the virus from agricultural pathogen to therapeutic bioplatform. We further highlight unresolved questions surrounding mechanisms of tumor selectivity, biosafety and host restriction, genetic stability, immune modulation, and regulatory translational barriers. Addressing these gaps will be essential for advancing GetV-based oncolytic platforms toward clinical applicability. Collectively, GetV represents a compelling example of how emerging zoonotic viruses may be strategically repositioned at the interface of infectious disease surveillance and cancer therapy innovation.