Virophages: mechanisms, ecological Roles, and therapeutic potential in combating giant virus infections

Virophages, identified when scientists discovered Sputnik, a double-stranded DNA (dsDNA) viruses that form a unique group of viral entities that can parasitize giant viruses. They rely on these giant viruses for replication and inhibiting them from spreading inside eukaryotic hosts. This review seeks to bring together current knowledge on dsDNA virophages. It details how they work, explains their roles in the host, giant virus, and virophage system, and evaluates their potential as new antiviral treatments. Mechanistically, virophages disrupt the giant by replication through competitive resource depletion inside the viral factory. It modifies viral gene expression, and disrupts progeny formation, thus supporting the survivability of the host cell. In addition to these intracellular effects, virophages participate in ecological processes, such as controlling microbial communities and facilitating nutrient recycling. The therapeutic potential of virophages is hypothesized in the context of diseases where the giant viruses have been detected (e.g., hospital-acquired pneumonia), though causal roles remain debated. Furthermore, their possible use as genetic vectors is being fully investigated. However, there are several challenges to overcome before clinical translation is possible: restricted host range, risks of immune activation, and difficulties in scalable production. Future research should focus on the discovery of new virophage species, their mechanism of actions, and bioengineering strategies to improve their antiviral characteristics.