Fig. 1

Synthetic “open-loop lethality” makes autorepression circuitry the viral Achilles’ heel. Virus-encoded specific protein can serve as trans-acting factor that binds to the cis-repression sequence on viral genome and auto-represses viral transcription to avoid aberrant viral protein expression, thus maintaining homeostasis beneficial for virus infection (left). Artificially synthesized nucleic acid decoys (molecular mimics of the cis-regulatory binding sites) can disrupt the normal negative feedback, raising viral protein expression to cytotoxic levels and leading to clearance of infected cells by apoptosis (right). This synthetic “open-loop lethality” turns the viral autorepression circuitry into a fatal weakness of virus life cycle, representing a novel and escape-resistant antiviral strategy