Defective viral genomes: Critical danger signals of viral infections

Viruses efficiently block the host antiviral response in order to replicate and spread before host intervention. The mechanism initiating antiviral immunity during stealth viral replication is unknown, but recent data demonstrate that defective viral ge-nomes generated at peak virus replication are critical for this process in vivo. This article summarizes the supporting evidence and highlights gaps in our understanding of the mechanisms and impact of immunostimulatory defective viral genomes gener-ated during natural infections. BATTLE FOR VIRUS AND HOST COEXISTENCE To ensure survival, living organisms must recognize and coun-teract harmful invaders. In higher species, an army of proteins and cells has evolved to quickly and effectively eliminate viruses andother dangerousmicrobes. Toprevent unnecessary damage to the host, this defense system is tightly controlled and only re-sponds following recognition of pathogen-associated molecular patterns (PAMPs). Viruses capable of escaping or counteracting the antiviral host response have an evolutionary advantage, as they can replicate to high titers and spread before being eradicated. Many examples of viruses that effectively counteract host defense