Corazonin signaling, a molecular switch for ascovirus-mediated manipulation of host development and molting

Ascoviruses, as obligate insect pathogens that exclusively infect lepidopteran hosts, are highly reliant on the precise modulation of key host physiological processes, including metabolism, developmental signaling, and immune homeostasis, to facilitate successful infection, subsequent viral replication and transmission. The corazonin signaling pathway serves as a key regulatory pathway in insect development and molting. Herein, we found that ascoviruses modulate the Corazonin signaling pathway to affect the host molting process, thereby influencing viral replication. Therefore, understanding the molecular mechanisms between ascovirus and the corazonin signaling pathway is of particular importance. In this study, we found that corazonin (HaCrz) and the receptor (HaCrzR) were essential for promoting the molting process in response to HvAV infection. Silencing of HaCrz or HaCrzR via RNAi extended larval instar stages, elevated host mortality, reduced transcript levels of downstream molting-related genes (HaTH and HaDDC), and substantially enhanced viral replication. In contrast, exogenous injection of synthetic mature HaCrz peptide, which interacts structurally with HaCrzR as validated by molecular docking, accelerated host molting and improved antiviral responses. These findings not only revealed the mechanism by which viruses manipulate the host molting process but more importantly, demonstrated that viruses create favorable conditions for viral replication and transmission by interfering with host developmental behaviors.