ME53 Modulates AcMNPV Proliferation via Interaction with GP64 and miR-34–5p-Targeted Synergistic Insecticidal Strategy against Spodoptera frugiperda

Abstract This study developed a chemical engineering strategy to improve baculovirus biopesticides by engineering the Autographa californica multiple nucleopolyhedrovirus (AcMNPV) and regulating host metabolism in Spodoptera frugiperda. Overexpression of the me53 gene enhanced the viral replication, nucleocapsid assembly, and budding virus titers. ME53 interacted with GP64 via hydrogen bonds to promote the membrane fusion. Meanwhile, miR-34-5p negatively regulated AcMNPV proliferation, and inhibition of this miRNA upregulated me53 and GP64. In larvae, miR-34-5p disturbed the metabolism and impaired development. Combining the me53-overexpressing virus with miR-34-5p inhibition synergistically accelerated killing and increased mortality. Engineered viruses were stably produced and showed an improved virulence and safety. This work provides an efficient, eco-friendly biopesticide platform through genetic engineering and host metabolic regulation, supporting sustainable pest control.