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Chinese sacbrood virus (CSBV) is one of the most dangerous diseases of Chinese honeybee (Apis cerana cerana), which causes serious and fatal infections of the entire colony.Infected larvae fail to pupate, and ecdysial fluid aggregates around the integument, forming the sac-like appearance.To better understand the underlying molecular mechanisms of symptoms and pathological changes, gel-based proteomic and shotgun proteomic strategies were employed for differential analysis of proteome alterations between healthy and CSBV infected Chinese honeybee larvae.Accordingly, eighty-eight protein spots altered their expression, of which sixty-five up-regulated in the healthy larvae, while only twenty-three up-regulated in the CSBV infected one.Although a strong up-regulation of most proteins was found in the healthy larvae, heat shot proteins only increased their expression by CSBV infection.Further functional enrichment analysis suggests that compared to sick larvae, proteins related to carbohydrate metabolism and energy production, development and cytoskeleton were highly expressed in the healthy larvae for organ generation and tissue development.Specifically, the juvenile hormone esterase (JHE) was almost disappeared in the infected larvae, which might be the reason why infected larvae fail to pupate.This first study of CSBV infection caused proteomic change in the honeybee larvae provide new insight into the molecular underpinnings of viral infection in the honeybee, may help us to find a potential method to protect Chinese honeybee from CSBV infection.