Baculoviruses are natural enemies of agricultural and forest insect pests and play an important role in biological pest control.Oral infection by baculovirus in the insect midgut is necessary for establishing systemic infection and eventually killing the insect.Since the insect midgut continuously encounters microbiota,the gut microbiota could affect baculovirus infection.Here,we demonstrated that gut microbiota modulates im-mune responses and promotes baculovirus infection in the cotton bollworm,Helicoverpa armigera.After oral infection,numerous host immunity-related genes including genes encoding Toll and immune deficiency (IMD) pathway components were upregulated in the midgut.Elimination of the gut microbiota significantly increased the resistance to viral infection in H.armigera.Quantitative real-time reverse transcription polymerase chain reaction and proteomic analysis showed that downregulation of the antiviral fac-tor prophenoloxidase (PPO) could be mediated by microbiota during infection.It implied that midgut microbiota diminishes the expression of PPO to facilitate viral infection in H.armigera.Our findings revealed that the microbiota plays an important role in modulating the resistance of H.armigera to baculovirus infection,providing new insights in applying biopesticide.