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The Antheraea pernyi nucleopolyhedrovirus (ApNPV) is an exclusive pathogen of A. pernyi. The intense interactions between ApNPV and A. pernyi cause a series of physiological and pathological changes to A. pernyi. However, no detailed report exists regarding the molecular mechanisms underlying the interactions between ApNPV and A. pernyi. In this study, four cDNA libraries of the A. pernyi midgut, including two ApNPV-infected groups and two control groups, were constructed for transcriptomic analysis to provide new clues regarding the molecular mechanisms that underlie these interactions. The transcriptome of the A. pernyi midgut was de novo assembled using the Trinity platform because of the lack of a genome resource for A. pernyi. Compared with the controls, a total of 5,172 differentially expressed genes (DEGs) were identified, including 2,183 up-regulated and 2,989 down-regulated candidates, of which 2,965 and 911 DEGs were classified into different GO categories and KEGG pathways, respectively. The DEGs involved in A. pernyi innate immunity were classified into several categories, including heat-shock proteins, apoptosis-related proteins, serpins, serine proteases and cytochrome P450s. Our results suggested that these genes were related to the immune response of the A. pernyi midgut to ApNPV infection via their essential roles in regulating a variety of physiological processes. Our results may serve as a basis for future research not only on the molecular mechanisms of ApNPV invasion but also on the anti-ApNPV mechanism of A. pernyi. [ABSTRACT FROM AUTHOR]