Bombyx mori nucleopolyhedrovirus (BmNPV) is one of the primary pathogens that causes severe economic losses to sericulture. Comparative transcriptomics analysis has been widely applied to explore the antiviral mechanism in resistant strains. Here, to identify genes involved in BmNPV infection, we identified differentially expressed genes (DEGs) and performed weighted gene co‐expression network analysis (WGCNA) between two Bombyx mori strains: strain 871 (susceptible to BmNPV infection) and the near‐isogenic strain 871C (resistant to BmNPV). Our results showed that 400 genes were associated with resistance in strain 871C, and 76 genes were related to susceptibility in strain 871. In addition, the correlation analysis of DEGs and WGCNA showed that 40 genes related to resistance were highly expressed in the resistant strain. Among them, gene BGIBMGA004291 was the most noticeable. We further identified the effect of gene BGIBMGA004291, which encoded a multiprotein bridge factor 2 (MBF2) family member (MBF2‐10), on viral infection in cells. Our data suggested that MBF2‐10 inhibited viral infection. Taken together, this study showed specific module trait correlations related to viral infection in strains 871 and 871C, and we identified a resistance‐related gene. These findings suggested promising candidate genes with antiviral activity, aiding in the analysis of the antiviral molecular mechanisms in resistant strains.
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