Cidofovir induces antiviral immunity against Bombyx mori nucleopolyhedrovirus by modulating multiple immune pathways...

Bombyx mori nucleopolyhedrovirus (BmNPV) is a serious pathogen that causes significant financial losses to the sericulture industry. Currently, no effective methods exist to avoid or treat this pathogen, underscoring the urgent need for novel BmNPV control tactics. This study assessed the antiviral activity of Cidofovir against BmNPV in the BmN cell line and silkworms. The cytotoxicity test revealed that 4 mg/mL Cidofovir was the optimal concentration to use for silkworms. Western blotting and qRT-PCR results showed a significant reduction of viral protein VP39 in BmN cells, fat body, and midgut tissues. Additionally, BmNPV DNA load was significantly lower in samples treated with Cidofovir, indicating effective suppression of viral replication. Gene expression analysis demonstrated significant upregulation of Relish, STAT, and Ago2 genes in both BmN cells and silkworm tissues after Cidofovir treatment, along with increased expression of antimicrobial peptides Cec-A and Cec-B. Enhanced activities of key immune and antioxidant enzymes, including phenoloxidase, superoxide dismutase, and catalase, were observed in the hemolymph of Cidofovir-treated larvae, suggesting an overall strengthening of host defense mechanisms. Additionally, the 16S rRNA sequencing suggests that both viral infection and Cidofovir treatment alter the composition of gut microbiota in silkworms, with some unique taxa emerging in response to each condition. Together, these findings demonstrate that Cidofovir not only suppresses BmNPV proliferation but also activates multiple innate immune responses, emphasizing Cidofovir's potential as a promising antiviral agent for controlling BmNPV infection in silkworms.