WSSV promotes its replication by inhibiting Dorsal activation via CypA in crayfish.

As a key therapeutic target for various diseases, Cyclophilin A (CypA) exhibits a dual nature in its biological functions. While the molecular mechanisms underlying its role in antiviral immunity have been well elucidated in vertebrates, research in invertebrates has merely been limited to expression responses induced by pathogens, and the underlying mechanisms through which CypA mediates immune regulation remain to be urgently deciphered. In this study, CypA expression was up-regulated in red swamp crayfish (Procambarus clarkii) following infection with white spot syndrome virus (WSSV). Functional analysis showed that CypA promote WSSV replication and reduce the survival rate of crayfish post-infection. Co-immunoprecipitation (Co-IP) assays showed that CypA interacted with WSSV VP28. Further studies have found that CypA inhibited the activity of transcription factor Dorsal, and then down-regulated the expression levels of Lysozyme-i1 (Lys-i1) and Lys-i2. Lys-i2 effectively inhibited WSSV replication and improved the survival of crayfish after WSSV infection. Pulldown and Co-IP assays confirmed the interaction between Lys-i2 and WSSV VP28. Collectively, these results suggest that WSSV hijacks CypA to inhibit Dorsal activity, thereby suppressing lysozyme expression and evading the host immune response in P. clarkii.