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

Area of Science:

• Invertebrate immunology
• Molecular virology
• Crustacean disease research

Background:

• Cyclophilin A (CypA) plays a known role in vertebrate antiviral immunity, but its function in invertebrates is poorly understood.
• Investigating CypA's role in invertebrate immune responses to viral pathogens is crucial for understanding host-pathogen interactions.

Purpose of the Study:

• To elucidate the mechanism by which CypA influences the immune response to white spot syndrome virus (WSSV) in red swamp crayfish (Procambarus clarkii).
• To determine how WSSV manipulates CypA for its own replication and evasion of the host immune system.

Main Methods:

• Analysis of CypA expression levels in crayfish post-WSSV infection.
• Functional assays to assess the impact of CypA on WSSV replication and crayfish survival.
• Co-immunoprecipitation (Co-IP) and pulldown assays to identify protein interactions.
• Investigation of CypA's effect on the transcription factor Dorsal and lysozyme expression.

Main Results:

• CypA expression was upregulated in crayfish infected with WSSV.
• CypA promoted WSSV replication and decreased crayfish survival rates.
• CypA interacted with WSSV VP28 and inhibited Dorsal activity, leading to reduced expression of Lysozyme-i1 (Lys-i1) and Lysozyme-i2 (Lys-i2).
• Lys-i2 demonstrated antiviral activity against WSSV, inhibiting replication and improving survival.

Conclusions:

• WSSV hijacks host CypA to suppress the Dorsal-mediated immune response, specifically downregulating lysozyme expression.
• This mechanism allows WSSV to evade the host immune system and enhance its replication in Procambarus clarkii.
• Understanding this interaction provides insights into antiviral strategies in crustaceans.