| The fatty acid hydroxylase superfamily consists of several subfamilies,including cholesterol 25-hydroxylase（CH25H）and fatty acid hydroxylase domain containing protein 2（FAXDC2）.The cholesterol-25-hydroxylase（CH25H）catalyzes the oxidation of cholesterol to form a soluble 25-hydroxycholesterol（25HC）and has been identified as a host restriction factor that inhibit viral infection.At present,all studies on CH25H are mainly in vertebrates,and no homologues genes are identified in invertebrates.The function of FAXDC2 in both vertebrates and invertebrates remains unknown.In this study,we identified two fatty acid hydroxylase domain containing protein 2 like molecules from Marsupenaeus japonicus and named them FAXDC2-like A（FAXDC2-LA）and FAXDC2-like B（FAXDC2-LB）.Faxdc2-la and Faxdc2-lb were significantly up-regulated in shrimp challenged by white spot syndrome virus（WSSV）.After knockdown of Faxdc2-la and Faxdc2-lb in shrimp,the 25HC continent was declined evidently,and WSSV proliferation was significantly increased.Injection or oral administration of 25HC,the viral load in the shrimp was significantly reduced and the survival rate of the shrimp was increased markedly.All the results suggest that FAXDC2-Ls function like vertebrate’s cholesterol-25-hydroxylase,and play an important role in shrimp antiviral response via their enzymatic product,25HC.Mechanically,Faxdc2-ls were the target genes of JAK/STAT pathway,and FAXDC2-Ls exert their antiviral function through Vago5-JAK/STAT-FAXDC2-25HC pathway in shrimp,which is similar to IFN-JAK/STAT-CH25H-25HC in vertebrates.At the same time,we also found that FAXDC2-LA and FAXDC2-LB intracellular parts can bind to WSSV envelope protein VP26,indicating that FAXDC2-Ls may further inhibit virus proliferation by interacting with WSSV envelope protein.The research provides a new evident on the present of the interferon system in invertebrates.It also provides a new strategy and candidate drug for the prevention and control of WSSV in shrimp aquaculture. |
