The shrimp IKK-NF-KB signaling pathway regulates antimicrobial peptide expression and may be subverted by white spot syndrome virus to facilitate viral gene expression

The IκB kinases IKKα and IKKβ and the IKK-related kinases TANK-binding kinase 1 （TBK1） and IKKε are the master regulators of the NF-κB signaling pathway. Although this pathway has been extensively studied in mammals, less attention has been paid in crustaceans, which have significant economic value. Here, we report the cloning and functional studies of two IKK homologs, LvlKKβ and LvlKKε, from Pacific white shrimp, Litopenaeus vannamei. LvlKKβ and LvlKKα mRNAs are widely expressed in different tissues and are responsive to white spot syndrome virus （WSSV） infection. When overexpressed in Drosophila S2 cells, LvlKKβ but not LvlKKε activates the promoters of NF-κB pathway-controlled antimicrobial peptide genes （AMPs）, such as the Penaeidins （PENs）. In HEK 293T cells, both LvlKKβ and LvlKKε activate an NF-κB reporter. The silencing of LvlKKβ or LvlKKε using double-stranded RNA （dsRNA）-mediated RNA interference （RNAi） decreases the expression of L. vannamei AMPs, including PENs, lysozyme and crustins. Intriguingly, LvlKKβ- or LvlKKε-silenced L. vannameiare resistant to WSSV infection. We hypothesized that successful infection with WSSV requires the activation of the IKK-NF-κB signaling pathway to modulate viral gene expression. We constructed luciferase reporters for 147 WSSV genes. By screening, we found that the WSSV051, WSSV059, WSSV069, WSSV083, WSSV090, WSSV107, WSSV244, WSSV303, WSSV371 and WSSV445 promoters can be activated by LvlKKβ or LvlKKε in Drosophila S2 cells. Taken together, our results reveal that LvlKKβ and LvlKKε may participate in the regulation of shrimp AMPs and that WSSV may subvert the L. vannamei IKK-NF-κB signaling pathway to facilitate viral gene expression.

Three-loop vacuum integral with four-propagators using hypergeometry

A hypergeometric function is proposed to calculate the scalar integrals of Feynman diagrams. In this study, we verify the equivalence between the Feynman parametrization and the hypergeometric technique for the scalar integral of the three-loop vacuum diagram with four propagators. The result can be described in terms of generalized hypergeometric functions of triple variables. Based on the triple hypergeometric functions, we establish the systems of homogeneous linear partial differential equations (PDEs) satisfied by the scalar integral of three-loop vacuum diagram with four propagators. The continuation of the scalar integral from its convergent regions to entire kinematic domains can be achieved numerically through homogeneous linear PDEs by applying the element method.