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

Abstract

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, LvIKKβ and LvIKKε, from Pacific white shrimp, Litopenaeus vannamei. LvIKKβ and LvIKKε mRNAs are widely expressed in different tissues and are responsive to white spot syndrome virus (WSSV) infection. When overexpressed in Drosophila S2 cells, LvIKKβ but not LvIKKε activates the promoters of NF-κB pathway-controlled antimicrobial peptide genes (AMPs), such as the Penaeidins (PENs). In HEK 293T cells, both LvIKKβ and LvIKKε activate an NF-κB reporter. The silencing of LvIKKβ or LvIKKε using double-stranded RNA (dsRNA)-mediated RNA interference (RNAi) decreases the expression of L. vannamei AMPs, including PENs, lysozyme and crustins. Intriguingly, LvIKKβ- or LvIKKε-silenced L. vannamei are 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 WSV051, WSV059, WSV069, WSV083, WSV090, WSV107, WSV244, WSV303, WSV371 and WSV445 promoters can be activated by LvIKKβ or LvIKKε in Drosophila S2 cells. Taken together, our results reveal that LvIKKβ and LvIKKε 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.

I(f) current channel inhibitor (ivabradine) deserves cardioprotective effect via down-regulating the expression of matrix metalloproteinase (MMP)-2 and attenuating apoptosis in diabetic mice

“…Our study showed that ivabradine was associated with the significant dephosphorylation of caspase 3 and BAX, indicating the anti-apoptotic effect of ivabradine in diabetic animals. In contrast, NF-κB was activated by ivabradine, and phosphorylated NF-κB would promote protein synthesis and thus inhibit apoptosis [ 37 ]. These results would provide additional evidences of anti-ischemic effect by ivabradine for diabetic setting, in line with previously published results confirming the cardioprotective effect by ivabradine for patients with ischemic heart disease [ 38 , 39 ].…”

Establishment of lysozyme gene RNA interference systemand its involvement in salinity tolerance in sea cucumber (Apostichopus japonicus)

“…LvIAP3 were significantly knocked down by dsRNA-mediated gene silencing [33] ). In the gills of LvIAP1-or LvIAP3-silenced shrimp, the expression of WSSV VP28 was significantly higher than that of the dsGFP control group, suggesting that LvIAP1 and LvIAP3 may play protective roles in host defense against WSSV infection [34].…”

Limited evidence for white spot syndrome virus susceptibility associated with expression of PmVRP15 in local population of giant tiger shrimp (Penaeus monodon)

“…Hence, we speculate that PmVRP15 is not universally associated with WSSV susceptibility in other populations besides the Thai population. Furthermore, there are extensive studies indicating that WSSV resistance and WSSV susceptibility in penaeid shrimps is synergic immune response regulated by many genes (Ghosh et al, 2011), such as anti-lipopolysaccharide factor (ALF), which plays a role in defense against WSSV (Liu et al, 2014;Wang et al ,2013), Penaeus monodon antiviral (PmAV), which presumably acts as an intermediate factor during antiviral reaction (Luo et al, 2003), and other antimicrobial peptides like penaeidin class 5 that protect shrimps at early infection of WSSV (Jeswin et al, 2013;Wang et al, 2013). Perhaps WSSV susceptibility Al Haq et al in G 8 and G 8iA can be marked with other considerable immune-related gene expression rather than PmVRP15.…”