Phenazine biosynthesis-like domain-containing protein (PBLD) and Cedrelone promote antiviral immune response by activating NF-ĸB
Peili Hou, Hongchao Zhu, Fengyun Chu, Yan Gao, Xiaonan Sun, Fuzhen Zhang, Xiaomeng Wang, Yueyue Feng, Xingyu Li, Yu Liu, Jun Wang, Xiaoyun Wang, Daniel Chang He, Hongmei Wang, Hongbin He
Abstract
Phenazine biosynthesis-like domain-containing protein (PBLD) and Cedrelone have been identified as tumor suppressors. However, their roles in virus infection remain unclear. Here, we demonstrate that PBLD upregulates the type I interferon (IFN-I) response through activating NF-kappaB (NF-κB) signaling pathway to resist viral infection in cells and mice. Mechanistically, PBLD activates NF-κB signaling pathway during viral infection via blocking tripartite motif containing 21 (TRIM21)-mediated phosphorylated inhibitory kappa B kinase beta (IKKβ) degradation. Furthermore, we show Cedrelone inhibits viral replication by increasing the PBLD protein expression and subsequently activating NF-κB-mediated IFN-I response. Furthermore, the therapeutic potential of Cedrelone lies in its ability to enhance antiviral immunity in primary macrophages and to promote survival and reduce lung tissue damage in HSV-1-infected mice in a PBLD-dependent manner. Consequently, our findings provide a potential combination model that targets PBLD for Cedrelone antiviral drug therapy, potentially paving the way for the development of broad-spectrum antiviral agents. Phenazine biosynthesis-like domain-containing protein (PBLD) and cedrelone play roles in tumor suppression. Here, authors suggest that PBLD and Cedrelone inhibit viral replication via activating the NF-κB-mediated IFN-I signaling response in cells and mice.