2. Academic Validation
  3. Phenazine biosynthesis-like domain-containing protein (PBLD) and Cedrelone promote antiviral immune response by activating NF-ĸB

Phenazine biosynthesis-like domain-containing protein (PBLD) and Cedrelone promote antiviral immune response by activating NF-ĸB

  • Nat Commun. 2025 Jan 8;16(1):496. doi: 10.1038/s41467-024-54882-y.
Peili Hou # 1 2,  Hongchao Zhu # 1,  Fengyun Chu 1,  Yan Gao 1,  Xiaonan Sun 1,  Fuzhen Zhang 2,  Xiaomeng Wang 1,  Yueyue Feng 1,  Xingyu Li 1,  Yu Liu 1,  Jun Wang 1,  Xiaoyun Wang 1,  Daniel Chang He 3,  Hongmei Wang 4,  Hongbin He 5 6
Affiliations

Affiliations

  • 1 Ruminant Diseases Research Center, College of Life Sciences, Shandong Normal University, Jinan, Shandong, China.
  • 2 Department of Preventive Veterinary Medicine, College of Veterinary Medicine, Shandong Agricultural University, Taian, Shandong, China.
  • 3 The College of Arts and Sciences, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • 4 Ruminant Diseases Research Center, College of Life Sciences, Shandong Normal University, Jinan, Shandong, China. hongmeiwang@sdnu.edu.cn.
  • 5 Ruminant Diseases Research Center, College of Life Sciences, Shandong Normal University, Jinan, Shandong, China. hongbinhe@sdnu.edu.cn.
  • 6 Department of Preventive Veterinary Medicine, College of Veterinary Medicine, Shandong Agricultural University, Taian, Shandong, China. hongbinhe@sdnu.edu.cn.
  • # Contributed equally.
PMID: 39779683 DOI: 10.1038/s41467-024-54882-y
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.

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