Journal Article

Enhancing MyD88 oligomerization is one important mechanism by which IBDV VP2 induces inflammatory response

Zhang, Yulong, Huang, Mengmeng, Wu, Ziwen, Cui, Hongyu, Ke, Erjing, Zhang, Yanping, Gao, Yulong, Qi, Xiaole, Wang, Suyan, Wang, Guodong, Xu, Mengmeng, Han, Jingzhe, Liu, Runhang, Liu, Yongzhen, Chen, Yuntong, Han, Jinze, Niu, Xinxin, Duan, Yulu, Yu, Hangbo

2025

Overview

The inflammatory response is an essential component of innate immunity to defense against pathogens. Infectious bursal disease (IBD) is the most important immunosuppressive disease in chickens and is caused by the infectious bursal disease virus (IBDV). Acute inflammation is a typical pathogenic process for IBD, however, the underlying mechanism is not clear. Here, we report that IBDV induces obvious inflammatory response in vivo and in vitro . Furthermore, viral VP2 is identified as an important inflammatory stimulus. It is observed that IBDV VP2 can activate NF-κB signaling pathway and then increase IL-1β production. In detail, IBDV VP2 interacts with myeloid differentiation primary response gene 88 (MyD88), potentiates the oligomerization of MyD88 and assembly of MyD88 complex, which is one important element leading to NF-κB signaling pathway activation and IL-1β production increase. More meaningfully, residues 253/284 of viral VP2 are significantly involved in IBDV-induced inflammatory response through modulating the interaction strength between VP2 and MyD88 and the following MyD88-NF-κB-IL-1β signaling pathway. This study reveals one molecular mechanism that trigger inflammation during IBDV infection, which is of great significance for a deeper understanding of the pathogenic mechanisms of IBDV.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Animals / Atrophy / B cells / Biology and Life Sciences / Birnaviridae Infections - immunology / Birnaviridae Infections - metabolism / Birnaviridae Infections - virology / Chickens / Cytokines / Development and progression / Diseases / Genes / Genomes / Health aspects / IL-1β / Immune response / Infectious bursal disease / Infectious bursal disease virus - immunology / Infectious bursal disease virus - metabolism / Inflammation / Inflammation - immunology / Inflammation - metabolism / Inflammation - virology / Inflammatory response / Innate immunity / Interleukin-1beta - immunology / Interleukin-1beta - metabolism / Kinases / Lymphocytes / Medicine and Health Sciences / Molecular modelling / MyD88 protein / Myeloid Differentiation Factor 88 - genetics / Myeloid Differentiation Factor 88 - immunology / Myeloid Differentiation Factor 88 - metabolism / NF-kappa B - immunology / NF-kappa B - metabolism / NF-κB protein / Oligomerization / Oligomers / Pathogens / Physiological aspects / Polymerization / Poultry / Poultry Diseases - immunology / Poultry Diseases - metabolism / Poultry Diseases - virology / Proteins / R&D / Research & development / Research and Analysis Methods / RNA polymerase / RNA virus infections / Signal transduction / Signal Transduction - immunology / Tumor necrosis factor-TNF / Viral infections / Viral Structural Proteins - genetics / Viral Structural Proteins - immunology / Viral Structural Proteins - metabolism / Viruses