Pseudorabies Virus UL24 Abrogates Tumor Necrosis Factor Alpha-Induced NF-κB Activation by Degrading P65.

Tong-Yun Wang,Ming-Xia Sun,Cong Feng,Jin-Mei Peng,Yue-Lin Yang,Xue-Hui Cai,Yan-Dong Tang,Zhi-Jun Tian

doi:10.3390/v12010051

Abstract

The transcription factor NF-κB plays a critical role in diverse biological processes. The NF-κB pathway can be activated by incoming pathogens and then stimulates both innate and adaptive immunity. However, many viruses have evolved corresponding strategies to balance NF-κB activation to benefit their replication. Pseudorabies virus (PRV) is an economically important pathogen that belongs to the alphaherpesvirus group. There is little information about PRV infection and NF-κB regulation. This study demonstrates for the first time that the UL24 protein could abrogate tumor necrosis factor alpha (TNF-α)-mediated NF-κB activation. An overexpression assay indicated that UL24 inhibits this pathway at or downstream of P65. Furthermore, co-immunoprecipitation analysis demonstrated that UL24 selectively interacts with P65. We demonstrated that UL24 could significantly degrade P65 by the proteasome pathway. For the first time, PRV UL24 was shown to play an important role in NF-κB evasion during PRV infection. This study expands our understanding that PRV can utilize its encoded protein UL24 to evade NF-κB signaling.

Highlights

Nuclear factor κB (NF-κB) plays important roles in diverse biological processes by regulating the expression of a large number of target genes that are involved in the immune and inflammatory response, cell proliferation and survival [1,2,3,4]
NF-κB always consists of dimeric transcription factors that belong to the Rel family; in mammalian cells, the predominant form of NF-κB is a heterodimer composed of p50 and RelA (P65) subunits [5]
We evaluated whether UL24 blocks NF-κB activation in HeLa cells

Summary

Introduction

Nuclear factor κB (NF-κB) plays important roles in diverse biological processes by regulating the expression of a large number of target genes that are involved in the immune and inflammatory response, cell proliferation and survival [1,2,3,4]. When cells are stimulated by stress, inflammatory cytokines, or bacterial or viral pathogens, IκBα is activated by an upstream kinase and degraded by the proteasome pathway, and NF-κB dimers are released and further translocate to the nucleus to activate the transcription of a variety of genes [4]. NF-κB does not require novel viral protein synthesis and is able to affect many critical steps in the host cell, making NF-κB an attractive target for an invading virus [4]. An increasing number of studies have indicated that triggering NF-κB activation is a double-edged sword, during viral infection

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Conclusion