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

Viruses. 2020 Jan 2;12(1):51. 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.

Keywords: NF-κB; P65; TNF-α; UL24; pseudorabies virus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Gene Knockout Techniques
  • Herpesvirus 1, Suid / genetics
  • Herpesvirus 1, Suid / metabolism*
  • Humans
  • NF-kappa B / metabolism
  • Proteasome Endopeptidase Complex / metabolism
  • Signal Transduction / drug effects
  • Transcription Factor RelA / metabolism*
  • Tumor Necrosis Factor-alpha / pharmacology*
  • Viral Nonstructural Proteins / genetics
  • Viral Nonstructural Proteins / metabolism*

Substances

  • NF-kappa B
  • RELA protein, human
  • Transcription Factor RelA
  • Tumor Necrosis Factor-alpha
  • UL24 protein, pseudorabies virus
  • Viral Nonstructural Proteins
  • Proteasome Endopeptidase Complex