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Updated: Oct 2, 2025

Studying RNA Interactors of Protein Kinase RNA-Activated during the Mammalian Cell Cycle
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Pseudorabies virus kinase UL13 phosphorylates H2AX to foster viral replication

Xin Ming1, Zongyi Bo1,2, Yurun Miao1

  • 1MOE Joint International Research Laboratory of Animal Health and Food Safety, MOA Key Laboratory of Animal Bacteriology, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China.

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
|February 24, 2022
PubMed

Insights

Pseudorabies virus (PRV) uses its UL13 kinase to phosphorylate H2AX, a DNA damage marker. This UL13-mediated H2AX phosphorylation is crucial for efficient PRV replication and virulence.

Area of Science:

  • Virology
  • Molecular Biology
  • Genomics

Background:

  • The DNA damage response (DDR) pathway is essential for genomic stability.
  • Viruses interact with the DDR pathway to promote their replication.
  • Pseudorabies virus (PRV) infection activates DDR, but mechanisms remain unclear.

Purpose of the Study:

  • To investigate the role of PRV infection in activating DDR pathways.
  • To elucidate the function of PRV-encoded serine/threonine kinase UL13 in DDR.
  • To determine the impact of UL13-mediated H2AX phosphorylation on PRV replication and virulence.

Main Methods:

  • PRV infection of cells and analysis of ATM and DNA-PK signaling.
  • Inhibition of ATM and DNA-PK signaling pathways.
  • Investigation of PRV UL13 interaction with and phosphorylation of H2AX.
  • Analysis of UL13 deletion mutants in vitro and in vivo.
  • H2AX knockdown experiments.

Main Results:

  • PRV infection activates ATM and DNA-PK signaling.
  • Inhibition of ATM, not DNA-PK, reduces PRV replication.
  • PRV UL13 kinase interacts with and phosphorylates H2AX.
  • UL13 deletion attenuates PRV neuroinvasiveness and virulence.
  • UL13-mediated H2AX phosphorylation is essential for PRV replication.

Conclusions:

  • PRV-encoded UL13 kinase regulates the DNA damage marker γH2AX.
  • UL13-mediated H2AX phosphorylation is critical for efficient PRV replication and progeny production.
  • UL13 plays a significant role in PRV pathogenesis.
Keywords:
ATMDNA damage responseUL13pseudorabies virusγH2AX

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